Phenothiazines (Systemic)

This monograph includes information on the following:

1) Chlorpromazine
2) Fluphenazine
3) Mesoridazine
4) Methotrimeprazine  *
5) Pericyazine  *
6) Perphenazine
7) Pipotiazine  *
8) Prochlorperazine
9) Promazine  *
10) Thioproperazine  *
11) Thioridazine
12) Trifluoperazine
13) Triflupromazine  


INN:
Methotrimeprazine— Levomepromazine
Pericyazine—Periciazine

BAN:
Pipotiazine—Pipothiazine
Triflupromazine—Fluopromazine


JAN:
Methotrimeprazine—Levomepromazine
Pericyazine—Propericiazine

VA CLASSIFICATION
Chlorpromazine
Primary: CN701
Secondary: GA609; AU305; CN309; CN206

Fluphenazine
Primary: CN701
Secondary: CN103

Mesoridazine
Primary: CN701

Methotrimeprazine
Primary: CN701
Secondary: CN103; CN309; GA609; CN206

Pericyazine
Primary: CN701

Perphenazine
Primary: CN701
Secondary: GA609

Pipotiazine
Primary: CN701

Prochlorperazine
Primary: CN701
Secondary: GA609

Promazine
Primary: CN701

Thioproperazine
Primary: CN701

Thioridazine
Primary: CN701
Secondary: AU305; CN309

Trifluoperazine
Primary: CN701
Secondary: GA609

Triflupromazine
Primary: CN701
Secondary: GA609


Commonly used brand name(s): Apo-Fluphenazine2; Apo-Perphenazine6; Apo-Thioridazine11; Apo-Trifluoperazine12; Chlorpromanyl-201; Chlorpromanyl-401; Chlorpromazine Hydrochloride Intensol1; Compazine8; Compazine Spansule8; Largactil1; Largactil Liquid1; Largactil Oral Drops1; Majeptil10; Mellaril11; Mellaril Concentrate11; Mellaril-S11; Modecate2; Modecate Concentrate2; Moditen Enanthate2; Moditen HCl2; Neuleptil5; Novo-Chlorpromazine1; Novo-Ridazine11; Novo-Trifluzine12; Nozinan4; Nozinan Liquid4; Nozinan Oral Drops4; Nu-Prochlor8; PMS Fluphenazine2; PMS Perphenazine6; PMS Prochlorperazine8; PMS Thioridazine11; PMS Trifluoperazine12; Permitil2; Permitil Concentrate2; Piportil L7; Prolixin2; Prolixin Concentrate2; Prolixin Decanoate2; Prolixin Enanthate2; Serentil3; Serentil Concentrate3; Stelazine12; Stelazine Concentrate12; Stemetil8; Stemetil Liquid8; Thorazine1; Thorazine Spansule1; Trilafon6; Trilafon Concentrate6; Vesprin13.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

*Not commercially available in the U.S.

Not commercially available in Canada.



Category:


Antipsychotic—Chlorpromazine ; Fluphenazine; Mesoridazine; Methotrimeprazine; Perphenazine; Pipotiazine ; Prochlorperazine; Promazine; Thioproperazine; Thioridazine; Trifluoperazine ; Triflupromazine;

Antipsychotic adjunct— Pericyazine;

Antiemetic—Chlorpromazine ; Methotrimeprazine; Perphenazine; Prochlorperazine ; Trifluoperazine; Triflupromazine;

Analgesic—Methotrimeprazine ;

Sedative—Chlorpromazine ; Methotrimeprazine; Thioridazine;

Antidyskinetic (Huntington's chorea) —Chlorpromazine; Thioridazine;

Antineuralgia adjunct— Fluphenazine;

Anesthetic adjunct— Chlorpromazine; Methotrimeprazine (intravenous) ;

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Psychotic disorders (treatment)—Chlorpromazine {75}7 {75}6, fluphenazine {75}5 {75}4, mesoridazine {75}3 {75}2, methotrimeprazine {75}1, perphenazine {75}0 {02}9, pipotiazine {02}8, prochlorperazine {02}7 {02}6, promazine {02}5, thioproperazine {02}4, thioridazine {02}3, trifluoperazine {02}2 {02}1, and triflupromazine {02}0 are indicated in the management of manifestations of psychotic conditions. They are clearly effective in schizophrenia , and produce a quieting effect in hyperactive or excited psychotic patients.

Note: Thioridazine and mesoridazine are indicated for the management of schizophrenic patients who fail to respond adequately to treatment with other antipsychotic drugs. Due to the risk of significant, potentially life-threatening, proarrhythmic effects with thioridazine and mesoridazine treatment, it is strongly recommended that a patient be given at least 2 trials, each with a different antipsychotic drug product, at an adequate dose, and for an adequate duration{75}9{75}8.


Note: Mesoridazine has not been proven to be effective in the treatment of refractory schizophrenic patients, as it has not been evaluated in clinical trials.{75}7

—Methotrimeprazine is used in elderly patients for the management of psychosis associated with dementia {75}6.
—Chlorpromazine {75}5 {75}4, methotrimeprazine {75}3, and thioproperazine {75}2 are indicated in the management of manifestations of the manic phase of manic-depressive illness.
—[Chlorpromazine], [fluphenazine ] {75}1, mesoridazine {75}0, [ thioridazine] , and [trifluoperazine] {02}9 are used in the treatment of adults with severe behavior problems associated with psychotic disorders who show combativeness and/or explosive, hyperexcitable behavior that is out of proportion to the immediate provocation. Chlorpromazine {02}8 {02}7, [ mesoridazine] , thioridazine {02}6, and [ trifluoperazine] {02}5 also are used in the treatment of children with severe behavior problems associated with psychotic disorders who show combativeness and/or explosive, hyperexcitable behavior that is out of proportion to the immediate provocation and in whom other approaches to management have failed {02}4.
—Long-acting parenteral forms, fluphenazine decanoate {02}3 and enanthate {02}2 {02}1 and pipotiazine palmitate {02}0, are indicated for the maintenance treatment of nonagitated patients with chronic schizophrenia who are stabilized with shorter-acting neuroleptics and who may benefit from transfer to a longer-acting drug.

Psychotic disorders (treatment adjunct)—Pericyazine is indicated as an adjunctive medication for the control of residual prevailing hostility, impulsivity, and aggressiveness in patients with psychoses {07}9.

Nausea and vomiting (treatment)—Prochlorperazine {07}8 {07}7, chlorpromazine {07}6 {07}5 {07}4, methotrimeprazine {07}3, perphenazine {07}2 {07}1, [trifluoperazine ] {07}0, and triflupromazine {65}9 are indicated in the control of severe nausea and vomiting in selected patients, with prochlorperazine being superior to other phenothiazines.

Pain (treatment)—Methotrimeprazine is indicated for the relief of moderate to severe pain in nonambulatory patients, and for the production of obstetrical analgesia when respiratory depression should be avoided {65}8.

Sedation—Methotrimeprazine is indicated as a presurgical or obstetrical medication to produce sedation and somnolence {65}7.
—Chlorpromazine is indicated for relief of apprehension and restlessness before surgery {65}6 {65}5 {65}4.

Anesthesia, general, adjunct—[Chlorpromazine ] {65}3 and intravenously-administered methotrimeprazine {65}2 are indicated as adjuncts to anesthesia, to increase the effects of anesthetics. The dose of a barbiturate or narcotic should be reduced by at least one half when used with chlorpromazine or methotrimeprazine during surgery or labor {65}1 {65}0.

Tetanus (treatment adjunct)1—Chlorpromazine is indicated, usually in conjunction with a barbiturate, for the treatment of tetanus {07}9.

Porphyria, acute, intermittent (treatment)1—Chlorpromazine is indicated in the treatment of acute intermittent porphyria {07}8 {07}7.

Hiccups, intractable (treatment)—Chlorpromazine is indicated for the relief of intractable hiccups {07}6 {07}5 {07}4.

[Pain, neurogenic (treatment adjunct) ]1—Fluphenazine has been used as an adjunct to tricyclic antidepressant therapy for some chronic pain states, such as in patients trying to withdraw from narcotics, and in treatment of symptoms of diabetic neuropathy {07}3.

[Huntington's disease, choreiform movement of (treatment)]1—Chlorpromazine and thioridazine are effective in reducing choreiform movement in Huntington's disease {07}2 {07}1, and have been used as alternatives to haloperidol.

Behavior problems, severe (treatment)—[ Chlorpromazine], [fluphenazine] {07}0, mesoridazine {07}9, [thioridazine ] , and [trifluoperazine] {07}8 may be used in the treatment of adults with severe behavior problems associated with neurologic disease other than Pretension's disease who show combativeness and/or explosive, hyperexcitable behavior that is out of proportion to the immediate provocation and in whom other approaches to management have failed {07}7.
—Chlorpromazine {07}6 {07}5, [ mesoridazine] , thioridazine {07}4, and [ trifluoperazine] {07}3 also may be used when other approaches to management have failed in the treatment of children with severe behavior problems associated with neurologic disease other than juvenile Pretension's disease and in the short-term treatment of hyperactive children who show excessive motor activity with accompanying conduct disorders such as impulsivity, mood lability, aggressiveness, short attention span, and poor frustration tolerance. Their use is acceptable only in children who are displaying combative, dangerous, or destructive behaviors {07}2.

—In exceptional cases, thioridazine {07}1 may be used in the short-term treatment of geriatric patients with multiple symptoms, such as anxiety, agitation, depressed mood, tension, sleep disturbances, and fears. However, because of the anticholinergic effects of thioridazine and the availability of safer antipsychotic medications, its use should be restricted to those patients in whom several other approaches to management have been tried and have failed {07}0.

—Although prochlorperazine and trifluoperazine have been used in the treatment of nonpsychotic anxiety {07}9 {07}8, they generally have been replaced by less potentially harmful agents. Their use for this indication may be acceptable only in unusual cases after several non-antipsychotic approaches to treatment have been tried and have failed and the potential benefit outweighs the risks associated with these drugs {07}7.

—Thioridazine {07}6 has been used in the short-term treatment of adult patients with moderate to severe mental depression with varying degrees of anxiety. However, this medication generally has been replaced by less potentially harmful agents and its use for this indication may be acceptable only in unusual cases after several other approaches to treatment have been tried and have failed {07}5.

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:

Chemical group—
    Aliphatic: Chlorpromazine {07}4; methotrimeprazine {07}3; promazine {07}2 {07}1; triflupromazine {07}0
    Piperazine: Fluphenazine {07}9 {07}8; perphenazine {07}7 {07}6; prochlorperazine {07}5; thioproperazine {07}4; trifluoperazine {07}3 {07}2
    Piperidine: Mesoridazine {07}1 {07}0; pericyazine {02}9; pipotiazine {02}8; thioridazine {02}7
Molecular weight—
    Chlorpromazine: 318.87 {02}6
    Chlorpromazine hydrochloride: 355.33 {02}5
    Fluphenazine decanoate: 591.8 {02}4
    Fluphenazine enanthate: 549.70 {02}3
    Fluphenazine hydrochloride: 510.45 {02}2
    Mesoridazine besylate: 544.77 {02}1
    Methotrimeprazine: 328.48 {02}0
    Pericyazine: 365.50 {07}9
    Perphenazine: 403.98 {07}8
    Pipotiazine palmitate: 714.10 {07}7
    Prochlorperazine: 373.95 {07}6
    Prochlorperazine edisylate: 564.15 {07}5
    Prochlorperazine maleate: 606.10 {07}4
    Prochlorperazine mesylate: 566.2 {07}3
    Promazine hydrochloride: 320.89 {07}2
    Thioproperazine mesylate: 638.84 {07}1
    Thioridazine: 370.59 {07}0
    Thioridazine hydrochloride: 407.05 {02}9
    Trifluoperazine hydrochloride: 480.43 {02}8
    Triflupromazine: 352.43 {02}7
    Triflupromazine hydrochloride: 388.89 {02}6

Mechanism of action/Effect:

Antipsychotic—Thought to improve psychotic conditions by blocking postsynaptic {02}5 dopamine D 2 receptors {02}4 in the mesolimbic area of the brain {02}3 and by producing alpha-adrenergic blockade {02}2 {02}1.

Antiemetic—Phenothiazines act centrally to inhibit or block the dopamine D 2 receptors in the medullary chemoreceptor trigger zone (CTZ) and peripherally by blocking the vagus nerve in the gastrointestinal tract. The antiemetic effects of phenothiazines may be augmented by their anticholinergic, sedative, and antihistaminic effects. {02}0

Analgesic; sedative—Methotrimeprazine raises pain threshold and produces amnesia by suppression of sensory impulses. The alpha-adrenergic blocking effects of phenothiazines may produce sedation and tranquilization {07}9.


Other actions/effects:


Drug
Action *

 
Legend:
I=Antiemetic
II=Anticholinergic
III=Extrapyramidal
IV=Hypotensive
V=Sedative

I
 
II
 
III
 
IV
 
V
 
Aliphatic
 
         
Chlorpromazine
S {07}8
S {07}7 {07}6
W {07}5 {07}4–M {07}3
S {07}2 {07}1
S {07}0 {02}9
Methotrimeprazine
S {02}8
M–S {02}7
W {02}6–M {02}5
S {02}4
S {02}3 {02}2
Promazine
M
S {02}1
W
S
S {02}0
Triflupromazine
S
S
M {07}9 {07}8
M {07}7
M {07}6–S {07}5
Piperazine
 
         
Fluphenazine
W {07}4
W {07}3 {07}2
S {07}1 {07}0
W {02}9 {02}8
W {02}7 {02}6
Perphenazine
S
W {02}5 {02}4–M
S {02}3 {02}2
W {02}1 {02}0
W {75}9 {75}8–M
Prochlorperazine
S
W {75}7
S {75}6 {75}5
W {75}4 {75}3
W {75}2 {75}1–M
Thioproperazine
W
W {75}0
S {31}9 {31}8
W {31}7 {31}6
W {31}5 {31}4
Trifluoperazine
S {31}3
W {31}2 {31}1
S {31}0 {31}9
W {31}8 {31}7
W {31}6 {31}5
Piperidine
 
         
Mesoridazine
W
M
W {31}4 {31}3
M {31}2–S {31}1 {31}0
S {75}9 {75}8
Pericyazine
S {75}7
S {75}6 {75}5
M
M
S {75}4 {75}3
Pipotiazine
W
W {75}2
S {75}1
W {75}0
W {40}9
Thioridazine
W {40}8
M–S {40}7
W {40}6 {40}5
M–S {40}4 {40}3
M–S
* S=strong; M=moderate; W=weak



Blockade of dopaminergic {40}2 {40}1 and alpha-adrenergic {40}0 receptors in the tuberoinfundibular system {31}9 by phenothiazines alters the release of hypothalamic and pituitary (hypophyseal) hormones {31}8, leading to increases in prolactin concentrations that persist throughout treatment {31}7 {31}6 {31}5.

Electrocardiogram (ECG) changes that reflect abnormal cardiac repolarization, including prolongation of the QT c interval, have been observed in patients taking phenothiazines {31}4. Sudden and unexpected deaths due to cardiac arrest have occurred in patients taking phenothiazines who previously had been found to have these ECG changes {31}3 {31}2. Thioridazine is the phenothiazine most frequently involved in cases of sudden cardiac death {31}1.

The cough reflex–suppressant effect of phenothiazines may increase the risk of aspiration {31}0 or asphyxia {31}9 {31}8.

Phenothiazines lower the seizure threshold {31}7.

Absorption:

Absorption may be erratic and peak plasma concentrations show large interindividual differences {31}6 {31}5, possibly due to large interindividual differences in extent of first-pass metabolism {31}4.

Distribution:

Phenothiazines have a large volume of distribution {31}3 {31}2, readily cross the placenta {31}1 {31}0, and are distributed into breast milk {75}9 {75}8 {75}7.

Protein binding:

Very high {75}6 (90% or more) {75}5.

Biotransformation:

Hepatic {75}4 {75}3 to active and inactive metabolites {75}2. Because parenteral administration bypasses first-pass metabolism, the proportions of parent drug and metabolites present in the circulation may differ with different routes of administration {75}1. Depending on the contributions of the parent drug and each metabolite to efficacy and/or adverse effects, these differences in proportion can result in differences in effects, leading the patient to experience the oral and parenteral dosage forms of the same medication differently {75}0.

Cytochrome P450 2D6 (CYP2D6) has been shown to be involved in the metabolism of perphenazine {40}9 and thioridazine {40}8.

Mesoridazine is an active metabolite of thioridazine {40}7.

Onset of action:


Antipsychotic effect:

Gradual (up to several weeks {40}6 {40}5) and variable between patients {40}4.



Long-acting parenteral dosage forms:

Fluphenazine decanoate injection: Antipsychotic effects usually begin between 24 and 72 hours after administration and become significant within 48 to 96 hours {40}3.

Pipotiazine palmitate injection: Antipsychotic effects usually begin within the first 48 to 72 hours after administration and become significant within 1 week {40}2.


Time to peak effect:

Antipsychotic effect—Approximately 4 to 7 days to achieve steady-state plasma concentrations with oral dosage forms {40}1, and 4 to 6 weeks with depot dosage forms {40}0; peak therapeutic effects may take from 6 weeks to 6 months {31}9.

Antipsychotic and antiemetic effects (perphenazine)—1 to 2 hours after intramuscular injection, maintained for an average of 6 hours {31}8.

Analgesic effect (methotrimeprazine)—Within 20 to 40 minutes after intramuscular injection, maintained for about 4 hours {31}7.

Elimination:
    Renal and biliary {31}6 {31}5 {31}4, with some enterohepatic recycling {31}3.
    In dialysis—Phenothiazines are not successfully dialyzed {31}2 {31}1 because of their high protein binding and large volume of distribution {31}0.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to one phenothiazine may be sensitive to other phenothiazines also {31}9 {31}8 {31}7.

Tumorigenicity

Phenothiazines produce an elevation in prolactin concentrations, which persists throughout administration. Tissue culture experiments indicate that approximately one third of human breast cancers are prolactin-dependent in vitro , a factor of potential importance if the prescription of these medications is contemplated in a patient with a previously detected breast cancer. Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported, the clinical significance of elevated serum prolactin concentrations is unknown for most patients. An increase in mammary neoplasms has been found in rodents after chronic administration of antipsychotic medications. However, neither clinical studies nor epidemiologic studies conducted to date have shown an association between long-term administration of these medications and mammary tumorigenesis; the available evidence is considered too limited to be conclusive at this time. {31}6 {31}5 {31}4

Pregnancy/Reproduction
Fertility—
Animal studies with several phenothiazines have shown a decrease in fertility {31}3 {31}2 {31}1.

Pregnancy—
Phenothiazines are not recommended for use during pregnancy {31}0 {75}9. Phenothiazines cross the placenta {75}8 {75}7 {75}6. Although adequate and well-controlled studies in humans have not been done, there have been reports of prolonged jaundice, hyporeflexia or hyperreflexia, and extrapyramidal effects in the neonates of mothers who received phenothiazines during pregnancy {75}5 {75}4 {75}3 {75}2.

Chlorpromazine: Reproductive studies in rodents have shown a potential for embryotoxicity, increased neonatal mortality, and decreased performance of the offspring in administered tests {75}1 {75}0. The possibility of permanent neurological damage in offspring of rodent mothers cannot be excluded {40}9.

Fluphenazine: Withdrawal effects, including severe rhinorrhea, vomiting, respiratory distress, and extrapyramidal effects, have been reported in neonates following in utero exposure to fluphenazine throughout gestation {40}8. Single injections of the decanoate dosage form during gestation in rabbits and rats revealed no teratogenic effects {40}7. However, in rabbits, a dose of 5.6 mg per kg of body weight (mg/kg) may have interfered with implantation and also may have contributed to delayed ossification in the fetuses {40}6.

Mesoridazine: Intrauterine resorptions were increased in rats and rabbits given 70 mg/kg and 125 mg/kg of mesoridazine, respectively {40}5. However, no drug-related teratology was seen {40}4.

Methotrimeprazine: Reproductive studies in animals and clinical experience have failed to show a teratogenic effect. However, a possible antifertility effect has been suggested since successive generations of animals administered methotrimeprazine have shown smaller litter sizes than those of controls. {40}3

Pericyazine: Reproductive studies in rats and rabbits failed to show a teratogenic effect {40}2. However, in the rats, which were administered pericyazine from 33 days precoitus throughout pregnancy and lactation, the average pairing-to-birth interval was lengthened, indicating a possible antifertility effect {40}1. In mice administered 5 to 15 mg/kg of pericyazine from 8 to 14 days postcoitus, increased fetal death and delayed ossification were seen {40}0.

Pipotiazine: No teratogenic effects were seen in reproductive studies in mice, rats, and rabbits {31}9. However, when pipotiazine was administered to rats (5 mg/kg and 15 mg/kg) and rabbits (10 mg/kg and 20 mg/kg) throughout pregnancy, fetal toxicity, increased fetal resorption, and inhibited intrauterine fetal growth were seen {31}8.

Thioridazine: Reproductive studies in animals and clinical experience have failed to show a teratogenic effect {31}7.

Trifluoperazine: Reproductive studies in rats given more than 600 times the human dose showed an increased incidence of malformations and reduced weight and litter size linked to maternal toxicity {31}6.

All phenothiazines—FDA pregnancy categories are not included in product labeling presently.

Breast-feeding

Phenothiazines are distributed into breast milk {31}5 {31}4 and may cause drowsiness or movement disorders in the nursing infant {31}3. Breast-feeding while receiving phenothiazines is not recommended {31}2.

Pediatrics

Children are prone to develop neuromuscular or extrapyramidal reactions {31}1, especially dystonias, and should be closely monitored while receiving therapeutic doses of phenothiazines. Children with acute illnesses, such as chickenpox, central nervous system (CNS) infections, measles, gastroenteritis, and dehydration, are especially at risk {31}0.


Geriatrics


Geriatric patients tend to develop higher plasma concentrations of phenothiazines {75}9. Therefore, these patients usually require lower initial dosage and a more gradual titration of dosage {75}8 {75}7.

Elderly patients appear to be more prone to orthostatic hypotension {75}6 {75}5 and exhibit an increased sensitivity to the anticholinergic and sedative effects of phenothiazines. In addition, they are more prone to develop extrapyramidal side effects {75}4, such as tardive dyskinesia {75}3 and parkinsonism {75}2.

It has been suggested that elderly patients receive half the usual adult dose. Patients with organic mental disorders or acute confusional states should initially receive one third to one half the usual adult dose {75}1, with the dose being increased no more frequently than every 2 or 3 days, preferably at intervals of 7 to 10 days, if possible. After clinical improvement occurs, periodic attempts should be made to discontinue medication {75}0 {31}9.


Pharmacogenetics

Cytochrome P450 2D6 (CYP2D6) has been shown to be involved in the metabolism of perphenazine {31}8 {31}7 and thioridazine {31}6. Approximately 7% of the white population are poor metabolizers of CYP2D6 substrates due to genotype and have reduced clearance and higher plasma concentrations of these medications {31}5 {31}4 {31}3. Single-dose studies have shown plasma concentrations of perphenazine and thioridazine to be about four times higher in poor metabolizers than in extensive metabolizers {31}2. However, one study of perphenazine serum concentrations corrected for dose (C/dose) at steady-state showed less variation in perphenazine C/dose between poor metabolizers and extensive metabolizers (twofold) than between individual subjects (thirtyfold) {31}1.


Dental

The peripheral anticholinergic effects of phenothiazines may decrease or inhibit salivary flow, especially in middle-aged or elderly patients, thus contributing to the development of caries, periodontal disease, oral candidiasis, and discomfort {31}0.

Extrapyramidal reactions induced by phenothiazines will result in increased motor activity of the head, face, and neck. Occlusal adjustments, bite registrations, and treatment for bruxism may be made less reliable. {07}9

The leukopenic and thrombocytopenic effects of phenothiazines may result in an increased incidence of microbial infection, delayed healing, and gingival bleeding. If leukopenia or thrombocytopenia occurs, dental work should be deferred until blood counts have returned to normal, and patients should be instructed in proper oral hygiene, including caution in use of regular toothbrushes, dental floss, and toothpicks.

Surgical

Patients receiving phenothiazines who must undergo surgery should be closely monitored for hypotension {07}8 {07}7. Also, dosage reductions of anesthetics and other CNS depressants are recommended {07}6 {07}5 {07}4.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: The isoenzyme cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of perphenazine {07}3 {07}2, thioridazine {07}1{07}0, and possibly other phenothiazines {07}9. Concurrent use of inhibitors of CYP2D6 and phenothiazines may lead to increased phenothiazine plasma concentrations and increased risk of developing adverse effects {07}8, including changes in cardiac rhythm {07}7{07}6. Also, phenothiazine use may inhibit the metabolism of other medications that are metabolized by CYP2D6 {07}5. Therefore, possible interactions between phenothiazines and medications that inhibit CYP2D6 or that are substrates of CYP2D6, other than those listed below, should be considered {07}4.
Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Alcohol or
» CNS depression–producing medications, other (see Appendix II )    (prolonged and intensified CNS {07}3 {07}2 {07}1 and respiratory depression {07}0 {07}9 and increased hypotensive effects {07}8 may occur during concurrent or sequential use {07}7; dosage reductions may be necessary, except that dosage of anticonvulsant medications should not be decreased {07}6 {07}5)

    (use of a high dose of barbiturate with mesoridazine has resulted in respiratory arrest {07}4)

    (dosage of CNS depressants such as anesthetics, barbiturates, and narcotics should be reduced by 50 to 75% when used with a phenothiazine {07}3 {07}2 {07}1, except in the case of anticonvulsant use of a barbiturate {07}0)

    (barbiturates {07}9 and carbamazepine {07}8 increase the metabolism of phenothiazines by induction of hepatic microsomal enzymes, thus decreasing plasma concentrations, and possibly the therapeutic effect, of the phenothiazine)

    (alcohol may increase the risk of heatstroke in patients receiving phenothiazines {07}7 {07}6)


Amantadine or
Anticholinergics or other medications with anticholinergic action (see Appendix II )    (anticholinergic side effects of these medications and/or phenothiazines may be intensified {07}5 {07}4; the hyperpyretic effect of phenothiazines may be potentiated by the loss of sweating as a cooling mechanism {07}3, possibly leading to heatstroke {07}2, especially when environmental temperatures are high {07}1; because of increased risk of paralytic ileus due to decreased intestinal motility, patients should be advised to report occurrence of gastrointestinal problems {07}0 {07}9 {07}8)

    (parenteral methotrimeprazine, used as preanesthetic medication, may be administered concurrently, but with caution, with lowered doses of atropine or scopolamine; tachycardia and a fall in blood pressure may occur, and CNS reactions, such as stimulation, delirium, and extrapyramidal reactions, may be aggravated {07}7)


Amphetamines    (stimulant effects may be decreased when amphetamines are used concurrently with phenothiazines since phenothiazines produce dopamine D 2 receptor blockade; also, the antipsychotic effectiveness of phenothiazines may be reduced)


Antacids, aluminum- or magnesium-containing or
Antidiarrheals, adsorbent    (ingestion of these medications within 2 hours of a phenothiazine may inhibit the absorption of an orally administered phenothiazine {07}6)


Anticoagulants, oral    (effects may be decreased by phenothiazines {07}5 {07}4)


Anticonvulsants, including barbiturates    (phenothiazines may lower the seizure threshold; dosage adjustment of anticonvulsant medications may be necessary {07}3 {07}2)

    (phenothiazines may inhibit phenytoin metabolism, leading to phenytoin toxicity {07}1 {07}0 {07}9)


» Antidepressants, tricyclic or
» Fluoxetine or
» Fluvoxamine or
» Paroxetine or
» Maprotiline    (concurrent use may prolong and intensify the sedative and anticholinergic effects of either these medications or phenothiazines {07}8; plasma concentrations of antidepressants and/or phenothiazines may be increased by mutual inhibition of metabolism {07}7 {07}6{07}5; the risk of neuroleptic malignant syndrome [NMS] may be increased {07}4; QT interval–prolonging effects of these medications and phenothiazines increase the risk of developing cardiac arrhythmias {07}3{07}2)


» Antithyroid agents    (concurrent use with phenothiazines may increase the risk of agranulocytosis {07}1)


Apomorphine    (prior ingestion of phenothiazine antiemetics may decrease the emetic response to apomorphine {07}0; also, the CNS depressant effects of phenothiazine antiemetics are additive to those of apomorphine and may induce dangerous respiratory depression, circulatory system effects, or prolonged sleep)


Appetite suppressants    (concurrent use with phenothiazines may antagonize the anorectic effect of appetite suppressants)


Beta-adrenergic blocking agents    (concurrent use of beta-blocking agents, possibly including ophthalmics, with phenothiazines may result in increased plasma concentrations of both medications {07}9 {07}8{07}7 because of inhibition of metabolism; this may result in additive hypotensive effects {07}6, irreversible retinopathy, cardiac arrhythmias, and tardive dyskinesia {07}5)

    (increases in plasma levels of thioridazine and its metabolites of 50 to 400% and 80 to 300%, respectively, have been reported with concurrent propranolol use {07}4)


Bromocriptine    (increased serum prolactin concentrations induced by phenothiazines may interfere with effects of bromocriptine; dosage adjustments may be necessary )


Diuretics, thiazide    (concurrent use may potentiate orthostatic hypotension {07}3 {07}2, hyponatremia {07}1, and water intoxication {07}0; alternate methods of hypertension control should be considered {36}9)


» Extrapyramidal reaction–causing medications, other (see Appendix II )    (concurrent use with phenothiazines may increase the severity and frequency of extrapyramidal effects)


Hepatotoxic medications, other (see Appendix II )    (concurrent use of phenothiazines with medications known to alter hepatic microsomal enzyme activity may result in an increased incidence of hepatotoxicity; patients, especially those on prolonged administration or with a history of liver disease, should be carefully monitored)


» Hypotension-producing medications, other (see Appendix II )    (concurrent use with phenothiazines may produce severe hypotension {36}8 {36}7 with postural syncope {36}6)

    (the antihypertensive effect of guanethidine may be antagonized by phenothiazines {36}5)


» Levodopa    (antiparkinsonian effects of levodopa may be inhibited when it is used concurrently with phenothiazines {36}4 because of blockade of dopamine receptors in the brain)


» Lithium    (an encephalopathic syndrome has been reported in a few patients receiving lithium concurrently with antipsychotic medications {36}3 {36}2; symptoms have included weakness, lethargy, fever, tremulousness, confusion, extrapyramidal symptoms, and, in some cases, irreversible brain damage {36}1 {36}0 {36}9; patients receiving this combination should be monitored closely for evidence of neurological toxicity {36}8 {36}7)

    (concurrent use with chlorpromazine and possibly other phenothiazines may reduce gastrointestinal absorption of the phenothiazine, thereby decreasing its serum concentrations {36}6 by as much as 40%; concurrent use may increase rate of renal excretion of lithium {36}5; extrapyramidal symptoms may be increased {36}4; also, nausea and vomiting, early indications of lithium toxicity, may be masked by the antiemetic effect of some phenothiazines)


» Metrizamide    (risk of having seizures is increased with intrathecal metrizamide administration; phenothiazines should be discontinued at least 48 hours before, and not resumed for at least 24 hours following, myelography {36}3)


Opioid (narcotic) analgesics    (in addition to increased CNS and respiratory depression, concurrent use with phenothiazines increases orthostatic hypotension and increases the risk of severe constipation, which may lead to paralytic ileus and/or urinary retention {36}2)


Ototoxic medications, especially ototoxic antibiotics (see Appendix II )    (phenothiazines may mask some symptoms of ototoxicity such as tinnitus, dizziness, or vertigo)


Paroxetine    (the CNS effects of perphenazine were shown to be increased in five subjects when paroxetine was added to perphenazine treatment {36}1; paroxetine may interfere with the metabolism of phenothiazines through inhibition of CYP2D6 {36}0)


Photosensitizing medications, other    (concurrent use with phenothiazines may cause additive photosensitizing effects)

    (in addition, concurrent use of systemic methoxsalen, trioxsalen, or tetracyclines with phenothiazines may potentiate intraocular photochemical damage to the choroid, retina, or lens {36}9 {36}8)


» QT interval–prolonging medications, other, including:
Astemizole or
Cisapride or
Disopyramide or
Erythromycin or
Pimozide or
Probucol or
Procainamide or
Quinidine    (additive QT interval prolongation may increase the risk of developing cardiac arrhythmias {36}7 {36}6)


Succinylcholine    (concurrent use with methotrimeprazine may cause tachycardia and a fall in blood pressure, CNS stimulation and delirium, and an aggravation of extrapyramidal effects {36}5)


Sympathomimetic agents for cardiovascular use, especially:
» Epinephrine    (the alpha-adrenergic blocking action of phenothiazines may reduce the pressor response to these medications and reduce their duration of action {36}4 {36}3)

    (sympathomimetics that stimulate both alpha- and beta-adrenergic receptors, such as epinephrine, may lead to hypotension and tachycardia when used with a phenothiazine, due to unopposed beta-adrenergic stimulation {36}2 {36}1 {36}0)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
Bilirubin tests, urine    (phenothiazine use may produce false-positive results {36}9 {36}8 due to the presence of metabolites in urine {36}7)


» Electrocardiogram (ECG) readings    (prolonged QT c intervals {36}6, lowered and inverted T waves, and the appearance of waves that may be bifid T or U waves have been reported {36}5 {36}4 {36}3; ECG changes seem to be caused by altered repolarization {36}2 and not by myocardial damage {36}1 {36}0 {13}9; however, deaths, presumably due to cardiac arrest, have occurred in patients who previously had shown these ECG changes during phenothiazine treatment {13}8 {13}7; ECG changes and sudden death have been seen more frequently with thioridazine use than with use of other phenothiazines {13}6 {13}5; the predictive utility of monitoring ECGs in patients taking phenothiazines is questionable {13}4 {13}3)


Gonadorelin test for hypothalamic-pituitary gonadotropic function     (phenothiazines may blunt the response to gonadorelin by increasing serum prolactin concentrations {13}2)


Metyrapone test of hypothalamic-pituitary complex    (interference may be caused by reduction of adrenocorticotropic hormone [ACTH] secretion due to phenothiazine use {13}1)


Phenylketonuria (PKU) test    (phenothiazines may produce false-positive results {13}0 {36}9 {36}8)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medicine should not be used when the following medical problems exist:
» Cardiovascular disease, severe hypertension or hypotension {36}7{36}6 or
» CNS depression, severe {36}5 {36}4 {36}3 or
» Comatose states or{36}2 {36}1 {36}0
» Congenital long QT syndrome or{36}9
» History of cardiac arrhythmias or{36}8
» Known genetic defect leading to reduced levels of activity of P450 2D6 isozyme activity {36}7    (may be exacerbated)


Risk-benefit should be considered when the following medical problems exist
» Alcoholism, active    (CNS depression {36}6 and hypotension {36}5 {36}4 may be potentiated; risk of heatstroke may be increased {36}3 {36}2; chronic alcohol abusers may be predisposed to hepatotoxic reactions during phenothiazine therapy {36}1; dosage reduction may be necessary {36}0)


Angina pectoris    (pain may be increased if phenothiazine treatment leads to an increase in physical activity {36}9 {36}8 {36}7)


» Blood dyscrasias    (may be exacerbated {36}6; treatment may have to be discontinued {36}5)


» Brain damage, subcortical or
» Cerebral atherosclerosis, marked    (a severe hyperthermic reaction may occur, sometimes 14 to 16 hours after phenothiazine administration {36}4 {36}3 {36}2)


Breast cancer    (potentially higher risk of disease progression and possible increased resistance to endocrine and cytotoxic treatment, due to phenothiazine-induced prolactin secretion {36}1 {36}0)


» Cardiac reserve deficiency, such as mitral insufficiency, severe or
» Cerebrovascular insufficiency or
» Pheochromocytoma or
» Renal insufficiency    (severe hypotension is more likely to occur {36}9 {36}8 {36}7 {36}6)


Cardiovascular disease {36}5    (increased risk of hypotension {36}4 and/or exacerbation of condition by phenothiazine-induced hypotension {36}3 {36}2; ECG changes related to repolarization have been seen in some patients without cardiovascular disease who were taking phenothiazines {36}1; myocardial depression, cardiomegaly, congestive heart failure [CHF], and arrhythmias may be induced)


Conditions for which vomiting is a sign, such as:
Brain tumor
Drug overdose
Intestinal obstruction
» Reye's syndrome    (diagnosis may be obscured by the antiemetic effect of phenothiazines {36}0 {36}9 {36}8; less likely with thioridazine {36}7)

    (increased risk of hepatotoxicity in children and adolescents with Reye's syndrome {36}6)


Glaucoma, or predisposition to    (may be potentiated by anticholinergic effects of phenothiazines {36}5 {36}4 {36}3)


» Hepatic function impairment    (phenothiazines can cause hepatic dysfunction {36}2 {36}1 {36}0)

    (metabolism may be decreased; higher serum phenothiazine concentrations may increase CNS effects {36}9)

    (patients with a history of hepatic encephalopathy due to cirrhosis have increased sensitivity to the CNS effects of phenothiazines {36}8)


Parkinson's disease    (potentiation of extrapyramidal effects {36}7)


Peptic ulcer or
Urinary retention    (may be exacerbated {36}6; phenothiazines have caused bladder paralysis in some patients {36}5)


Prostatic hypertrophy, symptomatic    (increased risk of urinary retention {36}4 {36}3)


Respiratory disorders, chronic, especially in children    (may be potentiated due to CNS depressant effect of phenothiazines {36}2 {36}1 {36}0; also, cough-suppressant effects of phenothiazines may be especially problematic in these patients {36}9)


Seizure disorders, or history of    (seizures may be precipitated {36}8 {36}7 {36}6)


» Sensitivity to any phenothiazine, or history of    (may be potentiated upon re-exposure to any phenothiazine in patients with a history of phenothiazine-induced blood dyscrasias, jaundice, or skin reactions {36}5 {36}4 {36}3)


Sensitivity to parabens, sulfites, or tartrazine    (some dosage forms of phenothiazines contain parabens {36}2, sulfites {36}1 {36}0 {36}9, or tartrazine [FD&C Yellow No. 5] {36}8)


Caution should also be used in geriatric, emaciated, and debilitated patients, who usually require a lower initial dose {36}7 , and in patients who will be exposed to organophosphate or carbamate pesticides {36}6 {36}5 , extreme heat {36}4 {36}3 {36}2 , or extreme cold {36}1 .

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Abnormal-movement determinations and
» Careful observation for early signs of tardive dyskinesia     (recommended at periodic intervals, especially in the elderly and in patients on high-dose or long-term maintenance therapy; reduction of the phenothiazine dosage, if clinically feasible, will aid in the detection of tardive dyskinesia since the medication may mask the syndrome {36}0 {36}9 {36}8; since there is no known effective treatment, the phenothiazine should be discontinued, if possible, or the dosage should be reduced at earliest signs, usually fine, worm-like movements of the tongue, to stop further development {36}7 {36}6 {36}5)

    (for institutionalized patients, recommended every 2 {36}4 to 3 {36}3 months during therapy using the abnormal involuntary movement scale [AIMS], and again at 8 to 12 weeks after therapy has been discontinued {36}2)


Blood cell counts and differential in patients with sore throat and fever or infections    (may be required during high-dose or prolonged therapy when symptoms of infection develop; agranulocytosis is most likely to occur between the 4th and 10th weeks of therapy; if significant cellular depression occurs, medication should be discontinued and appropriate therapy initiated; rechallenge in recovered patients will usually cause a recurrence of agranulocytosis; use of alternate neuroleptics, such as haloperidol or thioxanthenes, is recommended {36}1)


Blood pressure measurements    (recommended periodically to detect hypotension; fatal hypotension has occurred with phenothiazine use {36}0)


ECG, baseline measurement    (Patients being considered for treatment with thioridazine should have a baseline ECG performed. Patients with a QTc interval greater than 450 msec should not receive thioridazine. Periodic ECG's during thioridazine treatment may be useful and it should be discontinued in patients who are found to have a QTc interval over 500 msec {01})


Hepatic function determinations and
Urine tests for bilirubin and bile    (may be required at periodic intervals during prolonged therapy {07} {58}, or if jaundice or influenza-like symptoms occur {08}, to detect liver function impairment; jaundice is most likely to occur between the 2nd and 4th weeks of therapy and is thought to be a sensitivity reaction {08} {81}; phenothiazine should be discontinued if bilirubinemia, bilirubinuria, or jaundice occurs {08})


Ophthalmologic examinations    (recommended, if possible, prior to initiation of phenothiazine therapy as a baseline; initial screening should include measurement of visual acuity with and without refraction, a color vision test to detect possible central defects, and, if feasible, a slit-lamp microscopy study of the fundus and examination of the visual fields {76}. Tests may be required at periodic intervals [usually every 6 to 12 months] {03} during high-dose or prolonged therapy, since deposition of particulate matter in the lens and cornea has occurred with some phenothiazines {08} {38}, especially thioridazine {106}; therapy should be discontinued if corneal, retinal, or lens changes are noticed {03}; blurred vision, defective color vision, and night blindness are early symptoms of pigmentary retinopathy and may be reversible if the phenothiazine is discontinued in the early stages {69})


Phenothiazine concentrations, serum    (although generally not useful in determining dosage {18}, determinations may be useful when toxicity {13} or poor response {13} {18} occurs, or when noncompliance is suspected {13} {18})


» Potassium levels, serum    (patients being considered for thioridazine treatment should have a baseline serum potassium level measurement. Serum potassium should be normalized before starting treatment. Periodic serum potassium levels during thioridazine treatment may be useful {109})




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Akathisia {06} {08} {10} (restlessness or need to keep moving)
    
blurred vision associated with anticholinergic effect {10} {42}
    
dystonic extrapyramidal effects {08} {10} (muscle spasms of face, neck, body, arms, or legs, causing unusual postures or expressions on face; sticking out of tongue; tic-like or twitching movements; trouble in breathing, speaking, or swallowing; twisting movements of body; inability to move eyes)
    
hypotension {08} {10} ( fainting)— less common with the piperazine phenothiazines {38} {75}
    
ocular changes {08}
including deposition of opaque material in lens and cornea {06} {08} {10}
epithelial keratopathy {08}
or pigmentary retinopathy {06} {08} {69}( blurred vision; defective color vision ; difficulty seeing at night)
    
parkinsonian extrapyramidal effects {06} {08} {10} (difficulty in speaking or swallowing; loss of balance control; mask-like face; shuffling walk; stiffness of arms or legs; trembling and shaking of hands and fingers)
    
tardive dyskinesia {08} {10} (lip smacking or puckering; puffing of cheeks; rapid or worm-like movements of tongue; uncontrolled chewing movements; uncontrolled movements of arms or legs), or tardive dystonia {90} (unusual facial expressions or body positions ; increased blinking or spasms of eyelid ; uncontrolled twisting movements of neck, trunk, arms, or legs)

Note: Hypotension is more frequent in the elderly and at the beginning of treatment, especially if high doses are used {59}. Acute hypotensive crisis {59} leading to cardiac arrest has occurred rarely {06} {78}.
Parkinsonian effects occur more frequently in the elderly {15}, whereas dystonias occur more often in younger patients {15} {32} {33}. Symptoms may be seen in the first few days of treatment or after prolonged treatment, and can recur after even a single dose {23}. Extrapyramidal effects may be dose-related and may decrease with a decrease in dosage {61}. The effects are more common with the piperazine phenothiazines {38}.
Ocular changes occur more frequently with high-dose or long-term use of phenothiazines {06} {08}, which are absorbed by melanin in the uveal tract of the eye {106}. The deposition of a phenothiazine in the eye eventually can lead to damage of the rods and cones {106} and to blindness {104}. These ocular changes occur more frequently with thioridazine than with other phenothiazines {104} {106}. Although the greatest risk occurs with thioridazine doses above 800 mg per day, there have been cases reported with use of lower doses of thioridazine {106}.
Tardive dyskinesia is seen more frequently in elderly patients {06} {10}, patients with brain damage {13}, and patients who have received long-term treatment with antipsychotic medications {06} {08}. However, it can occur in any patient after as few as 3 months of antipsychotic therapy {06} {08} {64}. Tardive dyskinesia can be masked by antipsychotic medication and may become evident after discontinuation of the medication {06} {08}. The syndrome may be irreversible {06} {08}.


Incidence less frequent
    
Difficulty in urinating {06} {08}
    
photosensitivity {08} (skin rash; severe sunburn)
    
skin rash {06} {10} —associated with contact dermatitis (with liquid products) {08} , other allergic reaction {08} {53} , or cholestatic jaundice

Incidence rare
    
Blood dyscrasias {59}
including agranulocytosis {06} {10} {68}
leukocytopenia {06} {53}
or thrombocytopenia {06} {53} (sore throat; fever; unusual bleeding or bruising; unusual tiredness or weakness )—more frequent with aliphatic phenothiazines, less frequent with piperazine phenothiazines {38} {75}
    
cholestatic jaundice {08} {58} {67} (abdominal or stomach pains ; aching muscles and joints; fever and chills; severe skin itching; yellow eyes or skin ; fatigue; nausea, vomiting, or diarrhea)
    
dark urine {81}
    
fever, significant {38}
    
melanosis {06} {08} (tanning or blue-gray discoloration of skin)—more common in females {08} and with long-term, high-dose chlorpromazine or thioridazine therapy {73} {76}
    
neuroleptic malignant syndrome (NMS) {06} {10} {11} ( difficult or fast breathing; drooling ; fast heartbeat; fever; high or low [irregular] blood pressure; impaired consciousness, ranging from confusion to coma; increased sweating ; loss of bladder control; severe muscle stiffness; trembling or shaking; trouble in speaking or swallowing)
    
obstipation or paralytic ileus {06} (severe constipation)
    
paradoxical effects {38} {53}
including aggravation of psychosis {38} {53} {75}
agitation {38} {75}
bizarre dreams {75}
excitement {38} {75}
and insomnia {38} {75} (trouble in sleeping)
    
pneumonia {36} (chest pain; shortness of breath)— may be asymptomatic {63}
    
priapism {06} {08} {26} (prolonged, painful, inappropriate penile erection)
    
QT prolongation and torsades de pointes{109} (irregular or slow heart rate; recurrent fainting; sudden death)—appears to be dose related
    
seizures {59} {68} —more common in patients with a family history of seizures or febrile convulsions {53} {61}
    
systemic lupus erythematosus–like syndrome {07} {51} {53} (fever; hair loss; headaches; increased sensitivity of skin to sunlight; joint pain; redness of hands; skin rash; sores in mouth; unusual tiredness or weakness)
    
temperature regulation dysfunction {38} {59} {68}
including heatstroke {06} {10} (hot dry skin; inability to sweat; muscle weakness; confusion), or hypothermia {50} ( clumsiness; confusion; drowsiness; muscle weakness; shivering)

Note: Agranulocytosis can develop within the first 3 months of treatment, with recovery within 1 to 2 weeks after medication is discontinued; may recur upon rechallenge in recovered patients {24}.
Dark urine usually is caused by the presence of phenothiazine metabolites in the urine {81}; however, because hepatic dysfunction has been associated with phenothiazines {67}, this effect should be reported to the physician.
Significant fever not attributable to any other cause may represent an idiosyncratic reaction to the phenothiazine {38} {83}. Discontinuing the phenothiazine may be necessary {38} {83}.
Liver function tests may be abnormal without overt jaundice {67}. Jaundice may appear about 2 weeks after severe pruritus and may progress to chronic active hepatitis {67}. Discontinuing medication may be necessary {67} {68}.
Heatstroke, caused by phenothiazine-induced suppression of temperature regulation in the hypothalamus {11}, may occur in environmental conditions of high heat and high humidity. The effectiveness of sweating as a cooling mechanism may be reduced by humid conditions and by the anticholinergic effects of phenothiazines or their combination with other anticholinergic medications, such as nonprescription cold medications or antihistamines. Adequate interior environmental temperature control (air-conditioning) must be maintained for institutionalized patients during hot weather because of the increased risk of heatstroke and neuroleptic malignant syndrome (NMS). {54} Patients should be advised to stay in cool areas, to avoid exertion and dehydration, and not to take other anticholinergic medications. Phenothiazines may also cause hypothermia {50} in cold weather, since the disruption of the thermoregulatory mechanisms results in a poikilothermic state {41} {71}.
Skin pigmentation changes in melanosis occur on exposed areas of the body {08} {53} and may fade after discontinuation of the phenothiazine {08}.
NMS may occur at any time during neuroleptic therapy and is potentially fatal {64}. It is most commonly seen within the first month of therapy {91}, after the patient has switched from one neuroleptic to another {92}, or after a dosage increase {92}. Along with the overt signs of skeletal muscle rigidity, hyperthermia, autonomic dysfunction, and altered consciousness, differential diagnosis may reveal leukocytosis {64} {92} (9500 to 26,000 cells per cubic millimeter), elevated liver enzyme tests {92}, and elevated creatine kinase (CK) {64} {92}.




Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Anticholinergic effects {06} {08} (constipation; decreased sweating; dizziness [orthostatic hypotension]; drowsiness {10}; dry mouth)—less frequent with piperazine phenothiazines {75}
    
nasal congestion {06} {08}

Note: Drowsiness usually diminishes during the first few weeks of treatment {53} {58} {59} or with a reduction in dosage {53} {58}.


Incidence less frequent
    
Changes in menstrual period {06} {08} {10}
    
decreased sexual ability {10} {61}
    
fever, mild, after intramuscular injection of a phenothiazine {53} {68}
    
hypertrophic papillae of the tongue {86} (rough or “fuzzy” tongue)
    
increased salivation {61} (watering of mouth)
    
photophobia {10} (increased sensitivity of eyes to light)
    
secretion of milk, unusual {06} {08} {10}
    
swelling or pain in breasts {06} {08} {10}
    
weight gain, unusual {06} {10} {42}



Those indicating need for medical attention if they occur after the medication is discontinued
Incidence more frequent
    
Tardive dyskinesia, persistent {06} {08} {10} ( lip smacking or puckering; puffing of cheeks; rapid or worm-like movements of tongue; uncontrolled chewing movements ; uncontrolled movements of arms or legs ), or tardive dystonia, persistent {90} ( muscle spasms of face, neck, body, arms, or legs causing unusual postures or expressions on face; sticking out of tongue; tic-like or twitching movements ; trouble in breathing, speaking, or swallowing; twisting movements of body ; inability to move eyes)

Incidence less frequent
    
Dizziness {08} {68}
    
nausea and vomiting {08} {68}
    
stomach pain {08}
    
trembling of fingers and hands {08} {68}





Overdose
For specific information on the agents used in the management of phenothiazine overdose, see:
   • Benztropine in Antidyskinetics (Systemic) monograph;
   • Charcoal, Activated (Oral-Local) monograph;
   • Diazepam in Benzodiazepines (Systemic) monograph;
   • Digitalis Glycosides (Systemic) monograph;
   • Diphenhydramine in Antihistamines (Systemic) monograph;
   • Norepinephrine and/or Phenylephrine in Sympathomimetic Agents—Cardiovascular Use (Parenteral-Systemic) monograph; and/or
   • Phenytoin in Anticonvulsants, Hydantoin (Systemic) monograph.
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose

Note: Toxic blood concentration ranges have not been established for the phenothiazines {06}. However, for thioridazine, toxicity may begin at a blood concentration of 1 mg/dL and the lethal concentration range is thought to be 2 to 8 mg/dL {06}.

The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Acute
    
Areflexia or hyperreflexia {06} {10} (loss of or increase in reflexes )
    
blurred vision {10}
    
cardiac toxicity {06} {08} {10}
including cardiac arrhythmia {06} {08} {10}
cardiac arrest {08}
congestive heart failure {10}
hypotension {06} {08} {10}
shock {06}
tachycardia {06} {10}
QRS changes {06} {10}
or ventricular fibrillation {06} {10} (fainting; fast, slow, or irregular heartbeat; shortness of breath; unusual tiredness or weakness)
    
CNS toxicity {10}
including agitation {06} {08} {10}
confusion {06} {10}
convulsions {06} {08} {10} —may be followed by respiratory depression {10}
disorientation {10}
drowsiness, stupor, or coma {06} {08} {10}
    
dilated pupils {06} {10}
    
dryness of mouth {06} {08} {10}
    
hyperpyrexia {08} {10} (fever), or hypothermia {59} (clumsiness; confusion; drowsiness ; muscle weakness; shivering)
    
muscle rigidity {10}
    
pulmonary edema or respiratory depression {06} ( trouble in breathing)
    
vomiting {10}


Treatment of overdose
Treatment is essentially symptomatic and supportive {06} {42}.


To decrease absorption:
Attempting early gastric lavage {08} {10}; avoiding induction of vomiting because potential phenothiazine-induced impaired consciousness or dystonic reactions of the head and neck may result in aspiration of vomitus {06} {08} {68}.

Administering activated charcoal slurry repeatedly {06}.

Administering saline cathartic, especially if extended-release dosage form has been ingested {08} {68}.



Specific treatment:
Controlling cardiac arrhythmias with intravenous phenytoin, 9 to 11 mg per kg of body weight (mg/kg).

Digitalizing for cardiac failure {10} {83}.

Treating hypotension with intravenous fluids {06} {58} and a vasopressor such as norepinephrine or phenylephrine (not using a vasopressor with mixed alpha and beta agonist activity, such as epinephrine, because it may cause paradoxical hypotension due to alpha blockade by phenothiazine) {06} {08} {58}.

Controlling convulsions with diazepam {10} {75} followed by phenytoin while monitoring ECG; avoiding barbiturates since they may potentiate respiratory {06} and CNS {83} depression.

Administering benztropine or diphenhydramine to manage acute parkinsonian effects that may occur {06} {08} {83}.



Monitoring:
Monitoring CNS function {06}.

Monitoring cardiovascular function for not less than 5 days {83}.



Supportive care:
Maintaining respiratory function {08} {10}, including pharyngeal and tracheal suction to remove excess mucus, if necessary {75}.

Maintaining body temperature.

Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.


Note: Dialysis of phenothiazines has not been successful {08} {10} {68}.
If extended-release dosage form has been ingested, treatment should continue for as long as overdose signs and symptoms remain {08} {68}.
Patient may not show arousal for up to 48 hours even when supportive and counteractive measures are employed {81}.
Phenothiazines are radiopaque and ingested tablets may be seen on roentgenogram {75}.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Phenothiazines (Systemic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to any phenothiazine

Pregnancy—Not recommended for use during pregnancy because of reports of jaundice, hyporeflexia or hyperreflexia, and extrapyramidal symptoms in neonates





Breast-feeding—Distributed into breast milk; may cause drowsiness or movement disorders in the infant





Use in children—Children, especially those with acute illnesses, are more prone to extrapyramidal symptoms






Use in the elderly—Elderly patients are more likely to develop extrapyramidal, anticholinergic, hypotensive, and sedative effects; reduced dosage recommended





Dental—Phenothiazine-induced blood dyscrasias may result in infections, delayed healing, and bleeding; dry mouth may cause caries and candidiasis; increased motor activity of face, head, and neck may interfere with some dental procedures
Other medications, especially alcohol, antithyroid agents, other CNS depression-producing medications, epinephrine, other extrapyramidal reaction–causing medications, other hypotension-producing medications, levodopa, lithium, maprotiline, metrizamide, other QT interval–prolonging medications, or antidepressants, tricyclic or the following: fluoxetine, fluvoxamine, or paraoxetine
Other medical problems, especially active alcoholism, blood dyscrasias, brain damage, cardiovascular disease, severe CNS depression, cerebrovascular disease, congenital long QT syndrome, hepatic function impairment, history of cardiac arrhythmias, known genetic defect leading to reduced levels of activity of P450 2D6 isoenzyme activity, pheochromocytoma, renal insufficiency, or Reye's syndrome

Proper use of this medication
»
Proper administration of this medication

For oral dosage forms
Taking with food, milk, or water to reduce stomach irritation

Diluting each dose of medication that comes in dropper bottle with a recommended beverage immediately prior to use

Swallowing the extended-release dosage form whole

For rectal dosage forms
Chilling suppository if too soft to insert

How to insert suppository
» Compliance with therapy; not taking more or less medication than prescribed

» Several weeks of therapy may be required to produce desired effects in treatment of mental or emotional conditions

» Proper dosing
Missed dose when dosing schedule is:

• One dose a day—Taking as soon as possible if remembered the same day; skipping missed dose if not remembered until the next day; going back to regular dosing schedule; not doubling doses


• More than one dose a day—Taking as soon as possible if within an hour or so of missed dose; skipping missed dose if not remembered until later; going back to regular dosing schedule; not doubling doses


» Proper storage

Precautions while using this medication
Regular visits to physician to check progress of therapy

» Checking with physician before discontinuing medication; gradual dosage reduction may be needed

Avoiding use of antacids or antidiarrheal medication within 2 hours of taking phenothiazine

» Avoiding use of alcoholic beverages or other CNS depressants during therapy

Avoiding the use of over-the-counter medications for colds or allergies to prevent increased anticholinergic effects and risk of developing heatstroke

Caution if any laboratory tests required; possible changes in ECG readings, and interference with gonadorelin, metyrapone, phenylketonurea, and urine bilirubin test results

» Caution if any kind of surgery, dental treatment, or emergency treatment is required; telling physician or dentist in charge about phenothiazine because of possible drug interactions or hypotension

» Possible drowsiness or blurred vision; caution when driving, using machines, or doing other things requiring alertness or accurate vision

» Possible dizziness or lightheadedness (orthostatic hypotension); caution when getting up suddenly from a lying or sitting position

» Possible heatstroke: Caution during exercise, hot weather, or when taking hot baths

Possible hypothermia: Caution during prolonged exposure to cold

» Possible dryness of mouth; using sugarless gum or candy, ice, or saliva substitute for relief; checking with physician or dentist if dry mouth continues for more than 2 weeks

» Possible skin photosensitivity; avoiding unprotected exposure to sun; using protective clothing; using a sunblock product that includes protection against both UVA-caused photosensitivity reactions and UVB-caused sunburn reactions; avoiding use of sunlamp, tanning bed, or tanning booth; checking with physician if severe reaction occurs

» Possible eye photosensitivity; wearing sunglasses that block ultraviolet light

» Avoiding getting liquid dosage form on skin or clothing; may cause skin irritation

» Observing precautions for 6 {44} {51} to 12 {47} weeks with long-acting parenteral forms


Side/adverse effects
Side effects more likely to occur in the elderly

Signs of potential side effects, especially akathisia, blurred vision, dystonias, hypotension, ocular changes, parkinsonian effects, QT prolongation and torsades de pointes, tardive dyskinesia or tardive dystonia, difficulty in urinating, photosensitivity, skin rash, blood dyscrasias, cholestatic jaundice, dark urine, fever, melanosis, neuroleptic malignant syndrome, obstipation or paralytic ileus, paradoxical effects, pneumonia, priapism, seizures, systemic lupus erythematosus–like syndrome, temperature regulation dysfunction

» Stopping medication and notifying physician immediately if signs and symptoms of neuroleptic malignant syndrome appear, especially muscle rigidity, fever, difficult or fast breathing, drooling, fast heartbeat, impaired consciousness ranging from confusion to coma, increased sweating, loss of bladder control, trembling and shaking, trouble in speaking or swallowing

» Notifying physician immediately if early signs of tardive dyskinesia appear, such as fine worm-like movements of the tongue or other uncontrolled movements of the mouth, tongue, jaw, fingers, or arms and legs; dosage adjustment or discontinuation may be needed to prevent irreversibility

Stopping medication and notifying physician immediately if signs and symptoms of QT prolongation and torsades de pointes appear, such as irregular or slow heart rate and recurrent fainting.

Possibility of discontinuation symptoms


General Dosing Information
Dosage must be individualized by gradual adjustment from the lower dosage range {08}. After a favorable psychiatric response is noted (within several days to several months), that dosage should be continued for 2 weeks {08} to 6 months {108}, then gradually decreased to the lowest level that will maintain an adequate clinical response {08}.

When extended therapy is discontinued, a gradual reduction in phenothiazine dosage over several weeks is recommended, since abrupt withdrawal may cause some patients on high or long-term dosage to experience transient dyskinetic signs, nausea, vomiting, gastritis, trembling, and/or dizziness {08} {61}. The continuation of treatment with antidyskinetic medications for several weeks after discontinuing the phenothiazine may reduce these symptoms {53} but can precipitate psychosis {90}. Also, preliminary evidence suggests that gradual dosage reduction may decrease the relapse risk associated with discontinuation {107}.

The antiemetic effect of some phenothiazines may mask signs of drug toxicity or obscure diagnosis of conditions for which the primary symptom is nausea {08} {61} {68}. Phenothiazines have no antiemetic effect when nausea is a result of vestibular stimulation or local gastrointestinal irritation.

An antidyskinetic agent such as trihexyphenidyl or benztropine may be used concurrently to control phenothiazine-induced extrapyramidal symptoms {08} {83}. Generally, these agents should be used only when required (not prophylactically), and only for a few weeks to 2 or 3 months {08}. However, 2 to 3 weeks of prophylaxis may be considered in selected patients who have a history of or several risk factors for dystonic reactions or who exhibit paranoia {47}.

Avoid skin contact with liquid forms of phenothiazine medication; contact dermatitis has resulted {22} {68}.

For oral liquid dosage forms only
Mixing liquid dosage forms with carbamazepine suspension or ingesting liquid dosage forms with carbamazepine suspension can result in the formation of an orange, rubbery precipitate {37}.

For parenteral dosage forms only
Because hypotension is a possible side effect of phenothiazines, parenteral administration should be used only in patients who are bedfast or for acute therapy in ambulatory patients who can be closely monitored {08} {10} {68}. A possible exception may be those patients who are dose-stabilized on the long-acting injectable forms.

Intramuscular injections should be administered slowly and deeply into the upper outer quadrant of the buttock {08} {68}. Patient should remain lying down for at least 1/2 hour after injection to avoid possible hypotensive effects {08} {10} {68}.

To prevent irritation at the site of intramuscular injection, the following are recommended: rotation of the injection sites, dilution of the phenothiazine injection with sodium chloride injection, and/or addition of 2% procaine {08}.

Effects of the long-acting injectable forms may last for 6 {44} {51} to 12 {47} weeks. The side effects information and precautions apply during this period of time.

The dose of the long-acting injectable forms should not be increased to prolong the dosing interval {61}, because of the increased incidence of extrapyramidal reactions and other adverse effects at higher doses {50}. Each patient must be carefully supervised to determine the optimal dosing interval and lowest effective dose, depending on patient's response, age, physical condition, symptoms, severity of illness, and drug history {61}.

Geriatric and pediatric patients, especially those acutely ill or dehydrated {49}, should be monitored very carefully during parenteral therapy because of a higher incidence of hypotensive and extrapyramidal reactions in these age groups.

Diet/Nutrition
The oral dosage forms of this medication may be taken with food or a full glass (240 mL) of water or milk, if necessary, to lessen stomach irritation.

Requirements for riboflavin may be increased in patients receiving phenothiazines {01}.

For treatment of adverse effects


Neuroleptic malignant syndrome (NMS):
Treatment is essentially symptomatic and supportive and may include the following

   • Discontinuing phenothiazine immediately {06} {10}.
   • Hyperthermia—Administering antipyretics (aspirin or acetaminophen); using cooling blanket.
   • Dehydration—Restoring fluids and electrolytes.
   • Cardiovascular instability—Monitoring blood pressure and cardiac rhythm closely. Use of sodium nitroprusside may allow vasodilation with subsequent heat loss from the skin in patients with less-dominant muscle rigidity {29}.
   • Hypoxia—Administering oxygen; considering airway insertion and assisted ventilation.
   • Muscle rigidity—There is anecdotal evidence that administering dantrolene sodium (orally, 100 to 300 mg per day in divided doses {13} or intravenously, 1.25 to 1.5 {13} mg per kg of body weight [mg/kg]) for muscle relaxation, or administering amantadine (100 mg two times a day) or bromocriptine (5 mg three times a day) to restore balance of dopamine and acetylcholine at the receptor site {03}, may be helpful in reducing the duration and/or mortality rate of NMS {91}.
   • If neuroleptics must be continued because of severe psychosis, rechallenge should consist of:    —at least 5 days of neuroleptic abstinence before rechallenge {77}.
   —a neuroleptic of a different class from the one causing NMS.
   —a low dose.
   —using a neuroleptic only for controlling the psychosis.
   —avoiding parenteral and extended-action dosage forms {87}.




Parkinsonism:
Treatment may include:

   • Reducing the antipsychotic dosage, if possible, for treatment of milder effects.
   • Administering oral antiparkinsonian agents {08} {68} (of the anticholinergic type) {13} such as trihexyphenidyl, 2 mg three times per day, or benztropine for treatment of more severe parkinsonism and acute motor restlessness; using sparingly, only when side effects appear, and then usually for no longer than 3 months {08}. Observing caution to prevent hyperpyrexia with concomitant use of phenothiazines and other medications with anticholinergic action {28}.
   • In elderly patients, using amantadine, 100 to 200 mg at bedtime, to minimize severe anticholinergic effects that may occur with other antidyskinetics.



Restlessness (akathisia):
Reduce antipsychotic dosage, if possible {108}. May respond to antiparkinsonian drugs or propranolol {08} {68}, 30 to 80 mg per day; nadolol, 40 mg per day; lorazepam, 0.5 mg three times a day or 1 mg two times a day {47}; or diazepam {68}, 2 mg two or three times a day. May require substitution of a less potent neuroleptic or an atypical antipsychotic agent {108}.



Dystonia:
Acute dystonic postures or oculogyric crisis may be relieved by parenteral administration of benztropine {13} {23}, 2 mg intramuscularly or intravenously {23}; diphenhydramine {68}, 50 mg intramuscularly; or diazepam {13}, 5 to 7.5 mg intravenously, to be followed by oral antidyskinetic medication for 1 or 2 days to prevent recurrent dystonic episodes. Dosage adjustments of the phenothiazine may control these effects, and discontinuation of the phenothiazine may reverse severe symptoms.



Tardive dyskinesia or tardive dystonia:
No known effective treatment {08} {45}. Dosage of phenothiazine should be reduced or medication discontinued, if clinically feasible, at earliest signs of tardive dyskinesia or tardive dystonia to prevent possible irreversible effects {08} {10} {45}.



Pruritus associated with cholestasis:
   • Topical treatment may include:    —Topical corticosteroids combined with cool-water compresses, aluminum acetate solution, or calamine lotion.
   —For widespread itching, baths containing colloidal oatmeal or baking soda (2 cups per tubful).
   —For severe itching, topical anesthetics containing 20% benzocaine or 5% lidocaine; however, itching may be relieved for only 30 to 60 minutes.

   • Oral treatment may include:    —Initially, diphenhydramine, cyproheptadine, or hydroxyzine.
   —Bile acid sequestrants or cholestyramine, but only when topical and oral antipruritic agents fail to control symptoms.
   —Supplementation with fat-soluble vitamins (A, D, E, K) for patients with protracted jaundice.
   —Resuming therapy with a nonphenothiazine neuroleptic, such as loxapine, thioxanthenes, or molindone. {67}



CHLORPROMAZINE

Summary of Differences


Category:
Includes antiemetic, antidyskinetic (Huntington's chorea), sedative, and anesthetic adjunct uses.



Indications:
Includes treatment of intractable hiccups and acute, intermittent porphyria. Includes adjunctive treatment of tetanus.



Pharmacology/pharmacokinetics:


Chemical group—
Aliphatic



Actions—
Antiemetic: Strong

Anticholinergic: Strong

Extrapyramidal: Weak to moderate

Hypotensive: Strong

Sedative: Strong




Side/adverse effects:
Greater risk of developing melanosis than with other phenothiazines.



Additional Dosing Information
See also General Dosing Information .

For intractable hiccups, initially, chlorpromazine is administered orally. If symptoms persist for 2 or 3 days, intramuscular administration is indicated, followed by slow intravenous infusion if hiccups continue. {08}

For parenteral use
Chlorpromazine injection must not be administered subcutaneously, because it causes severe tissue necrosis {49}.

For intramuscular injection, diluting chlorpromazine injection with sodium chloride injection and/or adding 2% procaine may prevent irritation at the injection site {08}.

The intravenous route of administration is used only for severe hiccups, surgery, and tetanus {08}.

Before intravenous injection, chlorpromazine hydrochloride injection should be diluted with sodium chloride injection {08}.

Close monitoring of blood pressure for hypotension is necessary during parenteral administration {08}.


Oral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of chlorpromazine base (not the hydrochloride salt).


CHLORPROMAZINE HYDROCHLORIDE EXTENDED-RELEASE CAPSULES

Usual adult and adolescent dose
Psychotic disorders
Oral, 30 to 300 mg (base) one to three times per day, the dosage being adjusted as needed and tolerated {08} {42}.


Note: Geriatric, emaciated, or debilitated patients usually require a lower initial dose and more gradual dosage titration than do younger and healthier patients {08} {13}.


Usual adult prescribing limits
1 gram (base) per day {08}.

Note: Although sometimes doses are increased gradually to 2 grams or more per day for short periods, 1 gram or less usually is sufficient for extended therapy {08}.


Usual pediatric dose
The extended-release dosage form is not recommended for use in children.

Strength(s) usually available
U.S.—


30 mg (base) (Rx) [Thorazine Spansule (benzyl alcohol) (calcium sulfate) (cetylpyridinium chloride) (FD&C Yellow No. 6) (gelatin) (glyceryl distearate) (glyceryl monostearate) (iron oxide ) (povidone) (silicon dioxide) (sodium lauryl sulfate) ( starch) (sucrose) (titanium dioxide) (wax){08}]


75 mg (base) (Rx) [Thorazine Spansule (benzyl alcohol) (calcium sulfate) (cetylpyridinium chloride) (FD&C Yellow No. 6) (gelatin) (glyceryl distearate) (glyceryl monostearate) (iron oxide ) (povidone) (silicon dioxide) (sodium lauryl sulfate) ( starch) (sucrose) (titanium dioxide) (wax){08}]


150 mg (base) (Rx) [Thorazine Spansule (benzyl alcohol) (calcium sulfate) (cetylpyridinium chloride) (FD&C Yellow No. 6) (gelatin) (glyceryl distearate) (glyceryl monostearate) (iron oxide ) (povidone) (silicon dioxide) (sodium lauryl sulfate) ( starch) (sucrose) (titanium dioxide) (wax){08}]

Canada—
Not commercially available.

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F) {08}, in a tight, light-resistant container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.

Additional information:
Upon ingestion of the extended-release capsule, an initial dose is released promptly and the remaining medication is released gradually over a prolonged period {08}.

The extended-release capsule may be used for initial treatment when once-a-day dosing is desired {14}, and it may be used to help decrease side effects when large doses are required {14}.


CHLORPROMAZINE HYDROCHLORIDE ORAL CONCENTRATE USP

Usual adult and adolescent dose
Psychotic disorders
Oral, 10 to 25 mg (base) two to four times per day, the dosage being increased by 20 to 50 mg per day every three or four days as needed and tolerated {08}.

Nausea and vomiting
Oral, 10 to 25 mg (base) every four to six hours, as needed, the dosage being increased as needed and tolerated {08}.

Apprehension and restlessness, presurgical
Oral, 25 to 50 mg (base) two to three hours before surgery {08}.

Hiccups, intractable
Oral, 25 to 50 mg (base) three or four times per day {08}. Parenteral administration is required if symptoms persist for two to three days with oral administration {08}. (See Chlorpromazine Hydrochloride Injection USP .)

Porphyria, acute, intermittent
Oral, 25 to 50 mg (base) three or four times per day {08}. In most patients, treatment may be discontinued after several weeks {08}; however, some patients may require maintenance therapy {08}.


Note: Geriatric, emaciated, or debilitated patients usually require a lower initial dose and more gradual dosage titration than do younger and healthier patients {08} {13}.


Usual adult prescribing limits
1 gram (base) per day {08}.

Note: Although sometimes doses are increased gradually to 2 grams or more per day for short periods, 1 gram or less usually is sufficient for extended therapy {08}.


Usual pediatric dose
Psychotic disorders or
Nausea and vomiting
Children up to 6 months of age: Dosage has not been established.

Children 6 months to 12 years of age: Oral, 550 mcg (0.55 mg) (base) per kg of body weight {22} {42} or 15 mg per square meter of body surface area every four to six hours, the dosage being adjusted as needed and tolerated.

Apprehension and restlessness, presurgical
Oral, 550 mcg (0.55 mg) (base) per kg of body weight {22} {42} or 15 mg per square meter of body surface area two to three hours before surgery.


Strength(s) usually available
U.S.—


30 mg (base) per mL (Rx) [Chlorpromazine Hydrochloride Intensol ( alcohol 0.068%) (sodium sulfite) ( sodium bisulfite){22}][Generic]


100 mg (base) per mL (Rx) [Chlorpromazine Hydrochloride Intensol (alcohol 0.068%) (sodium sulfite) (sodium bisulfite){22}][Generic]

Canada—


40 mg (base) per mL (Rx) [Chlorpromanyl-40 (tartrazine [FD&C Yellow No. 5]) (parabens) ( sulfites) (sucrose){31}] [Largactil Oral Drops (alcohol 17.5% v/v) ( sucrose 200 mg/mL){42}]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F) {08}, in a tight container, unless otherwise specified by manufacturer. Protect from light. Protect from freezing.

Preparation of dosage form:
Dilute each dose immediately before administration in 60 mL or more of coffee, tea, milk, tomato or fruit juice, water, simple syrup, orange syrup, soup, pudding, or carbonated beverage {08}.

Use entire mixture immediately; do not save for later use {22}.

Stability:
A slight yellowing will not alter potency; however, do not use if markedly discolored or if a precipitate is present.

If chlorpromazine solutions are mixed with thiopental, atropine, or solutions with a pH out of the range of 4 to 5, a precipitate will form {42}.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Avoid contact with skin or clothing.
   • Must be diluted before use.


Caution:
Patients sensitive to sulfites may be sensitive to some chlorpromazine hydrochloride oral concentrate products because of the sulfite preservatives present.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted {22}.
Explain dosage measurement and dilution to patient, if self-administered, or to caregiver; however, concentrate dosage form is intended for institutional use {08}.



CHLORPROMAZINE HYDROCHLORIDE SYRUP USP

Usual adult and adolescent dose
See Chlorpromazine Hydrochloride Oral Concentrate USP .

Usual adult prescribing limits
See Chlorpromazine Hydrochloride Oral Concentrate USP .

Usual pediatric dose
See Chlorpromazine Hydrochloride Oral Concentrate USP .

Strength(s) usually available
U.S.—


10 mg (base) per 5 mL (Rx) [Thorazine (orange-custard flavored){08}][Generic]

Canada—


25 mg (base) per 5 mL (Rx) [Largactil Liquid (alcohol 0.5% v/v) (sucrose 3.9 grams per 5 mL){42}]


100 mg (base) per 5 mL (Rx) [Chlorpromanyl-20 (tartrazine [FD&C Yellow No. 5]) (parabens) (sulfites) (sucrose){31}] [Largactil Liquid (alcohol 0.5% [v/v] ) (sucrose 3.6 grams per 5 mL){42}]

Packaging and storage:
Store below 25 °C (77 °F) {08}, unless otherwise specified by manufacturer. Store in a tight, light-resistant container. Protect from freezing.

Stability:
A slight yellowing will not alter potency; however, do not use if markedly discolored or if a precipitate is present.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Avoid contact with skin or clothing.


Caution:
Patients sensitive to sulfites may be sensitive to some chlorpromazine hydrochloride syrup products because of the sulfite preservatives present.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted.



CHLORPROMAZINE HYDROCHLORIDE TABLETS USP

Usual adult and adolescent dose
See Chlorpromazine Hydrochloride Oral Concentrate USP .

Usual adult prescribing limits
See Chlorpromazine Hydrochloride Oral Concentrate USP .

Usual pediatric dose
See Chlorpromazine Hydrochloride Oral Concentrate USP .

Strength(s) usually available
U.S.—


10 mg (base) (Rx) [Thorazine ( lactose) (methylparaben) (propylparaben){08}][Generic]


25 mg (base) (Rx) [Thorazine ( lactose) (methylparaben) (propylparaben){08}][Generic]


50 mg (base) (Rx) [Thorazine ( lactose) (methylparaben) (propylparaben){08}][Generic]


100 mg (base) (Rx) [Thorazine ( lactose) (methylparaben) (propylparaben){08}][Generic]


200 mg (base) (Rx) [Thorazine ( lactose) (methylparaben) (propylparaben){08}][Generic]

Canada—


10 mg (base) (Rx) [Largactil{42}] [Novo-Chlorpromazine{40}]


25 mg (base) (Rx) [Largactil{42}] [Novo-Chlorpromazine{40}][Generic]


50 mg (base) (Rx) [Largactil{42}] [Novo-Chlorpromazine{40}][Generic]


100 mg (base) (Rx) [Largactil{42}] [Novo-Chlorpromazine{40}][Generic]


200 mg (base) (Rx) [Largactil{42}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F) {08}, unless otherwise specified by manufacturer. Store in a well-closed, light-resistant container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.



Parenteral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of chlorpromazine base (not the hydrochloride salt).


CHLORPROMAZINE HYDROCHLORIDE INJECTION USP

Usual adult dose
Psychotic disorders (severe)
Intramuscular, 25 {08} to 50 mg (base), the dose being repeated in one hour if needed {08}, and every three to twelve hours thereafter as needed and tolerated. The dosage may be increased gradually over several days as needed and tolerated {08}.

Nausea and vomiting
Intramuscular, initially, 25 mg (base) in a single dose; if the dose is well tolerated, 25 to 50 mg may be administered every three to four hours as needed and tolerated until vomiting stops {08}.

Nausea and vomiting during surgery
Intramuscular: 12.5 mg (base) in a single dose; if no hypotension occurs, the dose may be repeated in thirty minutes as needed and tolerated {08}.

Intravenous: 2 mg (base), diluted to a concentration of 1 mg per mL with sodium chloride injection, every two minutes as needed and tolerated, up to a cumulative dose of 25 mg {08}.

Apprehension and restlessness, presurgical
Intramuscular, 12.5 to 25 mg (base) one to two hours before surgery {08}.

Hiccups, intractable
If hiccups persist after oral treatment, intramuscular: 25 to 50 mg (base) {08} three or four times per day.

If hiccups persist after intramuscular treatment, intravenous infusion: 25 to 50 mg (base), diluted in 500 to 1000 mL sodium chloride injection, administered slowly while patient is lying down {08}. Blood pressure should be monitored closely {08}.

Porphyria, acute, intermittent 1
Intramuscular, 25 mg (base) every six to eight hours until patient can take oral therapy {08}.

Tetanus1
Intramuscular: 25 to 50 mg (base) three or four times per day {08}; dose and frequency of administration may be increased gradually, based on patient's response {08}.

Intravenous infusion: 25 to 50 mg (base), diluted to a concentration of not more than 1 mg per mL with sodium chloride injection, administered at a rate of 1 mg per minute {08}.


Note: Geriatric, emaciated, or debilitated patients usually require a lower initial dose and more gradual dosage titration than do younger and healthier patients {08} {13}.


Usual adult prescribing limits
1 gram (base) per day {08}.

Note: Although sometimes doses are increased gradually to 2 grams or more per day for short periods, 1 gram or less usually is sufficient for extended therapy {08}.


Usual pediatric dose
Psychotic disorders or
Nausea and vomiting
Children up to 6 months of age: Dosage has not been established.

Children 6 months to 12 years of age: Intramuscular, 550 mcg (0.55 mg) (base) per kg of body weight {42} or 15 mg per square meter of body surface area every six to eight hours as needed.

Nausea and vomiting during surgery
Children up to 6 months of age: Dosage has not been established.

Children 6 months to 12 years of age: Intramuscular, 275 mcg (0.275 mg) (base) per kg of body weight, the dose being repeated in thirty minutes as needed and tolerated {08}. Intravenous infusion, 275 mcg (0.275 mg) (base) per kg of body weight, diluted to a concentration of 1 mg per mL with 0.9% sodium chloride injection, administered at a rate of no more than 1 mg every 2 minutes {08}.

Apprehension and restlessness, presurgical
Children up to 6 months of age: Dosage has not been established.

Children 6 months to 12 years of age: Intramuscular, 550 mcg (0.55 mg) (base) per kg of body weight one to two hours before surgery {08}.

Tetanus1
Children up to 6 months of age: Dosage has not been established.

Children 6 months to 12 years of age: Intramuscular, 550 mcg (0.55 mg) (base) per kg of body weight every six to eight hours {08}. Intravenous infusion, 550 mcg (0.55 mg) (base) per kg of body weight, diluted to a concentration of not more than 1 mg per mL with 0.9% sodium chloride injection, administered at a rate of 1 mg per 2 minutes {08}.


Usual pediatric prescribing limits
Children 6 months to 5 years of age (up to 23 kg [50 pounds])—40 mg per day {08}.

Children 5 to 12 years of age (23 to 46 kg [50 to 101 pounds])—75 mg per day, except in unmanageable cases {08}.

Strength(s) usually available
U.S.—


25 mg (base) per mL (Rx) [Thorazine (sulfite) ( vials: benzyl alcohol 2%){08}][Generic]

Canada—


25 mg (base) per mL (Rx) [Largactil (sodium sulfite) (potassium metabisulfite){42}][Generic]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F) {08}, unless otherwise specified by manufacturer. Protect from light. Protect from freezing.

Preparation of dosage form:
To dilute chlorpromazine hydrochloride injection to 1 mg/mL for intravenous administration, mix 1 mL (25 mg) of chlorpromazine hydrochloride injection with 24 mL of sodium chloride injection {08}.

Stability:
A slight yellowing will not alter potency; however, do not use if markedly discolored {08} or if a precipitate is present.

Incompatibilities:
A precipitate will form if chlorpromazine hydrochloride injection is mixed with thiopental, atropine, or solutions not having a pH of 4 to 5 {42}. Mixing chlorpromazine hydrochloride injection with agents other than sodium chloride injection or 2% procaine in the syringe is not recommended {08}.


Caution:
Medications containing benzyl alcohol are not recommended for use in neonates (first 30 days of postnatal life). A fatal toxic syndrome consisting of metabolic acidosis, CNS depression, respiratory problems, renal failure, hypotension, and possibly seizures and intracranial hemorrhages has been associated with the use of diluents containing benzyl alcohol for preparation of medications for use in neonates.

Patients sensitive to sulfites may be sensitive to some chlorpromazine hydrochloride injection products because of the sulfite preservatives present.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted {08}.




Rectal Dosage Forms

CHLORPROMAZINE SUPPOSITORIES USP

Usual adult and adolescent dose
Nausea and vomiting
Rectal, 50 to 100 mg every six to eight hours as needed {08}.


Note: Geriatric, emaciated, or debilitated patients usually require a lower initial dose and more gradual dosage titration than do younger and healthier patients.


Usual adult prescribing limits
400 mg per day.

Usual pediatric dose
Psychotic disorders or
Nausea and vomiting
Children up to 6 months of age: Dosage has not been established.

Children 6 months to 12 years of age: Rectal, 1 mg per kg of body weight every six to eight hours as needed {08}.


Note: The 100-mg suppository dosage form is not recommended for pediatric use.


Strength(s) usually available
U.S.—


25 mg (Rx) [Thorazine (glycerin) ( glyceryl monopalmitate) (glyceryl monostearate) (hydrogenated coconut oil fatty acids) ( hydrogenated palm kernel oil fatty acids){08}]


100 mg (Rx) [Thorazine (glycerin) ( glyceryl monopalmitate) (glyceryl monostearate) (hydrogenated coconut oil fatty acids) ( hydrogenated palm kernel oil fatty acids){08}]

Canada—


100 mg (Rx) [Largactil{42}]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F) {08}. Store in a well-closed, light-resistant container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • For rectal use only.

Note: Explain administration technique to patient, if self-administered, or to caregiver.



FLUPHENAZINE

Summary of Differences


Category:
Includes use as antineuralgia adjunct in patients with chronic pain.



Pharmacology/pharmacokinetics:


Chemical group—
Piperazine



Actions—
Antiemetic: Weak

Anticholinergic: Weak

Extrapyramidal: Strong

Hypotensive: Weak

Sedative: Weak




Additional Dosing Information
See also General Dosing Information.

For long-acting parenteral dosage forms
A dry syringe and needle (at least 21 gauge) should be used, since use of a wet needle or syringe may cause the solution to become cloudy {51} {66}.

After the initial dose of the decanoate or enanthate extended-action injection, dosages and dosing intervals are determined by the patient's response {51} {66}.


Oral Dosage Forms

FLUPHENAZINE HYDROCHLORIDE ELIXIR USP

Usual adult and adolescent dose
Psychotic disorders
Initial: Oral, 2.5 to 10 mg per day in divided doses every six to eight hours, the dosage being increased gradually as needed and tolerated {78} {79}.

Maintenance: Oral, 1 to 5 mg per day as a single dose or in divided doses {78} {79}.


Note: Emaciated or debilitated patients usually require a lower initial dosage (1 to 2.5 mg per day), and more gradual dosage titration than do healthier patients {13}.


Usual adult prescribing limits
20 mg per day {79}.

Usual pediatric dose
Psychotic disorders
Oral, 250 to 750 mcg (0.25 to 0.75 mg) one to four times per day.


Usual geriatric dose
Psychotic disorders
Oral, 1 to 2.5 mg per day, the dosage being increased gradually as needed and tolerated {79}.


Strength(s) usually available
U.S.—


2.5 mg per 5 mL (0.5 mg per mL) (Rx) [Prolixin (alcohol 14% v/v) (FD&C Yellow No. 6) ( flavors) (glycerin) ( polysorbate 40) (purified water) ( sodium benzoate) (sucrose){78}][Generic]

Canada—


2.5 mg per 5 mL (0.5 mg per mL) (Rx) [PMS Fluphenazine{65}][Generic]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container. Protect from light. Protect from freezing.

Stability:
Flavoring oils may separate from the solution upon standing, producing a wispy precipitate or globular material; however, potency is not affected. If precipitate is present, shake gently to redisperse the oils. Discard if solution fails to clear. {78}

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Avoid contact with skin or clothing.
   • Keep container tightly closed.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted.
Explain proper measurement of dose to patient, if self-administered, or to caregiver.



FLUPHENAZINE HYDROCHLORIDE ORAL SOLUTION USP

Usual adult and adolescent dose
See Fluphenazine Hydrochloride Elixir USP .

Usual adult prescribing limits
See Fluphenazine Hydrochloride Elixir USP .

Usual pediatric dose
See Fluphenazine Hydrochloride Elixir USP .

Usual geriatric dose
See Fluphenazine Hydrochloride Elixir USP .

Strength(s) usually available
U.S.—


5 mg per mL (Rx) [Permitil Concentrate (alcohol 1%){55}] [Prolixin Concentrate (alcohol 14%) (sodium benzoate){85}][Generic]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container. Protect from light. Protect from freezing.

Preparation of dosage form:
Dilute each dose just before using in at least 60 mL (2 fluid ounces) of water; homogenized milk; caffeine-free carbonated beverages; pineapple, apricot, prune, orange, tomato, or grapefruit juice; or V-8 © juice {55} {85}.

Incompatibilities:
Do not mix fluphenazine hydrochloride oral solution with beverages containing caffeine (coffee, cola), tannins (tea), or pectins (apple juice), because of physical incompatibility {55} {85}.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Avoid contact with skin or clothing.
   • Must be diluted before use.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted {55}.
Explain dosage measurement and dilution to patient, if self-administered, or to caregiver.



FLUPHENAZINE HYDROCHLORIDE TABLETS USP

Usual adult and adolescent dose
See Fluphenazine Hydrochloride Elixir USP .

Usual adult prescribing limits
See Fluphenazine Hydrochloride Elixir USP .

Usual pediatric dose
See Fluphenazine Hydrochloride Elixir USP .

Usual geriatric dose
See Fluphenazine Hydrochloride Elixir USP .

Strength(s) usually available
U.S.—


1 mg (Rx) [Prolixin{78}][Generic]


2.5 mg (Rx) [Permitil (scored) (lactose){55}] [Prolixin{78}][Generic]


5 mg (Rx) [Permitil (scored) ( lactose){55}] [Prolixin ( tartrazine){78}][Generic]


10 mg (Rx) [Permitil (scored) ( lactose){55}] [Prolixin (D&C Red No. 27) (D&C Red No. 30){78}][Generic]

Canada—


1 mg (Rx) [Apo-Fluphenazine{86}] [PMS Fluphenazine{65}]


2 mg (Rx) [Apo-Fluphenazine{86}] [PMS Fluphenazine{65}]


5 mg (Rx) [Apo-Fluphenazine{86}] [PMS Fluphenazine{65}]


10 mg (Rx) [Moditen HCl{56}{79}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.



Parenteral Dosage Forms

FLUPHENAZINE DECANOATE INJECTION USP

Usual adult dose
Psychotic disorders
Initial: Intramuscular or subcutaneous, 12.5 to 25 mg {51} {66}, the dose being repeated or increased every one to three weeks as needed and tolerated.

Maintenance: Intramuscular or subcutaneous, usually up to 50 mg every one to four weeks, as needed and tolerated.


Note: For doses greater than 50 mg, increases should be made cautiously in increments of 12.5 mg {51}.
Patients who have had no previous exposure to phenothiazines or who are at high risk for adverse effects may begin fluphenazine therapy with a short-acting dosage form and change to the long-acting injection after response is established {51}.


Usual adult prescribing limits
100 mg per dose {50} {51}.

Usual pediatric dose
Psychotic disorders
Children 5 {03} to 12 years of age: Intramuscular or subcutaneous, 3.125 to 12.5 mg, the dose being repeated every one to three weeks as needed and tolerated {03}.

Children 12 years of age and older: Intramuscular or subcutaneous, initially 6.25 to 18.75 mg per week, the dose being increased to 12.5 to 25 mg and administered every one to three weeks as needed and tolerated {03}.


Strength(s) usually available
U.S.—


25 mg per mL (Rx) [Prolixin Decanoate (sesame oil) (benzyl alcohol 1.2% w/v){66}][Generic]{51}

Canada—


25 mg per mL (Rx) [Modecate (sesame oil) ( benzyl alcohol 1.5%){50}][Generic]


100 mg per mL (Rx) [Modecate Concentrate (sesame oil) (benzyl alcohol 1.5%){50}][Generic]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light. Protect from freezing.


Caution:
Medications containing benzyl alcohol are not recommended for use in neonates (first 30 days of postnatal life). A fatal toxic syndrome consisting of metabolic acidosis, CNS depression, respiratory problems, renal failure, hypotension, and possibly seizures and intracranial hemorrhages has been associated with the use of diluents containing benzyl alcohol for preparation of medications for use in neonates.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted.


Additional information:
The onset of action of the initial dose is generally between 24 and 72 hours after administration, and antipsychotic effects become significant within 48 to 96 hours {50} {66}.

The effects of a single injection of fluphenazine decanoate usually last for 2 to 4 weeks {50} {51}, but may last for up to 6 weeks in some patients {51}. The side effects information and precautions apply during this period of time.

The time to steady-state from a dosage change requires 6 to 12 weeks or longer {47}.


FLUPHENAZINE ENANTHATE INJECTION USP

Usual adult and adolescent dose
Psychotic disorders
Intramuscular or subcutaneous, initially, 25 mg every two weeks {44}; the dose and dosing interval may be adjusted based on patient response {44}.


Note: Patients who have had no previous exposure to phenothiazines or who are at high risk for adverse effects may begin fluphenazine therapy with a short-acting dosage form and change to the long-acting injection after response and dosage are established {44} {60}.
Although the usual dosage is 25 mg every two weeks, dosages have ranged from 12.5 to 100 mg every one to three weeks {44} {60}.
For doses greater than 50 mg, increases should be made cautiously in increments of 12.5 mg {44}.


Usual adult prescribing limits
100 mg per dose {44}.

Usual pediatric dose
Psychotic disorders
Children up to 12 years of age: Dosage has not been established.

Children 12 years of age and older: See Usual adult and adolescent dose.


Strength(s) usually available
U.S.—


25 mg per mL (Rx) [Prolixin Enanthate (sesame oil) (benzyl alcohol 1.5% w/v){44}]

Canada—


25 mg per mL (Rx) [Moditen Enanthate (sesame oil) (benzyl alcohol 1.5% w/v){60}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light. Protect from freezing.


Caution:
Medications containing benzyl alcohol are not recommended for use in neonates (first 30 days of postnatal life). A fatal toxic syndrome consisting of metabolic acidosis, CNS depression, respiratory problems, renal failure, hypotension, and possibly seizures and intracranial hemorrhages has been associated with the use of diluents containing benzyl alcohol for preparation of medications for use in neonates.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted.


Additional information:
The effects of a single dose of fluphenazine enanthate usually last for about 2 weeks {44} {60} {60}, but may last for up to 6 weeks in some patients {44}. The side effects information and precautions apply during this period of time.


FLUPHENAZINE HYDROCHLORIDE INJECTION USP

Usual adult and adolescent dose
Psychotic disorders
Intramuscular, initially, 1.25 mg, the dose being adjusted and repeated as needed and tolerated to a total initial dosage of 2.5 to 10 mg per day administered in divided doses at six- to eight-hour intervals {34} {80}.


Note: Emaciated or debilitated patients usually require a lower initial dose (1 to 2.5 mg daily) and more gradual dosage titration than do healthier patients {13}.
The parenteral dose of fluphenazine hydrochloride is usually about one third to one half the oral dose {34} {79}.


Usual adult prescribing limits
10 mg per day {34} {79}.

Usual pediatric dose
Psychotic disorders
Children up to 12 years of age: Dosage has not been established.

Children 12 years of age and older: See Usual adult and adolescent dose.


Usual geriatric dose
Psychotic disorders
Intramuscular, 1 to 2.5 mg per day, the dosage being increased gradually as needed and tolerated.


Strength(s) usually available
U.S.—


2.5 mg per mL (Rx) [Prolixin (pH 4.8 to 5.2) (methylparaben 0.1%) (propylparaben 0.01%) (sodium chloride){80}][Generic]{34}

Canada—


10 mg per mL (Rx) [PMS Fluphenazine{65}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light. Protect from freezing.

Stability:
A slight yellowing to a light amber color will not alter potency; however, do not use if markedly discolored or if a precipitate is present {34} {79} {80}.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted.



MESORIDAZINE

Summary of Differences


Pharmacology/pharmacokinetics:


Chemical group—
Piperidine



Actions—
Antiemetic: Weak

Anticholinergic: Moderate

Extrapyramidal: Weak

Hypotensive: Moderate to strong

Sedative: Strong



Side/Adverse Effects—
Involved in Torsade de Pointes-type arrhythmias and sudden cardiac death more frequently than other phenothiazines.




Oral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of mesoridazine base (not the besylate salt).


MESORIDAZINE BESYLATE ORAL SOLUTION USP

Usual adult and adolescent dose
Psychotic disorders
Oral, starting dose—50 mg (base) three times per day{10}, the dosage being adjusted as needed and tolerated.
{110}

Note: Geriatric, emaciated, or debilitated patients usually require a lower initial dose and more gradual dosage titration than do younger and healthier patients {13}.


Usual adult prescribing limits
The usual optimum total daily dose range is 100 to 400 mg per day.{110}

Usual pediatric dose
Psychotic disorders
Children up to 12 years of age: Dosage has not been established.

Children 12 years of age and older: See Usual adult and adolescent dose.


Strength(s) usually available
U.S.—


25 mg (base) per mL (Rx) [Serentil Concentrate (alcohol 0.6% v/v ) (citric acid) (FD&C Red No. 40) (flavors) ( methylparaben) (propylparaben) ( purified water) (sodium citrate) ( sorbitol){10}]

Canada—
Not commercially available.

Packaging and storage:
Store below 25 °C (77 °F) {10}. Store in a tight, light-resistant container {10}. Protect from freezing.

Preparation of dosage form:
Dilute each dose just before administration in distilled water, acidified tap water, orange juice, or grapefruit juice {10}. The recommended dilution is 25 mg per 2 teaspoonfuls of diluent {10}. Preparation and storage of bulk dilution is not recommended {10}.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Avoid contact with skin or clothing.
   • Must be diluted before use.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted.
Explain dosage measurement and dilution to patient, if self-administered, or to caregiver.



MESORIDAZINE BESYLATE TABLETS USP

Usual adult and adolescent dose
See Mesoridazine Besylate Oral Solution USP .

Usual pediatric dose
See Mesoridazine Besylate Oral Solution USP .

Strength(s) usually available
U.S.—


10 mg (base) (Rx) [Serentil (acacia) ( carnauba wax) (colloidal silicon dioxide) (FD&C Red No. 40 aluminum lake) ( microcrystalline cellulose) (povidone) (sodium benzoate) (stearic acid) (sucrose) (lactose) ( talc) (titanium dioxide) ( starch) (synthetic black iron oxide){10}]


25 mg (base) (Rx) [Serentil (acacia) ( carnauba wax) (colloidal silicon dioxide) (FD&C Red No. 40 aluminum lake) ( microcrystalline cellulose) (povidone) (sodium benzoate) (stearic acid) (sucrose) (lactose) ( talc) (titanium dioxide) ( synthetic black iron oxide){10}]


50 mg (base) (Rx) [Serentil (acacia) ( carnauba wax) (colloidal silicon dioxide) (FD&C Red No. 40 aluminum lake) ( microcrystalline cellulose) (povidone) (sodium benzoate) (stearic acid) (sucrose) (lactose) ( talc) (titanium dioxide) ( starch) (gelatin) (synthetic black iron oxide){10}]


100 mg (base) (Rx) [Serentil (acacia) ( carnauba wax) (colloidal silicon dioxide) (FD&C Red No. 40 aluminum lake) ( microcrystalline cellulose) (povidone) (sodium benzoate) (stearic acid) (sucrose) (lactose) ( talc) (titanium dioxide) ( starch) (gelatin) (synthetic black iron oxide){10}]

Canada—


10 mg (base) (Rx) [Serentil (corn starch) (lactose){63}]


25 mg (base) (Rx) [Serentil (lactose){63}]


50 mg (base) (Rx) [Serentil (corn starch) (lactose){63}]

Packaging and storage:
Store below 30 °C (86 °F) {10}, unless otherwise specified by manufacturer. Store in a well-closed, light-resistant {10} container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.



Parenteral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of mesoridazine base (not the besylate salt).


MESORIDAZINE BESYLATE INJECTION USP

Usual adult and adolescent dose
Psychotic disorders
Intramuscular, 25 mg (base), the dose being repeated in one-half hour to one hour as needed and tolerated {10}.


Note: The usual dosage range is 25 to 200 mg (base) per day {10}.
Geriatric, emaciated, or debilitated patients usually require a lower initial dose and more gradual dosage titration than do younger and healthier patients {13}.


Note: Because of possible hypotensive effects, reserve parenteral administration for bedfast patients or for acute ambulatory cases, and keep patient lying down for 30 minutes post-administration.{110}


Usual adult prescribing limits
The usual optimum total daily dose range is 25 to 200 mg per day.{110}

Usual pediatric dose
Psychotic disorders
Children up to 12 years of age: Dosage has not been established.

Children 12 years of age and older: See Usual adult and adolescent dose.


Strength(s) usually available
U.S.—


25 mg (base) per mL (Rx) [Serentil (carbon dioxide gas) (edetate disodium 0.5 mg) (sodium chloride 7.2 mg) (water for injection){10}]

Canada—
Not commercially available.

Packaging and storage:
Store below 30 °C (86 °F) {10}, unless otherwise specified by manufacturer. Protect from light {10}. Protect from freezing.

Stability:
A slight yellowing will not alter potency; however, do not use if markedly discolored or if a precipitate is present.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted.



METHOTRIMEPRAZINE

Summary of Differences


Category:
Includes use as an analgesic, anesthetic adjunct, antiemetic, and sedative {57} {58}.



Indications:
Also indicated for relief of moderate to severe pain in nonambulatory patients, and for obstetrical pain and sedation when respiratory depression should be avoided; sedation and somnolence before surgery; adjunctive therapy in general anesthesia to increase effects of anesthetics.



Pharmacology/pharmacokinetics:


Chemical group—
Aliphatic



Actions—
Antiemetic: Strong

Anticholinergic: Moderate to strong

Extrapyramidal: Weak to moderate

Hypotensive: Strong

Sedative: Strong




Precautions:


Drug interactions and/or related problems—
Concurrent use with succinylcholine may cause tachycardia, a fall in blood pressure, CNS stimulation and delirium, and aggravation of extrapyramidal effects.




Oral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of methotrimeprazine base (not the hydrochloride or maleate salts).


METHOTRIMEPRAZINE HYDROCHLORIDE ORAL SOLUTION

Usual adult and adolescent dose
Psychotic disorders or
Pain, severe
Oral, initially, 50 to 75 mg (base) per day in two or three divided doses with meals, the dosage being increased gradually as needed and tolerated {58}.

Note: If initial doses of 100 to 200 mg per day are required, the patient should be confined to bed for the first few days to prevent orthostatic hypotension {58}.
Treatment of severe psychosis may require 1 gram or more per day {58}.


Sedation or
Pain, moderate
Oral, initially, 6 to 25 mg (base) per day in three divided doses with meals, the dosage being increased gradually as needed and tolerated {58}.


Note: Daytime drowsiness may be decreased, if necessary, by dividing the daily dose unevenly and using lower doses during the day and higher doses at night {58}.


Usual pediatric dose
Psychotic disorders or
Pain or
Sedation
Oral, initially, 250 mcg (0.25 mg) (base) per kg of body weight per day in two or three divided doses with meals, the dosage being increased gradually as needed and tolerated {58}.

Note: Dosage should not exceed 40 mg per day in children younger than twelve years of age {58}.



Strength(s) usually available
U.S.—
Not commercially available.

Canada—


25 mg (base) per 5 mL (Rx) [Nozinan Liquid (alcohol 2% ) (sucrose 3.7 grams/5 mL){58}]


40 mg (base) per mL (Rx) [Nozinan Oral Drops (alcohol 16.5%) (sucrose 200 mg/mL){58}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), protected from light, unless otherwise specified by manufacturer. Protect from freezing.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Avoid contact with skin or clothing.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis may result.


Additional information:
Only enclosed calibrated dropper should be used for measuring doses of the 40 mg (base) per mL solution.


METHOTRIMEPRAZINE MALEATE TABLETS

Usual adult and adolescent dose
See Methotrimeprazine Hydrochloride Oral Solution .

Usual pediatric dose
See Methotrimeprazine Hydrochloride Oral Solution .

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


2 mg (base) (Rx) [Nozinan{58}]


5 mg (base) (Rx) [Nozinan{58}]


25 mg (base) (Rx) [Nozinan{58}]


50 mg (base) (Rx) [Nozinan{58}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), protected from light, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.



Parenteral Dosage Forms

METHOTRIMEPRAZINE INJECTION USP

Usual adult and adolescent dose
Psychotic disorders, severe or
Pain, acute or intractable
Intramuscular, initially, 10 to 20 mg every four to six hours, the dosage being increased as needed for pain and sedation {57}.

Pain, obstetrical
Intramuscular, initially, 15 to 20 mg, the dose being adjusted and repeated as needed.

Pain, postoperative
Intramuscular, 2.5 to 7.5 mg immediately after surgery, the dose being adjusted and repeated every three to four hours as needed.

Note: After administration of the initial dose, the patient should be confined to bed or carefully supervised for at least 6 hours to prevent orthostatic hypotension, dizziness, or fainting {57}.
Residual effects of anesthetic agents may be additive to the effects of methotrimeprazine.


Sedation, preanesthetic
Intramuscular, 2 to 20 mg administered forty-five minutes to three hours before surgery {57}.

Anesthesia adjunct during surgery or labor
Intravenous infusion, 10 to 25 mg in 500 mL of 5% dextrose injection administered at a rate of 20 to 40 drops per minute {58}.


Usual pediatric dose
Psychotic disorders, severe or
Pain
Intramuscular, 62.5 to 125 mcg (0.062 to 0.125 mg) per kg of body weight per day in single or divided doses {58}.

Anesthesia adjunct during surgery
Intravenous infusion, 62.5 mcg (0.062 mg) per kg of body weight in 250 mL of 5% dextrose injection, administered at a rate of 20 to 40 drops per minute {58}.


Usual geriatric dose
Pain
Intramuscular, initially, 5 to 10 mg every four to six hours, the dosage being increased gradually as needed and tolerated.


Strength(s) usually available
U.S.—
Not commercially available.

Canada—


25 mg per mL (Rx) [Nozinan (sodium sulfite){58}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light. Protect from freezing.

Incompatibilities:
Methotrimeprazine should not be mixed in the same syringe with any drugs other than atropine sulfate or scopolamine hydrobromide {57}.


Caution:
Patients sensitive to sulfites may be sensitive to some methotrimeprazine injection products because of the sulfite preservatives present.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis may result.



PERICYAZINE

Summary of Differences


Indications:
Indicated as an adjunct in some patients with psychoses for the control of residual prevailing hostility, impulsivity, and aggressiveness.



Pharmacology/pharmacokinetics:


Chemical group—
Piperidine



Actions—
Antiemetic: Strong

Anticholinergic: Strong

Extrapyramidal: Moderate

Hypotensive: Moderate

Sedative: Strong




Oral Dosage Forms

PERICYAZINE CAPSULES

Usual adult dose
Psychotic disorders adjunct
Initial: Oral, 5 mg in the morning and 10 mg in the evening {59}; the dosage being adjusted as needed and tolerated {59}.

Maintenance: Oral, 2.5 to 15 mg in the morning and 5 to 30 mg in the evening has been suggested {59}; rarely will the dosage exceed 20 mg in the morning and 40 mg in the evening {59}.


Usual pediatric dose
Psychotic disorders adjunct
Children up to 5 years of age: Dosage has not been established.

Children 5 years of age and older: Oral, 2.5 to 10 mg in the morning and 5 to 30 mg in the evening as needed and tolerated {59}.

Note: Dosage is approximately 1 to 3 mg per year of age per day {59}.



Usual geriatric dose
Psychotic disorders adjunct
Oral, initially 5 mg per day, the dosage being increased gradually as needed and tolerated; rarely will dosage exceed 30 mg per day {59}.


Strength(s) usually available
U.S.—
Not commercially available.

Canada—


5 mg (Rx) [Neuleptil{59}]


10 mg (Rx) [Neuleptil{59}]


20 mg (Rx) [Neuleptil{59}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), protected from light, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


PERICYAZINE ORAL SOLUTION

Usual adult dose
See Pericyazine Capsules .

Usual pediatric dose
See Pericyazine Capsules .

Usual geriatric dose
See Pericyazine Capsules .

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


10 mg per mL (Rx) [Neuleptil (alcohol 12% v/v) (sucrose 250 mg/mL){59}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), protected from light, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Avoid contact with skin or clothing.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis may result.


Additional information:
Only enclosed calibrated dropper should be used for measuring dose.


PERPHENAZINE

Summary of Differences


Category:
Includes antiemetic use.



Pharmacology/pharmacokinetics:


Chemical group—
Piperazine



Actions—
Antiemetic: Strong

Anticholinergic: Weak to moderate

Extrapyramidal: Strong

Hypotensive: Weak

Sedative: Weak to moderate




Oral Dosage Forms

PERPHENAZINE ORAL SOLUTION USP

Usual adult and adolescent dose
Psychotic disorders (hospitalized patients)
Oral, 8 to 16 mg two to four times per day, the dosage being adjusted as needed and tolerated {83}.


Note: Geriatric, emaciated, or debilitated patients usually require a lower initial dose and more gradual dosage titration than do younger and healthier patients {13}.
Adolescents usually require dosages at the lower end of the adult dosage range {83}.


Usual adult prescribing limits
Psychotic disorders (hospitalized patients)
64 mg per day {83}.


Usual pediatric dose
Psychotic disorders
Children up to 12 years of age: Dosage has not been established.

Children 12 years of age and older: See Usual adult and adolescent dose.


Strength(s) usually available
U.S.—


16 mg per 5 mL (Rx) [Trilafon Concentrate{83}]

Canada—


16 mg per 5 mL (Rx) [PMS Perphenazine{65}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed, light-resistant container. Protect from freezing.

Preparation of dosage form:
Dilute each dose immediately before administration in water, salt solution, milk, tomato or fruit juice (except apple juice), soup, or a caffeine-free carbonated beverage {83}. The recommended dilution is 2 fluid ounces (60 mL) of diluent for each teaspoonful (5 mL) of perphenazine oral solution {81} {83}.

Incompatibilities:
Because of physical incompatibility, the oral solution should not be mixed with beverages containing caffeine or tannins (colas, coffee, or tea) or pectinates (apple juice) {83}.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Avoid contact with skin or clothing.
   • Must be diluted before use.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted.
Explain dosage measurement and dilution to patient, if self-administered, or to caregiver; however, the oral solution is intended primarily for institutional use.



PERPHENAZINE TABLETS USP

Usual adult and adolescent dose
Psychotic disorders
Oral, 4 to 16 mg two to four times per day, the dosage being adjusted gradually as needed and tolerated {83}.

Nausea and vomiting
Oral, 8 to 16 mg per day in divided doses {38} {83}, the dosage being decreased as early as possible {83}.


Note: Geriatric, emaciated, or debilitated patients usually require a lower initial dose and more gradual dosage titration than do younger and healthier patients {13}.
Adolescents usually require dosages at the lower end of the adult dosage range.


Usual adult prescribing limits
Psychotic disorders
Hospitalized patients: 64 mg per day {83}.

Nonhospitalized patients: 24 mg per day for long-term use {83}.

Nausea and vomiting
24 mg per day {83}.


Usual pediatric dose
Psychotic disorders or
Nausea and vomiting
Children up to 12 years of age: Dosage has not been established.

Children 12 years of age and older: See Usual adult and adolescent dose.


Strength(s) usually available
U.S.—


2 mg (Rx) [Trilafon (butylparaben) (lactose){83}][Generic]


4 mg (Rx) [Trilafon (butylparaben) (lactose){83}][Generic]


8 mg (Rx) [Trilafon (butylparaben) (lactose){83}][Generic]


16 mg (Rx) [Trilafon (butylparaben) (lactose){83}][Generic]

Canada—


2 mg (Rx) [Apo-Perphenazine{38}][Generic]


4 mg (Rx) [Apo-Perphenazine{38}][Generic]


8 mg (Rx) [Apo-Perphenazine{38}][Generic]


16 mg (Rx) [Apo-Perphenazine{38}][Generic]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.



Parenteral Dosage Forms

PERPHENAZINE INJECTION USP

Usual adult and adolescent dose
Psychotic disorders
Intramuscular, initially 5 mg (in most patients) to 10 mg (in severely agitated patients) {81} {83}. Dose may be adjusted, as needed and tolerated, and repeated every six hours until oral therapy is possible {81} {83}.

Nausea and vomiting
Intramuscular, 5 to 10 mg as needed and tolerated for rapid control of severe vomiting {81} {83}.

Intravenous, up to 5 mg, diluted, as a slow-drip infusion (preferred in surgical patients) or up to 5 mg, diluted to 0.5 mg per mL with 0.9% sodium chloride injection, in fractional injections of up to 1 mg each, administered at intervals of not less than one to two minutes {81} {83}.


Note: Geriatric, emaciated, or debilitated patients usually require a lower initial dose and more gradual dosage titration than do younger and healthier patients {13}.
For intramuscular administration, adolescents usually require dosages at the lower end of the adult dosage range {83}.
Intravenous administration is recommended only for use in recumbent hospitalized adults when needed to control severe vomiting or violent retching during surgery {81} {83}.
In psychotic conditions, most patients are controlled and amenable to oral therapy within 24 to 48 hours {81} {83}.


Usual adult prescribing limits
Intramuscular administration, nonhospitalized patients: 15 mg per day {81} {83}.

Intramuscular administration, hospitalized patients: 30 mg per day {81} {83}.

Intravenous administration: 5 mg {81} {83}.

Usual pediatric dose
Psychotic disorders
Children up to 12 years of age: Dosage has not been established.

Children 12 years of age and older: See Usual adult and adolescent dose.


Strength(s) usually available
U.S.—


5 mg per mL (Rx) [Trilafon (sodium bisulfite){83}]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light. Protect from freezing.

Stability:
A slight yellowing will not alter potency; however, do not use if markedly discolored or if a precipitate is present {83}.


Caution:
Patients sensitive to sulfites may be sensitive to some perphenazine injection products because of the sulfite preservatives present.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted.



PIPOTIAZINE

Summary of Differences


Indications:
For the control of residual prevailing hostility, impulsivity, and aggressiveness in psychotic patients already receiving antipsychotic medication.



Pharmacology/pharmacokinetics:


Chemical group—
Piperidine



Actions—
Antiemetic: Weak

Anticholinergic: Weak

Extrapyramidal: Strong

Hypotensive: Weak

Sedative: Weak




Additional Dosing Information
See also General Dosing Information.

A dry syringe and needle (at least 21-gauge) should be used, since use of a wet needle or syringe may cause the solution to become cloudy {61}.

After the initial dose of pipotiazine palmitate extended-action injection, doses and dosing intervals are determined by the patient's response {61}.


Parenteral Dosage Forms

PIPOTIAZINE PALMITATE INJECTION

Usual adult and adolescent dose
Psychotic disorders
Intramuscular, initially 50 to 100 mg, the dose being increased in increments of 25 mg every two to three weeks, as needed and tolerated, usually up to a maintenance dose of 75 to 150 mg every four weeks {61}.


Note: Geriatric patients usually require lower initial doses and, after initial titration, dosage should be reduced to the lowest effective maintenance dosage as soon as possible {61}.


Usual pediatric dose


Children up to 12 years of age: Dosage has not been established.

Children 12 years of age and older: See Usual adult and adolescent dose .

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


25 mg per mL (Rx) [Piportil L4 ( sesame oil){61}]


50 mg per mL (Rx) [Piportil L4 ( sesame oil){61}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), protected from light, unless otherwise specified by manufacturer. Protect from freezing.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis may result {17}.


Additional information:
The onset of action is usually within the first 2 or 3 days after injection, and antipsychotic effects become significant within 1 week {61}.

The effects of a single injection may last from 3 to 6 weeks, but adequate symptom control may be maintained with one injection every 4 weeks {61}.


PROCHLORPERAZINE

Summary of Differences


Category:
Includes antiemetic use.



Pharmacology/pharmacokinetics:


Chemical group—
Piperazine



Actions—
Antiemetic: Strong

Anticholinergic: Weak

Extrapyramidal: Strong

Hypotensive: Weak

Sedative: Weak to moderate




Additional Dosing Information
See also General Dosing Information.
For parenteral dosage forms only

   • Must be injected deeply into upper outer quadrant of the buttock.
   • Subcutaneous administration is not recommended because of possible irritation at injection site {68}.


Oral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of prochlorperazine base (not the edisylate, maleate, or mesylate salts).


PROCHLORPERAZINE ORAL SOLUTION USP

Usual adult and adolescent dose
Psychotic disorders
Oral, 5 to 10 mg (base) three or four times per day, the dosage being increased gradually every two to three days as needed and tolerated {68}.

Nausea and vomiting
Oral, 5 to 10 mg (base) three or four times per day {68}.


Note: Geriatric, emaciated, or debilitated patients usually require a lower initial dose and more gradual dosage titration than do younger and healthier patients {68}.


Usual adult prescribing limits
Psychotic disorders
150 mg (base) per day {68}.

Nausea and vomiting
40 mg (base) per day {68}.


Usual pediatric dose
Psychotic disorders
Children up to 2 years of age or less than 9 kg of body weight: Dosage has not been established.

Children 2 to 12 years of age: Oral, 2.5 mg (base) two or three times per day, not to exceed 10 mg on the first day {68}. Dosage may be increased based upon patient response {68}.

Children 12 years of age and older: See Usual adult and adolescent dose.

Nausea and vomiting
Children 9 to 14 kg of body weight: Oral, 2.5 mg (base) one or two times per day {68}.

Children 14 to 18 kg of body weight: Oral, 2.5 mg (base) two or three times per day {68}.

Children 18 to 39 kg of body weight: Oral, 2.5 mg (base) three times per day or 5 mg two times per day {68}.


Usual pediatric prescribing limits
Psychotic disorders
Children 2 to 6 years of age: 20 mg per day {68}.

Children 6 to 12 years of age: 25 mg per day {68}.

Nausea and vomiting
Children 9 to 14 kg of body weight: 7.5 mg per day {68}.

Children 14 to 18 kg of body weight: 10 mg per day {68}.

Children 18 to 39 kg of body weight: 15 mg per day {68}.


Strength(s) usually available
U.S.—


5 mg (base [as the edisylate salt]) per 5 mL (Rx) [Compazine ( fruit-flavored) (FD&C Yellow No. 6) (flavors) (polyoxyethylene polyoxypropylene glycol) (sodium benzoate) ( sodium citrate) (sucrose) ( water){68}]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container. Protect from freezing.

Stability:
A slight yellowing will not affect potency; however, do not use if markedly discolored or if a precipitate is present.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Avoid contact with skin or clothing.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted.



PROCHLORPERAZINE MALEATE EXTENDED-RELEASE CAPSULES

Usual adult and adolescent dose
Psychotic disorders
Dosage must be determined by physician {82}.

Nausea and vomiting
Oral, initially 15 mg (base) as a single dose in the morning or 10 mg every twelve hours, the dosage being increased as needed and tolerated {68}.


Note: Geriatric, emaciated, or debilitated patients usually require a lower initial dose and more gradual dosage titration than do younger and healthier patients {13}.


Usual adult prescribing limits
Psychotic disorders
150 mg (base) per day {68}.

Nausea and vomiting
40 mg (base) per day {68}.


Usual pediatric dose
The extended-release dosage form is not recommended for use in children.

Strength(s) usually available
U.S.—


10 mg (base) (Rx) [Compazine Spansule (benzyl alcohol) (cetylpyridinium chloride) (D&C Green No. 5) (D&C Yellow No. 10) (FD&C Blue No. 1) (FD&C Red No. 40) (FD&C Yellow No. 6) ( gelatin) (glyceryl monostearate) ( sodium lauryl sulfate) (starch) ( sucrose) (wax){68}]


15 mg (base) (Rx) [Compazine Spansule (benzyl alcohol) (cetylpyridinium chloride) (D&C Green No. 5) (D&C Yellow No. 10) (FD&C Blue No. 1) (FD&C Red No. 40) (FD&C Yellow No. 6) ( gelatin) (glyceryl monostearate) ( sodium lauryl sulfate) (starch) ( sucrose) (wax){68}]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer. Protect from light.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Swallow capsule whole.

Additional information:
The extended-release capsule releases a dose of prochlorperazine promptly upon ingestion and releases the remainder of the medication over a prolonged period {68}. Blood concentrations remain in the therapeutic range for 10 to 12 hours after a single dose {82}.


PROCHLORPERAZINE MALEATE TABLETS USP

Usual adult and adolescent dose
See Prochlorperazine Oral Solution USP .

Usual adult prescribing limits
See Prochlorperazine Oral Solution USP .

Usual pediatric dose
See Prochlorperazine Oral Solution USP .

Note: The oral solution dosage form usually is preferred for use in children.


Usual pediatric prescribing limits
See Prochlorperazine Oral Solution USP .

Strength(s) usually available
U.S.—


5 mg (base) (Rx) [Compazine (lactose) (sodium croscarmellose){68}][Generic]


10 mg (base) (Rx) [Compazine (lactose) (sodium croscarmellose){68}][Generic]

Canada—


5 mg (base) (Rx) [Nu-Prochlor{31}] [Stemetil{84}]


10 mg (base) (Rx) [Nu-Prochlor] [Stemetil{84}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed container. Protect from light.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


PROCHLORPERAZINE MESYLATE ORAL SOLUTION

Usual adult and adolescent dose
See Prochlorperazine Oral Solution USP .

Usual adult prescribing limits
See Prochlorperazine Oral Solution USP .

Usual pediatric dose
See Prochlorperazine Oral Solution USP .

Usual pediatric prescribing limits
See Prochlorperazine Oral Solution USP .

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


5 mg (base) per 5 mL (Rx) [Stemetil Liquid (sucrose 4 grams per 5 mL){84}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a tight container, protected from light, unless otherwise specified by manufacturer. Protect from freezing.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Avoid contact with skin or clothing.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted.




Parenteral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of prochlorperazine base (not the edisylate or mesylate salts).


PROCHLORPERAZINE EDISYLATE INJECTION USP

Usual adult and adolescent dose
Psychotic disorders
For immediate control of severely disturbed patients: Intramuscular, 10 to 20 mg (base); the dose may be repeated every two to four hours as needed, usually up to three or four doses {68}. In resistant cases, the dose may be repeated every hour if needed {68}.

Maintenance if prolonged parenteral administration is required: Intramuscular, 10 to 20 mg (base) every four to six hours {68}.

Nausea and vomiting
Intramuscular, 5 to 10 mg (base); the dose may be repeated every three to four hours, as needed {68}.

Intravenous, 2.5 to 10 mg as a slow injection or infusion, at a rate not exceeding 5 mg per minute {68}.

Note: For intravenous use, prochlorperazine edisylate injection may be administered undiluted or may be diluted in isotonic solution {68}.
Single intravenous doses should not exceed 10 mg {68}.


Nausea and vomiting in surgery
Intramuscular, 5 to 10 mg (base) one to two hours before induction of anesthesia or during or after surgery to control acute symptoms; the dose may be repeated once in thirty minutes if needed {68}.

Intravenous, 5 to 10 mg (base) administered as a slow injection or infusion (at a rate not exceeding 5 mg per minute) fifteen to thirty minutes before induction of anesthesia or during or after surgery to control acute symptoms; the dose may be repeated once if needed {68}.

Note: For intravenous use, prochlorperazine edisylate injection may be administered undiluted or diluted in isotonic solution {68}.
Single intravenous doses should not exceed 10 mg {68}.



Note: Geriatric, emaciated, or debilitated patients usually require a lower initial dose and more gradual dosage titration than do younger and healthier patients {68}.


Usual adult prescribing limits
Psychotic disorders
200 mg (base) per day.

Nausea and vomiting
40 mg (base) per day with no single intravenous dose exceeding 10 mg {68}.


Usual pediatric dose
Psychotic disorders or
Nausea and vomiting
Children up to 2 years of age or 9 kg of body weight: Dosage has not been established.

Children 2 to 12 years of age: Intramuscular, 132 mcg (0.132 mg) (base) per kg of body weight {68} {84}.

Children 12 years of age and older: See Usual adult and adolescent dose.

Note: Usually control is obtained with one dose, after which patient may be switched to an oral dosage form at the same or a higher dosage level {68} {84}.
Not recommended in pediatric surgery {68} {84}.



Usual pediatric prescribing limits
Children 2 to 6 years of age: 20 mg per day {68} {84}.

Children 6 to 12 years of age: 25 mg per day {68} {84}.

Strength(s) usually available
U.S.—


5 mg (base) per mL (Rx) [Compazine (sodium biphosphate 5 mg/mL ) (sodium tartrate 12 mg/mL) ( sodium saccharin 0.9 mg/mL) (benzyl alcohol 0.75% ){68}][Generic]

Canada—
Not commercially available.

Packaging and storage:
Store below 30 °C (86 °F) {68}, unless otherwise specified by manufacturer. Protect from light. Protect from freezing.

Preparation of dosage form:
For intravenous administration, prochlorperazine edisylate injection may be diluted with isotonic solution or may be used undiluted {68}.

Stability:
A slight yellowing will not alter potency; however, do not use if markedly discolored {68} or if a precipitate is present.

Incompatibilities:
A white milky precipitate may form when prochlorperazine edisylate injection is mixed in the same syringe with a morphine sulfate injection that contains phenol {72}.


Caution:
Medications containing benzyl alcohol are not recommended for use in neonates (first 30 days of postnatal life). A fatal toxic syndrome consisting of metabolic acidosis, CNS depression, respiratory problems, renal failure, hypotension, and possibly seizures and intracranial hemorrhages has been associated with the use of diluents containing benzyl alcohol in preparation of medications for use in neonates.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted {68}.
Subcutaneous administration is not recommended due to possible local irritation {68}.



PROCHLORPERAZINE MESYLATE INJECTION

Usual adult and adolescent dose
Psychotic disorders
For immediate control of severely disturbed patients: Intramuscular, 10 to 20 mg (base); the dose may be repeated every two to four hours as needed, usually up to three or four doses {84}.

Maintenance if prolonged parenteral administration is required: Intramuscular, 10 to 20 mg (base) every four to six hours {68}.

Nausea and vomiting
Intramuscular, 5 to 10 mg (base); the dose may be repeated every three to four hours if needed {68}.

Nausea and vomiting in surgery
Intramuscular, 5 to 10 mg (base) one to two hours before induction of anesthesia or during or after surgery to control acute symptoms {84}; the dose may be repeated once in thirty minutes {68} and may be repeated every three to four hours to a total dose of 40 mg per day {84} if needed.

Intravenous, 5 to 10 mg (base), administered (at a rate not exceeding 5 mg per minute) fifteen to thirty minutes before induction of anesthesia or during or after surgery to control acute symptoms; the dose may be repeated once if needed {68}.

Intravenous infusion, 20 mg (base) in 1 liter of isotonic solution, administered during or after surgery {84}.


Note: Geriatric, emaciated, or debilitated patients usually require a lower initial dose and more gradual dosage titration than do younger and healthier patients {13}.


Usual adult prescribing limits
Psychotic disorders
200 mg (base) per day.

Nausea and vomiting
40 mg (base) per day {84}.


Usual pediatric dose
Psychotic disorders or
Nausea and vomiting
Children up to 2 years of age or less than 9 kg of body weight: Dosage has not been established.

Children 2 to 12 years of age: Intramuscular, 132 mcg (0.132 mg) (base) per kg of body weight {68}, not exceeding 10 mg the first day {84}, the dosage being increased thereafter as needed and tolerated.

Children 12 years of age and over: See Usual adult and adolescent dose .

Note: Usually control is obtained with one dose, after which patient may be switched to an oral dosage form at the same or at a higher dosage level {68} {84}.
Not recommended in pediatric surgery {68} {84}.



Usual pediatric prescribing limits
Children 2 to 6 years of age: 20 mg per day {68} {84}.

Children 6 to 12 years of age: 25 mg per day {68} {84}.

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


5 mg (base) per mL (Rx) [PMS Prochlorperazine] [Stemetil (sulfite){84}][Generic]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), protected from light, unless otherwise specified by manufacturer. Protect from freezing.

Stability:
A slight yellowing will not alter potency; however, do not use if markedly discolored or if a precipitate is present.


Caution:
Patients sensitive to sulfites may be sensitive to some prochlorperazine products because of the sulfite preservatives present.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted.




Rectal Dosage Forms

PROCHLORPERAZINE SUPPOSITORIES USP

Usual adult and adolescent dose
Psychotic disorders
Rectal, initially 10 mg three or four times per day {84}; the dosage may be increased by 5 to 10 mg every two to three days as needed and tolerated {84}.

Nausea and vomiting
Rectal, 25 mg two times per day {68}.


Note: Geriatric, emaciated, or debilitated patients usually require a lower initial dose and more gradual dosage titration than do younger and healthier patients {68}.


Usual pediatric dose
Psychotic disorders
Children 2 to 12 years of age: Rectal, initially 2.5 mg two or three times a day, not to exceed 10 mg on the first day {68} {84}; dosage may be increased based upon response {68} {84}.

Children 12 years of age and older: See Usual adult and adolescent dose .

Nausea and vomiting
Children up to 2 years of age or less than 9 kg of body weight: Dosage has not been established.

Children 9 to 14 kg of body weight: Rectal, 2.5 mg one or two times per day {68} {84}.

Children 14 to 18 kg of body weight: Rectal, 2.5 mg two or three times per day {68} {84}.

Children 18 to 39 kg of body weight: Rectal, 2.5 mg three times per day or 5 mg two times per day {68} {84}.


Usual pediatric prescribing limits
Psychotic disorders
Children 2 to 6 years of age: 20 mg per day {68} {84}.

Children 6 to 12 years of age: 25 mg per day {68} {84}.

Nausea and vomiting
Children 9 to 14 kg of body weight: 7.5 mg per day {68} {84}.

Children 14 to 18 kg of body weight: 10 mg per day {68} {84}.

Children 18 to 39 kg of body weight: 15 mg per day {68} {84}.


Strength(s) usually available
U.S.—


2.5 mg (Rx) [Compazine{68}]


5 mg (Rx) [Compazine{68}]


25 mg (Rx) [Compazine{68}][Generic]

Canada—


10 mg (Rx) [Stemetil{84}][Generic]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F). Store in a tight container. Protect from light.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • For rectal use only.

Note: The 25-mg suppository is not recommended for use in children.
Explain administration technique to patient, if self-administered, or to caregiver.



PROMAZINE

Summary of Differences


Pharmacology/pharmacokinetics:


Chemical group—
Aliphatic



Actions—
Antiemetic: Moderate

Anticholinergic: Strong

Extrapyramidal: Weak

Hypotensive: Strong

Sedative: Strong




Parenteral Dosage Forms

PROMAZINE HYDROCHLORIDE INJECTION USP

Usual adult dose
Psychotic disorders
Initial: Intramuscular, a single dose of 50 to 150 mg; dose may be adjusted and repeated after thirty minutes, if necessary, up to a cumulative dose of 300 mg {53}.

Maintenance: Intramuscular, 10 to 200 mg every four to six hours may be used {53}.


Note: Geriatric, emaciated, or debilitated patients usually require a lower initial dose and more gradual dosage titration than do younger and healthier patients {13}.
Intravenous injection is not recommended generally {53}, but may be used in severely agitated hospitalized patients {52}. For intravenous use, dilute promazine hydrochloride injection to 25 mg or less per mL with 0.9% sodium chloride injection and administer slowly {52}.
In acutely inebriated patients, the initial dose should not exceed 50 mg {53}.


Usual adult prescribing limits
1 gram per day {53}.

Note: Although doses sometimes are increased gradually to 2 grams or more per day for short periods, extended therapy with 1 gram or less per day usually is sufficient.


Usual pediatric dose
Psychotic disorders
Children up to 12 years of age: Dosage has not been established.

Children 12 years of age and older: Intramuscular, 10 to 25 mg every four to six hours {53}.


Strength(s) usually available
U.S.—
Not commercially available.

Canada—


50 mg per mL (Rx)[Generic]{46}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light. Protect from freezing.

Stability:
A slight yellowing will not alter potency; however, do not use if markedly discolored or if a precipitate is present {53}.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted {53}.



THIOPROPERAZINE

Summary of Differences


Pharmacology/pharmacokinetics:


Chemical group—
Piperazine



Actions—
Antiemetic: Weak

Anticholinergic: Weak

Extrapyramidal: Strong

Hypotensive: Weak

Sedative: Weak




Oral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of thioproperazine base (not the mesylate salt).


THIOPROPERAZINE MESYLATE TABLETS

Usual adult and adolescent dose
Psychotic disorders
Oral, initially 5 mg (base) per day, the dosage being adjusted gradually by 5 mg every two or three days as needed and tolerated {70}.


Note: The usual effective dose is about 30 to 40 mg per day. In some patients, 90 mg or more per day may be necessary to control symptoms {70}. Once symptoms are controlled, dosage should be reduced gradually to the lowest effective maintenance dose {70}.


Usual pediatric dose
Psychotic disorders
Children up to 3 years of age: Use is not recommended {70}.

Children 3 to 11 years of age: Dosage has not been established {70}.

Children 11 years of age and older: Oral, initially 1 to 3 mg (base) per day in a single dose or in divided doses {70}; dosage may be increased every two to three days, as needed and tolerated {70}.


Strength(s) usually available
U.S.—
Not commercially available.

Canada—


10 mg (base) (Rx) [Majeptil (scored {31}){70}]

Packaging and storage:
Store below 40 °C (104 °F), in a well-closed, light-resistant container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


THIORIDAZINE

Summary of Differences


Category:
Includes sedative and antidyskinetic (Huntington's chorea) uses.



Pharmacology/pharmacokinetics:


Chemical group—
Piperidine



Actions—
Antiemetic: Weak

Anticholinergic: Moderate to strong

Extrapyramidal: Weak

Hypotensive: Moderate to strong

Sedative: Moderate to strong




Side/adverse effects:
More likely to cause pigmentary retinopathy than other phenothiazines.

Greater risk of developing melanosis than with other phenothiazines.

Involved in sudden cardiac death more frequently than other phenothiazines.



Oral Dosage Forms

THIORIDAZINE ORAL SUSPENSION USP

Note: The oral suspension dosage form contains thioridazine base, but the dosage and strength are expressed in equivalents of the hydrochloride salt {06}.


Usual adult and adolescent dose
Psychotic disorders
Initial: Oral, 50 to 100 mg (hydrochloride) one to three times per day, the dosage being adjusted gradually as needed and tolerated {06} {108}.

Maintenance: Oral, 50 to 200 mg (hydrochloride) two to four times per day {06}.

Sedation
Initial: Oral, 25 mg (hydrochloride) three times per day, the dosage being adjusted gradually as needed and tolerated {06}.

Maintenance: Oral, 10 to 50 mg (hydrochloride) two to four times per day {06}.


Note: Geriatric, emaciated, or debilitated patients usually require a lower initial dose and more gradual dosage titration than do younger and healthier patients {13}.


Usual adult prescribing limits
Psychotic disorders
800 mg (hydrochloride) per day {06}.

Note: Dosages greater than 300 mg (hydrochloride) per day should be used only in severe neuropsychiatric conditions {06}.


Sedation
200 mg (hydrochloride) per day {06}.


Usual pediatric dose
Psychotic disorders
Children up to 2 years of age: Dosage has not been established.

Children 2 to 12 years of age: Oral, initially 10 to 25 mg (hydrochloride) two or three times per day, the dosage being adjusted gradually as needed and tolerated {06}; the usual dosage range is 250 mcg (0.25 mg) to 3 mg per kg of body weight {06} or 7.5 mg per square meter of body surface area four times per day.

Children 12 years of age and older: See Usual adult and adolescent dose .


Strength(s) usually available
U.S.—


25 mg (hydrochloride) per 5 mL (Rx) [Mellaril-S (buttermint flavor ) (carbomer 934) (flavor ) (polysorbate 80) (purified water) (sodium hydroxide) ( sucrose){06}]


100 mg (hydrochloride) per 5 mL (Rx) [Mellaril-S ( buttermint flavor) (carbomer 934) (flavor) (polysorbate 80) (purified water) (sodium hydroxide ) (sucrose) (D&C Yellow No. 10) (FD&C Yellow No. 6){06}]

Canada—


10 mg (hydrochloride) per 5 mL (Rx) [Mellaril{31}] [Novo-Ridazine]{40}

Packaging and storage:
Store below 25 °C (77 °F) in a tight, light-resistant container {06}. Protect from freezing.

Auxiliary labeling:
   • Shake well before using.
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Avoid contact with skin or clothing.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted.



THIORIDAZINE HYDROCHLORIDE ORAL SOLUTION USP

Usual adult and adolescent dose
See Thioridazine Oral Suspension USP .

Usual adult prescribing limits
See Thioridazine Oral Suspension USP .

Usual pediatric dose
See Thioridazine Oral Suspension USP .

Strength(s) usually available
U.S.—


30 mg per mL (Rx) [Mellaril Concentrate (alcohol 3%){06}][Generic]


100 mg per mL (Rx) [Mellaril Concentrate (alcohol 4.2%){06}][Generic]

Canada—


30 mg per mL (Rx) [Mellaril (alcohol 24.5 mg/mL) (parabens){31}] [PMS Thioridazine]{65}

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container. Protect from freezing.

Preparation of dosage form:
Each dose must be diluted just before administration in a half glass (120 mL) of distilled water, acidified tap water, orange juice, or grapefruit juice.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Avoid contact with skin or clothing.
   • Must be diluted before use.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted.
Explain dosage measurement and dilution to patient, if self-administered, or to caregiver.



THIORIDAZINE HYDROCHLORIDE TABLETS USP

Usual adult and adolescent dose
See Thioridazine Oral Suspension USP .

Usual adult prescribing limits
See Thioridazine Oral Suspension USP .

Usual pediatric dose
See Thioridazine Oral Suspension USP .

Strength(s) usually available
U.S.—


10 mg (Rx) [Mellaril{06}][Generic]


15 mg (Rx) [Mellaril{06}][Generic]


25 mg (Rx) [Mellaril{06}][Generic]


50 mg (Rx) [Mellaril{06}][Generic]


100 mg (Rx) [Mellaril{06}][Generic]


150 mg (Rx) [Mellaril{06}][Generic]


200 mg (Rx) [Mellaril{06}][Generic]

Canada—


10 mg (Rx) [Apo-Thioridazine{31}] [Novo-Ridazine{40}]


25 mg (Rx) [Apo-Thioridazine{31}] [Novo-Ridazine{40}]


50 mg (Rx) [Apo-Thioridazine{31}] [Novo-Ridazine{40}]


100 mg (Rx) [Apo-Thioridazine{31}] [Novo-Ridazine{40}]


200 mg (Rx) [Novo-Ridazine{40}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


TRIFLUOPERAZINE

Summary of Differences


Category:
Includes antiemetic use.



Pharmacology/pharmacokinetics:


Chemical group—
Piperazine



Actions—
Antiemetic: Strong

Anticholinergic: Weak

Extrapyramidal: Strong

Hypotensive: Weak

Sedative: Weak




Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.
The dosing and strengths of the dosage forms available are expressed in terms of trifluoperazine base (not the hydrochloride salt).


TRIFLUOPERAZINE HYDROCHLORIDE SYRUP USP

Usual adult and adolescent dose
Psychotic disorders
Oral, initially 2 to 5 mg (base) one to two times per day, the dosage being increased gradually as needed and tolerated {02} {75} {108}.

Note: The optimal dosage range is 15 to 20 mg per day for most patients {02} {75}.


[Nausea and vomiting]
Oral, 1 to 2 mg (base) two times per day or as needed {75}.


Note: Geriatric, emaciated, or debilitated patients usually require a lower initial dose and more gradual dosage titration than do younger and healthier patients {02} {75}.


Usual adult prescribing limits
Psychotic disorders
40 mg (base) per day {02} {75}.


Usual pediatric dose
Psychotic disorders
Children up to 6 years of age: Dosage has not been established.

Children 6 to 12 years of age: Oral, initially 1 mg (base) one or two times per day, the dosage being adjusted gradually as needed and tolerated {02} {75}.

Children 12 years of age and older: See Usual adult and adolescent dose .


Note: Most children 6 to 12 years of age will not need doses greater than 15 mg per day {02}.


Strength(s) usually available
U.S.—


10 mg (base) per mL (Rx) [Stelazine Concentrate (banana-vanilla flavored) (sulfite) (sodium bisulfite) (sucrose){07}][Generic]

Canada—


10 mg (base) per mL (Rx) [PMS Trifluoperazine{65}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a tight, light-resistant container, unless otherwise specified by manufacturer. Protect from freezing.

Preparation of dosage form:
Dilute each dose just before administration in 60 mL (2 fluid ounces) or more of milk, tomato or fruit juice, simple syrup, orange syrup, carbonated beverages, coffee, tea, water, pudding, or soup {07}.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Avoid contact with skin or clothing.
   • Must be diluted before use.


Caution:
Patients sensitive to sulfites may be sensitive to some trifluoperazine hydrochloride syrup products because of the sulfite preservatives present.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted {07}.
Explain dosage measurement and dilution to patient, if self-administered, or to caregiver; however, the syrup is intended primarily for institutional use {07}.



TRIFLUOPERAZINE HYDROCHLORIDE TABLETS USP

Usual adult and adolescent dose
See Trifluoperazine Hydrochloride Syrup USP .

Usual adult prescribing limits
See Trifluoperazine Hydrochloride Syrup USP .

Usual pediatric dose
See Trifluoperazine Hydrochloride Syrup USP .

Strength(s) usually available
U.S.—


1 mg (base) (Rx) [Stelazine (lactose){07}][Generic]{02}


2 mg (base) (Rx) [Stelazine (lactose){07}][Generic]{02}


5 mg (base) (Rx) [Stelazine (lactose){07}][Generic]{02}


10 mg (base) (Rx) [Stelazine (lactose){07}][Generic]{02}

Canada—


1 mg (base) (Rx) [Apo-Trifluoperazine{75}] [Stelazine{31}][Generic]{31}


2 mg (base) (Rx) [Apo-Trifluoperazine{75}] [Novo-Trifluzine{40}] [Stelazine{31}][Generic]{31}


5 mg (base) (Rx) [Apo-Trifluoperazine{75}] [Novo-Trifluzine{40}] [Stelazine{31}][Generic]{31}


10 mg (base) (Rx) [Apo-Trifluoperazine{75}] [Novo-Trifluzine{40}] [Stelazine{31}]


20 mg (base) (Rx) [Apo-Trifluoperazine{75}][Generic]{31}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed, light-resistant container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.



Parenteral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of trifluoperazine base (not the hydrochloride salt).


TRIFLUOPERAZINE HYDROCHLORIDE INJECTION USP

Usual adult and adolescent dose
Psychotic disorders
Intramuscular, 1 to 2 mg (base) every four to six hours as needed {07}.


Note: Geriatric, emaciated, or debilitated patients usually require a lower initial dose and more gradual dosage titration than do younger and healthier patients {07}.


Usual adult prescribing limits
10 mg (base) per day, although most patients will not require more than 6 mg in twenty-four hours {07}.

Usual pediatric dose
Psychotic disorders
Children up to 6 years of age: Dosage has not been established.

Children 6 to 12 years of age: Intramuscular, 1 mg (base) one or two times per day {07}.

Children 12 years of age and older: See Usual adult and adolescent dose .


Strength(s) usually available
U.S.—


2 mg (base) per mL (Rx) [Stelazine (benzyl alcohol 0.75%) (sodium tartrate 4.75 mg/mL) (sodium biphosphate 11.6 mg/mL) (sodium saccharin 0.3 mg/mL ){07}]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light. Protect from freezing.

Stability:
A slight yellowing will not alter potency; however, do not use if markedly discolored or if a precipitate is present {07}.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted {07}.



TRIFLUPROMAZINE

Summary of Differences


Category:
Includes antiemetic use.



Pharmacology/pharmacokinetics:


Chemical group—
Aliphatic



Actions—
Antiemetic: Strong

Anticholinergic: Strong

Extrapyramidal: Moderate

Hypotensive: Moderate

Sedative: Moderate to strong




Parenteral Dosage Forms

TRIFLUPROMAZINE HYDROCHLORIDE INJECTION USP

Usual adult and adolescent dose
Psychotic disorders
Intramuscular, initially 60 mg; additional doses may be administered as needed {36}.

Nausea and vomiting
Intramuscular, 5 to 15 mg every four hours as needed {36}.

Intravenous, 1 mg; additional doses may be administered as needed {36}.


Note: Geriatric, emaciated, or debilitated patients usually require a lower initial dose {36} and more gradual dosage titration than do younger and healthier patients {13}.


Usual adult prescribing limits
Psychotic disorders
Intramuscular, 150 mg per day {36}.

Nausea and vomiting
Intramuscular, 60 mg per day {36}.

Intravenous, 3 mg per day {36}.


Usual pediatric dose
Psychotic disorders or
Nausea and vomiting
Children up to 21/2 years of age: Dosage has not been established.

Children 21/2 years of age and older: Intramuscular, 200 to 250 mcg (0.2 to 0.25 mg) per kg of body weight, not to exceed 10 mg per day {36}.


Note: Intravenous administration is not recommended in children {36} because of hypotension and rapid onset of severe extrapyramidal reactions.


Strength(s) usually available
U.S.—


10 mg per mL (Rx) [Vesprin (pH 3.5 to 5.2) (benzyl alcohol 1.5% w/v) (sodium chloride ) (sodium hydroxide and/or hydrochloric acid){36}]


20 mg per mL (Rx) [Vesprin (pH 3.5 to 5.2) (benzyl alcohol 1.5% w/v) (sodium chloride ) (sodium hydroxide and/or hydrochloric acid){36}]

Canada—
Not commercially available.

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light. Protect from freezing.

Stability:
Normally, solution may appear clear to faintly yellowish-green {36}. If it appears darker or otherwise discolored, or if a precipitate is present, do not use {36}.


Caution:
Medications containing benzyl alcohol are not recommended for use in neonates (first 30 days of postnatal life). A fatal toxic syndrome consisting of metabolic acidosis, CNS depression, respiratory problems, renal failure, hypotension, and possibly seizures and intracranial hemorrhages has been associated with the use of diluents containing benzyl alcohol for preparation of medications for use in neonates.

Note: Avoid skin contact with liquid forms of this medication; contact dermatitis has resulted.




Revised: 07/26/2001



References
  1. Pinto JT, Rivlan RS. Drugs that promote renal excretion of riboflavin. Drug Nutr Interact 1987; 5: 143-51.
  1. Trifluoperazine hydrochloride tablets package insert (Mylan—US), Rev 3/97, Rec 8/97.
  1. Panelist comment.
  1. Holtkamp W, Nagel GA, Wander HE, et al. Hyperprolactinemia is an indicator of progressive disease and poor prognosis in advanced breast cancer. Int J Cancer 1984; 34: 323-8.
  1. Theodorakis SP, Tedesco VE, Sutherland CM. Breast cancer in a patient with prolactinoma. Surgery 1985; 98(2): 367-9.
  1. Thioridazine package insert (Mellaril, Sandoz—US), Rev 10/96, Rec 8/98.
  1. Trifluoperazine hydrochloride package insert (Stelazine, SmithKline Beecham—US), Rev 1/95, Rec 10/98.
  1. Chlorpromazine package insert (Thorazine, SmithKline Beecham—US), Rev 3/96, Rec 8/98.
  1. Probucol package insert (Lorelco, Merrell Dow—US), Rev 6/88, Rec 4/94.
  1. Mesoridazine package insert (Serentil, Boehringer Ingelheim—US), Rev 7/96, Rec 7/98.
  1. Birkhimer LJ, deVane CL. The neuroleptic malignant syndrome: presentation and treatment. Drug Intell Clin Pharm 1984; 18: 462-5.
  1. Trioxsalen package insert (Trisoralen, Elder—US), Rev 12/85, Rec 7/88.
  1. Kaplan HI, Sadock BJ, Grebb JA. Kaplan and Sadock's synopsis of psychiatry. 7th ed. Baltimore, MD: Williams & Wilkins; 1994. p. 940-59.
  1. Personal communication, Drug Information Division, SmithKline Beecham, US, 9/4/98.
  1. Neuroleptics in the treatment of the confused elderly patient. Drug Therapy for the Elderly 1987; 2(5): 25-30. From Thompson TL, Moran MG, Nies AS. Psychotropic drug use in the elderly (in two parts). N Eng J Med 1983; 308: 134-8, 194-9.
  1. Gringauz A. Control of nausea and vomiting in the cancer patient. U.S. Pharmacist 1987 Jul. From Fiore JJ, Gralla RJ. Pharmacologic treatment of chemotherapy-induced nausea and vomiting. Cancer Invest 1984; 2: 351.
  1. Manufacturer comment, 5/89.
  1. Silver JM, Yudofsky SC, Hurowitz GI. Psychopharmacology and electroconvulsive therapy. In: Hales RE, Yudofsky SC, Talbott JA, editors. The American Psychiatric Press textbook of psychiatry. 2nd ed. Washington DC: American Psychiatric Press; 1994. p. 900-19.
  1. White W. Hypotension with postural syncope secondary to the combination of chlorpromazine and captopril. Arch Intern Med 1986; 146: 1833-4.
  1. Silver JM, Yudofsky SC, Kogan M, et al. Elevation of thioridazine plasma levels by propranolol. Am J Psychiatry 1986; 143: 1290-2.
  1. Gennaro AR, Chase GD, Marderosian AD, et al, editors. Remington's pharmaceutical sciences. 18th ed. Easton, PA: Mack Publishing Company; 1990. p. 950-1.
  1. Chlorpromazine hydrochloride oral concentrate package insert (Chlorpromazine Hydrochloride Intensol, Roxane—US), Rev 5/94, Rec 8/98.
  1. Rupniak NMJ, Jenner P, Mardsen CD. Acute dystonia induced by neuroleptic drugs. Psychopharmacology 1986; 88: 403-19.
  1. Phenothiazine-induced agranulocytosis. (Questions and answers.) JAMA 1986; 256(14): 1957.
  1. Lamy P, Zuckerman IH. Pharmacologic considerations in the treatment of Alzheimer's disease, part III. The Maryland Pharmacist 1987 Mar; 63(3): 10-2.
  1. Mesoridazine—priapism. Reactions, 1986 Jul. From: Lazarus A. Priapism and psychotropic drug therapy [letter]. J Clin Psychopharmacol 1986; 6(1): 60-1.
  1. Mephentermine sulfate package insert (Wyamine, Wyeth—US), Rev 10/92, Rec 7/93.
  1. Jacknowitz AI. Thioridazine-induced hyperpyrexia—a case report. Am J Hosp Pharm 1979; 36: 674-8.
  1. Blue MG, Schneider SM, Noro S, et al. Successful treatment of neuroleptic malignant syndrome with sodium nitroprusside. Ann Intern Med 1986; 104(1): 56-7.
  1. Levine S, McManus BM, Blackbourne BD, et al. Fatal water intoxication, schizophrenia, and diuretic therapy for systemic hypertension. Am J Med 1987; 82(1): 153-5.
  1. Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. G75, 116, 122, 307, 634, 935, 962, 1018, 1174, 1192, 1579.
  1. Lal S, AlAnsari E. Tourette-like syndrome following low-dose short-term neuroleptic treatment. Can J Neurol Sci 1986; 13: 125-8.
  1. Gualtieri CT, Patterson DR. Neuroleptic-induced tics in two hyperactive children. Am J Psychiatry 1986; 143(9): 1176-7.
  1. Fluphenazine hydrochloride injection package insert (Fujisawa—US), Rev 10/95, Rec 8/98.
  1. Martin JB, Gusella JF. Huntington's disease: pathogenesis and management. N Eng J Med 1986; 315(20): 1267-76.
  1. Triflupromazine hydrochloride injection package insert (Vesprin, Apothecon—US), Rec 9/98.
  1. Precipitation of carbamazepine suspension and other liquid drugs. WHO Drug Information 1998; 12(2): 81.
  1. Perphenazine tablets product monograph (Apotex—Canada), Rec 1/96.
  1. Morphine sulfate immediate release oral solution package insert (Astra—US), Rev 8/97, Rec 10/98.
  1. Personal communication, Novopharm, Canada, 11/9/98.
  1. Reynolds JEF, editor. Martindale: the extra pharmacopoeia. 31st ed. London: Royal Pharmaceutical Society of Great Britain; 1996. p. 671, 692-3, 711, 731.
  1. Chlorpromazine product monograph (Largactil, Rhône-Poulenc Rorer—Canada), Rev 5/91, Rec 8/98.
  1. Oxsoralen-Ultra (Methoxsalen, ICN—US). In: PDR Physicians' desk reference. 52nd ed. 1998. Montvale, NJ: Medical Economics Company; 1998. p. 1257-60.
  1. Fluphenazine enanthate injection package insert (Prolixin Enanthate, Apothecon—US), Rev 3/98, Rec 10/98.
  1. Reviewers' responses to Psychiatric Disease Advisory Panel Memo #6 of 9/16/91.
  1. Personal communication, Abbott, Canada, 8/3/98.
  1. Panel comment, 6/88.
  1. Gonadorelin hydrochloride package insert (Factrel, Wyeth—US), Rev 6/96, Rec 3/98.
  1. Manufacturer comment, 5/88.
  1. Fluphenazine decanoate injection product monograph (Modecate, Squibb—Canada), Rev 7/91, Rec 12/95.
  1. Fluphenazine decanoate injection package insert (Fujisawa—US), Rev 10/95, Rec 7/97.
  1. Manufacturer comment, 6/88.
  1. Promazine package insert (Sparine, Wyeth—US), Rev 2/94, Rec 12/95.
  1. Panel comment, 7/88.
  1. Fluphenazine hydrochloride package insert (Permitil, Schering—US), Rev 11/93, Rec 12/95.
  1. Personal communication, Squibb Canada, 7/31/98.
  1. Methotrimeprazine package insert (Levoprome, Lederle Parenterals—US), Rev 3/87.
  1. Methotrimeprazine product monograph (Nozinan, Rhône-Poulenc Rorer—Canada), Rev 5/91, Rec 8/98.
  1. Pericyazine product monograph (Neuleptil, Rhône-Poulenc Rorer—Canada), Rev 5/91, Rec 8/98.
  1. Moditen Enanthate product monograph. In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 1019.
  1. Pipotiazine palmitate injectable product monograph (Piportil L 4, Rhône-Poulenc Rorer—Canada), Rev 5/91, Rec 8/98.
  1. Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention Inc; 1997. p. 158-9, 320, 455, 462, 563-4, 579, 604, 607, 728, 757-8.
  1. Serentil product monograph. In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 1530-1.
  1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders DSM-IV. 4th ed. Washington, DC: American Psychiatric Association, 1994. p. 736-49.
  1. Personal communication, Drug Information and Customer Service departments, Pharmascience—Canada, 10/9/98 and 11/9/98.
  1. Fluphenazine decanoate injection package insert (Prolixin Decanoate Injection, Apothecon—US), Rev 5/96, Rec 10/98.
  1. Regal RE, Billi JE, Glazer HM. Phenothiazine-induced cholestatic jaundice. Clin Pharm 1987; 6: 787-94.
  1. Prochlorperazine package insert (Compazine, SmithKline Beecham—US), Rev 2/97, Rec 5/97.
  1. Ocular toxicity from systemic drug therapy—Part 2. Reactions 1986 Jul 26: 10-1. From: Davidson SI, Rennie IG. Ocular toxicity from systemic drug therapy: an overview of clinically important adverse reactions. Med Toxicol 1986; 1(3): 217-24.
  1. Thioproperazine product monograph (Majeptil, Rhône-Poulenc Rorer—Canada), Rev 5/91, Rec 8/98.
  1. Hansten PD, Horn JR. Heat stroke due to drug combinations. Drug Interactions Newsletter 1985; 5(6): 23-4.
  1. Zuber DEL. Compatibility of morphine sulfate injection and prochlorperazine edisylate injection [letter]. Am J Hosp Pharm 1987; 44: 67.
  1. Gupta MA, Gupta AK, Haberman HF. Psychotropic drugs in dermatology: a review and guidelines for use. J Am Acad Dermatol 1986; 14: 633-45.
  1. Borst D, Schneiweiss F. Phenothiazines and body temperature. Drug Intell Clin Pharm 1984; 18: 882.
  1. Trifluoperazine product monograph (Apotex—Canada), Rec 1/96.
  1. Bond WS, Yee GC. Ocular and cutaneous effects of chronic phenothiazine therapy. Am J Hosp Pharm 1980; 37: 74-8.
  1. Wells AJ, Sommi RW, Crismon ML. Neuroleptic rechallenge after neuroleptic malignant syndrome: case report and literature review. Drug Intell Clin Pharm 1988; 22: 475-80.
  1. Fluphenazine hydrochloride tablets and elixir package insert (Prolixin, Apothecon—US), Rev 7/96, Rec 10/98.
  1. Fluphenazine hydrochloride product monograph (Moditen-HCl, Squibb—Canada), Rev 8/84, Rec 12/95.
  1. Fluphenazine hydrochloride injection package insert (Prolixin Injection, Apothecon—US), Rev 1/96, Rec 10/98.
  1. Perphenazine injection package insert and perphenazine package labels (Trilafon, Schering—Canada), Rec 12/95.
  1. Personal communication, Drug Information, SmithKline Beecham, US, 6/18/98.
  1. Perphenazine package insert (Trilafon, Schering—US), Rev 11/93, Rec 12/95.
  1. Stemetil product monograph. In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 1579-81.
  1. Fluphenazine hydrochloride oral solution package insert (Prolixin, Apothecon—US), Rev 6/87, Rec 10/98.
  1. Fluphenazine hydrochloride tablets product monograph (Apo-Fluphenazine, Apotex—Canada), Rev 1/90, Rec 1/96.
  1. Olmsted TR. Neuroleptic malignant syndrome: guidelines for treatment and reinstitution of neuroleptics. South Med J 1988; 81(7): 888-91.
  1. Panel comment, 6/88.
  1. Reviewers' responses to monograph revision of 5/99.
  1. Panel comment, 1/99.
  1. Caroff SN, Mann SC. Neuroleptic malignant syndrome. Med Clin North Am 1993 Jan; 77(1): 185-202.
  1. Heiman-Patterson TD. Neuroleptic malignant syndrome and malignant hyperthermia. Med Clin North Am 1993 Mar; 77(2): 477-92.
  1. Gomez-Perez FJ, Rull JA, Dies H, et al. Nortriptyline and fluphenazine in the symptomatic treatment of diabetic neuropathy: a double-blind cross-over study. Pain 1985; 23: 395-400.
  1. Hartigan-Go K, Bateman DN, Nyberg G, et al. Concentration-related pharmacodynamic effects of thioridazine and its metabolites in humans. Clin Pharmacol Ther 1996; 60(5): 543-53.
  1. Ereshefsky L. Pharmacokinetics and drug interactions: update for new antipsychotics. J Clin Psychiatry 1996; 57 Suppl 11: 12-25.
  1. Linnet K, Wiborg O. Steady-state serum concentrations of the neuroleptic perphenazine in relation to CYP2D6 genetic polymorphism. Clin Pharmacol Ther 1996; 60: 41-7.
  1. Eap CB, Guentert TW, Schäublin-Loidl M, et al. Plasma levels of the enantiomers of thioridazine, thioridazine 2-sulfoxide, thioridazine 2-sulfone, and thioridazine 5-sulfoxide in poor and extensive metabolizers of dextromethorphan and mephenytoin. Clin Pharmacol Ther 1996; 59(3): 322-31.
  1. Bertilsson L. Geographical/interracial differences in polymorphic drug oxidation: current state of knowledge of cytochromes P450 (CYP) 2D6 and 2C19. Clin Pharmacokinet 1995; 29(3): 192-209.
  1. Jerling M, Dahl M-L, Åberg-Wistedt A, et al. The CYP2D6 genotype predicts the oral clearance of the neuroleptic agents perphenazine and zuclopenthixol. Clin Pharmacol Ther 1996; 59(4): 423-8.
  1. Hubbard JW, Midha KK, Hawes G, et al. Metabolism of phenothiazine and butyrophenone antipsychotic drugs: a review of some recent research findings and clinical implications. Br J Psychiatry 1993: 163 Suppl 22: 19-24.
  1. Ereshefsky L, Saklad SR, Jann MW, et al. Future of depot neuroleptic therapy: pharmacokinetic and pharmacodynamic approaches. J Clin Psychiatry 1984; 45(5, Section 2): 50-9.
  1. Nath SP, Miller DA, Muraskas JK. Severe rhinorrhea and respiratory distress in a neonate exposed to fluphenazine hydrochloride prenatally. Ann Pharmacother 1996; 30(1): 35-7.
  1. Özdemir V, Herrmann N, Walker S, et al. Paroxetine potentiates CNS side-effects of perphenazine [abstract]. Clin Pharmacol Ther 1996; 59(2): 188.
  1. Panel comment, 2/99.
  1. Thomas SHL, Reilly JG, Jones SJ, et al. Prolongation of the QT c interval in psychiatric patients: frequency and risk factors [abstract]. Clin Pharmacol Ther 1998; 61(2): 231.
  1. Tekell JL, Silva JA, Maas JA, et al. Thioridazine-induced retinopathy [letter]. Am J Psychiatry 1996; 153(9): 1234-5.
  1. Viguera AC, Baldessarini RJ, Hegarty JD, et al. Clinical risk following abrupt and gradual withdrawal of maintenance neuroleptic treatment. Arch Gen Psychiatry 1997 Jan; 54: 49-55.
  1. Panel comment, 2/99.
  1. Product Information: Mellaril®, thioridazine. Novartis Pharmaceuticals, East Hanover, NJ, (PI revised 6/2000) reviewed 8/2000.
  1. Product Information: Serentil®, mesoridazine besylate. Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, (PI revised 8/2000) reviewed 7/2001.
Hide
(web5)