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Antihistamines, Phenothiazine-derivative (Systemic)

This monograph includes information on the following:

1) Methdilazine  
2) Promethazine
3) Trimeprazine


INN:
Trimeprazine —Alimemazine

VA CLASSIFICATION
Methdilazine
Primary: AH101

Promethazine
Primary: AH101
Secondary: CN309; GA753

Trimeprazine
Primary: AH101


Commonly used brand name(s): Anergan 252; Anergan 502; Antinaus 502; Histantil2; Panectyl3; Pentazine2; Phenazine 252; Phenazine 502; Phencen-502; Phenergan2; Phenergan Fortis2; Phenergan Plain2; Phenerzine2; Phenoject-502; Pro-502; Pro-Med 502; Promacot2; Promet2; Prorex-252; Prorex-502; Prothazine2; Prothazine Plain2; Shogan2; Tacaryl1; Temaril3; V-Gan-252; V-Gan-502.

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

Not commercially available in Canada.



Category:


Antihistaminic (H 1-receptor)—Methdilazine;  Promethazine; Trimeprazine;

Antiemetic—Promethazine;

Antivertigo agent—Promethazine;

Sedative-hypnotic—Promethazine; Trimeprazine;

Indications

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

Accepted

Rhinitis, perennial and seasonal allergic or vasomotor (treatment) or
Conjunctivitis, allergic (treatment)—Antihistamines are indicated in the symptomatic treatment of perennial and seasonal allergic rhinitis, vasomotor rhinitis , and allergic conjunctivitis due to inhalant allergens and foods. {01} {04} {07} {23} {30} {38}

Pruritus (treatment)
Urticaria (treatment)
Angioedema (treatment)
Dermatographism (treatment) or
Transfusion reactions, urticarial (treatment)— Antihistamines are indicated for the symptomatic treatment of pruritus associated with allergic reactions and of mild, uncomplicated allergic skin manifestations of urticaria and angioedema, in dermatographism, and in urticaria associated with transfusions. Methdilazine is also indicated in the treatment of pruritus associated with pityriasis rosea. {01} {04} {07} {23} {30} {38} {58} {59}

Sneezing (treatment) or
Rhinorrhea (treatment)—Antihistamines are indicated for the relief of sneezing and rhinorrhea associated with the common cold . However, controlled clinical studies have not demonstrated that antihistamines are significantly more effective than placebo in relieving cold symptoms. {18} {24}

Anaphylactic or anaphylactoid reactions (treatment adjunct)—Antihistamines are indicated as adjunctive therapy to epinephrine and other standard measures for anaphylactic reactions after the acute manifestations have been controlled, and to ameliorate the allergic reactions to blood or plasma. {01} {04}

Motion sickness (prophylaxis and treatment) or
Vertigo (treatment)—Promethazine is indicated for the prevention and treatment of the nausea, vomiting, dizziness, or vertigo of motion sickness. {01} {04} {05} {07} {23} {26} {30}

Nausea or vomiting (prophylaxis and treatment)— Promethazine is indicated in the control of nausea and vomiting associated with certain types of anesthesia and surgery. {01} {04} {07} {23} {30}

Sedation—Promethazine and [ trimeprazine]1 are indicated for their sedative and hypnotic effects and as adjuncts to preoperative and postoperative medication. {01} {04} {07} {30}

Pain, postoperative (treatment adjunct)—Promethazine is indicated as an adjunct to analgesics for control of postoperative pain. {01} {04} {07} {31}

Analgesia adjunct, during surgery
Anesthesia, general, adjunct or
Anesthesia, local, adjunct—Intravenous administration of promethazine is indicated in special surgical situations (such as repeated bronchoscopy, ophthalmic surgery, and poor-risk patients) in combination with reduced amounts of meperidine or other narcotic analgesics as an adjunct to anesthesia and analgesia. {01} {04} {30}

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:

Chemical group—
    Phenothiazine derivatives
Molecular weight—
    Methdilazine hydrochloride: 332.89
    Promethazine hydrochloride: 320.88
    Trimeprazine tartrate: 746.98

pKa—
    Promethazine: 9.1

Mechanism of action/Effect:

Antihistaminic (H 1-receptor)—Antihistamines used in the treatment of allergy act by competing with histamine for H 1-receptor sites on effector cells. They thereby prevent, but do not reverse, responses mediated by histamine alone. Antihistamines antagonize, in varying degrees, most of the pharmacological effects of histamine, including urticaria and pruritus. In addition, the anticholinergic actions of most antihistamines provide a drying effect on the nasal and oral mucosa. {04} {05} {26} {29} {59}

Antiemetic; antivertigo—The mechanism by which some antihistamines exert their antiemetic, anti-motion sickness, and antivertigo effects is not precisely known but may be related to their central anticholinergic actions. They diminish vestibular stimulation and depress labyrinthine function. Activity on the medullary chemoreceptive trigger zone may also be involved in the antiemetic effect. {02} {04} {05} {25}

Sedative-hypnotic—Most antihistamines cross the blood-brain barrier and produce sedation due to inhibition of histamine N-methyltransferase and blockage of central histaminergic receptors. Antagonism of other central nervous system receptor sites, such as those for serotonin, acetylcholine, and alpha-adrenergic stimulation, may also be involved {27}. Phenothiazines are thought to cause indirect reduction of stimuli to the brain stem reticular system. {19}


Other actions/effects:

Anticholinergic—Antihistamines prevent responses to acetylcholine that are mediated via muscarinic receptors. {04}

Antiemetic—Methdilazine and trimeprazine also possess antiemetic properties. However, only promethazine is labeled for this indication.

Absorption:

Well absorbed after oral administration. {01} {05} {23} {26} {30}

Protein binding:

Promethazine—High (65–90%). {23}

Biotransformation:

Hepatic; some renal. {01} {30}

Half-life:

Elimination—Promethazine: 7 to 14 hours. {23} {35} {36}

Onset of action:


Oral:

15 to 60 minutes. {01} {05} {23} {26}



Parenteral:


Promethazine—

Intramuscular—20 minutes. {01} {05} {23} {26}

Intravenous—3 to 5 minutes. {01} {05} {23} {26}




Rectal:


Promethazine—

20 minutes. {01} {05} {23} {26}



Duration of action:

Methdilazine—6 to 12 hours. {01}

Promethazine—4 to 6 hours; may persist for up to 12 hours. {01} {59} {60}

Trimeprazine—3 to 6 hours. {01}

Elimination:
    Renal. Most of the antihistamines studied are excreted as metabolites within 24 hours. {26}


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to other phenothiazines may be sensitive to methdilazine, promethazine, and trimeprazine also. {25}

Carcinogenicity/Tumorigenicity/Mutagenicity

Long-term animal studies to evaluate the carcinogenic, tumorigenic, or mutagenic potential of most antihistamines have not been performed. {30}

Pregnancy/Reproduction

Pregnancy—
Phenothiazines have been reported to cause jaundice and extrapyramidal symptoms in infants whose mothers received these medications during pregnancy.


For promethazine

Adequate and well-controlled studies in humans have not been done. However, promethazine taken within 2 weeks prior to delivery may inhibit platelet aggregation in the newborn.

Studies in rats with doses 2.1 to 4.2 times the maximum recommended human daily dose have not shown that promethazine causes adverse effects on fetal development. {01} {02} {06} {30}

FDA Pregnancy Category C. {30}


Breast-feeding

Small amounts of antihistamines may be distributed into breast milk; use is not recommended in nursing mothers because of the risk of adverse effects, such as unusual excitement or irritability, in infants. {10}

Antihistamines may inhibit lactation because of their anticholinergic actions.

Some studies have indicated that the use of promethazine in children up to 2 years of age may be associated with the sudden infant death syndrome (SIDS) and an increase in sleep apnea, thus possibly increasing the risk to the nursing infant. Therefore, the use of phenothiazine-derivative antihistamines by nursing mothers should be discouraged until more studies have been performed to confirm the potential risk to the nursing infant. {10} {37} {39} {40}

Pediatrics

Use is not recommended in newborn or premature infants because this age group has an increased susceptibility to anticholinergic side effects, such as central nervous system (CNS) excitation, and an increased tendency toward convulsions. {23} {26}

A paradoxical reaction characterized by hyperexcitability may occur in children taking antihistamines. {07} {23}

The use of phenothiazine-derivative antihistamines is not recommended in infants up to 3 months of age, because of the possible absence or deficiency of detoxifying enzyme and inefficient renal function usually noted in this age group. {07} Also, increased susceptibility to dystonias has been reported in newborn or premature infants, acutely ill or dehydrated children, and children with acute infections who have received phenothiazine medication. {01} {23}

Some studies have associated the use of promethazine with sudden infant death syndrome (SIDS) and with an increase in infant sleep apnea. Until more studies have been performed to confirm this potential risk, phenothiazine derivatives should not be used in children up to 2 years of age. {05} {07} {10} {20} {23} {34} {37} {38} {39} {40} {59}

In children with signs and symptoms suggestive of Reye's syndrome, phenothiazine-derivative antihistamines should not be used since the extrapyramidal symptoms that may occur, especially after parenteral administration of large doses, may be confused with the CNS signs of this syndrome, thus making diagnosis difficult. {25}



Adolescents

In adolescents with signs and symptoms suggestive of Reye's syndrome, phenothiazine-derivative antihistamines should not be used since the extrapyramidal symptoms that may occur, especially after parenteral administration of large doses, may be confused with the CNS signs of this syndrome, thus making diagnosis difficult. {25}


Geriatrics


Dizziness, sedation, confusion, and hypotension may be more likely to occur in geriatric patients taking antihistamines.

A paradoxical reaction characterized by hyperexcitability may occur in geriatric patients taking antihistamines.

Geriatric patients are especially susceptible to the anticholinergic side effects, such as dryness of the mouth and urinary retention (especially in males), of the antihistamines. If these side effects occur and continue or are severe, the medication should probably be discontinued.

Extrapyramidal signs, especially parkinsonism, akathisia, and persistent dyskinesia, may also be more likely to occur in geriatric patients, especially at the higher doses or with parenteral administration. {25}


Dental

Prolonged use of antihistamines 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.

Involuntary orofacial muscle movement may result from extrapyramidal effects. These involuntary movements may result in occlusal adjustments, bite registrations, and treatment for bruxism being less reliable. {41}

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: Combination products containing any of the following medications, depending on the amount present, may also interact with this medication. {59}

» Alcohol or
» CNS depression–producing medications, other (See Appendix II )    (concurrent use may potentiate the CNS depressant effects of either these medications or antihistamines; also, concurrent use of maprotiline or tricyclic antidepressants may potentiate the anticholinergic effects of either antihistamines or these medications {07} {30} {38})


Amphetamines    (concurrent use may decrease stimulant effects of amphetamines since phenothiazine derivatives produce alpha-adrenergic blockade {54})


» Anticholinergics or other medications with anticholinergic activity (See Appendix II )    (anticholinergic effects may be potentiated when these medications are used concurrently with antihistamines; patients should be advised to report occurrence of gastrointestinal problems promptly since paralytic ileus may occur with concurrent therapy {44} {45} {54})


Anticonvulsants, including barbiturates    (phenothiazine derivatives may lower the convulsion threshold; dosage adjustment of anticonvulsant medications may be necessary; potentiation of anticonvulsant effects does not occur {30} {38} {46} {54})


Appetite suppressants    (concurrent use with phenothiazine derivatives may antagonize the anorectic effect of appetite suppressants {54})


Beta-adrenergic blocking agents, especially propranolol    (concurrent use with phenothiazine derivatives may result in increased plasma concentration of each medication because of inhibition of metabolism; this may result in additive hypotensive effects, irreversible retinopathy, cardiac arrhythmias, and tardive dyskinesia {28} {46} {54})


Bromocriptine    (concurrent use may increase serum prolactin concentrations and interfere with effects of bromocriptine; dosage adjustments of bromocriptine may be necessary {38})


Dopamine    (concurrent use may antagonize peripheral vasoconstriction produced by high doses of dopamine because of the alpha-adrenergic blocking action of phenothiazine derivatives {42} {43})


Ephedrine or
Metaraminol or
Methoxamine    (alpha-adrenergic blocking action of phenothiazine derivatives may decrease the pressor response to these medications when used concurrently {52})


» Epinephrine    (alpha-adrenergic effects of epinephrine may be blocked when it is used concurrently with phenothiazine derivatives, possibly resulting in severe hypotension and tachycardia {41})


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


Guanadrel or
Guanethidine    (neuronal uptake of these medications may be inhibited when they are used concurrently with phenothiazine derivatives, causing a decrease of their antihypertensive effect {05} {21} {22} {54})


Hepatotoxic medications, other (See Appendix II )    (concurrent use of phenothiazine derivatives with other hepatotoxic medications may increase the potential for hepatotoxicity; patients, especially those on prolonged therapy or with a history of liver disease, should be carefully monitored {28})


Hypotension-producing medications, other (See Appendix II )    (concurrent use with phenothiazine derivatives may produce additive hypotensive effects {01} {05} {25} {41} {48})


» Levodopa    (antiparkinsonian effects of levodopa may be inhibited when used concurrently with phenothiazine derivatives because of blockade of dopamine receptors in the brain; levodopa has not been shown to be effective in phenothiazine-induced parkinsonism {50} {51})


» Metrizamide, intrathecal    (concurrent use with phenothiazine derivatives may lower the seizure threshold; phenothiazine derivatives should be discontinued at least 48 hours before, and not resumed for at least 24 hours following, myelography {38} {53})


» Monoamine oxidase (MAO) inhibitors, including furazolidone, procarbazine, and selegiline    (concurrent use of MAO inhibitors with antihistamines in general may prolong and intensify the anticholinergic and CNS depressant effects of antihistamines; concurrent use of MAO inhibitors with phenothiazine-derivative antihistamines may increase the risk of hypotension and extrapyramidal reactions; concurrent use is not recommended {41} {49} {54})


Ototoxic medications (See Appendix II )    (concurrent use with antihistamines may mask the symptoms of ototoxicity such as tinnitus, dizziness, or vertigo)


Quinidine    (concurrent use with phenothiazine-derivative antihistamines may result in additive cardiac effects {55})


Riboflavin    (requirements for riboflavin may be increased in patients receiving phenothiazine-derivative antihistamines {56} {57})



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
Glucose tolerance test    (an increase in glucose tolerance has been reported in patients receiving phenothiazine-derivative antihistamines {01} {30} {38})


Immunologic urine pregnancy tests    (may produce false-positive or false-negative results in patients receiving phenothiazine-derivative antihistamines, depending on the test used {01} {30})


Skin tests using allergen extracts    (antihistamines may inhibit the cutaneous histamine response, thus producing false-negative results; it is recommended that antihistamines be discontinued at least 72 hours before testing begins {04})


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).


Risk-benefit should be considered when the following medical problems exist
» Bladder neck obstruction or
» Prostatic hypertrophy, symptomatic or
» Urinary retention, predisposition to    (anticholinergic effects may precipitate or aggravate urinary retention {01} {30})


Bone marrow depression    (increased risk of leukopenia and agranulocytosis {02})


Cardiovascular disease    (increased risk of transient hypotension {01} {05} {23} {25} {30})


» Coma    (may be exacerbated)


Epilepsy    (parenteral administration of promethazine may increase severity of seizures {01} {30})


» Glaucoma, angle-closure or predisposition to    (mydriatic effect resulting in increased intraocular pressure may precipitate an attack of angle-closure glaucoma {01} {30})


Glaucoma, open-angle    (mydriatic effect may cause a slight increase in intraocular pressure; glaucoma therapy may need to be adjusted {01})


Hepatic function impairment    (metabolism may be decreased; higher serum concentrations may increase sensitivity to CNS effects {01} {05} {25} {30})


» Jaundice    (may be exacerbated with parenteral administration of promethazine {01} {05} {30})


Reye's syndrome    (extrapyramidal symptoms that may be produced by parenteral administration of promethazine may be confused with CNS signs of Reye's syndrome {25})


Sensitivity to the antihistamine used
Caution is recommended when phenothiazine-derivative antihistamines are used, since their antiemetic action may impede diagnosis of such conditions as appendicitis and obscure signs of toxicity from overdosage of other drugs.{03}{07}{25}


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 less frequent or rare
    
Blood dyscrasias (sore throat; fever; unusual bleeding or bruising; unusual tiredness or weakness){25}{26}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Drowsiness {01}{23}{30}
    
thickening of mucus {01}

Note: Sedative effects are more pronounced with promethazine and less pronounced with trimeprazine and methdilazine, in that order. {02}


Incidence less frequent or rare
    
Blurred vision or any change in vision {01}{05}{23}{26}{33}
    
burning or stinging of rectum {01}{05}{23}{26}{33}—for promethazine rectal dosage form only
    
confusion{01}{05}{23}{26}{33} {01}{05}{23}{26}{33}
    
difficult or painful urination {01}{05}{23}{26}{33}
    
dizziness {01}{05}{23}{26}{33}
    
dryness of mouth, nose, or throat {01}{05}{23}{26}{33}
    
hypotension {01}{05}{23}{26}{33}(feeling faint)
    
increased sweating {01}{05}{23}{26}{33}
    
loss of appetite {01}{05}{23}{26}{33}
    
paradoxical reaction {01}{05}{23}{26}{33}(nightmares; unusual excitement, nervousness, restlessness, or irritability)
    
photosensitivity {01}{05}{23}{26}{33}(increased sensitivity of skin to sun)
    
ringing or buzzing in ears {01}{05}{23}{26}{33}
    
skin rash {01}{05}{23}{26}{33}
    
tachycardia {01}{05}{23}{26}{33}(fast heartbeat)


Note: Confusion; difficult or painful urination; dizziness; drowsiness; and dryness of mouth, nose, or throat are more likely to occur in the elderly.
Nightmares, unusual excitement, nervousness, restlessness, or irritability are more likely to occur in children and elderly patients.





Overdose
For specific information on the agents used in the management of phenothiazine-derivative antihistamines overdose, see:
   • Antidyskinetics (Systemic) monograph;
   • Antihistamines (Systemic) monograph;
   • Barbiturates (Systemic) monograph; and/or
   • Ipecac (Oral-local) 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
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 and chronic
    
Anticholinergic effects (clumsiness or unsteadiness; severe drowsiness; severe dryness of mouth, nose, or throat; flushing or redness of face; shortness of breath or troubled breathing){23}
    
CNS depression (severe drowsiness){01}
    
CNS stimulation (hallucinations; seizures; trouble in sleeping){01}
    
extrapyramidal effects (muscle spasms, especially of neck and back; restlessness; shuffling walk; tic-like [jerky] movements of head and face; trembling and shaking of hands){01}{05}{14}{15}{16}{23}{25}{30}
    
hypotension, severe {01}{05}{30}(feeling faint)

Note: Anticholinergic and CNS stimulant effects are more likely to occur in children with overdose. Hypotension may also occur in the elderly at usual doses.



Treatment of overdose
Since there is no specific antidote for overdose with antihistamines, treatment is symptomatic and supportive with possible utilization of the following: {30}


To decrease absorption:
Induction of emesis (syrup of ipecac recommended); however, precaution against aspiration is necessary, especially in infants and children.

Gastric lavage (isotonic or 0.45% sodium chloride solution) if patient is unable to vomit within 3 hours of ingestion.



To enhance elimination:
Saline cathartics (milk of magnesia) are sometimes used.



Specific treatment:
Vasopressors to treat hypotension; however, epinephrine should not be used since it may further lower blood pressure.

Anticholinergic antiparkinson agents, diphenhydramine, or barbiturates, to control extrapyramidal reactions. {32}

Precaution against use of stimulants (analeptic agents) because they may cause seizures. {30}



Supportive care:
Oxygen and intravenous fluids.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Antihistamines, Phenothiazine-derivative (Systemic).

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

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to the antihistamine used or to phenothiazine medications

Pregnancy—Not taking during the 2 weeks before delivery, to avoid possible inhibition of platelet aggregation in newborn; also, jaundice and extrapyramidal effects may occur in infant





Breast-feeding—Use not recommended; may cause unusual excitement or irritability in nursing infant; possible association with sudden infant death syndrome (SIDS) and sleep apnea





Use in children—Increased susceptibility to anticholinergic side effects in newborn or premature infants; hyperexcitability (paradoxical reaction) may occur in children; possible association with sudden infant death syndrome (SIDS) and sleep apnea; diagnosis of Reye's syndrome may be obscured if extrapyramidal effects occur




Use in adolescents—
Diagnosis of Reye's syndrome may be obscured if extrapyramidal effects occur





Use in the elderly—— Increased susceptibility to CNS and anticholinergic side effects; hyperexcitability (paradoxical reaction) may occur; extrapyramidal symptoms more likely to occur





Dental—Increased risk of dental problems with prolonged use because of decrease or inhibition of salivary flow; involuntary orofacial muscle movements may result from extrapyramidal effects
Other medications, especially alcohol or other CNS depressants, anticholinergics, epinephrine, extrapyramidal reaction–causing medications, levodopa, MAO inhibitors, or metrizamide (intrathecal)
Other medical problems, especially angle-closure glaucoma (or predisposition to), bladder neck obstruction, prostatic hypertrophy, or urinary retention; jaundice (for parenteral promethazine)

Proper use of this medication
» Importance of not taking more medication than the amount recommended

» Proper dosing
Missed dose: If on scheduled dosing regimen—Using as soon as possible; not using if almost time for next dose; not doubling doses

» Proper storage

For oral dosage forms
Taking with food, water, or milk to minimize gastric irritation

Swallowing extended-release dosage forms whole

For injection dosage forms
Knowing correct administration technique for self-administration; checking with physician if necessary

For rectal dosage forms
Proper administration technique

For promethazine when used to prevent motion sickness
Taking 30 minutes to 1 hour before traveling

Precautions while using this medication
Possible interference with skin tests using allergens; need to inform physician of using medication

May mask ototoxic effects of large doses of salicylates

» Avoiding use of alcohol or other CNS depressants

» Caution if drowsiness occurs

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

Need to inform physician of use: Possible interference with diagnosis of appendicitis; may mask signs of toxicity from overdosage of other drugs


Side/adverse effects
Signs of potential side effects, especially blood dyscrasias


General Dosing Information

For oral dosage forms only
Most antihistamines may be taken with food, water, or milk to lessen gastric irritation. {01} {05} {26}

For parenteral dosage forms only


For promethazine:
The preferred route of administration is by deep intramuscular injection. Although intravenous administration is well tolerated, promethazine should not be administered in concentrations greater than 25 mg per mL and at a rate in excess of 25 mg per minute. Rapid intravenous administration of promethazine may produce a transient fall in blood pressure. {01} {13}

Intra-arterial administration is not recommended because of the possibility of severe arteriospasm and resultant gangrene; also, subcutaneous administration is not recommended, since chemical irritation has been noted and necrotic lesions have resulted on rare occasions.


METHDILAZINE

Summary of Differences
Indications: Used in the treatment of pruritus associated with pityriasis rosea.

Pharmacology/pharmacokinetics: Duration of action—6 to 12 hours.

Side/adverse effects: Least sedative effects.


Oral Dosage Forms

METHDILAZINE HYDROCHLORIDE SYRUP USP

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, 8 mg every six to twelve hours as needed.


Usual pediatric dose
Antihistaminic (H 1-receptor)
Children up to 3 years of age: Use is not recommended.

Children 3 to 12 years of age: Oral, 4 mg every six to twelve hours as needed.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


4 mg per 5 mL (Rx) [Tacaryl (alcohol 7.37%)]

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.

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


METHDILAZINE HYDROCHLORIDE TABLETS USP

Usual adult and adolescent dose
See Methdilazine Hydrochloride Syrup USP .

Usual pediatric dose
See Methdilazine Hydrochloride Syrup USP .

Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


8 mg (Rx) [Tacaryl (scored)]

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.

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


METHDILAZINE HYDROCHLORIDE TABLETS (CHEWABLE) USP

Usual adult and adolescent dose
See Methdilazine Hydrochloride Syrup USP .

Usual pediatric dose
See Methdilazine Hydrochloride Syrup USP .

Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


4 mg (Rx) [Tacaryl]

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.

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


PROMETHAZINE

Summary of Differences
Pharmacology/pharmacokinetics: Duration of action—Usually 4 to 6 hours.

Precautions: Medical considerations/contraindications—Caution needed in epilepsy, jaundice, and Reye's syndrome (with parenteral administration).

Side/adverse effects: Most pronounced sedative effects.


Oral Dosage Forms

PROMETHAZINE HYDROCHLORIDE SYRUP USP

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, 10 to 12.5 mg four times a day before meals and at bedtime; or 25 mg at bedtime as needed. {01}

Antiemetic
Oral, 25 mg initially, then 10 to 25 mg every four to six hours as needed. {01}

Antivertigo agent
Oral, 25 mg two times a day as needed.

Note: For motion sickness, the initial 25-mg dose should be taken one-half to one hour before travel, and the dose repeated eight to twelve hours later, if necessary. {01}


Sedative-hypnotic
Oral, 25 to 50 mg for nighttime, presurgical, postsurgical, or obstetrical sedation. {01}

Note: A 50-mg dose (with an equal amount of meperidine and an appropriate dose of an atropine-like drug) is used the night before surgery to relieve apprehension and produce sleep.



Usual adult prescribing limits
Up to 150 mg daily.

Usual pediatric dose


Children up to 2 years of age:
Use is not recommended. {01} {11} {12}



Children 2 years of age and older:


Antihistaminic (H 1-receptor)—
Oral, 125 mcg (0.125 mg) per kg of body weight or 3.75 mg per square meter of body surface every four to six hours, or 500 mcg per kg of body weight or 15 mg per square meter of body surface at bedtime as needed; or 5 to 12.5 mg three times a day or 25 mg at bedtime as needed. {01} {11} {12}



Antiemetic—
Oral, 250 to 500 mcg (0.25 to 0.5 mg) per kg of body weight or 7.5 to 15 mg per square meter of body surface every four to six hours as needed; or 10 to 25 mg every four to six hours as needed. {01} {11} {12}



Antivertigo agent—
Oral, 500 mcg (0.5 mg) per kg of body weight or 15 mg per square meter of body surface every twelve hours as needed; or 10 to 25 mg two times a day as needed. {01} {11} {12}



Sedative-hypnotic—
Oral, 500 mcg (0.5 mg) to 1 mg per kg of body weight or 15 to 30 mg per square meter of body surface as needed; or 10 to 25 mg as needed. {01} {11} {12}

Note: For preoperative sedation, children require doses of 1.1 mg per kg of body weight in combination with an equal dose of meperidine and the appropriate dose of an atropine-like drug. {01}
For postoperative sedation, 10 to 25 mg may be used. {01}




Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


6.25 mg per 5 mL (Rx) [Pentazine] [Phenergan Plain (alcohol 7%)] [Prothazine Plain (alcohol 7%)][Generic]


25 mg per 5 mL (Rx) [Phenergan Fortis (alcohol 1.5%)][Generic]

Canada—


10 mg per 5 mL (OTC) [Phenergan (alcohol 3%)]

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.

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


PROMETHAZINE HYDROCHLORIDE TABLETS USP

Usual adult and adolescent dose
See Promethazine Hydrochloride Syrup USP .

Usual adult prescribing limits
Up to 150 mg daily.

Usual pediatric dose
See Promethazine Hydrochloride Syrup USP . {11} {12}

Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


12.5 mg (Rx) [Phenergan (scored)][Generic]


25 mg (Rx) [Phenergan (scored)] [Promacot][Generic]


50 mg (Rx) [Phenergan][Generic]

Canada—


10 mg (OTC) [Phenergan (scored)]


25 mg (OTC) [Histantil (film coated)] [Phenergan (film coated)]


50 mg (OTC) [Histantil (film coated)] [Phenergan (scored)]

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

PROMETHAZINE HYDROCHLORIDE INJECTION USP

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Intramuscular or intravenous, 25 mg; may be repeated within two hours if necessary.

Antiemetic
Intramuscular or intravenous, 12.5 to 25 mg every four hours as needed.

Sedative-hypnotic
Intramuscular or intravenous, 25 to 50 mg for nighttime, presurgical, postsurgical, or obstetrical sedation.

Note: For preoperative and postoperative sedation, 25 to 50 mg of promethazine may be combined with appropriately reduced doses of analgesics and anticholinergics. {01}
For obstetrical sedation, in the early stages of labor, 50 mg of promethazine will provide sedation and relief of apprehension. After labor is definitely established, 25 to 75 mg of promethazine may be administered with an appropriately reduced dose of an opioid analgesic, and may be repeated once or twice every four hours during the course of a normal labor. {01}



Usual adult prescribing limits
Up to 150 mg daily.

Usual pediatric dose


Children up to 2 years of age:
Use is not recommended. {11} {12}



Children 2 years of age and older:


Antihistaminic (H 1-receptor)—
Intramuscular, 125 mcg (0.125 mg) per kg of body weight or 3.75 mg per square meter of body surface every four to six hours or 500 mcg (0.5 mg) per kg of body weight or 15 mg per square meter of body surface at bedtime as needed; or 6.25 to 12.5 mg three times a day or 25 mg at bedtime as needed. {11} {12}



Antiemetic—
Intramuscular, 250 to 500 mcg (0.25 to 0.5 mg) per kg of body weight or 7.5 to 15 mg per square meter of body surface every four to six hours as needed; or 12.5 to 25 mg every four to six hours as needed. {11} {12}



Sedative-hypnotic—
Intramuscular, 500 mcg (0.5 mg) to 1 mg per kg of body weight as needed; or 12.5 to 25 mg as needed. {11} {12}

Note: For preoperative sedation, children require doses of 1.1 mg per kg of body weight in combination with an equal dose of meperidine and the appropriate dose of an atropine-like drug. {01}
For postoperative sedation, 12.5 to 25 mg may be used. {01}




Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


25 mg per mL (Rx) [Anergan 25] [Phenazine 25] [Phenergan] [Prorex-25] [Prothazine] [Shogan] [V-Gan-25][Generic]


50 mg per mL (Rx) [Anergan 50] [Antinaus 50] [Pentazine] [Phenazine 50] [Phencen-50] [Phenergan] [Phenerzine] [Phenoject-50] [Pro-50] [Promacot] [Pro-Med 50] [Promet] [Prorex-50] [Prothazine] [Shogan] [V-Gan-50][Generic]

Canada—


25 mg (base) per mL (Rx) [Phenergan][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.

Stability:
Do not use if discolored or if a precipitate is present.



Rectal Dosage Forms

PROMETHAZINE HYDROCHLORIDE SUPPOSITORIES USP

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Rectal, 25 mg; may be repeated in two hours if necessary.

Antiemetic
Rectal, 25 mg initially, then 12.5 to 25 mg every four to six hours as needed.

Antivertigo agent
Rectal, 25 mg two times a day as needed.

Sedative-hypnotic
Rectal, 25 to 50 mg for nighttime, presurgical, postsurgical, or obstetrical sedation.

Note: A 50-mg dose (with an equal amount of meperidine and an appropriate dose of an atropine-like drug) is used the night before surgery to relieve apprehension and produce sleep.



Usual adult prescribing limits
Up to 150 mg daily.

Usual pediatric dose


Children up to 2 years of age:
Use is not recommended. {11} {12}



Children 2 years of age and older:


Antihistaminic (H 1-receptor)—
Rectal, 125 mcg (0.125 mg) per kg of body weight or 3.75 mg per square meter of body surface every four to six hours, or 500 mcg (0.5 mg) per kg of body weight or 15 mg per square meter of body surface at bedtime as needed; or 6.25 to 12.5 mg three times a day or 25 mg at bedtime as needed. {11} {12}



Antiemetic—
Rectal, 250 to 500 mcg (0.25 to 0.5 mg) per kg of body weight or 7.5 to 15 mg per square meter of body surface every four to six hours as needed; or 12.5 to 25 mg every four to six hours as needed. {11} {12}



Antivertigo agent—
Rectal, 500 mcg (0.5 mg) per kg of body weight or 15 mg per square meter of body surface every twelve hours as needed; or 12.5 to 25 mg two times a day as needed. {11} {12}



Sedative-hypnotic—
Rectal, 500 mcg (0.5 mg) to 1 mg per kg of body weight or 15 to 30 mg per square meter of body surface as needed; or 12.5 to 25 mg as needed. {11} {12}

Note: For preoperative sedation, children require doses of 1.1 mg per kg of body weight in combination with an equal dose of meperidine and the appropriate dose of an atropine-like drug. {01}
For postoperative sedation, 12.5 to 25 mg may be used. {01}




Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


12.5 mg (Rx) [Phenergan]


25 mg (Rx) [Phenergan]


50 mg (Rx) [Phenergan][Generic]

Canada—
Not commercially available.

Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F), in a tight, light-resistant container, unless otherwise specified by manufacturer.

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

Note: Include patient instructions when dispensing.
Explain administration technique.



TRIMEPRAZINE

Summary of Differences
Pharmacology/pharmacokinetics: Duration of action—3 to 6 hours.


Oral Dosage Forms

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


TRIMEPRAZINE TARTRATE EXTENDED-RELEASE CAPSULES

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, 5 mg (base) every twelve hours as needed.


Usual pediatric dose
Antihistaminic (H 1-receptor)
Children up to 6 years of age: Use is not recommended.

Children 6 years of age and over: Oral, 5 mg (base) once a day as needed.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


5 mg (base) (Rx) [Temaril]

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.

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


TRIMEPRAZINE TARTRATE SYRUP USP

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, 2.5 mg (base) four times a day as needed.


Usual pediatric dose
Antihistaminic (H 1-receptor)
Children up to 2 years of age: Use is not recommended.

Children 2 to 3 years of age: Oral, 1.25 mg (base) at bedtime or three times a day as needed.

Children 3 years of age and over: Oral, 2.5 mg (base) at bedtime or three times a day as needed.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


2.5 mg (base) per 5 mL (Rx) [Temaril (alcohol 5.7%)][Generic]

Canada—


2.5 mg (base) per 5 mL (Rx) [Panectyl (alcohol 0.6%)]

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.

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


TRIMEPRAZINE TARTRATE TABLETS USP

Usual adult and adolescent dose
Antihistaminic (H 1-receptor)
Oral, 2.5 mg (base) four times a day as needed.


Usual pediatric dose
Antihistaminic (H 1-receptor)
Children up to 2 years of age: Use is not recommended.

Children 2 to 3 years of age: The available strength of the tablet may not conform to the recommended pediatric dosage. See Trimeprazine Tartrate Syrup USP .

Children 3 years of age and over: Oral, 2.5 mg (base) at bedtime or three times a day as needed.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—


2.5 mg (base) (Rx) [Temaril]

Canada—


2.5 mg (base) (Rx) [Panectyl]


5 mg (base) (Rx) [Panectyl]

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.



Revised: 07/26/1994



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  1. Gilman AG, Goodman LS, Rall TW, Murad F, editors. Goodman and Gilman's the pharmocological basis of therapeutics. 7th ed. New York: Macmillan, 1985: 422; 622-24.
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