Clozaril

Generic name: Clozapine

What is Clozaril?

Clozaril belongs to a class of drugs known as atypical antipsychotics. Clozaril is used for the management of treatment-resistant schizophrenia (patients who fail to adequately respond to standard drug treatment for schizophrenia). This is usually due to insufficient effectiveness or inability to achieve an effective dose because of intolerable side effects of standard drug treatment.

Clozaril is also used for reducing the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder who are at chronic risk for re-experiencing suicidal behavior. People with schizoaffective disorder have symptoms of both schizophrenia and mood disorders, such as mental or physical mania (overactivity).

What is the most important information I should know about Clozaril?

Elderly patients with who are on Clozaril are at an increased risk of death. These patients should not take Clozaril.

Although it is extremely rare, a blood disorder called agranulocytosis has been associated with Clozaril. In this disorder, white blood cells are not made in adequate numbers or are not made at all; this reduces the body's resistance to infection. Even though the risk of agranulocytosis is low, people who take Clozaril must have their blood tested on a regular basis. If you experience lethargy, weakness, fever, sore throat, malaise, or any other sign of possible infection contact your doctor immediately, as this may a sign of a more serious problem.

Those patients who have an established diagnosis of diabetes and are started on Clozaril should be regularly monitored for signs and symptoms of elevated sugar levels in the blood (increased thirst, hunger, urination, and weakness).

Clozaril has been associated with causing seizures, especially at certain dosages. Caution should be used in patients who have a pre-existing seizure disorder or other predisposing factors.

When initiating Clozaril therapy you should not drive, operate machinery, or participate in any activity where a sudden loss of consciousness could cause serious risk to you or to others (such as swimming or climbing).

Clozaril has been associated with an increased risk of fatal myocarditis (inflammation of the myocardium or the muscular part of the heart), especially during, but not limited to, the first month of therapy. If you are experiencing fatigue, a fast heartbeat, fever, or chest pain, contact your doctor immediately.

Clozaril may cause a drop in your blood pressure, especially when you first start taking this medication or if the dose is increased. If this happens, try not to stand up too quickly and contact your doctor concerning this problem. Sometimes the decrease in blood pressure may be accompanied with loss of consciousness and in rare cases may lead to respiratory and/or cardiac arrest.

Clozaril should be used with caution in patients with known cardiovascular and/or lung disease; a gradual titration of dose and careful monitoring is recommended.

Clozaril should not be taken with other medicines that may cause blood problems. Also, Clozaril may increase the effects of certain drugs used to lower blood pressure, anticholinergic drugs (sometimes used as ophthalmics or in treating an extremely low heart rate), and medicines used for pain relief. Let your doctor know the medication you are currently using or have used in the past.

Clozaril may cause some slowing down or obstruction of your bowel muscles, which may cause constipation or a more serious side effect. On rare occasion these cases may be fatal.

Clozaril should be taken exactly as prescribed by your doctor. It may take a few weeks for Clozaril to work; do not stop taking the drug if you do not see results right away. It may take as long as 6 to 8 weeks to determine the correct dose of Clozaril. Do not take more or less of the medication without speaking to your doctor. If a dose is missed or forgotten for more than 2 days, do not start taking the drug again without speaking to your doctor.

Who should not take Clozaril?

Do not use if you have exhibited previous sensitivity to Clozaril or any other component of this drug.

Elderly patients with dementia-related psychosis should not take Clozaril due to an increased risk of death.

Do not use Clozaril if you have bone marrow problems.

Do not use Clozaril if you have uncontrolled seizures (epilepsy) or loss of bowel muscle movements.

Clozaril should not be used if you have a history of blood problems caused by Clozaril.

What should I tell my doctor before I take the first dose of Clozaril?

Tell your doctor about all prescription, over-the-counter, and herbal medications you are taking before beginning treatment with Clozaril. Also, talk to your doctor about your complete medical history, especially if you have ever had the following: liver problems, narrow-angle glaucoma, diabetes, prostate enlargement, dementia-related psychosis, heart disease, lung disease, loss of bowel muscle movement, seizure disorder, prolonged or painful erections, agranulocytosis (inadequate white blood cell production), blood clots or any blood problems, and high cholesterol

What is the usual dosage?

The information below is based on the dosage guidelines your doctor uses. Depending on your condition and medical history, your doctor may prescribe a different regimen. Do not change the dosage or stop taking your medication without your doctor's approval.

Adults: The recommended beginning dose of Clozaril is one-half of a 25 milligram (mg) tablet (12.5mg) once or twice daily, followed by a continued daily dosage increments of 25 to 50 mg daily. If well tolerated, the targeted dose of 300 to 450 mg daily can be achieved by the end of 2 weeks. Dosage increments after that should not be made more than once or twice weekly with increments not exceeding 100 mg. Cautious dosage increase and divided doses are necessary to minimize side effects.

Many patients respond adequately to doses between 300 to 600 mg daily, but it may be necessary to raise the dose within the range of 600 to 900 mg daily to obtain acceptable response. The daily dose should not exceed 900 mg. It may take as long as 6 to 8 weeks to determine the correct dose of Clozaril.

When going off of Clozaril, a gradual reduction over a 1 to 2 week period is recommended. However, if a medical condition requires abrupt discontinuation, careful observation for recurrence of psychotic symptoms as well as symptoms such as headache, nausea, vomiting, and diarrhea is required.

The safety and effectiveness of Clozaril have not been established in pediatric patients.

How should I take Clozaril?

Clozaril should be taken exactly as prescribed by your doctor. It may take a few weeks for Clozaril to work, do not stop taking the drug if you do not see results right away. It may take as long as 6 to 8 weeks to determine the correct dose of Clozaril. Do not take more or less of the medication without speaking to your doctor. If a dose is missed or forgotten for more than 2 days, do not start taking the drug again without speaking to your doctor.

What should I avoid while taking Clozaril?

Avoid standing up too quickly when beginning treatment with Clozaril as the drug may cause a drop in your blood pressure, especially when you first start taking this medication or if the dose is increased. Call your doctor if this problem continues or increases in intensity.

You may experience drowsiness when you start this medication. Avoid driving or operating dangerous machinery until you know how this medication affects you.

Avoid taking Clozaril with other medicines which may cause blood problems as well as severe drowsiness. Avoid the consumption of alcohol, a CNS depressant, while on Clozaril due to potential increase in side effects.

What are possible food and drug interactions associated with Clozaril?

If Clozaril is taken with certain other drugs, the effects of either could be increased, decreased, or altered. It is especially important to check with your doctor before combining Clozaril with the following: alcohol, antiarrhythmics (propafenone, quinidine), anticholinergics (benztropine), barbiturates (phenobarbital), benzodiazepines (lorazepam), carbamazepine, cimetidine, debrisoquin, dextromethorphan, erythromycin, hydantoins (phenytoin), nicotine, phenothiazines (chlorpromazine), quinolone antibiotics (ciprofloxacin), rifampin, risperidone, SSRIs (fluoxetine), and tricyclic antidepressants (amitriptyline).

What are the possible side effects of Clozaril?

Side effects cannot be anticipated. If any develop or change in intensity, tell your doctor as soon as possible. Only your doctor can determine if it is safe for you to continue taking this drug.

Side effects may include: drowsiness, sedation, seizures, dizziness, decrease in blood pressure, fast heartbeat, headache, tremor, constipation, abdominal discomfort, nausea, profuse salivation during sleep, fever, constipation

A rare but serious—and possibly life-threatening—condition known as neuroleptic malignant syndrome can occur with Clozaril. If you experience a very high fever, rigidity in your muscles, shaking, confusion, sweating, or increased heart rate and blood pressure, seek emergency medical care immediately.

Can I receive Clozaril if I am pregnant or breastfeeding?

The effects of Clozaril during pregnancy and breastfeeding are unknown. Tell your doctor immediately if you are pregnant, plan to become pregnant, or are breastfeeding.

This drug should only be used during pregnancy if it is clearly needed.

Women receiving Clozaril should not breastfeed due to the possible excretion of the drug into breast milk.

What should I do if I miss a dose of Clozaril?

Take the dose as soon as possible unless it is almost time for the next dose. If a dose is skipped, you should not double the next dose. If a dose is missed or forgotten for more than 2 days, do not start taking the drug again without speaking to your doctor.

How should I store Clozaril?

Store at room temperature.