PIMOZIDE

PIMOZIDE (pi'moe-zide) Orap Classifications: psychotherapeutic; antipsychotic; butyrophenone; Therapeutic: antipsychotic Prototype: Haloperidol Pregnancy Category: C

Availability

2 mg tablet

Action

Potent central dopamine antagonist that alters release and turnover of central dopamine stores; has no effect on turnover of norepinephrine. Blockade of CNS dopaminergic receptors results in suppression of the motor and phonic tics that characterize Tourette's disorder.

Therapeutic Effect

Effective in suppressing motor and phonic tics associated with Tourette's disorder.

Uses

To suppress severe motor and phonic tics in patient with Tourette's disorder who has failed to respond satisfactorily to standard treatment (e.g., haloperidol).

Contraindications

Treatment of simple tics other than those associated with Tourette's disorder; drug-induced tics; history of cardiac dysrhythmias and conditions marked by prolonged QT syndrome, patient taking drugs that may prolong QT interval (e.g., quinidine); congenital heart defects, cardia arrhythmias; electrolyte imbalance; Parkinson's disease; severe toxic CNS depression; pregnancy (category C), lactation.

Cautious Use

Kidney and liver dysfunction; patients receiving anticonvulsant therapy; cardiac disease; glaucoma; BPH; urinary retention. Safe use in children <12 y is not known.

Route & Dosage

Tourette's Disorder Adult: PO 1–2 mg/d in divided doses, gradually increase dose q.o.d. up to 0.2 mg/kg/d or 7–16 mg/d in divided doses, whichever is less (max: 0.2 mg/kg/d or 10 mg/d)

Administration

Oral

• Increase drug dose gradually, usually over 1–3 wk, until maintenance dose is reached.
• Follow regimen prescribed by physician for withdrawal: Usually slow, gradual changes over a period of days or weeks (drug has a long half-life). Sudden withdrawal may cause reemergence of original symptoms (motor and phonic tics) and of neuromuscular adverse effects of the drug.

Adverse Effects (≥1%)

Body as a Whole: Akathisia, speech disorder, torticollis, tremor, handwriting changes, akinesia, fainting, hyperpyrexia, tardive dyskinesia, rigidity, oculogyric crisis, hyperreflexia; seizures, neuroleptic malignant syndrome; extrapyramidal dysfunction, hyperthermia, autonomic dysfunction; diaphoresis, weight changes, asthenia, chest pain, periorbital edema. CNS: Headache, sedation, drowsiness, insomnia, seizures, stupor. CV: Prolongation of QT interval, inverted or flattened T wave, appearance of U wave, labile blood pressure. Urogenital: Loss of libido, impotence, nocturia, urinary frequency, amenorrhea, dysmenorrhea, mild galactorrhea, urinary retention, acute renal failure. Respiratory: Dyspnea, respiratory failure. Skin: Sweating, skin irritation. Special Senses: Visual disturbances, photosensitivity, decreased accommodation, blurred vision, cataracts. GI: Increased salivation, nausea, vomiting, diarrhea, anorexia, abdominal cramps, constipation.

Interactions

Drug: Alcohol and other cns depressants increase CNS depression; anticholinergic agents (e.g., tricyclic antidepressants, atropine) increase anticholinergic effects; phenothiazines, tricyclic antidepressants, antiarrhythmics, macrolide antibiotics, azole antifungals (itraconazole, ketoconazole, fluconazole), protease inhibitors, nefazodone, sertraline, zileuton increase risk of arrhythmias and heart block; pimozide antagonizes effects of anticonvulsants—there is loss of seizure control. Food: Grapefruit juice (>1 qt/d) may increase plasma concentrations and adverse effects.

Pharmacokinetics

Absorption: Slowly and variably from GI tract (40–50% absorbed). Peak: 6–8 h. Metabolism: In liver (by CYP3A4). Elimination: 80–85% in urine, 15–20% in feces. Half-Life: 55 h.

Nursing Implications

Note: See haloperidol for additional nursing implications.

Assessment & Drug Effects

• Obtain ECG baseline data at beginning of therapy and check periodically, especially during dosage adjustments.
• Notify physician immediately for widening or prolongation of the QT interval, which suggests developing cardiotoxicity [QT interval (QRS complex and T wave) representing both ventricular depolarization and repolarization].
• Risk of tardive dyskinesia appears to be greatest in women, older adults, and those on high-dose therapy.
• Be aware that extrapyramidal reactions often appear within the first few days of therapy, are dose-related, and usually occur when dose is high.
• Be aware that anticholinergic effects (dry mouth, constipation) may increase as dose is increased.

Patient & Family Education

• Adhere to established drug regimen (i.e., do not change dose or intervals and discontinue only with physician's guidance).
• Use measures to relieve dry mouth (frequent rinsing with water, saliva substitute, increased fluid intake) and constipation (increased dietary fiber, drink 6–8 glasses of water daily).
• Do not drive or engage in potentially hazardous activities because drug-caused hand tremors, drowsiness, and blurred vision may impair alertness and abilities.
• Pseudoparkinsonism symptoms are usually mild and reversible with dose adjustment.
• Be alert to the earliest symptom of tardive dyskinesia ("flycatching"—an involuntary movement of the tongue), and report promptly to the physician.
• Return to physician for periodic assessments of therapy benefit and cardiac status.
• Understand dangers of ingesting alcohol to prevent augmenting CNS depressant effects of pimozide.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug