Brand Names: Clozaril, Versacloz
Tablets: 25 mg, 50 mg, 100 mg, and 200 mg.
Orally Dissolving Tablets: 12.5 mg, 25 mg, 100 mg, 150 mg, and 200 mg.
For the management of severely ill schizophrenic patients who fail to respond adequately to standard antipsychotic drug treatment: Begin with 12.5 mg once or twice daily, making daily dosage increases of 25 to 50 mg per day up to 300 to 450 mg per day by the end of 2 weeks. Additional dosage adjustments, at no more than 100 mg, can be made every once or twice a week. Dosage increases should be carefully titrated to minimize hypotension and seizures. Maximum daily dose is 900 mg. Maintenance dose should be given three times a day and at the lowest effective level. It is best to terminate therapy gradually over a 2 week period although leukopenia warrants abrupt discontinuation. Clozapine is available only through the Clozapine Patient Management System. This program links WBC testing and patient monitoring to the dispensing of the drug by the pharmacy.
Pharmacology/Pharmacokinetics:
Clozapine is classified as an “atypical” antipsychotic drug because its profile of binding to dopamine receptors and its effects on various dopamine mediated behaviors differ from those exhibited by more typical antipsychotic drugs. In particular, although clozapine dose interfere with the binding of dopamine at both D-1 and D-2 receptors, it does not induce catalepsy nor inhibit apomorphine-induced stereotypy. This may explain its relative freedom from extrapyramidal side effects. Clozapine also acts as an antagonist adrenergic, cholinergic, histaminergic, and serotonergic receptors. Peak plasma levels are reached in 2.5 hours and elimination half-life after reaching steady state is 12 hours.
Drug Interactions:
May increase the effects of antihypertensive and anticholinergics. Use with other drugs which suppress bone marrow function is not recommended.
Contraindications/Precautions:
Contraindicated in myeloproliferative disorders, history of agranulocytosis or severe granulocytopenia, when used with other drugs when suppress bone marrow function, and in patients in a comatose state from any cause. Use may cause agranulocytosis (granulocyte count <500/mm^3). A baseline WBC count and weekly WBC counts are mandatory for the first 6 months of therapy and bi-weekly thereafter and should be continued for 4 weeks post-termination. Use caution in patients with seizures, cardiovascular disease, prostatic enlargement, or narrow-angle. Atypical antipsychotics have been associated with severe hyperglycemic reactions. These reactions have ketoacidosis, coma, and death. Patients with established diagnosis of diabetes mellitus who are started on clozapine should be monitored regularly for worsening of glucose control. Do not use in nursing mothers. Pregnancy Category B.
Adverse Effects:
Drowsiness (39%), salivation (31%), tachycardia (25%), tachycardia (25%), dizziness (19%), constipation (14%), orthostatic hypotension (9%), headache (7%), tremor, syncope, sweating, or dry mouth (6%), nausea, fever or visual disturbances (5%), heartburn, nightmares, restlessness, hypertension, hypokinesia/akinesia or weight gain (4%), seizures, rigidity, confusion, or leukopenia/neutropenia (3%).
Continuation of this drug therapy requires weekly WBC counts because of the serious risk of agranulocytosis.
This drug may cause seizures--advise patients to refrain from activities where a sudden loss of consciousness is a serious risk (operating machinery, swimming, climbing).
This drug may cause orthostatic hypotension--use caution when rising from lying or sitting position.
Notify your physician if you become pregnant or intend to become pregnant or you plan on breast feeding your infant.
Notify your physician if you experience any sign of infection including fever, sore throat, lethargy, weakness, or any “flu-like” symptoms.
Contact a physician if the above side effects are severe or persistent.
May be taken without regard to food.
Store in a cool, dry place away from sunlight and children.
If a dose is missed, take it as soon as possible. If it closer to the time of your next dose than the dose you missed, skip it and return to your dosing schedule. Do not double doses.
