Clozaril® (clozapine)

Novartis manufactures and markets clozapine under the brand name Clozaril®. Generic forms of clozapine are marketed by Zenith Goldline and Mylan Pharmaceuticals.

Available forms…

• Clozaril® /Clozapine tablets

– 25 mg

– 100 mg

• Generic name = clozapine
What is the most important information I should know about Clozaril?

Clozaril is approved for the treatment of schizophrenia that has not responded to other treatments. Blood work to obtain a white blood cell count must be done before you start taking the medication and then weekly for the first six months of treatment and every 2 weeks thereafter. This is to watch for agranulocytosis, in which the white blood cell count drops and increases the risk of infection. This condition is rare but potentially fatal. Also:

• Do not stop taking clozaril or change your dose without first talking with your health care provider.

• Clozaril treatment must be closely monitored by a healthcare provider. Be sure to keep all scheduled appointments.

• You should not use illegal drugs or drink alcohol while taking clozaril. Clozapine may reduce the incidence of alcohol and drug use – possibly
by reducing craving for substances of abuse.

• Clozaril may increase the chances of having: diabetes, seizures and other potentially serious adverse effects.

• Clozapine has been shown to reduce suicide in persons with schizophrenia. It is the only antipsychotic medication that has been demonstrated to have this effect to date. Schizophrenia carries a 10% rate of actual suicide so this is key for consumers and families to
know as they make decisions.

• Clozapine is a unique medicine and has important possible benefits as well as risks. The most noteworthy risk is weight gain and the risk
of diabetes. For many people, being active physically and eating a good diet can keep this risk to a minimum. If you have a family history of diabetes or are part of a group that has increased risk (African American, Asian American, Native American) you should understand this clearly with your doctor.
What is Clozaril?

Clozaril is an atypical antipsychotic medication for patients with treatment-resistant schizophrenia. Approved by the FDA for general use in the U.S. in 1990, the medication is used for patients with schizophrenia and other mental disorders who have not responded well to standard antipsychotic medications or who have had intolerable side effects to them. In December 2002, clozaril was also approved for reducing the risk of recurring suicidal behavior in people with schizophrenia and schizoaffective disorder. Clozaril is also being studied for the treatment of bipolar disorder that has not responded to other treatments.

In schizophrenia, clozaril is useful for treating positive symptoms such as hallucinations, delusions, bizarre behavior and hostility. It also treats the negative symptoms-withdrawal, blunted emotions, lack of motivation, and inability to experience pleasure or enjoyment. Negative symptoms seem to respond better to clozaril than to the traditional antipsychotics.

Clozaril is effective for about 60 percent of those who try it. A patient should try clozaril for at least four to six weeks. Some symptoms, such as hallucinations, anxiety, paranoia, and bizarre behavior, should improve within that time; other symptoms may take longer. Additional improvements may be noticed over six to twelve months.
What should I discuss with my healthcare provider before taking Clozaril?

• Which symptoms of schizophrenia are most bothersome to you.

• The medications you have taken in the past for schizophrenia. It would be helpful for your provider to know which medications were effective and which were not.

• If you had any serious side effects to other antipsychotic medications like dystonia, tardive dyskinesia, neuroleptic malignant syndrome, weight gain, or diabetes, tell your healthcare provider.

• If you have ever had seizures.

• All other medications you are currently taking.

• If you smoke cigarettes, use illegal drugs, or drink alcohol.

• About any medication allergies you have.

• If you are pregnant, plan to get pregnant, or are breast feeding.

• Tell your doctor if you have thoughts of suicide.
How should I take Clozaril?

Clozaril is usually taken once or twice daily. It is usually started at a low dose and then gradually increased to prevent some of the side effects from developing. While many people may be treated with between 300–500 mg/day, the highest FDA approved dose is 900 mg/day.
What happens if I miss a dose?

If a dose of clozaril is missed, take it as soon as you remember to, if it is not too close to when your next dose is due. Do not double up on your next dose. If you have been off of the medication for 2 or more days, don’t start taking the full dose again without first speaking to your healthcare professional. You may need to start at the initial dose and gradually increase it again, to prevent side effects.
What happens if I overdose?

You may experience drowsiness, delirium or coma; low blood pressure, increased heart rate, or an abnormal heart rhythm; trouble breathing; and drooling. You should immediately go to the nearest emergency department or call 911.
What should I avoid while taking Clozaril?

• Please check with your healthcare provider before taking any other prescription, over-the-counter, or herbal/nutritional supplements.

• Avoid smoking cigarettes, using illegal drugs, or drinking alcohol.

• Some people get drowsy on clozaril, avoid driving a car until you are sure how the medication will affect you.
What are the possible side effects of Clozaril?

Common adverse effects of clozaril usually include sleepiness, dizziness, rapid heart beat, constipation, excess saliva production and weight gain. Another important adverse effect that occurs commonly is orthostatic hypotension (a lowering of your blood pressure when your are sitting up or standing up). Occasionally this can lead to fainting and falling down, therefore, people taking clozaril should be careful when they change positions These adverse effects are usually mild and usually go away after the first several days of starting treatment or increasing a dose.

One to two percent of patients who take clozaril will develop a condition called agranulocytosis, in which the white blood cell count drops dramatically. The patient becomes extremely vulnerable to infections and unable to fight them off. This condition is dangerous and potentially fatal. Fortunately, if agranulocytosis does occur, most patients can be successfully treated by stopping clozaril. In addition to stopping clozaril, hospitalization and treatment with a drug that increases white blood cell production are available. To maintain safety, the white blood cell count for all patients taking clozaril must be checked each week for the first six months and then every other week after that. The results are sent to the patient’s pharmacy before the next week’s supply can be picked up. If detected early enough, the condition can be reversed by simply withdrawing the patient from clozaril. Hospitalization and treatment with medication to stimulate production of white blood cells may be necessary in some cases.

Seizures may occur in roughly one to five percent of patients. The higher the dose, the greater the risk of seizures. Cardiovascular and respiratory side effects are also possible but extremely rare. Lowered blood pressure and increased heart rate can usually be managed by gradually increasing a patient’s clozaril dosage from an initially low level. Some patients may notice weight gain, drooling, and initial lethargy but these can be managed by dose adjustment or other interventions.

Clozaril has virtually no incidence of extrapyramidal symptoms such as muscle spasms, cramps, or posturing movements common to other antipsychotic medications, and a low incidence of side effects such as restlessness, muscle rigidity, and tremor. Clozaril does not seem to cause tardive dyskinesia (TD), a potentially permanent side effect of standard antipsychotic medications. TD is characterized by involuntary movements such as grimacing, sucking/smacking of lips, and spasmodic movements of the extremities. It usually begins after several months of treatment and may be irreversible. There have been no confirmed cases of TD directly caused by clozaril alone.

Although rare, there are some additional, serious adverse effects that may occur with clozaril treatment. Specifically, these are: myocarditis (a swelling of the heart muscle), cardiomyopathy (a widening of the lower heart chambers with weak contraction of the heart muscle that surrounds these two chambers), pulmonary embolism (a clot that blocks blood flow through the lungs) and respiratory depression (a decrease in breathing). If you experience being extremely tired all of the time, changes in your breathing, a rapid heart beat, chest pain, or if you develop pain or discomfort in your legs, contact your doctor right away.
What other drugs interact with Clozaril?

There are many other medications that may interact with clozaril. Any other medication that causes sleepiness or low blood pressure may increase the same side effects of clozaril and increase your chances of falling.

• Medications that may increase levels of clozaril in your body: ciprofloxacin (Cipro®), cimetidine (Tagamet®), erythromycin, fluoxetine (Prozac®), fluvoxamine (Luvox®), isoniazid (INH), mexiletine (Mexitil®), paroxetine (Paxil®).

• Medications that may decrease levels of clozaril in your body: carbamazepine (Tegretol®), lopinavir/ritonavir (Kaletra®), ritonavir (Norvir®), phenobarbital, phenytoin (Dilantin®), rifampin (Rifadin®), omeprazole (Prilosec®), oxcarbazepine (Trileptal®).

• Combining clozaril with some seizure medications (especially carbamazepine ) may increase the risk of agranulocytosis.
How long does it take for Clozaril to work?

A patient should try clozaril for at least four to six weeks. Some symptoms such as hallucinations, anxiety, paranoia, and bizarre behavior should improve within that time. Other symptoms may take longer. Additional improvements may be noticed over six to twelve months.
Are there any risks for taking this medication for long periods of time?

Long term treatment with antipsychotics has caused TD in some patients. There have been no confirmed cases of TD directly caused by clozaril alone, but patients should be regularly monitored for the development of TD. While agranulocytosis usually occurs most commonly within the first 4–6 months of treatment, you are at risk of this rare adverse effect for as long as you take clozaril. In most of the cases reported, cardiomyopathy occurred in those people who had been treated with clozaril for more than six months.

Updated by Carla Cobb, Pharm.D., BCPP
August 2004


For further more information please contact the pharmaceutical company listed below.

IVAX Pharmaceuticals, Inc

4400 Biscayne Blvd.

Miami, Florida 33137

800-327-4114 x6367

Free or low-cost medications provided by pharmaceutical companies

Some pharmaceutical companies offer medication assistance programs to low-income individuals and families. These programs typically require a doctor’s consent and proof of financial status. They may also require that you have either no health insurance, or no prescription drug benefit through your health insurance. Please contact the pharmaceutical company directly for specific eligibility requirements and application information.

Clozapine Rx Assistance: 1-800-327-4114, ext. 4344

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