Orap


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pimozide

(pi-mo-zide) ,

Orap

(trade name)

Classification

Therapeutic: antipsychotics
Pregnancy Category: C

Indications

Suppression of motor and vocal tics in Tourette's Disorder with severe, compromising symptoms in patients with an unfavorable response to haloperidol.Second line treatment after failure with atypical antipsychotics.Psychotic disorders that fail to respond to standard treatment.

Action

Blocks dopamine receptors in the CNS.
Increases brain turnover of dopamine, blocks calcium channels, and may antagonize opiate receptors.

Therapeutic effects

Decreased tics in patients with Tourette’s disorder.

Pharmacokinetics

Absorption: 50% absorbed following oral administration.
Distribution: Unknown.
Metabolism and Excretion: Undergoes extensive first-pass hepatic metabolism, primarily by CYP3A4 and to a lesser extent by CYP1A2 and CYP2D6 enzyme systems; the CYP2D6 enzyme system exhibits genetic polymorphism (genetic implication ∼7% of population may be poor metabolizers 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 (blood levels)

ROUTEONSETPEAKDURATION
POunknown6–8 hrunknown

Contraindications/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, heart failure; Concurrent use of agents that prolong the QT interval, including dofetilide, sotalol, quinidine, disopyramide, amiodarone, dronedarone, thioridazine, chlorpromazine, droperidol, moxifloxacin, mefloquine, pentamidine, arsenic trioxide, dolasetron, tacrolimus, ziprasidone, erythromycin, citalopram, escitalopram, clarithromycin and azithromycin (↑ risk of serious arrhythmias); Concurrent use of CYP3A4 enzyme inhibitors, including erythromycin, clarithromycin, azithromycin, itraconazole, ketoconazole, ritonavir, saquinovir, indinavir, nelfinavir, nefazodone, zileuton, and fluvoxamine (↑ risk of serious arrhythmias); Concurrent use of strong CYP2D6 enzyme inhibitors, including paroxetine (↑ risk of serious arrhythmias); Concurrent use of sertraline; CNS depression or comatose state; Motor or vocal tics not caused by Tourette’s Disorder; Hypokalemia or hypomagnesemia (↑ risk of serious arrhythmias).
Use Cautiously in: History of breast cancer; Angle-closure glaucoma; History of paralytic ileus; Hepatic or renal impairment; Prostatic hyperplasia; History of seizures (threshold may be lowered); Hypokalemia (↑ risk of arrhythmias); Obstetric: Neonates at ↑ risk for extrapyramidal symptoms and withdrawal after delivery when exposed during the 3rd trimester; use only if benefit outweighs risk to fetus; Lactation: Safety not established, discontinue drug or bottle feed; Pediatric / Geriatric: ↑ sensitivity; ↑ risk of mortality in elderly patients treated for dementia-related psychosis.

Adverse Reactions/Side Effects

Central nervous system

  • neuroleptic malignant syndrome (life-threatening)
  • mood/behavior effects
  • weakness
  • drowsiness (most frequent)

Ear, Eye, Nose, Throat

  • blurred vision
  • dry eyes

Cardiovascular

  • arrhythmias (prolonged QTc interval) (life-threatening)
  • hypotension (most frequent)

Gastrointestinal

  • constipation
  • dry mouth
  • ↓ appetite
  • nausea
  • vomiting
  • weight loss

Genitourinary

  • ↓ libido
  • erectile dysfunction

Dermatologic

  • skin discoloration (most frequent)

Endocrinologic

  • galactorrhea (women) (most frequent)

Hematologic

  • agranulocytosis (life-threatening)
  • leukopenia
  • neutropenia

Neurologic

  • akathisia
  • parkinsonism (most frequent)
  • dystonic reactions
  • tardive dyskinesia
  • akinesia (most frequent)

Interactions

Drug-Drug interaction

Concurrent use of macrolide anti-infectives (erythromycin, clarithromycin, azithromycin ), dofetilide, sotalol, quinidine, other Class IA or III antiarrhythmics, thioridazine, chlorpromazine, droperidol, gemifloxacin, moxifloxacin, mefloquine, pentamidine, arsenic trioxide, dolasetron, citalopram, escitalopramtacrolimus, and ziprasidone ↑ the risk of serious ventricular arrhythmias and should be avoided; similar effects may occur with tricyclic antidepressants, disopyramide, or procainamide.Blood levels and risk of cardiac arrhythmias are ↑ by concurrent use of ritonavir ; concurrent use is contraindicated.Metabolism of pimozide may be impaired by azoleantifungals ; concurrent use of itraconazole, fluvoxamine, and ketoconazole is 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.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

Tourette’s Disorder
Oral (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; genetic implicationPoor CYP2D6 metabolizers-Do not exceed 4 mg/day and do not titrate dose any earlier than every 14 days.
Oral (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; genetic implicationPoor CYP2D6 metabolizers-Do not exceed 0.05 mg/kg/day and do not titrate dose any earlier than every 14 days.
Oral (Geriatric Patients) Use lower initial doses and more gradual titration.
Psychotic Disorders (Unlabeled)
Oral (Adults) 2–4 mg/day as a single morning dose, may be ↑ by 2–4 mg/day at weekly intervals as needed and tolerated (usual dose is 6 mg/day, range 2–12 mg/day); up to 0.3 mg/kg/day or 20 mg/day, whichever is less.

Availability

Tablets: 1 mg, 2 mg, 4 mg, 10 mg

Nursing implications

Nursing assessment

  • Assess patient for frequency of tics during therapy.
  • Assess positive (hallucinations, delusions, agitation) and negative (social withdrawal) symptoms of psychotic disorder.
  • 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.
  • Monitor intake and output ratios and daily weight.
  • 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 CPK.
  • Lab Test Considerations: May cause false-positive pregnancy tests with immunologic urine.
  • Lab Test Considerations: Obtain serum potassium levels initially and throughout therapy.
  • Lab Test Considerations: Obtain fasting blood glucose and cholesterol levels initially and throughout therapy.
    • Monitor CBC frequently during initial months of therapy in patients with pre-existing or history of low WBC. May cause leukopenia, neutropenia, or agranulocytosis. Discontinue therapy if this occurs.

Potential Nursing Diagnoses

Impaired social interaction (Indications)
Risk for injury (Side Effects)

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.
  • genetic implicationTourette's Disorder: When dosing exceeds 0.05 mg/kg/day in children or 4 mg in adults CYP 2D6 genotyping should be obtained. In poor CYP 2D6 metabolizers, doses should not exceed 0.05 mg/kg/day, and should not be increased earlier than 14 days.
  • Oral: 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 weeks 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 weeks 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.
  • 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 or clay-colored stools, sore throat, fever, or symptoms of neuroleptic malignant syndrome occur.
  • Emphasize the importance of routine follow-up exams to monitor response to medication and detect side effects.

Evaluation/Desired Outcomes

  • Decrease in the frequency and severity of tics in patients with Tourette’s Disorder.
  • Decrease in positive (hallucinations, delusions, agitation) symptoms of psychotic disorders.

Orap

(ôr′ăp′)
A trademark for the drug pimozide.

Orap

a trademark for an oral neuroleptic drug (pimozide).

Orap

A brand name for the antipsychotic and movement disorder drug PIMOZIDE.
References in periodicals archive ?
Finally, ORAP claimed that the district court made errors in its issuance of the injunction.
45 and others; Halcion (triazolam); Orap (pimozide); Propulsid (cisapride); quinidine, also known as Quinaglute, Cardioquin, Quinidex and others; Revatio (sildenafil) only when used for the treatment of pulmonary arterial hypertension; Rythmol (propafenone); Tambocor (flecainide); Uroxatral (alfuzosin hydrochloride); Vascor (bepridil); Versed (oral midazolam); and Vfend (voriconazole).
After selling its interest in a European professional service company, ORAP Consulting Group, which was employing 160 consultants on various international technology projects, Mr.