pimozide

Absorption: 50% absorbed following oral administration.

Distribution: Unknown.

Metabolism/Excretion: Undergoes extensive first-pass hepatic metabolism, primarily by the CYP3A4 isoenzyme and to a lesser extent by the CYP1A2 and CYP2D6 isoenzymes; the CYP2D6 isoenzyme exhibits genetic polymorphism (∼7% of population may be poor metabolizers [PMs] and may have significantly ↑ pimozide concentrations and an ↑ risk of adverse effects). Some metabolites have CNS activity.

Half-Life: 29–111 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	6–8 hr	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity (cross-sensitivity with other antipsychotics may occur);
Concurrent use of agents that may be causing the motor and vocal tics;
Congenital long QT syndrome (↑ risk of serious arrhythmias);
Recent MI or HF;
Concurrent use of agents that prolong the QT interval;
Concurrent use of CYP3A4 enzyme inhibitors;
Concurrent use of strong CYP2D6 enzyme inhibitors;
CNS depression or comatose state;
Motor or vocal tics not caused by Tourette’s disorder;
Hypokalemia or hypomagnesemia (↑ risk of serious arrhythmias);
Lactation: Lactation.

Use Cautiously in:

History of breast cancer;
Angle-closure glaucoma;
History of paralytic ileus;
Renal impairment;
Hepatic impairment;
Prostatic hyperplasia;
History of seizures (threshold may be lowered);
Hypokalemia (↑ risk of arrhythmias);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Pedi: Children 12 yr (safety and effectiveness not established);
Geri: sensitivity in older adults; risk of mortality in older adults treated for dementia-related psychosis.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension, QT interval prolongation, TORSADES DE POINTES

Derm: skin discoloration

EENT: blurred vision, dry eyes

Endo: galactorrhea (women)

GI: constipation, dry mouth, ↓appetite, nausea, vomiting, weight loss

GU: ↓libido, erectile dysfunction

Hemat: AGRANULOCYTOSIS, leukopenia, neutropenia

Neuro: akinesia, drowsiness, parkinsonism, akathisia, dystonic reactions, mood/behavior effects, NEUROLEPTIC MALIGNANT SYNDROME, tardive dyskinesia, weakness

Interactions ⬆ ⬇

Drug-drug:

Concurrent use of macrolide anti-infectives (erythromycin, clarithromycin, azithromycin), dofetilide, sotalol, quinidine, other Class IA or III antiarrhythmics, thioridazine, chlorpromazine, droperidol, moxifloxacin, mefloquine, pentamidine, arsenic trioxide, citalopram, escitalopramtacrolimus, and ziprasidone↑ the risk of serious ventricular arrhythmias; concurrent use contraindicated. Similar effects may occur with tricyclic antidepressants, disopyramide, or procainamide.
Levels and risk of cardiac arrhythmias are ↑ by concurrent use of ritonavir; concurrent use contraindicated.
Itraconazole, fluvoxamine, and ketoconazole may ↑ levels and risk of toxicity; concurrent use contraindicated.
↑risk of CNS depression with alcohol or other CNS depressants.
Amphetamines or methylphenidate may provoke tics that cannot be treated with pimozide; discontinue these before initiating therapy with pimozide.
Blocks the effects of amphetamines.
Concurrent use with MAO inhibitors↑ risk of sedative, hypotensive, and anticholinergic adverse reactions.
Concurrent use with fluoxetine may result in bradycardia.

Drug-Natural Products:

Concomitant use of kava, valerian, or chamomile can ↑ CNS depression.
See sedative interactions.
St. John's wort may affect pimozide levels and effectiveness; avoid concurrent use.

Grapefruit juice↑ risk of arrhythmias.

Route/Dosage ⬆ ⬇

PO (Adults ): 1–2 mg/day in divided doses, may be ↑ gradually as needed and tolerated up to 0.2 mg/kg/day or 10 mg/day, whichever is less; CYP2D6 PMs—Do not exceed 4 mg/day and do not titrate dose any earlier than every 14 days.
PO (Children >12 yr): 0.05 mg/kg/day as a single bedtime dose, may be ↑ every third day as needed and tolerated up to 0.2 mg/kg/day or 10 mg/day, whichever is less; CYP2D6 PMs—Do not exceed 0.05 mg/kg/day and do not titrate dose any earlier than every 14 days.

Availability ⬆ ⬇

(Generic available)

Tablets: 1 mg; 2 mg; 4 mg

Assessment ⬆ ⬇

Assess patient for frequency of tics during therapy.
Assess weight and BMI initially and throughout therapy.
Monitor BP (sitting, standing, lying) and ECG prior to and periodically during therapy, especially during period of dosage adjustment. May cause QT interval changes, flattening, notching, and inverting of T-wave, and the appearance of U-waves on ECG.
Assess fluid intake and bowel function. Increased bulk and fluids in the diet help minimize constipating effects.
Monitor patient for onset of akathisia (restlessness or desire to keep moving), which may appear within 6 hr of 1st dose and may be difficult to distinguish from psychotic agitation; benztropine may be used to differentiate. Observe closely for extrapyramidal side effects (parkinsonian: difficulty speaking or swallowing, loss of balance control, pill rolling of hands, mask-like face, shuffling gait, rigidity, tremors; and dystonic: muscle spasms, twisting motions, twitching, inability to move eyes, weakness of arms or legs). Trihexyphenidyl or benztropine may control these symptoms. Benzodiazepines may alleviate akathisia.
Monitor for tardive dyskinesia (uncontrolled rhythmic movement of mouth, face, and extremities; lip smacking or puckering; puffing of cheeks; uncontrolled chewing; rapid or worm-like movements of tongue, excessive eye blinking) at least every 3 mo. Report immediately; may be irreversible.
Monitor for development of neuroleptic malignant syndrome (fever, respiratory distress, tachycardia, convulsions, diaphoresis, hypertension or hypotension, pallor, tiredness, severe muscle stiffness, loss of bladder control). Report symptoms immediately. May also cause leukocytosis, elevated liver function tests, and elevated creatine kinase.

Lab Test Considerations:

May cause false-positive pregnancy tests with immunologic urine.
Monitor serum potassium levels before starting and periodically during therapy.
Monitor fasting blood glucose and cholesterol levels before starting and periodically during therapy.
- Monitor CBC frequently during initial month of therapy in patients with pre-existing or history of low WBC. May cause leukopenia, neutropenia, or agranulocytosis. Discontinue therapy if this occurs.

Implementation ⬆ ⬇

Dose should be reduced periodically to determine whether tics persist. Increase in tics may be due to withdrawal phenomenon rather than the persistence of tics. Allow 1–2 wk to elapse before concluding that an increase in symptoms is due to an increase in tics instead of withdrawal symptoms.
Tourette's disorder: When dosing exceeds 0.05 mg/kg/day in children or 4 mg in adults, CYP2D6 genotyping should be obtained. In poor CYP2D6 metabolizers, doses should not exceed 0.05 mg/kg/day and should not be increased earlier than 14 days.
PO: May be administered as a single daily dose.
- Do not administer with grapefruit juice.

Patient/Family Teaching ⬆ ⬇

Advise patient to take medication exactly as directed and to avoid grapefruit juice during therapy. Skip missed doses and return to regular schedule; do not double doses. May require several wk to obtain desired effects. Do not increase dose or discontinue medication without consulting health care professional. Abrupt withdrawal may cause dizziness; nausea; vomiting; GI upset; trembling; or uncontrolled movements of mouth, tongue, or jaw. Dose should be gradually decreased over several wk to minimize withdrawal symptoms.
Inform patient of possibility of extrapyramidal symptoms and tardive dyskinesia. Caution patient to report symptoms immediately.
Advise patient to change positions slowly to minimize orthostatic hypotension.
May cause drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's wort, kava, valerian, and chamomile.
Caution patient to avoid taking alcohol or other CNS depressants concurrently with this medication.
Advise patient to use sunscreen and protective clothing when exposed to the sun to prevent photosensitivity reactions. Extremes of temperature should also be avoided, because this drug impairs body temperature regulation.
Advise patient of possibility of weight gain or cholesterol elevation; refer as appropriate for nutrition/weight management and medical management.
Instruct patient to use frequent mouth rinses, good oral hygiene, and sugarless gum or candy to minimize dry mouth.
Advise patient to notify health care professional of medication regimen prior to treatment or surgery.
Instruct patient to notify health care professional promptly if weakness, tremors, visual disturbances, dark-colored urine, clay-colored stools, sore throat, fever, or symptoms of neuroleptic malignant syndrome occur.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding. Advise patients that use during 3rd trimester may cause extrapyramidal and/or withdrawal symptoms (agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder).
Emphasize the importance of routine follow-up exams to monitor response to medication and detect side effects.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇