What is Clozaril?

For schizophrenia

Clozaril (Clozapine) is a second generation antipsychotic (SGA) medication approved for the treatment of schizophrenia. Clozaril can improve symptoms of schizophrenia such as: hallucinations, delusions, and disorganized thinking; in some people, improvement in social isolation, reduced speech productivity and motivation also occur.

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

Relapse is very common in schizophrenia and the most frequent cause is that patients stop taking their medication. Even when medication is taken exactly as prescribed, relapse may still occur for some people. Therefore it is recommended that you take your medication exactly as prescribed by your healthcare provider as this has been shown to decrease relapse.

Schizophrenia requires long-term treatment. Only your healthcare provider can determine the length of Clozaril treatment that right for you.

Do not stop taking Clozaril or change your dose without talking to your healthcare provider first.

Some people may develop side effects on Clozaril such as extrapyramidal effects (restlessness, tremor, stiffness) or tardive dyskinesia (slow or jerky movements that one cannot control, often starting in the mouth with tongue rolling or chewing movements). These symptoms are likely to be less severe and occur less often than with the older antipsychotic medications (e.g., Haldol, Prolixin, Thorazine). If you develop movements that you cannot control, call your healthcare provider immediately.

Many second generation or atypical antipsychotics may cause an increase in weight, blood sugar levels, or lipid levels. If you gain more than 5% of your original weight during therapy, talk to your healthcare provider about whether switching to another antipsychotic medication should be considered.

Clozaril treatment may be associated with strokes and/or transient ischemic attacks (TIAs) in elderly people with dementia and accompanying behavioral problems. This safety concern has not been proven confidently, but there is some evidence. Talk with your healthcare provider if you are concerned or have questions.

Both older first and newer second generation antipsychotics have been associated with the risk of sudden cardiac death due to an arrhythmia (irregular conduction of an electrical impulse in the heart). To minimize this possibility, antipsychotic medications should be used in the smallest effective dose in situations where the benefits outweigh the risks, such as schizophrenia or bipolar disorder. Often an EKG tracing may be ordered to monitor for conduction changes.

Clozaril treatment must be monitored by a healthcare provider. Be sure to keep all your scheduled appointment so that you stay healthy while on Clozaril.

You should not take illegal drugs or drink alcohol while taking Clozaril.

Are there specific concerns about Clozaril and pregnancy?

If you are planning on becoming pregnant, notify your healthcare provider so that he/she can best manage your medications. People living with schizophrenia who wish to become pregnant face important decisions, each with risks and benefits related to how the illness, medications and the risks to the fetus may interact. This is a complex decision, as untreated schizophrenia has risks to the fetus as well as the mother. There are many dimensions to these choices, so be sure to confer with your doctor and caregivers.

Regarding breast-feeding, caution is advised since Clozaril does pass into breast milk.

What should I discuss with my healthcare provider before taking Clozaril?

Symptoms of schizophrenia which are bothersome to you.

If you had any serious side effects with other antipsychotic medications like muscle stiffness, muscle cramping, shaking, tardive dyskinesia, neuroleptic malignant syndrome, weight gain, or diabetes.

If you have had an allergic reaction to Clozaril or any other medication.
History of heart problems, such as heart rhythm problems, long QT syndrome, or heart attacks. These illnesses may make Clozaril unsafe for you to take

Medical problems you have, especially diabetes, high cholesterol or triglycerides, increased body weight, seizures, or kidney disease or impairment.

How should I take Clozaril?

Clozaril can be taken with or without food but should be taken with a full glass of water.

Only your doctor can determine the correct dose for you. Typically patients begin at a low dose of medicine and the dose is increased slowly over several weeks.

Use a calendar or pill box to help you remember to take your medication. Or, have a family member or friend remind you or check in with you to be sure you are taking your medication.

What happens if I miss a dose of Clozaril?

If you miss a dose of Clozaril, take it as soon as you remember it, if it is not too close to when your next dose is due—discuss this with your healthcare provider. Do not double your next dose or take more than what is prescribed.

What should I avoid while taking Clozaril?

Clozaril may cause dizziness or drowsiness, especially when first starting the medication. Make sure you know how you react to the medication before you drive, operate machinery, or do other activities that may be dangerous if you are not alert.

Avoid drinking alcohol or using illegal drugs while taking Clozaril.

What happens if I overdose with Clozaril?

If an overdose occurs, whether intentional or accidental, immediate medical attention may be necessary. Call your doctor or emergency medical service (911). You may also contact the poison control center at 1-800-222-1222.

Brand and Generic Names:

Generic name: Clozapine
Brand Name: Clozaril, FazaClo
Tablets: Clozapine 25 mg, 50 mg, 100 mg, 200 mg,
Clozaril 25 mg, 100 mg
Orally disintegrating tablets (ODT): 12.5 mg, 25 mg,100 mg, 150 mg, 200 mg

What are the possible side effects of Clozaril?
What are the common side effects seen with Clozaril?

Common adverse effects of Clozaril include sleepiness, rapid heartbeat, constipation, drooling and weight gain. Another important adverse effect that occurs commonly is orthostatic hypotension (a lowering of your blood pressure when changing positions from sitting to standing). Occasionally this can lead to dizziness and fainting, therefore, people taking Clozaril should move slowly when going from a seated to standing position. These adverse effects are usually mild and usually go away after the first several days of starting treatment or increasing a dose.

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 other antipsychotic medications. TD is characterized by involuntary movements such as grimacing, sucking/smacking of lips, and spasmodic movements of the extremities. There have been no confirmed cases of TD directly caused by Clozaril alone.

What are the more serious side effects of antipsychotics?

With newer second generation antipsychotics (SGA), more commonly seen are diabetes/weight gain/increased cholesterol and triglycerides as noted in stronger warnings mandated by the FDA in individual drug labeling.

Less commonly seen, but important, is the early death/dementia risk as noted in the FDA boxed warning. In some clinical trials, it was determined that elderly people developed strokes at a higher rate than those on placebo medication (sugar pill). The SGA group has less tardive dyskinesia (TD), neuroleptic malignant syndrome, seizures, and changes in heart rhythm than FGA drugs but not zero.

Approximately one percent of patients who take Clozaril develop a condition called agranulocytosis, in which white blood cells drop dramatically, causing patients to become extremely vulnerable to infections. This condition is dangerous and potentially fatal. Fortunately, if agranulocytosis does occur, most patients can be successfully treated by stopping Clozaril. 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 for the next six months then every four weeks thereafter. The results are sent to the patient’s pharmacy before the next supply can be picked up. Hospitalization and treatment with medication to stimulate production of white blood cells may be necessary in some cases. If you experience lethagry, weakness, sore throat or any other signs of infection during treatment with Clozaril therapy report it to your doctor immediately.

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, chest pain, or if you develop pain or discomfort in your legs, contact your doctor right away.

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.
What do I do about the more serious risks?

Please let your doctors know if you have any of these medical conditions prior to starting Clozaril.

It is important to be aware of prevention with attention to nutrition, exercise, and reducing your plate size (because the medications may reduce your ability to feel full after eating).

Also, obtain Abnormal Involuntary Movement testing (AIMS) to monitor for TD. While it is very rare and essentially unreported with Clozaril, it is still important to monitor. If you are taking an older FGA, then regular AIMS testing is needed for monitoring, so you can make good choices about the use of the drug when weighing the risks and benefits.

Are there any risks for taking Clozaril for long periods of time?

Tardive dyskinesia (TD) is a side effect that may develop with prolonged use of antipsychotics. Clozaril has been show to have a very low risk of TD, and in fact it has been shown to help TD. Should you develop symptoms of TD, such as grimacing, sucking and smacking of lips, and other movements that you cannot control, contact your healthcare provider immediately.

While agranulocytosis usually occurs most commonly within the first 4–6 months of treatment, you are at risk for this rare adverse effect as long as you are being treated with Clozaril .

While rare, in most of the cases reported, cardiac enlargement occurred in those people who had been treated with Clozaril for more than six months.

No one can predict how much weight a person will gain on any medicine, but an approach that includes exercise and diet and monitoring for weight gain and diabetes is recommended.

What other drugs may 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: Cipro, Tagamet, Kaletra, Norvir, Prozac, Luvox, and Zoloft.

Medications that may decrease levels of Clozaril in your body: Tegretol, Dilantin, Rifadin, Prilosec, Trileptal.

Combining Clozaril with some seizure medications (especially Tegretol) may increase the risk of agranulocytosis.

Smoking will decrease the levels of Clozaril in your body. If you are a smoker and you stop smoking, your dose of Clozaril may need to be decreased.

How long does it take for Clozaril to work?

Clozaril rebalances dopamine and serotonin to improve thinking, mood, and behavior. Improvement of some symptoms may be noticed in some patients within a few weeks. The full benefit of Clozaril may not be seen for 6-12 weeks or longer.

FDA Alerts
Agranulocytosis

Because of a significant risk of agranulocytosis, a potentially life-threatening adverse effect, Clozaril should be reserved for the use in the treatment of severely ill patients with schizophrenia who fail to show an acceptable response to adequate courses of standard antipsychotics drug treatment.

Patients being treated with Clozaril must have a baseline white blood cell (WBC) and differential count before initiation of treatment as well as regular WBC counts during treatment and for 4 weeks after discontinuation of treatment.

Clozaril is available only through a distribution system that ensures monitoring of WBC counts prior to delivery of the next supply of medication.

Seizures

Seizures have been associated with the use of Clozaril. Dose appears to be an important predictor of seizure, with a greater risk at higher doses. Caution should be used when administering Clozaril to patients with a history of seizures or other predisposing factors. Patients should be advised not to engage in any activity where sudden loss of consciousness could cause serious risk to themselves or others.

Myocarditis

Clozaril may be associated with an increased risk of fatal myocarditis, an inflammation of the heart muscle, especially during, but not limited to, the first month of therapy. In patients in whom myocarditis is suspected, Clozaril treatment should be promptly discontinued.

Updated by
R. Allwine, PharmD, BCPS
(July 2010)