Clozaril® (clozapine)
Brand and Generic Names:
- 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
- Generic name: Clozapine
All FDA warnings are at the end of this fact sheet. Please consult them before taking this medication.
What is CLOZARIL® and what does it treat?
Clozapine is a second generation antipsychotic (SGA) medication approved for the treatment of schizophrenia. Clozapine 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 clozapine treatment that right for you.
- Do not stop taking clozapine or change your dose without talking to your healthcare provider first.
- Some people may develop side effects on clozapine 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® [haloperidol], Prolixin® [fluphenazine], Thorazine® [chlorpromazine]). 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.
- Clozapine 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.
- Clozapine treatment must be monitored by a healthcare provider. Be sure to keep all your scheduled appointment so that you stay healthy while on clozpine.
- You should not take illegal drugs or drink alcohol while taking clozapine.
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 clozapinedoes 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. (See the NAMI Hearts and Minds Program.)
- If you have had an allergic reaction to clozapine or any other medication.
- History of heart problems, such as heart rhythm problems, long QT syndrome, or heart attacks. These illnesses may make clozapine 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®?
- Clozapine 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 clozapine, 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®?
- Clozapine 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 clozapine.
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.
What are the possible side effects of Clozaril®?
What are the common side effects seen with clozapine?
- Common adverse effects of clozapineinclude 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 clozapine 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.
- Clozapine 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. Clozapine 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 clozapine 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. For the relative risk of weight gain and diabetes seen with the various drugs, see Table 2 in the Consensus Conference on Antipsychotic Drugs. These guidelines make recommendations for the monitoring of cardiac risk factors while on atypical antipsychotics.
Please also consult the Metabolic and Diabetes tab on the Hearts and Minds section for the current monitoring information regarding triglycerides, cholesterol, fasting blood glucose, etc. to help plan preventative interventions. (See the NAMI Hearts and Minds Program.)
- 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 clozapine 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 clozapine. To maintain safety, the white blood cell count for all patients taking clozapine 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 clozapine therapy report it to your doctor immediately.
- Although rare, there are some additional, serious adverse effects that may occur with clozapine 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 clozapine.
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). For more ideas, see the NAMI Hearts and Minds Program.
Also, obtain Abnormal Involuntary Movement testing (AIMS) to monitor for TD. While it is very rare and essentially unreported with clozapine, 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. Clozapine 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 clozapine.
While rare, in most of the cases reported, cardiac enlargement occurred in those people who had been treated with clozapine 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 clozapine. Any other medication that causes sleepiness or low blood pressure may increase the same side effects of clozapine and increase your chances of falling.
- Medications that may increase levels of clozapine in your body: ciprofloxacin (Cipro®), cimetidine (Tagamet®), erythromycin, lopinavir/ritonavir (Kaletra®), ritonavir (Norvir®), fluoxetine (Prozac®), fluvoxamine (Luvox®), and sertraline (Zoloft®)
- Medications that may decrease levels of clozapine in your body: carbamazepine (Tegretol®), phenobarbital, phenytoin (Dilantin®), rifampin (Rifadin®), omeprazole (Prilosec®), and oxcarbazepine (Trileptal®).
- Combining clozapine with some seizure medications (especially carbamazepine [Tegretol®]) may increase the risk of agranulocytosis.
- Smoking will decrease the levels of clozapine in your body. If you are a smoker and you stop smoking, your dose of clozapine may need to be decreased.
How long does it take for Clozapine®to work?
Clozapine 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 clozapine 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, clozapine 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 clozapine 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.
Clozapine 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 clozapine. Dose appears to be an important predictor of seizure, with a greater risk at higher doses. Caution should be used when administering clozapine 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
Clozapine 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, clozapine treatment should be promptly discontinued. |
Updated by
Rachael Allwine, PharmD, BCPS
(July 2010)
NAMI wishes to thank the College of Psychiatric and Neurologic Pharmacists for producing this fact sheet.
Reviewed by Dr. Ken Duckworth, NAMI Medical Director |
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