Pimozide

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Your doctor may occasionally change your dose to make sure you get the best results.

Tell your doctor if you have a prolonged illness that causes diarrhea or vomiting. You may develop an electrolyte imbalance, which could cause heart rhythm problems while you are taking pimozide.

It may take several weeks before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve, or if they get worse.

Do not stop using pimozide suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to avoid withdrawal symptoms when you stop using pimozide.

Store at room temperature away from moisture, heat, and light.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include some of the serious side effects listed in this medication guide.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Treatment with ORAP exposes the patient to serious risks. A decision to use ORAP chronically in Tourette's Disorder is one that deserves full consideration by the patient (or patient's family) as well as by the treating physician. Because the goal of treatment is symptomatic improvement, the patient's view of the need for treatment and assessment of response are critical in evaluating the impact of therapy and weighing its benefits against the risks. Since the physician is the primary source of information about the use of a drug in any disease, it is recommended that the following information be discussed with patients and/or their families.

ORAP is intended only for use in patients with Tourette's Disorder whose symptoms are severe and who cannot tolerate, or who do not respond to HALDOL® (haloperidol).

Given the likelihood that a proportion of patients exposed chronically to antipsychotics will develop tardive dyskinesia, it is advised that all patients in whom chronic use is contemplated be given, if possible, full information about this risk. The decision to inform patients and/or their guardians must obviously take into account the clinical circumstances and the competency of the patient to understand the information provided.

There is limited information available on the use of ORAP in children under 12 years of age.

The information available on ORAP from foreign marketing experience and from U.S. clinical trials indicates that ORAP has a side effect profile similar to that of other antipsychotic drugs. Patients should be informed that all types of side effects associated with the use of antipsychotics may be associated with the use of ORAP.

In addition, sudden, unexpected deaths have occurred in patients taking high doses of ORAP for conditions other than Tourette's Disorder. These deaths may have been the result of an effect of ORAP upon the heart. Therefore, patients should be instructed not to exceed the prescribed dose of ORAP and they should realize the need for the initial ECG and for follow-up ECGs during treatment.

Also, pimozide, at a dose about 15 times that given humans, caused an increase in the number of benign tumors of the pituitary gland in female mice. It is not possible to say how important this is. Similar tumors were not seen in rats given pimozide, nor at lower doses in mice, which is reassuring. However, any such finding must be considered to suggest a possible risk of long term use of the drug.

Because substances in grapefruit juice may inhibit the metabolism of pimozide by CYP 3A4, patients should be advised to avoid grapefruit juice.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.  Especially tell your doctor if you take: 

• azithromycin (Zithromax, Z-pak)
• clarithromycin (Biaxin)
• erythromycin (E.E.S., Erythrocin, E-mycin)
• moxifloxacin (Avelox)
• dofetilide (Tikosyn)
• amiodarone (Cordarone)
• sotalol (Betapace)
• citalopram (Celexa)
• escitalopram (Lexapro)
• sertraline (Zoloft)
• moxifloxacin (Avelox)
• tacrolimus (Prograf)
• ziprasidone (Geodon)
• indinavir (Crixivan)
• ritonavir (Norvir)
• chlorpromazine (Thorazine)
• droperidol (Inapsine)
• tricyclic antidepressants such as trimipramine (Surmontil), amitriptyline (Elavil), nortriptyline (Pamelor, Aventyl), protriptyline (Vivactil), and clomipramine (Anafranil)
• medications that block a protein in the body (CYP3A4) such as some macrolide antibiotics (clarithromycin, telithromycin), some HIV protease inhibitors (indinavir, nelfinavir, ritonavir, saquinavir), some HCV protease inhibitors (boceprevir, telaprevir), some azole antifungals (ketoconazole, itraconazole, posaconazole, voriconazole), conivaptan (Vaprisol), delavirdine (Rescriptor), and nefazodone (Serzone)
• medications that block a protein in the body (CYP2D6) such as quinidine (Qualaquin), fluoxetine (Prozac,Sarafem), amitriptyline (Elavil, Amitril), and paroxetine (Paxil)

This is not a complete list of pimozide interactions. Ask your doctor or pharmacist for more information.

Before taking pimozide, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to pimozide or any of its ingredients
• are taking medications that may cause tics such as methylphenidate (Ritalin, Concerta), amphetamines (Adderall), or dextroamphetamine (Dexedrine)
• have ever had long QT syndrome (a potentially serious irregular heartbeat)
• have kidney or liver problems
• if any drug you have taken in the past has lowered your white blood cells (cells that help your body fight infection)
• if you are allergic to any other antipsychotic medications
• have a history of seizures
• are taking anti-seizure medication
• if you have already tried haloperidol (Haldol) to treat your Tourette's condition
• have other heart problems

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins and herbal supplements.

The recommended dose of pimozide for the treatment of speech and movement tics in patients with Tourette’s Syndrome is:

• Adults: starting dose of 1 to 2 mg a day by mouth in divided doses. It may be increased every other day up to 10 mg daily.
• Children (12 to 18 years old): starting dose of 0.05 mg/kg by mouth at bedtime. It may be increased every 3 days up to 10 mg per day.

• Store pimozide at controlled room temperature between 59˚and 86˚F.
• Keep in a tight, light resistant container.
• Keep this and all medications out of the reach of children.

Pimozide is an antipsychotic medication. It works by changing the actions of chemicals in the brain.

Pimozide is used to suppress the motor and phonic tics associated with Tourette's disorder.

Pimozide may also be used for purposes not listed in this medication guide.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

• seizure (convulsions);

• twitching or uncontrollable movements of your eyes, lips, tongue, face, arms, or legs; or

• very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, feeling like you might pass out.

Less serious side effects may include:

• fever;

• headache, dizziness, drowsiness;

• feeling restless;

• vision problems;

• constipation; or

• dry mouth.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Usual Adult Dose for Tourette's Syndrome:

Initial dose: 1 to 2 mg orally per day in divided doses
Maintenance dose: Typically less than 0.2 mg/kg or 10 mg/day, whichever is less
Maximum dose: 10 mg/day

Comments:
-Use should be limited to patients with Tourette's Disorder whose development and/or daily life function is severely compromised by motor and phonic tics. This drug is not indicated for use as first-line therapy or in patients with tics that are merely annoying or cosmetically troublesome.
-Initial doses may be increased every other day if tolerated.
-Patients requiring doses greater than 4 mg/day should undergo CYP 450 2D6 genotyping.

Use: Suppression of motor and phonic tics in patients with Tourette's Disorder who have failed to respond to standard treatment

Usual Pediatric Dose for Tourette's Syndrome:

12 years and older:
-Initial dose: 0.05 mg/kg orally at bedtime
-Maximum dose: 0.2 mg/kg, not to exceed 10 mg/day

Comments:
-Use should be limited to patients with Tourette's Disorder whose development and/or daily life function is severely compromised by motor and phonic tics. This drug is not indicated for use as first-line therapy or in patients with tics that are merely annoying or cosmetically troublesome.
-Doses may be increased every 3 days to a maximum of 0.2 mg/kg.
-CYP450 2D6 genotyping should be performed in patients taking greater than 0.05 mg/kg/day.

Use: Suppression of motor and phonic tics in patients with Tourette's Disorder who have failed to respond to standard treatment

• If you have an allergy to pimozide or any other part of pimozide.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have ever had a long QT on ECG or other heartbeat that is not normal.
• If you have any of these health problems: Low potassium or magnesium levels.
• If you are very sleepy.
• If you take any drugs (prescription or OTC, natural products, vitamins) that must not be taken with this medicine, like certain drugs that are used for HIV, infections, or depression. There are many drugs that must not be taken with pimozide. Your doctor or pharmacist can tell you if you are taking a drug that must not be taken with this medicine.

This is not a list of all drugs or health problems that interact with pimozide.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Keep taking pimozide as you have been told by your doctor or other health care provider, even if you feel well.
• To gain the most benefit, do not miss doses.
• Take with or without food. Take with food if it causes an upset stomach.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

1. Pimozide is contraindicated in the treatment of simple tics or tics other than those associated with Tourette’s Disorder.

2. Pimozide should not be used in patients taking drugs that may, themselves, cause motor and phonic tics (e.g., pemoline, methylphenidate and amphetamines) until such patients have been withdrawn from these drugs to determine whether or not the drugs, rather than Tourette’s Disorder, are responsible for the tics

3. Because Pimozide prolongs the QT interval of the electrocardiogram it is contraindicated in patients with congenital long QT syndrome, patients with a history of cardiac arrhythmias, patients taking other drugs which prolong the QT interval of the electrocardiogram or patients with known hypokalemia or hypomagnesemia (see also PRECAUTIONS - Drug Interactions).

4. Pimozide is contraindicated in patients with severe toxic central nervous system depression or comatose states from any cause.

5. Pimozide is contraindicated in patients with hypersensitivity to it. As it is not known whether cross-sensitivity exists among the antipsychotics, Pimozide should be used with appropriate caution in patients who have demonstrated hypersensitivity to other antipsychotic drugs.

6. Ventricular arrhythmias have been rarely associated with the use of macrolide antibiotics in patients with prolonged QT intervals, as might be produced by Pimozide. Specifically, two sudden deaths have been reported when clarithromycin was added to ongoing Pimozide therapy.Furthermore, some evidence suggests that Pimozide is metabolized partly by the enzyme system cytochrome P450 3A4 (CYP 3A4). Macrolide antibiotics are inhibitors of CYP 3A4, and thus could potentially impede Pimozide metabolism. For these reasons, Pimozide is contraindicated in patients receiving the macrolide antibiotics clarithromycin, erythromycin, azithromycin,dirithromycin, and troleandomycin.

7. Concomitant use in patients taking Celexa or Lexapro is contraindicated (see Precautions - Drug Interactions - Pimozide and Celexa).

8. Clinical drug interaction studies have demonstrated that Pimozide is also metabolized by CYP 2D6. Concomitant use of Pimozide with paroxetine and other strong CYP 2D6 inhibitors is contraindicated (See PRECAUTIONS – Drug Interactions).

9. Concomitant use of Pimozide in patients taking sertraline is contraindicated.

(See PRECAUTIONS – Drug Interactions).

Because azole antifungal agents are also inhibitors of the CYP 3A4 enzymes and thus may likewise impair Pimozide metabolism, Pimozide is contraindicated in patients receiving the azole antifungal agents itraconazole and ketoconazole.

Similarly, protease inhibitor drugs are also inhibitors of CYP 3A4, and thus Pimozide is contraindicated in patients receiving protease inhibitors such as ritonavir, saquinovir, indinavir, and nelfinavir. (See PRECAUTIONS - Drug Interactions.)

Nefazodone is a potent inhibitor of CYP 3A4, and its concomitant use with Pimozide is also contraindicated.

Other drugs that are relatively less potent inhibitors of CYP 3A4 should also be avoided, in view of the risks: e.g. zileuton, fluvoxamine.

A chronic study in dogs indicated that Pimozide caused gingival hyperplasia when administered for several months at about 5 times the maximum recommended human dose. This condition was reversible after withdrawal.

• First Generation (Typical) Antipsychotic

Note: An ECG should be performed baseline and periodically thereafter, especially during dosage adjustment.

Tourette disorder: Oral:

Children 2 to 12 years: Initial: 0.05 mg/kg preferably once at bedtime; may be increased every third day to a maximum of 0.2 mg/kg/day (do not exceed 10 mg/day); usual range: 2 to 4 mg/day. Note: If therapy requires exceeding dose of 0.05 mg/kg/day, CYP2D6 geno-/phenotyping should be performed; CYP2D6 poor metabolizers should be dose titrated in ≥14-day increments and should not receive doses in excess of 0.05 mg/kg/day.

Children >12 years and Adolescents: Refer to adult dosing.

Frequencies as reported in adults (limited data) and/or children with Tourette's disorder.

>10%:

Central nervous system: Sedation (70%), akathisia (40%), drowsiness (35%; children: ≤25%), behavioral changes (22% to 25%), hypertonia (15%)

Gastrointestinal: Xerostomia (25%), constipation (20%)

Genitourinary: Impotence (15%)

Neuromuscular & skeletal: Akinesia (40%), weakness (14%)

Ophthalmic: Decreased accommodation (20%), visual disturbance (3% to 20%)

1% to 10%:

Cardiovascular: ECG abnormality (3%)

Central nervous system: Depression (10%), insomnia (10%), speech disturbance (10%), nervousness (5% to 6%), writing difficulty (handwriting change: 5%), headache (3% to 5%), abnormal dreams (3%)

Dermatologic: Skin rash (3%)

Endocrine & metabolic: Increased thirst (5%)

Gastrointestinal: Sialorrhea (6%), diarrhea (5%), dysgeusia (5%), increased appetite (5%), dysphagia (3%)

Neuromuscular & skeletal: Muscle rigidity (10%), stooped posture (10%), hyperkinesia (3%), myalgia (3%), torticollis (3%), tremor (3%)

Ophthalmic: Photophobia (5%)

Frequency not defined (some reported for disorders other than Tourette's disorder):

Cardiovascular: Chest pain, hypertension, hypotension, orthostatic hypotension, prolonged Q-T interval on ECG, syncope, tachycardia, ventricular arrhythmia

Central nervous system: Dizziness, excitement, drug-induced extrapyramidal reaction (dystonia, pseudoparkinsonism, tardive dyskinesia), neuroleptic malignant syndrome, palpitations, seizure

Dermatologic: Diaphoresis, skin irritation

Endocrine & metabolic: Decreased libido, hyponatremia, weight changes (gain/loss)

Gastrointestinal: Anorexia, gastrointestinal distress, nausea, vomiting

Genitourinary: Nocturia

Hematologic & oncologic: Hemolytic anemia

Ophthalmic: Blurred vision, cataract, periorbital edema

Renal: Polyuria

<1% (Limited to important or life-threatening): Gingival hyperplasia

Use with caution.

Administration advice:
-Therapy should be initiated slowly and gradually.

General:
-A risk/benefit assessment is warranted for this drug, as use could result in serious adverse events (e.g., tardive dyskinesia, neuroleptic malignant syndrome, and sudden, unexpected death due to QT prolongation).
-When determining the initial dose for a patient, consideration should be given to the patient's age, symptom severity, and previous response to other neuroleptic drugs. Patients should be on the lowest possible dose that suppresses symptoms but limits side effects.
-Patients should be evaluated regularly to verify that the lowest possible dose is used.

Monitoring:
-Complete Blood Count before and periodically during treatment
-ECGs at baseline and periodically during treatment
-Electrolyte levels periodically, especially in patients with electrolyte disturbances

Patient advice:
-Warn patients to avoid abrupt discontinuation of this drug.
-Tell patients to immediately report any signs/symptoms of neutropenia/leukopenia, neuroleptic malignant syndrome, or tardive dyskinesia.
-Patients should be advised to report all concurrent prescription and nonprescription medications or herbal products they are taking.
-Inform patients that this drug may cause drowsiness, and they should avoid driving or operating machinery until the full effects of the drug are known.
-Patients should be advised to speak to a healthcare provider if pregnant, intend to become pregnant, or are breastfeeding.