Prochlorperazine

Pronunciation

Pronunciation: pro-klor-PURR-uh-zeen
Class: Antidopaminergic, Phenothiazine derivative

Trade Names

Prochlorperazine
- Tablets 5 mg (as maleate)
- Tablets 10 mg (as maleate)
- Injection (as edisylate) 5 mg/mL

Compro
- Suppositories 25 mg

Apo-Prochlorazine (Canada)

Pharmacology

Effects apparently related to dopamine receptor blocking in CNS. Antiemetic activity may be caused by direct inhibition on medullary chemoreceptor trigger zone.

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Pharmacokinetics

Absorption

May be erratic. C max shows large interindividual differences. Food slows the absorption and decreases C max 23% and AUC 13%.

Distribution

Large volume of distribution; crosses the placenta and is distributed into breast milk. Protein binding is at least 90%.

Metabolism

Hepatic to active and inactive metabolites.

Elimination

Renal and biliary, with some enterohepatic recycling.

Onset

10 to 20 min (IM).

Peak

4 to 7 days (antipsychotic effect).

Duration

3 to 4 h (IM).

Indications and Usage

Treatment of schizophrenia; short-term treatment of generalized nonpsychotic anxiety; control of severe nausea and vomiting.

Unlabeled Uses

Treatment of migraines (IV).

Contraindications

Coma or severely depressed states; allergy to any phenothiazine; presence of large amounts of other CNS depressants; children younger than 2 yr of age or less than 20 lb; surgery in children.

Dosage and Administration

Individualize dosage. Subcutaneous administration is not advised because of local irritation.

Nonpsychotic Anxiety
Adults

PO 5 mg 3 to 4 times daily. Do not exceed 20 mg/day or give for more than 12 wk.

Schizophrenia
Adults

IM Start with 10 to 20 mg for immediate control of schizophrenic patients with severe symptomatology; if necessary, repeat initial dose every 2 to 4 h to gain control of patient. More than 3 or 4 doses are seldom necessary. If IM therapy is needed for a prolonged period, give 10 to 20 mg every 4 to 6 h.

Mild conditions

PO 5 to 10 mg 3 or 4 times daily.

Moderate to severe conditions

PO 10 mg 3 to 4 times daily, increasing dosage gradually (every 2 or 3 days) until symptoms are controlled or adverse reactions become bothersome. Some patients respond satisfactorily on 50 to 75 mg/day; in more severe disturbances, the optimum dosage is usually 100 to 150 mg/day.

Children 2 to 12 yr of age

PO 2.5 mg 2 or 3 times daily. Do not exceed 10 mg the first day.

Children 2 to 5 yr of age

PO Do not exceed 20 mg/day.

Children 6 to 12 yr of age

PO Do not exceed 25 mg/day. IM For children younger than 12 yr of age, calculate each dose on the basis of 0.03 mg/kg given by deep IM injection.

Nausea and Vomiting
Adults

PO 5 or 10 mg tablet 3 to 4 times daily. PR 25 mg twice daily. IM 5 to 10 mg. May repeat every 3 to 4 h. Do not exceed 40 mg/day. IV 2.5 to 10 mg by slow IV or infusion at a rate not to exceed 5 mg/min (single dose not to exceed 10 mg; max, 40 mg/day).

Children

Adjust according to patient response and severity of symptoms.

Children 18 to 38.5 kg

PO 2.5 mg 3 times daily or 5 mg twice daily; do not exceed 15 mg/day. IM 0.03 mg/kg given by deep IM injection.

Children 13.6 to 17.6 kg

PO 2.5 mg given 2 to 3 times daily; do not exceed 10 mg/day. IM 0.03 mg/kg given by deep IM injection.

Children 9 to 13 kg

PO 2.5 mg given once or twice daily; do not exceed 7.5 mg/day. IM 0.03 mg/kg given by deep IM injection.

Nausea and Vomiting (Surgery)
Adults

IM 5 to 10 mg 1 to 2 h prior to induction of anesthesia (may repeat once in 30 min) or to control acute symptoms during and after surgery (may repeat once).

Adults

IV injection or infusion 5 to 10 mg 15 to 30 min before induction of anesthesia or to control acute symptoms during or after surgery. Repeat once if necessary. Rate of administration should not exceed 5 mg/min and a single dose should not exceed 10 mg.

General Advice

  • Administer tablets without regard to meals. Administer with food if GI upset occurs.
  • Administer IM dose by slow, deep injection into outer quadrant of buttock.
  • Administer IV dose by slow IV injection or infusion at rate not exceeding 5 mg/mL. Injection may be administered undiluted or diluted in isotonic solution (eg, normal saline, D5W). Do not administer as bolus.
  • Injection is not for intradermal or subcutaneous administration.
  • Do not administer injection if particulate matter or marked discoloration are noted. A slight yellowish discoloration is normal and will not alter potency.
  • Do not mix injection with other drugs in syringe.
  • If injection is spilled on skin or clothing, rinse area immediately with water to prevent contact dermatitis.

Storage/Stability

Store injection below 86°F. Do not freeze. Store tablets and suppositories at controlled room temperature (59° to 86°F); protect from light.

Drug Interactions

Alcohol or other CNS depressants

May result in increased CNS depression and may precipitate dystonic reactions.

Anticholinergics

May reduce therapeutic effects of prochlorperazine and worsen anticholinergic effects.

Barbiturate anesthetics

Frequency and severity of neuromuscular excitation and hypotension may be increased.

Beta-blockers

May result in increased plasma levels of beta-blocker and prochlorperazine.

Cisapride, sparfloxacin

The risk of life-threatening cardiac arrhythmias, including torsades de pointes, may be increased.

Guanethidine

Hypotensive action of guanethidine may be inhibited.

Metrizamide

Possibility of seizure may be increased when subarachnoid metrizamide injection is used.

Paroxetine

Plasma levels of prochlorperazine may be elevated, increasing the risk of adverse reactions.

Incompatibility

Do not mix prochlorperazine injection with other agents in syringe. Do not dilute with any diluent containing parabens as preservative.

Laboratory Test Interactions

May discolor urine pink to red-brown. False-positive pregnancy tests may occur but are less likely to occur with serum test. Increases in protein-bound iodine reported.

Adverse Reactions

Cardiovascular

Orthostatic hypotension; hypertension; tachycardia; bradycardia, syncope; cardiac arrest; circulatory collapse; ECG changes.

CNS

Lightheadedness; faintness; dizziness; pseudoparkinsonism; dystonia; dyskinesia; motor restlessness; oculogyric crises; opisthotonos; hyperreflexia; tardive dyskinesia; drowsiness; headache; weakness; tremor; fatigue; slurring of speech; insomnia; vertigo; abnormalities of CSF proteins; paradoxical excitement or exacerbation of psychotic symptoms; catatonic-like states; paranoid reactions; lethargy; seizures; hyperactivity; nocturnal confusion; bizarre dreams.

Dermatologic

Photosensitivity; skin pigmentation; dry skin; pruritus; exfoliative dermatitis; urticarial rash; maculopapular hypersensitivity reaction; seborrhea; eczema.

EENT

Pigmentary retinopathy; glaucoma; photophobia; blurred vision; mydriasis; glaucoma; dry mouth or throat; nasal congestion.

GI

Nausea; vomiting; dyspepsia, adynamic ileus (which may result in death); constipation.

Genitourinary

Urinary hesitancy or retention; impotence, sexual dysfunction; menstrual irregularities; priapism; breast enlargement; galactorrhea.

Hepatic

Jaundice.

Hematologic

Agranulocytosis; eosinophilia; leukopenia; hemolytic anemia; thrombocytopenic purpura; pancytopenia; aplastic anemia.

Metabolic

Hyperglycemia; hypoglycemia; increased cholesterol levels.

Respiratory

Laryngospasm; bronchospasm; dyspnea.

Miscellaneous

Increases in appetite and weight; polydipsia; increased prolactin levels; heat stroke.

Precautions

Pregnancy

Undetermined.

Lactation

Undetermined.

Children

Do not give to children under 9 kg or younger than 2 yr of age. Do not use in pediatric surgery. Extrapyramidal adverse reactions may develop even at moderate doses. Use lowest effective dose. Some children respond with restlessness and excitement; do not give additional doses. Use with caution in children with acute illnesses or dehydration.

Elderly

More susceptible to effects; consider lower dose.

Special Risk Patients

Use caution in patients with CV disease or mitral insufficiency, history of glaucoma, EEG abnormalities or seizure disorders, prior brain damage, hepatic or renal function impairment, or those who will be exposed to extreme heat.

Sulfite Sensitivity

Some parenteral products may contain sulfites.

Aspiration

As result of suppression of cough reflex, aspiration of vomitus possible.

Bone marrow suppression

Patients with bone marrow depression or who have previously demonstrated a hypersensitivity reaction with a phenothiazine should not receive prochlorperazine unless, in the judgment of the health care provider, the potential benefits outweigh the possible risks.

CNS effects

May impair mental or physical abilities, especially during first few days of therapy.

Hepatic effects

Jaundice usually occurs between weeks 2 and 4 of treatment; considered hypersensitivity reaction. Usually reversible.

Neuroleptic malignant syndrome (NMS)

NMS has occurred with agents in this class; is potentially fatal. Signs and symptoms are hyperpyrexia, muscle rigidity, altered mental status, irregular pulse, fluctuating BP, tachycardia, and diaphoresis.

Pulmonary

Cases of bronchopneumonia (some fatal) occurred.

Sudden death

Sudden death reported; predisposing factors may be seizures or previous brain damage. Flare-ups of psychotic behavior may precede death.

Tardive dyskinesia

Syndrome of potentially irreversible involuntary body and facial movements may develop. Prevalence highest in elderly, especially women. Use smallest effective doses for shortest possible time.

Overdosage

Symptoms

CNS depression (somnolence to coma), fever, agitation, restlessness, hypotension, extrapyramidal effects, circulatory collapse, seizures, arrhythmias.

Patient Information

  • Advise patient, family, or caregiver that dose will be adjusted periodically until max benefit has been obtained.
  • Advise patient, family, or caregiver not to change the dose or stop taking unless advised by health care provider.
  • Instruct patient, family, or caregiver to immediately report fainting or loss of consciousness, palpitations, dizziness, high fever, muscle rigidity, altered mental status, irregular pulse, sore throat, unusual bruising, yellowing of the skin or eyes.
  • Advise patient, family, or caregiver to notify health care provider of the following: excessive drowsiness, increased agitation or anxiety, involuntary body or facial movements.
  • Advise patient to avoid strenuous activity during periods of high temperature or humidity.
  • Instruct patient to avoid alcoholic beverages and other depressants while taking this medication.
  • Instruct patient to get up slowly from lying or sitting position and to avoid sudden position changes to prevent postural hypotension. Advise patient to report dizziness with position changes to health care provider. Caution patient that hot tubs and hot showers or baths may make dizziness worse.
  • Advise patient to take sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
  • Advise patient drug may cause drowsiness and impaired judgment or thinking skills and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
  • Caution patient that medication may cause sensitivity to sunlight and to avoid unnecessary exposure to UV light (eg, sunlight, tanning booths) and to use sunscreen and wear protective clothing when exposed to UV light until tolerance is determined.

Copyright © 2009 Wolters Kluwer Health.

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