Yes

Antipsychotic Agent, Phenothiazine, Aliphatic

Psychoses and mania; to control nausea and vomiting; relief of restlessness and apprehension before surgery; acute intermittent porphyria; adjunct in the treatment of tetanus; intractable hiccups; combativeness and/or explosive hyperexcitable behavior in children 1-12 years of age and in short-term treatment of hyperactive children

C

Hypersensitivity to chlorpromazine or any component (cross reactivity between phenothiazines may occur); severe CNS depression, coma

Highly 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 neuroleptics. 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). Significant hypotension may occur, particularly with parenteral administration. Injection contains sulfites and benzyl alcohol.

May cause extrapyramidal reactions, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is low-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. 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 benztropine mesylate I.V. 1-2 mg (adults) may be effective. These agents are generally effective within 2-5 minutes.

CYP1A2, 2D6, and 3A3/4 enzyme substrate; CYP2D6 enzyme inhibitor

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

Chloroquine may increase CPZ concentrations

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

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

Antihypertensive effects of guanethidine and guanadrel may be inhibited by CPZ

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

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

CPZ plus lithium may rarely produce neurotoxicity

Barbiturates may reduce CPZ concentrations

Propranolol may increase CPZ concentrations

Sulfadoxine-pyrimethamine may increase CPZ concentrations

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

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

CPZ and trazodone may produce additive hypotensive effects

Protect from light; a slightly yellowed solution does not indicate potency loss, but a markedly discolored solution should be discarded; diluted injection (1 mg/mL) with NS and stored in 5 mL vials remains stable for 30 days

Blocks postsynaptic mesolimbic dopaminergic receptors in the brain; exhibits a strong alpha-adrenergic blocking effect and 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

Peak concentration after oral dose: 1-2 hours

Distribution: Crosses the placenta; appears in breast milk

Metabolism: Extensively in the liver to active and inactive metabolites

Half-life, biphasic: Initial: 2 hours; Terminal: 30 hours

Elimination: <1% excreted in urine as unchanged drug within 24 hours

Children >6 months:

Psychosis:

Oral: 0.5-1 mg/kg/dose every 4-6 hours; older children may require 200 mg/day or higher

I.M., I.V.: 0.5-1 mg/kg/dose every 6-8 hours; maximum dose for <5 years (22.7 kg): 40 mg/day; maximum for 5-12 years (22.7-45.5 kg): 75 mg/day

Nausea and vomiting:

Oral: 0.5-1 mg/kg/dose every 4-6 hours as needed

I.M., I.V.: 0.5-1 mg/kg/dose every 6-8 hours; maximum dose for <5 years (22.7 kg): 40 mg/day; maximum for 5-12 years (22.7-45.5 kg): 75 mg/day

Rectal: 1 mg/kg/dose every 6-8 hours as needed

Adults:

Psychosis:

Oral: Range: 30-2000 mg/day in 1-4 divided doses, initiate at lower doses and titrate as needed; usual dose: 400-600 mg/day; some patients may require 1-2 g/day

I.M., I.V.: Initial: 25 mg, may repeat (25-50 mg) in 1-4 hours, gradually increase to a maximum of 400 mg/dose every 4-6 hours until patient is controlled; usual dose: 300-800 mg/day

Intractable hiccups: Oral, I.M.: 25-50 mg 3-4 times/day

Nausea and vomiting:

Oral: 10-25 mg every 4-6 hours

I.M., I.V.: 25-50 mg every 4-6 hours

Rectal: 50-100 mg every 6-8 hours

Elderly (nonpsychotic patient; dementia behavior): Initial: 10-25 mg 1-2 times/day; increase at 4- to 7-day intervals by 10-25 mg/day. Increase dose intervals (bid, tid, etc) as necessary to control behavior response or side effects; maximum daily dose: 800 mg; gradual increases (titration) may prevent some side effects or decrease their severity.

Dosing adjustment/comments in hepatic impairment: Avoid use in severe hepatic dysfunction

Alcohol: Additive CNS effects, avoid use

Orthostatic blood pressures; tremors, gait changes, abnormal movement in trunk, neck, buccal area, or extremities; monitor target behaviors for which the agent is given; watch for hypotension when administering I.M. or I.V.

Therapeutic: 50-300 ng/mL (SI: 157-942 nmol/L)

Toxic: >750 ng/mL (SI: >2355 nmol/L); serum concentrations poorly correlate with expected response

False-positives for phenylketonuria, amylase, uroporphyrins, urobilinogen; may cause photosensitivity; avoid excessive sunlight; do not stop taking without consulting physician

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. Do not discontinue without consulting prescriber. Tablets/capsules may be taken with food. Mix oral solution with 2-4 ounces of liquid (eg, juice, milk, water). Do not take within 2 hours of any antacid. Store away from light. 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). May turn urine red-brown (normal). You may experience excess drowsiness, lightheadedness, dizziness, or blurred vision (use caution driving or when engaging in tasks requiring alertness until response to drug is known); dry mouth, upset stomach, nausea, vomiting, anorexia (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum 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); ejaculatory dysfunction (reversible); decreased perspiration (avoid strenuous exercise in hot environments); or photosensitivity (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight). Report persistent CNS effects (trembling fingers, altered gait or balance, excessive sedation, seizures, unusual movements, anxiety, abnormal thoughts, confusion, personality changes); chest pain, palpitations, rapid heartbeat, or severe dizziness; unresolved urinary retention or changes in urinary pattern; altered menstrual pattern, change in libido, swelling or pain in breasts (male or female); vision changes, skin rash, irritation, or changes in color of skin (gray-blue); or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Avoid contact of oral solution or injection with skin (contact dermatitis)

Capsule, as hydrochloride, sustained action: 30 mg, 75 mg, 150 mg, 200 mg, 300 mg

Concentrate, oral, as hydrochloride: 30 mg/mL (120 mL); 100 mg/mL (60 mL, 240 mL)

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

Suppository, rectal, as base: 25 mg, 100 mg

Syrup, as hydrochloride: 10 mg/5 mL (120 mL)

Tablet, as hydrochloride: 10 mg, 25 mg, 50 mg, 100 mg, 200 mg

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