Pimozide



Definition

Pimozide is an atypical antipsychotic drug used to treat serious motor and verbal tics associated with Tourette's syndrome. It is sold under the brand name Orap.

Purpose

Pimozide is classified as an atypical antipsychotic drug. It is structurally similar to another drug, haloperidol , which was the first drug to be used in Tourette's syndrome. Pimozide is most often used to treat symptoms of Tourette's syndrome, although it has also been used for treating schizophrenia mania, and other behavioral disorders.

Description

Excess dopamine activity in the brain is associated with the verbal and physical tics observed in Tourette's syndrome. Like haloperidol, pimozide is believed to inhibit the actions of the brain chemical, dopamine.

Pimozide is broken down by the liver and eliminated from the body by the kidneys. Because pimozide is associated with health risks, it should not be used for tics that are simply annoying or cosmetic. Pimozide should be used only in patients with severe symptoms after other drug therapy has been tried and failed.

Pimozide is available in 1-mg and 2-mg tablets.

Recommended dosage

The common starting dose of pimozide in adults is 1-2 mg per day. The dose may be increased every other day until 0.2 mg per kg (or 0.9 mg per pound) of body weight per day or 10 mg per day is reached, whichever is less. Doses that exceed 0.2 mg per kg per day or 10 mg daily are not recommended.

In children, the usual initial dose is 0.05 mg per kg daily, and increased every three days to a maximum dose of 0.2 mg per kg (or 10 mg) per day.

Periodically, the dosage of pimozide should be reduced to determine if tics are still present. Patients should be maintained on the lowest dose that is effective in treating their disorder.

Precautions

Pimozide may alter the rhythm of the heart. As a result, it should be used with caution in people with heart disease, and these patients should be observed carefully while receiving the drug.

Pimozide should not be taken with grapefruit juice.

Pimozide should be used with close physician supervision by people who have a history of seizure disorders, because it may increase the tendency to have seizures .

Pimozide may cause extreme drowsiness and should be used carefully by people who need to be mentally alert.

Patients should not take pimozide while pregnant or breast-feeding.

Pimozide should not be used by people with mild tics, by individuals taking stimulants such as methylphenidate (Ritalin), pemoline (Cylert), or dextroamphetamine (Dexedrine) since these drugs may cause tics.

Side effects

The most common side effects associated with pimozide are sleepiness, headache, stomach upset, muscle tightness, muscle weakness, difficulty moving, tremor, abnormal behavior, visual disturbances, and impotence.

Other side effects that might also occur with pimozide involve rapid heart rates or irregular heart rhythms, low blood pressure, constipation, dry mouth and eyes, rash, breast pain, breast milk production, loss of bladder control, or low blood cell counts.

Pimozide use may lead to the development of symptoms that resemble Parkinson's disease. These symptoms may include a tight or mask-like expression on the face, drooling, tremors, pill-rolling motions in the hands, cog-wheel rigidity (abnormal rigidity in muscles characterized by jerky movements when the muscle is passively stretched), and a shuffling gait. Taking anti-Parkinson drugs benztropine mesylate or trihexyphenidyl hydrochloride along with the pimozide usually controls these symptoms.

Pimozide has the potential to produce a serious side effect called tardive dyskinesia . This syndrome consists of involuntary, uncoordinated movements that may appear late in therapy and not disappear even after the drug is stopped. Tardive dyskinesia involves involuntary movements of the tongue, jaw, mouth or face or other groups of skeletal muscles. The incidence of tardive dyskinesia increases with increasing age and with increasing dosage of pimozide. Women are at greater risk than men for developing tardive dyskinesia. There is no known effective treatment for tardive dyskinesia, although gradual (but rarely complete) improvement may occur over a long period.

An occasionally reported side effect of pimozide is neuroleptic malignant syndrome. This is a complicated and potentially fatal condition characterized by muscle rigidity, high fever, alterations in mental status, and cardiac symptoms such as irregular pulse or blood pressure, sweating, tachycardia (fast heartbeat), and arrhythmias (irregular heartbeat). People who think they may be experiencing any side effects from this or any other medication should talk to their physician promptly.

Interactions

If pimozide is used with bethanechol (Urecholine), clonidine (Catapres), fluoxetine (Prozac), indomethacin (Indocin), meperidine (Demerol), paroxetine (Paxil), quinidine, or trazodone (Desyrel), the side effects associated with pimozide may be increased.

There is an increased risk of irregular heart rhythms if pimozide is used with other antipsychotics, certain antidepressants, some heart drugs, and antibiotics like erythromycin.

The beneficial effects of pimozide may be reduced if used with bromocriptine (Parlodel), carbamazepine (Tegretol), levodopa (Larodopa, Sinemet), lithium, or phenobarbital.

Some antibiotics, antifungals, antidepressants, and drugs used for AIDS may prevent the breakdown of pimozide by the liver and thus, increase the amount of pimozide in the body. The combination of pimozide and the above classes of drugs should be used cautiously if at all.

Pimozide may interact with other central nervous system depressants such as alcohol, sleeping pills, antihistamines, and antidepressants.

Resources

BOOKS

Ellsworth, Allan J., and others. Mosby's Medical Drug Reference. St. Louis, MO: Mosby, Inc, 1999.

Facts and Comparisons Staff. Drug Facts and Comparisons. 6th Edition. St. Louis, MO: A Wolter Kluwer Company, 2002.

Medical Economics Co. Staff. Physician's Desk Reference. 56th edition Montvale, NJ: Medical Economics Company, 2002.

Kelly Karpa, RPh, Ph.D.



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