Yes: Injection and tablet

Antipsychotic Agent, Phenothazine, Piperazine

Management of nausea and vomiting; psychosis; anxiety

C

Clinical effects on the fetus: Crosses the placenta. Isolated reports of congenital anomalies, however some included exposures to other drugs. Available evidence with use of occasional low doses suggests safe use during pregnancy.

Breast-feeding/lactation: No data available. American Academy of Pediatrics considers compatible with breast-feeding.

Hypersensitivity to prochlorperazine or any component (cross reactivity between phenothiazines may occur); severe CNS depression; coma; bone marrow suppression; should not be used in children <2 years of age or <20 pounds.

May be sedating; use with caution in disorders where CNS depression is a feature. May impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (ie, operating machinery or driving). Effects with other sedative drugs or ethanol may be potentiated. Avoid use in Reye's syndrome. Use with caution in Parkinson's disease; hemodynamic instability; bone marrow suppression; predisposition to seizures; subcortical brain damage; and in severe cardiac, hepatic, renal or respiratory 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 hypotension or where transient hypotensive episodes would be poorly tolerated (cardiovascular disease or cerebrovascular disease). Hypotension may occur following administration, particularly when parenteral form is used or in high dosages.

Cardiovascular: Hypotension, orthostatic hypotension, hypertension, tachycardia, bradycardia, dizziness, cardiac arrest

Central nervous system: Extrapyramidal signs (pseudoparkinsonism, akathisia, dystonias, tardive dyskinesia), dizziness, cerebral edema, seizures, headache, drowsiness, paradoxical excitement, restlessness, hyperactivity, insomnia, neuroleptic malignant syndrome (NMS), impairment of temperature regulation

Dermatologic: Increased sensitivity to sun, rash, discoloration of skin (blue-gray)

Endocrine & metabolic: Hypoglycemia, hyperglycemia, galactorrhea, lactation, breast enlargement, gynecomastia, menstrual irregularity, amenorrhea, SIADH, changes in libido

Gastrointestinal: Constipation, weight gain, vomiting, stomach pain, nausea, xerostomia, salivation, diarrhea, anorexia, ileus

Genitourinary: Difficulty in urination, ejaculatory disturbances, incontinence, polyuria, ejaculating dysfunction, priapism

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

Hepatic: Cholestatic jaundice, hepatotoxicity

Neuromuscular & skeletal: Tremor

Ocular: Pigmentary retinopathy, blurred vision, cornea and lens changes

Respiratory: Nasal congestion

Miscellaneous: Diaphoresis

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. Extrapyramidal symptoms (eg, dystonic reactions) may require 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 prochlorperazine and excess anticholinergic effects may occur

Chloroquine may increase prochlorperazine concentrations

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

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

Antihypertensive effects of guanethidine and guanadrel may be inhibited by prochlorperazine

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

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

Prochlorperazine plus lithium may rarely produce neurotoxicity

Barbiturates may reduce prochlorperazine concentrations

Propranolol may increase prochlorperazine concentrations

Sulfadoxine-pyrimethamine may increase prochlorperazine concentrations

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

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

Prochlorperazine and trazodone may produce additive hypotensive effects

Protect from light; clear or slightly yellow solutions may be used; incompatible when mixed with aminophylline, amphotericin B, ampicillin, calcium salts, cephalothin, foscarnet (Y-site), furosemide, hydrocortisone, hydromorphone, methohexital, midazolam, penicillin G, pentobarbital, phenobarbital, thiopental

Blocks postsynaptic mesolimbic dopaminergic D₁ and D₂ receptors in the brain, including the medullary chemoreceptor trigger zone; exhibits a strong alpha-adrenergic and anticholinergic 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

Onset of effect: Oral: Within 30-40 minutes; I.M.: Within 10-20 minutes; Rectal: Within 60 minutes

Duration: Persists longest with I.M. and oral extended-release doses (12 hours); shortest following rectal and immediate release oral administration (3-4 hours)

Distribution: Crosses the placenta; appears in breast milk

Metabolism: Hepatic

Half-life: 23 hours

Elimination: Primarily by hepatic metabolism

Antiemetic: Children:

Oral, rectal:

>10 kg: 0.4 mg/kg/24 hours in 3-4 divided doses; or

9-14 kg: 2.5 mg every 12-24 hours as needed; maximum: 7.5 mg/day

14-18 kg: 2.5 mg every 8-12 hours as needed; maximum: 10 mg/day

18-39 kg: 2.5 mg every 8 hours or 5 mg every 12 hours as needed; maximum: 15 mg/day

I.M.: 0.1-0.15 mg/kg/dose; usual: 0.13 mg/kg/dose; change to oral as soon as possible

I.V.: Not recommended in children <10 kg or <2 years

Antiemetic: Adults:

Oral: 5-10 mg 3-4 times/day; usual maximum: 40 mg/day

I.M.: 5-10 mg every 3-4 hours; usual maximum: 40 mg/day

I.V.: 2.5-10 mg; maximum 10 mg/dose or 40 mg/day; may repeat dose every 3-4 hours as needed

Rectal: 25 mg twice daily

Antipsychotic:

Children 2-12 years:

Oral, rectal: 2.5 mg 2-3 times/day; increase dosage as needed to maximum daily dose of 20 mg for 2-5 years and 25 mg for 6-12 years

I.M.: 0.13 mg/kg/dose; change to oral as soon as possible

Adults:

Oral: 5-10 mg 3-4 times/day; doses up to 150 mg/day may be required in some patients for treatment of severe disturbances

I.M.: 10-20 mg every 4-6 hours may be required in some patients for treatment of severe disturbances; change to oral as soon as possible

Dementia behavior (nonpsychotic): Elderly: Initial: 2.5-5 mg 1-2 times/day; increase dose at 4- to 7-day intervals by 2.5-5 mg/day; increase dosing intervals (twice daily, 3 times/day, etc) as necessary to control response or side effects; maximum daily dose should probably not exceed 75 mg in elderly; gradual increases (titration) may prevent some side effects or decrease their severity

Hemodialysis: Not dialyzable (0% to 5%)

Limit caffeine; increase dietary intake of riboflavin; should be administered with food or water

False-positives for phenylketonuria, urinary amylase, uroporphyrins, urobilinogen

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.

>10% of patients experience dry mouth

Tardive dyskinesia: Prevalence rate may be 40% in elderly; development of the syndrome and the irreversible nature are proportional to duration and total cumulative dose over time

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

Take exact amount as prescribed. Do not change brand names. Do not crush or chew tablets or capsules. Do not discontinue without consulting prescriber. Avoid alcohol or other sedatives or sleep-inducing drugs. Avoid skin contact with drug; wash immediately with warm soapy water. You may experience appetite changes; small frequent meals may help. Maintain adequate fluid intake (2-3 L/day of fluids unless instructed to restrict fluid intake). May cause dizziness, tremors, or visual disturbance (especially during early therapy); use caution when driving or engaging in tasks that require alertness until response to drug is known. Do not change position rapidly (rise slowly). May cause photosensitivity reaction; use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight. Report immediately any changes in gait or muscular tremors. Report unresolved changes in voiding or elimination (constipation or diarrhea), acute dizziness or unresolved sedation, any vision changes, palpitations, yellowing of skin or eyes, and changes in color of urine or stool (pink or red brown urine is expected). Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Avoid skin contact with oral solution or injection, contact dermatitis has occurred; observe for extrapyramidal symptoms

Capsule, sustained action, as maleate: 10 mg, 15 mg, 30 mg

Injection, as edisylate: 5 mg/mL (2 mL, 10 mL)

Suppository, rectal: 2.5 mg, 5 mg, 25 mg (12/box)

Syrup, as edisylate: 5 mg/5 mL (120 mL)

Tablet, as maleate: 5 mg, 10 mg, 25 mg

Berk BZ, "Reaction to Prochlorperazine?" Lancet, 1969, 1(598):776.

Goldstein D, Levi JA, Woods RL, et al, "Double-Blind Randomized Cross-Over Trial of Dexamethasone and Prochlorperazine as Antiemetics for Cancer Chemotherapy," Oncology, 1989, 46(2):105-8.

Hesketh PJ, Gandara DR, Hesketh AM, et al, "Improved Control of High-Dose-Cisplatin-Induced Acute Emesis With the Addition of Prochlorperazine to Granisetron/Dexamethasone," Cancer J Sci Am, 1997, 3(3):180-3.

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