BMA Concise Guide to Medicine & Drugs

Clozapine

Brand names Clozaril, Denzapine, Zaponex

Used in the following combined preparations None

QUICK REFERENCE

Drug group Antipsychotic drug

Overdose danger rating Medium

Dependence rating Low

Prescription needed Yes

Available as generic No

GENERAL INFORMATION

Clozapine is an atypical antipsychotic drug for schizophrenia. It is given to patients who have not responded to other treatments or who have experienced intolerable side effects with other drugs. Clozapine helps control severe resistant schizophrenia. The improvement is gradual, and relief of severe symptoms can take several weeks to months.

All treatment is supervised by a consultant psychiatrist, and the patient and the pharmacist must be registered with the drug manufacturer. The drug can cause a very serious side effect: agranulocytosis (a large decrease in white blood cells). Blood tests are performed before and during treatment; the drug is supplied only if results are normal. Clozapine may also cause heart muscle problems, which must be monitored for.

INFORMATION FOR USERS

This drug is given only under strict medical supervision and continual monitoring.

How taken/used Tablets, liquid.

Frequency and timing of doses 1–2 x daily; a larger dose may be given at night.

Adult dosage range 12.5–900mg daily.

Onset of effect Gradual. Some effect may appear within 3–5 days, but the full beneficial effect may not be felt for some months.

Duration of action Up to 16 hours.

Diet advice None.

Storage Keep in original container at room temperature out of the reach of children.

Missed dose Take as soon as you remember. If your next dose is due within 2 hours, take a single dose now and skip the next. If you miss more than 2 days of tablets, notify your doctor because you may need to restart at a lower dose.

Stopping the drug Do not stop the drug without consulting your doctor because symptoms may recur.

Exceeding the dose An occasional unintentional extra dose is unlikely to cause problems. Large overdoses may cause unusual drowsiness, seizures, and agitation. Notify your doctor.

POSSIBLE ADVERSE EFFECTS

Clozapine is less likely to cause parkinsonian side effects (tremor and stiffness) than other antipsychotics. The most serious side effect is a large decrease in white blood cells (agranulocytosis), and strict monitoring of the white cell count is therefore necessary. Common adverse effects of the drug include drowsiness, tiredness, dry mouth or excessive salivation, weight gain, a fast heartbeat, dizziness, fainting, constipation, and blurred vision. Rarely, clozapine may cause fever, sore throat, or seizures. If any of these occur, seek urgent medical advice.

INTERACTIONS

General note A number of drugs increase the risk of adverse effects on the blood. Do not take other medication without checking with your doctor or pharmacist. Smoking lowers clozapine levels, which may reduce its effect.

Sedatives Drugs with a sedative effect on the central nervous system are likely to increase the sedative properties of clozapine.

Anticholinergic drugs There is a risk of severe constipation or even bowel obstruction when these drugs are used with clozapine.

SPECIAL PRECAUTIONS

Be sure to tell your doctor if:

· You have long-term liver or kidney problems.

· You have a history of blood disorders.

· You have had epileptic seizures.

· You have heart problems.

· You have colon problems or have had bowel surgery.

· You have diabetes.

· You have glaucoma.

· You have prostate problems.

· You are taking other medicines.

Pregnancy Not usually prescribed. Safety not established. Discuss with your doctor.

Breast-feeding The drug passes into the breast milk and may affect the baby adversely. Discuss with your doctor.

Infants and children Not prescribed.

Over 60 Adverse effects are more likely. Initial dose is low and is slowly increased.

Driving and hazardous work Avoid such activities until you know how clozapine affects you because the drug can cause blurred vision, drowsiness, and dizziness.

Alcohol Avoid. Alcohol may increase the sedative effects of this drug.

PROLONGED USE

Agranulocytosis and heart muscle problems may occur, and occasionally liver function may be upset. Significant weight gain may also occur.

Monitoring Blood tests are carried out weekly for 18 weeks, fortnightly until the end of the first year, and, if blood counts are stable, every 4 weeks thereafter. Liver function tests, weighing, and tests for diabetes are performed every 3–6 months. Heart monitoring is also carried out.