Chlorpromazine Hydrochloride

Pronunciation

Class: Phenothiazines
VA Class: CN701
Chemical Name: 2-Chloro-10-[3-(dimethylamino)propyl]-phenothiazine monohydrochloride
Molecular Formula: C17H19CIN2S HCl
CAS Number: 69-09-0

Warning(s)

  • Increased Mortality in Geriatric Patients with Dementia-related Psychosis
  • Geriatric patients with dementia-related psychosis treated with antipsychotic agents are at an increased risk of death.101 105 106 n

  • Analyses of 17 placebo-controlled trials in geriatric patients mainly receiving atypical antipsychotic agents revealed an approximate 1.6- to 1.7-fold increase in mortality compared with that in patients receiving placebo.101 105 106 n

  • Most fatalities appeared to result from cardiovascular-related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).105 106 n

  • Observational studies suggest that conventional or first-generation antipsychotic agents also may increase mortality in such patients.101 105 106

  • Antipsychotic agents, including chlorpromazine, are not approved for the treatment of dementia-related psychosis.101 105 106 n

Introduction

Propylamino-derivative phenothiazine; conventional (prototypical, first-generation) antipsychotic agent.105 106 c d g i

Uses for Chlorpromazine Hydrochloride

Psychotic Disorders

Symptomatic management of psychotic disorders (i.e., schizophrenia).105 106 c d g

Nausea and Vomiting

Management of nausea and vomiting, including during surgery.105 106 c d

Preoperative Sedation

Relief of restlessness and apprehension before surgery.105 106 c

Slideshow: 18 Herbal Supplements with Risky Drug Interactions

Herbal and Dietary Supplements Deserve Your Attention

Acute Intermittent Porphyria

Treatment of acute intermittent porphyria.105 106 c d

Tetanus

Adjunct in the treatment of tetanus.105 106 c d

Bipolar Disorder

Symptomatic management of manic phase of bipolar disorder.105 106 c

Intractable Hiccups

Treatment of intractable hiccups.105 106 c d

Disruptive Behavior Disorder and Attention Deficit Hyperactivity Disorder (ADHD)

Treatment of severe behavioral problems in children marked by combativeness and/or explosive hyperexcitable behavior (out of proportion to immediate provocations).105 106 c

Short-term treatment of hyperactive children who exhibit excessive motor activity with accompanying conduct disorders manifested as impulsivity, difficulty sustaining attention, aggression, mood lability, and/or poor frustration tolerance.105 106 c

Chlorpromazine Hydrochloride Dosage and Administration

General

  • Adjust dosage carefully according to individual requirements and response; use the lowest possible effective dosage.105 106 c

  • Periodically evaluate patients receiving long-term therapy to determine whether maintenance dosage can be decreased or drug therapy discontinued.105 106 c (See Tardive Dyskinesia under Cautions.)

Psychotic Disorders

  • For symptomatic relief of psychotic disorders, initial therapeutic response to antipsychotic therapy usually occurs within 1–4 weeks and optimum therapeutic response occurs within 6 months or longer.105 106 d g

  • For prompt control of severe psychotic symptoms, administer IM; after symptoms are controlled, oral therapy should replace parenteral therapy.105 106 c d

  • Once optimum dosage is achieved, continue this dosage for 2 weeks, then gradually reduce to lowest possible effective dosage.105 106 c

Administration

Administer orally, by deep IM or direct IV injection, or by IV infusion.105 106 c

Sub-Q administration not recommended because of local irritation.106 c

Avoid skin and clothing contact with chlorpromazine hydrochloride injection, since contact dermatitis has occurred rarely.106 c

Reserve parenteral therapy for recumbent patients;106 c however, if cautions are taken to avoid orthostatic hypotension (i.e., patient remains recumbent for ≥30 minutes after injection), acutely agitated ambulatory patients may receive the drug IM.106 c

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Direct IV injection for use only during surgery to control nausea and vomiting and in the adjunctive treatment of tetanus.106 c

IV infusion is intended only for use in adjunctive treatment of intractable hiccups in adults.106 c

Avoid IV administration of undiluted drug.106 c

Dilution

For direct IV injection, dilute with 0.9% sodium chloride injection to a concentration not exceeding 1 mg/mL.106 c

For IV infusion, add injection to 500–1000 mL of 0.9% sodium chloride.106 c

Rate of Administration

Children: For direct IV injection, administer diluted solution at a rate of 0.5 mg/minute.106 c

Adults: For direct IV injection, administer diluted solution at a rate of 1 mg/minute.106 c For IV infusion, administer diluted solution slowly.106 c

IM Administration

Inject slowly, deep into a large muscle mass such as the upper outer quadrant of the gluteus maximus.106 c

Dilution

If irritation at IM injection site occurs, may dilute with 0.9% sodium chloride injection or 2% procaine hydrochloride.106 c

Dosage

Available as chlorpromazine hydrochloride; dosage expressed in terms of the hydrochloride salt.105 106 c

Manufacturers state that the 100- and 200-mg tablets are intended for use in patients with severe neuropsychiatric conditions.105 c

Chlorpromazine should generally not be used in children <6 months of age unless the condition to be treated is potentially life-threatening; dosage in this age group has not been established.105 106 c

Pediatric Patients

Adolescents 13–17 years of age: No specific dosage recommendations; dosage is based on patient weight and clinician judgment.k l

Nausea and Vomiting
Oral

Children 6 months to 12 years of age: Usually, 0.55 mg/kg every 4–6 hours as necessary.105 c Adjust dosage based on symptom severity and patient response.105 c

IM

Children 6 months to 12 years of age: Initially, 0.55 mg/kg every 6–8 hours as necessary; carefully adjust subsequent dosage based on symptom severity and patient response.106 c

Surgery
Preoperative Sedation
Oral

Children 6 months to 12 years of age: 0.55 mg/kg administered 2–3 hours before surgery.105 c

IM

Children 6 months to 12 years of age: 0.55 mg/kg administered 1–2 hours before surgery.106 c

Nausea and Vomiting During Surgery
IV

Children 6 months to 12 years of age: Fractional 1-mg doses may be given at 2-minute intervals up to a total dosage of 0.275 mg/kg;106 c may repeat fractional dosage regimen after 30 minutes if necessary and if hypotension does not occur.106 c

IM

Children 6 months to 12 years of age: 0.275 mg/kg;106 c may repeat dosage in 30 minutes if necessary and if hypotension does not occur.106 c

Tetanus
IM or IV

Children 6 months to 12 years of age: 0.55 mg/kg every 6–8 hours by IM or direct IV injection.106 c

In children weighing <22.7 kg, maximum parenteral dosage is 40 mg daily.106 c In children weighing 22.7–45.5 kg, maximum parenteral dosage is ≤75 mg daily, except in severe cases.106 c

Disruptive Behavior Disorder and ADHD
Outpatients
Oral or IM

Children 1–12 years of age: Initially, 0.55 mg/kg orally every 4–6 hours or IM every 6–8 hours as necessary;105 106 c increase dosage gradually as required.105 106 c

Hospitalized Patients
Oral or IM

Initiate with low dosage as with outpatients and increase dosage gradually.105 106 c For severe behavior disorders, higher dosages (50–100 mg daily, and in older children: ≥200 mg daily) may be necessary.105 106 c There is little evidence that behavior improvement in severely disturbed, mentally retarded patients is further enhanced at dosages >500 mg daily.105 106 c

IM

Maximum 40 mg daily for children <5 years (or 22.7 kg).106 c

Maximum ≤75 mg daily for children 5–12 years of age (or 22.7–45.5 kg);106 c dosage may be further increased in unmanageable patients.106 c

Adults

Psychotic Disorders

Usual oral dosage during maintenance therapy is 200 mg daily; however, oral dosages up to 800 mg daily may be required in some patients.105 106 c

Outpatients with Relatively Mild Symptomatology
Oral

30–75 mg daily, given in 2–4 divided doses.105 c

Outpatients with More Severe Symptomatology
Oral

Initially, 25 mg 3 times daily.105 c After 1 or 2 days, may gradually increase dosage twice weekly by 20–50 mg until symptoms are controlled.105 c

If used to replace parenteral therapy after prompt control of symptoms achieved, initiate oral therapy at 25–50 mg 3 times daily.105 106 c

IM

For prompt control of severe symptoms, 25 mg IM initially; may repeat in 1 hour if necessary.106 c After symptoms are controlled, replace parenteral therapy with oral therapy at dosage of 25–50 mg 3 times daily.105 106 c

Hospitalized Patients
Oral

Dosages of 500 mg daily are generally sufficient in most patients.105 c Dosages >2 g daily may be required in some patients; however, little therapeutic gain is achieved with dosages >1 g daily administered for extended periods.105 c

Less acutely agitated patients: Initially, 25 mg 3 times daily;105 c gradually increase subsequent dosage.105 Usually do not exceed 400 mg daily.105 c

IM

In acute schizophrenic or manic patients: Initially, 25 mg.106 c May administer an additional IM dose of 25–50 mg in 1 hour if necessary.106 c Increase subsequent dosage gradually over several days to a maximum of 400 mg every 4–6 hours in exceptionally severe cases until symptoms are controlled.106 c

Usually, patients become quiet and cooperative within 24–48 hours after therapy initiation;105 106 oral therapy can then replace parenteral therapy.106

Nausea and Vomiting
Oral

10–25 mg every 4–6 hours;105 c may increase dosage if necessary.105 c

IM

Initially, usual dose is 25 mg.106 c If hypotension does not occur, may administer additional IM doses of 25–50 mg every 3–4 hours until symptoms subside; oral therapy should then replace parenteral therapy if necessary.106 c

Surgery
Preoperative Sedation
Oral

25–50 mg, 2–3 hours before surgery.105 c

IM

12.5–25 mg, 1–2 hours before surgery.106 c

Nausea and Vomiting During Surgery
IV

Fractional 2-mg doses may be given IV at 2-minute intervals up to a maximum total dosage of 25 mg.106 c

IM

12.5 mg; may repeat dose in 30 minutes if hypotension does not occur.106 c

Acute Intermittent Porphyria
Oral

25–50 mg 3 or 4 times daily.105 c Can discontinue therapy after several weeks; however, some patients may require maintenance therapy.105 c

IM

25 mg 3 or 4 times daily until patient can take oral therapy.106 c

Tetanus
IV

25–50 mg by direct IV injection.106 c

IM

25–50 mg 3 or 4 times daily, usually in conjunction with barbiturates.106 c Determine total dosage and administration frequency by patient response, starting with low dosage and increasing gradually.106

Intractable Hiccups
Oral or IM

Initially, 25–50 mg orally 3 or 4 times daily.105 c If symptoms persist for 2–3 days, may give 25–50 mg IM.105 106 c

IV

If hiccups persist after oral and IM therapy, may administer 25–50 mg by slow IV infusion with patient in a supine position.106 c Closely monitor BP.106 c

Prescribing Limits

Pediatric Patients

Nausea and Vomiting
IM

Maximum 40 mg daily for children 6 months to <5 years of age (or <22.7 kg).106 c

Maximum 75 mg daily for children 5–12 years of age (or 22.7–45.5 kg), except in severe cases.106 c

Tetanus
IM or IV

Maximum 40 mg daily for children <22.7 kg.106 c

Maximum ≤75 mg daily for children 22.7–45.5 kg, except in severe cases.106 c

Disruptive Behavior Disorder and ADHD
Hospitalized Patients
Oral or IM

Maximum effective dosage not established, but there is little evidence that behavior improvement in severely disturbed mentally retarded patients is further enhanced at dosages >500 mg daily.105 106 c

IM

Maximum 40 mg daily for children <5 years (or <22.7 kg).106 c

Maximum ≤75 mg daily for children 5–12 years of age (or from 22.7–45.5 kg); dosage may be further increased in unmanageable patients.106 c

Adults

Psychotic Disorders
Hospitalized Patients
Oral

Little therapeutic gain achieved by dosages >1 g daily administered for extended periods.105 c

Less acutely agitated patients: Usually do not exceed 400 mg daily.105 c

IM

Maximum IM dosage of 400 mg every 4–6 hours.106 c

Surgery
Nausea and Vomiting During Surgery
IV

Maximum total dosage of 25 mg.106 c

Special Populations

Geriatric Patients

No specific dosage recommendations for geriatric patients, but generally select dosage at the lower end of recommended range; increase dosage more gradually and monitor closely.105 106 c d (See Geriatric Use under Cautions.)

Debilitated or Emaciated Patients

Increase dosage more gradually.105 106 c d

Cautions for Chlorpromazine Hydrochloride

Contraindications

  • Comatose states or in the presence of large amounts of CNS depressants (e.g., alcohol, barbiturates, opiates).105 106 d (See Specific Drugs and Laboratory Tests under Interactions.)

  • Known hypersensitivity to phenothiazines.105 106

Warnings/Precautions

Warnings

Shares the toxic potentials of other phenothiazines; observe the usual precautions of phenothiazine therapy.105 106 c d

Increased Mortality in Geriatric Patients with Dementia-related Psychosis

Increased risk of death with use of either conventional (first-generation) or atypical (second-generation) antipsychotics in geriatric patients with dementia-related psychosis.101 105 106 n

Antipsychotic agents, including chlorpromazine, are not approved for the treatment of dementia-related psychosis.101 105 106 n (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis in Boxed Warning.)

Extrapyramidal Reactions

Possible extrapyramidal reactions.105 106 d Signs and symptoms may be similar to those accompanying certain disorders (e.g., encephalitis, Reye’s syndrome, encephalopathy, meningitis, tetanus); diagnosis of these disorders may be obscured or the disease-associated signs and symptoms may be incorrectly diagnosed as drug induced.105 106 d Avoid use in children and adolescents whose signs and symptoms suggest Reye’s syndrome.105 106

Tardive Dyskinesia

Tardive dyskinesia, a syndrome of potentially irreversible, involuntary dyskinetic movements, reported with use of antipsychotic agents, including chlorpromazine.105 106 d g

Reserve long-term antipsychotic treatment for patients with chronic illness known to respond to antipsychotic agents, and for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate.105 106 In patients requiring chronic treatment, use smallest dosage and shortest duration of treatment producing a satisfactory clinical response; periodically reassess need for continued therapy.105 106

APA recommends assessing patients receiving conventional antipsychotic agents for abnormal involuntary movements every 6 months; for patients at increased risk for tardive dyskinesia, assess every 3 months.g Consider discontinuance of chlorpromazine if signs and symptoms of tardive dyskinesia appear.105 106 However, some patients may require treatment despite the presence of the syndrome.105 106

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome characterized by hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability, reported with antipsychotic agents, including chlorpromazine.105 106 d g

Immediately discontinue therapy and initiate supportive and symptomatic therapy if NMS occurs.105 106 Careful monitoring recommended if therapy is reinstituted following recovery; the risk that NMS can recur must be considered.105 106

Concomitant Therapy with Lithium

Although most patients receiving lithium and an antipsychotic agent concurrently do not develop unusual adverse effects, an acute encephalopathic syndrome occasionally has occurred, especially when high serum lithium concentrations were present.105 106 d (See Specific Drugs and Laboratory Tests under Interactions.)

Cognitive and Motor Impairment

May impair mental and/or physical abilities, especially during the first few days of therapy; use caution with activities requiring alertness (e.g., operating vehicles or machinery).105 106 d g (See Specific Drugs and Laboratory Tests under Interactionsand see also Advice to Patients.)

Because of CNS depressant effects, use with caution in patients with chronic respiratory disorders (e.g., severe asthma, emphysema, acute respiratory tract infections), particularly in children 1–12 years of age.105 106 d

Fetal/Neonatal Morbidity

Safety of use during pregnancy not established.105 106 Prolonged jaundice, extrapyramidal signs and symptoms, hyperreflexia, and hyporeflexia reported in some neonates born to women who received phenothiazines during pregnancy.105 106

Risk of extrapyramidal and/or withdrawal symptoms (e.g., agitation, hypertonia, hypotonia, tardive dyskinetic-like symptoms, tremor, somnolence, respiratory distress, feeding disorder) in neonates exposed to antipsychotic agents during the third trimester; monitor neonates exhibiting such symptoms.105 o p q Symptoms were self-limiting in some neonates but varied in severity; some infants required intensive support and prolonged hospitalization.105 o p q

Generally, use during pregnancy only when potential benefits justify possible risks to the fetus.105 106

Sensitivity Reactions

Hypersensitivity and Cross-sensitivity

Possible sensitivity reactions (e.g., cholestatic jaundice, blood dyscrasias, skin reactions, anaphylactoid reactions).105 106 d Use generally not recommended in patients who have previously demonstrated a hypersensitivity reaction (e.g., blood dyscrasias, jaundice) to a phenothiazine, unless potential benefits outweigh the possible risks.105 106 d

Contact dermatitis occurs rarely following skin contact with chlorpromazine hydrochloride injection; use care to avoid skin contact with injection.106 c

Photosensitivity

Photosensitivity may occur; avoid excessive exposure to sun during therapy.105 106 d

Sulfite Sensitivity

Some formulations contain sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.106 c

General Precautions

Hematologic Effects

Leukopenia and neutropenia temporally related to antipsychotic agents, including chlorpromazine, reported during clinical trial and/or postmarketing experience.105 106 r Agranulocytosis (including fatal cases) also reported with antipsychotic agents.105 106

Possible risk factors for leukopenia and neutropenia include preexisting low WBC count and a history of drug-induced leukopenia or neutropenia.105 106 r Monitor CBC frequently during the first few months of therapy in patients with such risk factors.105 106 Discontinue chlorpromazine at the first sign of a decline in WBC count in the absence of other causative factors.105 106

Carefully monitor patients with clinically significant neutropenia for fever or other signs and symptoms of infection and treat promptly if they occur.105 106 In patients with severe neutropenia (ANC <1000/mm3), discontinue chlorpromazine and monitor WBC until recovery occurs.105 106

Nervous System Effects

Possible suppression of the cough reflex and aspiration of gastric contents.105 106 d

Possible risk of seizures; may lower seizure threshold.105 106 d Use with caution in patients with a history of seizures or EEG abnormalities or in those receiving anticonvulsant agents.105 106 d Maintain adequate anticonvulsant therapy.105 106 d Chlorpromazine does not intensify anticonvulsant action of barbiturates; dosage of anticonvulsants should not be reduced.105 d

Hyperprolactinemia

May cause elevated serum prolactin concentrations, which may persist during chronic administration and cause clinical disturbances (e.g., galactorrhea, amenorrhea, gynecomastia, impotence); chronic hyperprolactinemia associated with hypogonadism may lead to decreased bone density.105 106 d g

If contemplating chlorpromazine therapy in a patient with previously detected breast cancer, consider that approximately one-third of human breast cancers are prolactin-dependent in vitro.105 106 d g

Hepatic Effects

Cholestatic jaundice or liver damage reported.105 106 d g

Perform hepatic function tests immediately in patients who develop fever accompanied by flu-like symptoms (e.g., nausea, vomiting, anorexia) during therapy; if hepatic function tests results are abnormal, discontinue drug.105 106 d g

Anticholinergic Effects

Possible anticholinergic effects (e.g., dry mouth, blurred vision, mydriasis, constipation, obstipation, nausea, adynamic ileus, atonic colon, urinary retention, decreased perspiration, and impotence).105 106 d

Use with caution in patients with glaucoma or prostatic hypertrophy.105 106 d

Cardiovascular Effects

Possible hypotension (including orthostatic hypotension), tachycardia, momentary fainting and dizziness, and ECG changes.105 106 d g

To minimize hypotension following IM administration, patient should remain in supine position under observation for ≥30 minutes.106

If hypotension occurs, place patient in Trendelenburg’s position and, if required, administer norepinephrine or phenylephrine; epinephrine or dopamine should not be used.105 106 d (See Specific Drugs and Laboratory Tests under Interactions.)

Use with caution in patients with cardiovascular disease.105 106 d

Ocular Effects

Consider possibility of pigmentary retinopathy and lenticular and corneal deposits in patients receiving prolonged therapy.105 106 d g Periodic ophthalmic examinations recommended in patients receiving prolonged phenothiazine therapy with moderate to high dosages.105 106 d g

Body Temperature Regulation

Phenothiazines depress the hypothalamic mechanism for body temperature regulation; possible hyperthermia or hypothermia when exposed to temperature extremes.105 106 d g

Use with caution in patients exposed to extreme heat or cold.105 106 d

Mutagenicity

Chromosomal aberrations in spermatocytes and abnormal sperm have been demonstrated in rodents receiving certain antipsychotic agents.105 106 d

Abrupt Withdrawal

Possible gastritis, nausea and vomiting, dizziness, and tremulousness after abrupt discontinuance of high-dose therapy;105 106 d may avoid or reduce symptoms by gradual withdrawal or by continuing antiparkinsonian agents for several weeks after therapy is withdrawn.105 106 d

Other Precautions

Antiemetic effects may mask signs of overdosage of other drugs (e.g., antineoplastic agents) or obscure cause of vomiting in various disorders (e.g., intestinal obstruction, Reye’s syndrome, brain tumor).105 106 d

Use phenothiazines with caution in debilitated patients, patients with renal or hepatic disease, and patients exposed to organophosphate insecticides.105 106 d

Use phenothiazines with caution in patients with hypocalcemia, since susceptibility to dystonic reactions may be increased.d

Specific Populations

Pregnancy

Category C.e (See Fetal/Neonatal Morbidity under Cautions.)

Lactation

Distributed into milk.105 106 c d e i Discontinue nursing or the drug.105 106 d

Pediatric Use

Safety and efficacy in children <6 months of age not established; generally, do not use unless condition to be treated is potentially life-threatening.105 106 c Do not use in conditions for which pediatric dosage not established.105 106 c

Geriatric Use

Geriatric patients appear to be particularly sensitive to adverse CNS (e.g., tardive dyskinesia, parkinsonian manifestations, akathisia, sedation), anticholinergic, and cardiovascular (e.g., orthostatic hypotension) effects of antipsychotic agents.105 106 d g Possible increased risk for falls and consequent hip fractures.d

Use with caution.d (See Geriatric Patients under Dosage and Administration.)

Geriatric patients with dementia-related psychosis treated with either conventional or atypical antipsychotic agents are at an increased risk of death.101 105 106 n (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis in Boxed Warning and also under Cautions.)

Common Adverse Effects

Extrapyramidal reactions (e.g., Parkinson-like symptoms, dystonia, akathisia, tardive dyskinesia), drowsiness, dizziness, skin reactions or rash, dry mouth, orthostatic hypotension, amenorrhea, galactorrhea, weight gain.105 106 c d g

Interactions for Chlorpromazine Hydrochloride

Metabolized principally by CYP2D6 and to a lesser extent CYP1A2.d f j

Drugs Affecting Hepatic Microsomal Enzymes

Pharmacokinetic interactions with substrates, inhibitors, or inducers of CYP2D6 are possible.d f j

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Alcohol

Potential additive CNS effects; concomitant use with alcohol potentiates hypotension observed with chlorpromazine105 106 d

Advise patients to avoid alcohol105 106

Anticoagulants, oral

Potential decreased effect of oral anticoagulants105 106

Anticonvulsants (phenytoin, phenobarbital)

Chlorpromazine may lower seizure threshold; CNS depressant effects do not potentiate anticonvulsant activity of anticonvulsants105 106 d

Chlorpromazine may interfere with phenytoin metabolism and precipitate phenytoin toxicity105 106 d

Phenobarbital may decrease plasma chlorpromazine concentrationsd

Dosage adjustments of anticonvulsants may be necessary105 106 d

Atropine and other anticholinergic drugs

Possible potentiated anticholinergic effects 105 106 i

Possible disruption of body temperature regulation105 106

Use with caution105 106

CNS depressants (e.g., antihistamines, barbiturates, general anesthetics, opiate analgesics, sedative/hypnotics)

Possible additive effects or potentiated action of other CNS depressants105 106 c i

Use concomitantly with caution to avoid excessive sedation or CNS depression105 106 d

When administered concomitantly, about one-fourth to one-half the usual dosage of CNS depressant generally is needed105 106 i

Epinephrine or dopamine

Possible further lowering of BP105 106 d

Do not use epinephrine or dopamine for phenothiazine-induced hypotension105 106 d (see Cardiovascular Effects under Cautions)

Guanethidine and related compounds

Potential for decreased effectiveness of guanethidine and related compounds105 106 i

Lithium

An acute encephalopathic syndrome reported occasionally, especially when high serum lithium concentrations present 105 106 d

Observe patients receiving combined therapy for evidence of adverse neurologic effects; promptly discontinue if such signs or symptoms appear105 106 d

Propranolol

Possible increased plasma concentrations of chlorpromazine and propranolol105 106

Test for phenylketonuria (PKU)

Potential false-positive test results may occur during phenothiazine use105 106 d

Tests for pregnancy

False-positive results reported in some patients receiving phenothiazines; less likely to occur when serum test is used105 106 d

Thiazide diuretics

Potential for increased orthostatic hypotension105 106

Chlorpromazine Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed from GI tract and from parenteral sites of injection.c i Appears to undergo substantial first-pass metabolism.c h Peak plasma concentrations generally attained within 2–4 hours after oral administration;h i considerable interindividual variation in peak concentrations reported.c i

Onset

Usually occurs within 30–60 minutes following oral administration.c

Duration

4–6 hours following oral administration.c Following IM administration for nausea and vomiting in pediatric patients, may last up to 12 hours.106

Distribution

Extent

Widely distributed into most body tissues and fluids.c d h i Crosses blood-brain barrier; brain concentrations exceed those in plasma.c h i

Crosses the placenta.c d e i Distributed into breast milk.105 106 c d e i

Plasma Protein Binding

92–97% (mainly albumin).c i

Elimination

Metabolism

Metabolic fate not fully elucidated.c h Appears to be extensively metabolized, principally in the liver and kidneys.c h

Elimination Route

Phenothiazines and their metabolites are excreted in urine and feces.c d

Unlikely to be substantially removed by hemodialysis and peritoneal dialysis.105 106 d

Half-life

Biphasic half-life; half-life of initial phase is 2 hours and half-life of terminal phase is about 30 hours.i

Stability

Storage

Oral

Tablets

Tight, light-resistant containers at 20–25°C (may be exposed to 15–30°C); protect from moisture.105 c

Parenteral

Injection

Light-resistant containers at 20–25°C (may be exposed to 15–30°C);106 avoid freezing.106 c

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Compatible

Dextrose–Ringer’s injection combinations

Dextrose–Ringer’s injection, lactated, combinations

Dextrose–saline combinations

Dextrose 2.5, 5, or 10% in water

Ionosol products

Ringer’s injection

Ringer’s injection, lactated

Sodium chloride 0.45 or 0.9%

Sodium lactate (1/6) M

Drug Compatibility
Admixture CompatibilityHID

Compatible

Ascorbic acid injection

Ethacrynate sodium

Theophylline

Incompatible

Aminophylline

Amphotericin B

Ampicillin sodium

Chloramphenicol sodium succinate

Chlorothiazide sodium

Cloxacillin sodium

Furosemide

Floxacillin sodium

Methohexital sodium

Penicillin G potassium or sodium

Phenobarbital sodium

Y-Site CompatibilityHID

Compatible

Amsacrine

Cisatracurium besylate

Cladribine

Dexmedetomidine HCl

Docetaxel

Doxorubicin HCl liposome injection

Famotidine

Fenoldopam mesylate

Filgrastim

Fluconazole

Gemcitabine HCl

Granisetron HCl

Heparin sodium

Hetastarch in lactated electrolyte injection (Hextend)

Hydrocortisone sodium succinate

Ondansetron HCl

Oxaliplatin

Potassium chloride

Propofol

Teniposide

Thiotepa

Vinorelbine tartrate

Incompatible

Allopurinol sodium

Amifostine

Amphotericin B cholesteryl sulfate complex

Aztreonam

Bivalirudin

Etoposide phosphate

Fludarabine phosphate

Furosemide

Linezolid

Melphalan HCl

Paclitaxel

Pemetrexed disodium

Piperacillin sodium–tazobactam sodium

Sargramostim

Tigecycline

Variable

Remifentanil HCl

Syringe CompatibilityHID

Compatible

Atropine sulfate

Benztropine mesylate

Butorphanol tartrate

Diphenhydramine HCl

Doxapram HCl

Droperidol

Fentanyl citrate

Glycopyrrolate

Hydromorphone HCl

Hydroxyzine HCl

Meperidine HCl

Metoclopramide HCl

Midazolam HCl

Morphine sulfate

Pentazocine lactate

Prochlorperazine edisylate

Promethazine HCl

Scopolamine HBr

Incompatible

Heparin sodium

Pantoprazole sodium

Pentobarbital sodium

Variable

Dimenhydrinate

Ranitidine HCl

Actions

  • Principal pharmacologic effects are similar to those of other propylamino derivatives of phenothiazines.c

  • Chlorpromazine has actions at all levels of CNS, particularly at subcortical levels; also acts on multiple organ systems.105

  • Precise mechanism(s) of antipsychotic action not determined, but may be principally related to antidopaminergic effects.105 106 d

  • Exhibits strong anticholinergic effects and sedative effects and moderate extrapyramidal effects; has strong antiemetic activity.105 106 c d g

  • Also exhibits weak ganglionic blocking, antihistaminic, and antiserotonergic activity.105 106 c

Advice to Patients

  • Importance of advising patients and caregivers that elderly patients with dementia-related psychosis treated with antipsychotic agents are at an increased risk of death.101 105 106 n Patients and caregivers also should be informed that chlorpromazine is not approved for treating elderly patients with dementia-related psychosis.105 106 n

  • Importance of informing patients with a sulfite allergy that chlorpromazine hydrochloride injection contains sulfites and may precipitate allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes).106

  • Potential for drug to impair mental alertness or physical coordination; use caution when driving or operating machinery until effects on individual are known.105 106

  • Importance of avoiding alcohol during chlorpromazine therapy.105 106

  • Importance of informing patients in whom chronic use is contemplated of risk of tardive dyskinesia, taking into account clinical circumstances and competency of patient to understand information provided.105 106 d

  • Importance of clinicians informing patients of risk of extrapyramidal reactions and providing reassurance that these reactions usually can be controlled by administration of antiparkinsonian drugs (e.g., benztropine) and by subsequent dosage reduction.105 106 d

  • Importance of avoiding exposure to temperature extremes.105 106 d

  • Risk of leukopenia/neutropenia.105 106 Importance of advising patients with a preexisting low WBC count or history of drug-induced leukopenia/neutropenia that their CBC count should be monitored during chlorpromazine therapy.105 106

  • Importance of informing clinician if sore throat or other signs of infection occur.105 106 d

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., cardiovascular disease).105 106 d

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.105 106 q Importance of clinicians informing patients about the benefits and risks of taking antipsychotics during pregnancy (see Fetal/Neonatal Morbidity under Cautions).105 q Importance of advising patients not to stop taking chlorpromazine if they become pregnant without consulting their clinician; abruptly stopping antipsychotic agents may cause complications.q Importance of advising patients not to breast-feed during chlorpromazine therapy.105 106

  • Importance of informing patients of other important precautionary information.105 106 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Chlorpromazine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

10 mg*

Chlorpromazine Hydrochloride Tablets

25 mg*

Chlorpromazine Hydrochloride Tablets

50 mg*

Chlorpromazine Hydrochloride Tablets

100 mg*

Chlorpromazine Hydrochloride Tablets

200 mg*

Chlorpromazine Hydrochloride Tablets

Parenteral

Injection

25 mg/mL*

Chlorpromazine Hydrochloride Injection

Baxter

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

ChlorproMAZINE HCl 10MG Tablets (UPSHER-SMITH): 60/$52.99 or 120/$94.48

ChlorproMAZINE HCl 100MG Tablets (UPSHER-SMITH): 60/$182.99 or 180/$424.95

ChlorproMAZINE HCl 200MG Tablets (UPSHER-SMITH): 60/$114.08 or 180/$295.86

ChlorproMAZINE HCl 25MG Tablets (UPSHER-SMITH): 60/$79.36 or 180/$183.12

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 19, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

100. Sandoz, Inc. ChlorproMAZINE hydrochloride tablets prescribing information. Princeton, NJ; 2008 Sep.

101. Food and Drug Administration. FDA Alert: Information for healthcare professionals: antipsychotics. Rockville, MD; 2008 Jun 16. From the FDA website: ().

102. Food and Drug Administration. FDA News: FDA requests boxed warnings on older class of antipsychotic drugs. Rockville, MD; 2008 Jun 16. From the FDA website ().

103. Schneeweiss S, Setoguchi S, Brookhart A et al. Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients. CMAJ. 2007; 176:627-32. [PubMed 17325327]

104. Gill SS, Bronskill SE, Normand SL et al. Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med. 2007; 146:775-86. [PubMed 17548409]

105. Upsher-Smith Laboratories, Inc. Chlorpromazine hydrochloride tablets prescribing information. Minneapolis, MN; 2011 Jun.

106. Baxter Healthcare Corporation. Chlorpromazine hydrochloride injection, solution prescribing information. Deerfield, IL; 2010 Sep.

c. AHFS drug information 2007. McEvoy GK, ed. Chlorpromazine. Bethesda, MD: American Society of Health-System Pharmacists; 2007:2450-3.

d. AHFS drug information 2007. McEvoy GK, ed. Phenothiazines general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2007:2439-50.

e. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 7th ed. Baltimore, MD: Williams & Wilkins; 2005:291-3.

f. Yoshii K, Kobayashi K, Tsumuji M et al. Identification of human cytochrome P450 isoforms involved in the 7-hydroxylation of chlorpromazine by human liver microsomes. Life Sci. 2000; 67:175-84. [PubMed 10901285]

g. American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004; 161(Suppl):1-56.

h. DeVane CL. Brief comparison of the pharmacokinetics and pharmacodynamics of the traditional and newer antipsychotic drugs. Am J Health-Syst Pharm.1995; 52: (Suppl. 1):S15-8.

i. Speicher CE, Walters MI. Phenothiazines. Clin Lab Med. 1981; 1:547-57. [PubMed 6125291]

j. Otani K, Aoshima T. Pharmacogenetics of classical and new antipsychotic drugs. Ther Drug Monit. 2000; 22:118-21. [PubMed 10688273]

HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013:259-64.

k. Upsher-Smith Laboratories Incorporated, Minneapolis, MN: Personal communication.

l. Baxter Healthcare Corporation, Deerfield, IL: Personal communication.

n. US Food and Drug Administration. Public health advisory: deaths with antipsychotics in elderly patients with behavioral disturbances. Rockville, MD; 2005 Apr 11. From the FDA website.

o. Sexson WR, Barak Y. Withdrawal emergent syndrome in an infant associated with maternal haloperidol therapy. J Perinatol. 1989; 9:170-2. [PubMed 2738729]

p. Coppola D, Russo LJ, Kwarta RF Jr. et al. Evaluating the postmarketing experience of risperidone use during pregnancy: pregnancy and neonatal outcomes. Drug Saf. 2007; 30:247-64. [PubMed 17343431]

q. US Food and Drug Administration. FDA drug safety communication: Antipsychotic drug labels updated in use during pregnancy and risk of abnormal muscle movements and withdrawal symptoms in newborns. Rockville, MD; 2011 Feb 22. From the FDA website: .

r. Qureshi SU, Rubin E. Risperidone- and aripiprazole-induced leukopenia: a case report. Prim Care Companion J Clin Psychiatry. 2008; 10:482-3. [PubMed 19287562]

Hide
(web3)