Injection only

Antipsychotic Agent, Phenothiazine, Aliphatic

Management of manifestations of psychotic disorders

C

Hypersensitivity to promazine or any component (cross reactivity between phenothiazines may occur); severe CNS depression, bone marrow suppression and coma; intra-arterial injection of the parenteral formulation

Moderately sedating, use with caution in disorders where CNS depression is a feature. Use with caution in Parkinson's disease. Caution in patients with hemodynamic instability; bone marrow suppression; predisposition to seizures; subcortical brain damage; severe cardiac, hepatic, renal, or respiratory disease. Esophageal dysmotility and aspiration have been associated with antipsychotic use - use with caution in patients at risk of pneumonia (ie, Alzheimer's disease). Caution in breast cancer or other prolactin-dependent tumors (may elevate prolactin levels). May alter temperature regulation or mask toxicity of other drugs due to antiemetic effects. May alter cardiac conduction - life-threatening arrhythmias have occurred with therapeutic doses of phenothiazines. May cause orthostatic hypotension - use with caution in patients at risk of this effect or those who would tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, or other medications which may predispose).

May cause extrapyramidal reactions, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is moderate relative to other neuroleptics). May be associated with neuroleptic malignant syndrome (NMS) or pigmentary retinopathy.

Cardiovascular: Postural hypotension, tachycardia, dizziness, nonspecific QT changes

Central nervous system: Drowsiness, dystonias, akathisia, pseudoparkinsonism, tardive dyskinesia, neuroleptic malignant syndrome, seizures

Dermatologic: Photosensitivity, dermatitis, skin pigmentation (slate gray)

Endocrine & metabolic: Lactation, breast engorgement, false-positive pregnancy test, amenorrhea, gynecomastia, hyper- or hypoglycemia

Gastrointestinal: Xerostomia, constipation, nausea

Genitourinary: Urinary retention, ejaculatory disorder, impotence

Hematologic: Agranulocytosis, eosinophilia, leukopenia, hemolytic anemia, aplastic anemia, thrombocytopenic purpura

Hepatic: Jaundice

Ocular: Blurred vision, corneal and lenticular changes, epithelial keratopathy, pigmentary retinopathy

Symptoms of overdose include deep sleep, coma, extrapyramidal symptoms, abnormal involuntary muscle movements, hypotension

Following initiation of essential overdose management, toxic symptom treatment and supportive treatment should be initiated. Hypotension usually responds to I.V. fluids or Trendelenburg positioning. If unresponsive to these measures, the use of a parenteral inotrope may be required (eg, norepinephrine 0.1-0.2 mcg/kg/minute titrated to response). Seizures commonly respond to diazepam (I.V. 5-10 mg bolus in adults every 15 minutes if needed up to a total of 30 mg; I.V. 0.25-0.4 mg/kg/dose up to a total of 10 mg in children) or to phenytoin or phenobarbital. Critical cardiac arrhythmias often respond to I.V. phenytoin (15 mg/kg up to 1 g), while other antiarrhythmics can be used. Neuroleptics often cause extrapyramidal symptoms (eg, dystonic reactions) requiring management with diphenhydramine 1-2 mg/kg (adults) up to a maximum of 50 mg I.M. or I.V. slow push followed by a maintenance dose for 48-72 hours. When these reactions are unresponsive to diphenhydramine, benztropine mesylate I.V. 1-2 mg (adults) may be effective. These agents are generally effective within 2-5 minutes.

Phenothiazines inhibit the ability of bromocriptine to lower serum prolactin concentrations

Benztropine (and other anticholinergics) may inhibit the therapeutic response to promazine and excess anticholinergic effects may occur

Chloroquine may increase promazine concentrations

Cigarette smoking may enhance the hepatic metabolism of promazine. Larger doses may be required compared to a nonsmoker.

Concurrent use of promazine with an antihypertensive may produce additive hypotensive effects

Antihypertensive effects of guanethidine and guanadrel may be inhibited by promazine

Concurrent use with TCA may produce increased toxicity or altered therapeutic response

Promazine may inhibit the antiparkinsonian effect of levodopa; avoid this combination

Promazine plus lithium may rarely produce neurotoxicity

Barbiturates may reduce promazine concentrations

Propranolol may increase promazine concentrations

Sulfadoxine-pyrimethamine may increase promazine concentrations

Promazine and possibly other low potency antipsychotics may reverse the pressor effects of epinephrine

Promazine and CNS depressants (ethanol, narcotics) may produce additive CNS depressant effects

Promazine and trazodone may produce additive hypotensive effects

Protect all dosage forms from light, clear or slightly yellow solutions may be used; should be dispensed in amber or opaque vials/bottles. Solutions may be diluted or mixed with fruit juices or other liquids, but must be administered immediately after mixing

Blocks postsynaptic mesolimbic dopaminergic D₁ and D₂ receptors in the brain; exhibits a strong alpha-adrenergic blocking and anticholinergic effect, depresses the release of hypothalamic and hypophyseal hormones; believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis

The specific pharmacokinetics of promazine are poorly established but probably resemble those of other phenothiazines.

Metabolism: Extensively in the liver

Half-life: Most phenothiazines have long half-lives in the range of 24 hours or more

Oral, I.M.:

Adults:

Psychosis: 10-200 mg every 4-6 hours not to exceed 1000 mg/day

Antiemetic: 25-50 mg every 4-6 hours as needed

Hemodialysis: Not dialyzable (0% to 5%)

cholesterol (S), glucose; uric acid (S)

Most pharmacology textbooks state that in presence of phenothiazines, systemic doses of epinephrine paradoxically decrease the blood pressure. This is the so called "epinephrine reversal" phenomenon. This has never been observed when epinephrine is given by infiltration as part of the anesthesia procedure.

Significant hypotension may occur, especially when the drug is administered parenterally; orthostatic hypotension is due to alpha-receptor blockade, the elderly are at greater risk for orthostatic hypotension

Extrapyramidal reactions are more common in elderly with up to 50% developing these reactions after 60 years of age; drug-induced Parkinson's syndrome occurs often; Akathisia is the most common extrapyramidal reaction in elderly

Increased confusion, memory loss, psychotic behavior, and agitation frequently occur as a consequence of anticholinergic effects

Antipsychotic associated sedation in nonpsychotic patients is extremely unpleasant due to feelings of depersonalization, derealization, and dysphoria

Use exactly as directed (do not increase dose or frequency); may cause physical and/or psychological dependence. It may take 2-3 weeks to achieve desired results; do not discontinue without consulting prescriber. Dilute oral concentration with milk, water, or citrus juice; drink immediately after mixing. Do not take within 2 hours of any antacid. Avoid excess alcohol or caffeine and other prescription or OTC medications not approved by prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). Avoid skin contact with medication; may cause contact dermatitis (wash immediately with warm, soapy water). You may experience excess drowsiness, restlessness, dizziness, or blurred vision (use caution driving or when engaging in tasks requiring alertness until response to drug is known); dry mouth, nausea, vomiting (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); constipation (increased exercise, fluids, or dietary fruit and fiber may help); postural hypotension (use caution climbing stairs or when changing position from lying or sitting to standing); urinary retention (void before taking medication); photosensitivity (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight); or decreased perspiration (avoid strenuous exercise in hot environments). Report persistent CNS effects (eg, trembling fingers, altered gait or balance, excessive sedation, seizures, unusual muscle or skeletal movements, anxiety, abnormal thoughts, confusion, personality changes); chest pain, palpitations, rapid heartbeat, severe dizziness; unresolved urinary retention or changes in urinary pattern; menstrual pattern changes, change in libido or ejaculatory difficulty; vision changes; skin rash or yellowing of skin; difficulty breathing; or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Watch for hypotension

Injection, as hydrochloride: 25 mg/mL (10 mL); 50 mg/mL (1 mL, 2 mL, 10 mL)

Tablet, as hydrochloride: 25 mg, 50 mg, 100 mg

Gold N, "Attempted Suicide With Chlorpromazine," Med J Aust, 1966, 1(12):492-4.

John E, "Promazine and Neonatal Hyperbilirubinemia," Med J Aust, 1975, 2(9):342-4.

Peabody CA, Warner MD, Whiteford HA, et al, "Neuroleptics and the Elderly," J Am Geriatr Soc, 1987, 35(3):233-8.

Risse SC and Barnes R, "Pharmacologic Treatment of Agitation Associated With Dementia," J Am Geriatr Soc, 1986, 34(5):368-76.

Saltz BL, Woerner MG, Kane JM, et al, "Prospective Study of Tardive Dyskinesia Incidence in the Elderly," JAMA, 1991, 266(17):2402-6.

Seifert RD, "Therapeutic Drug Monitoring: Psychotropic Drugs," J Pharm Pract, 1984, 6:403-16.