CLOZAPINE ( kloe' za peen)
PREGNANCY CATEGORY B
Dopaminergic blocking agent
Mechanism not fully understood: blocks dopamine receptors in the brain, depresses the RAS; anticholinergic, antihistaminic (H
1), and alpha-adrenergic blocking activity may contribute to some of its therapeutic (and adverse) actions. Clozapine produces fewer extrapyramidal effects than other antipsychotics.
Management of severely ill schizophrenics who are unresponsive to standard antipsychotic drugs.
Reduction of the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder.
Contraindications and cautions
Contraindicated with allergy to clozapine, myeloproliferative disorders, history of clozapine-induced agranulocytosis or severe granulocytopenia, severe CNS depression, comatose states, history of seizure disorders, lactation.
Use cautiously with CV disease, prostate enlargement, narrow-angle glaucoma, pregnancy.
Tablets—25, 100 mg
Initial: 25 mg PO daily or bid; then gradually increase with daily increments of 25–50 mg/day, if tolerated, to a dose of 300–450 mg/day by the end of second week. Adjust later dosage no more often than twice weekly in increments < 100 mg. Do not exceed 900 mg/day.
Maintenance: Maintain at the lowest effective dose for remission of symptoms.
Discontinuation: Gradual reduction over a 2-wk period is preferred. If abrupt discontinuation is required, carefully monitor patient for signs of acute psychotic symptoms.
Reinitiation of treatment: Follow initial dosage guidelines, use extreme care; increased risk of severe adverse effects with re-exposure.
Safety and efficacy in patients < 16 yr not established.
Metabolism: Hepatic; T
½: 4–12 hr
Distribution: Crosses placenta; enters breast milk
Excretion: Urine and feces
Adverse effects in
Italics are most common; those in
Bold are life-threatening.
Drowsiness, sedation, seizures, dizziness, syncope, headache, tremor, disturbed sleep, nightmares, restlessness, agitation, increased salivation, sweating, tardive dyskinesia,
neuroleptic malignant syndrome
Tachycardia, hypotension, ECG changes, hypertension
Nausea, vomiting, constipation, abdominal discomfort, dry mouth
GU: Urinary abnormalities
Hematologic: Leukopenia, granulocytopenia, agranulocytopenia
Fever, weight gain, rash
Increased therapeutic and toxic effects with cimetidine
Decreased therapeutic effect with phenytoin, mephenytoin, ethotoin
Name confusion has occurred with Clozaril (clozapine) and Colazal (balsalazide); dangerous effects could occur. Use extreme caution.
History: Allergy to clozapine, myeloproliferative disorders, history of clozapine-induced agranulocytosis or severe granulocytopenia, severe CNS depression, comatose states, history of seizure disorders, CV disease, prostate enlargement, narrow-angle glaucoma, lactation, pregnancy
Physical: T, weight; reflexes, orientation, intraocular pressure, ophthalmologic exam; P, BP, orthostatic BP, ECG; R, adventitious sounds; bowel sounds, normal output, liver evaluation; prostate palpation, normal urine output; CBC, urinalysis, liver and kidney function tests, EEG
Use only when unresponsive to conventional antipsychotic drugs.
Obtain clozapine through the Clozaril Patient Management System.
Dispense only 1 wk supply at a time.
Monitor WBC carefully prior to first dose.
Weekly monitoring of WBC during treatment and for 4 wk thereafter. Dosage may be adjusted based on WBC count.
Monitor T. If fever occurs, rule out underlying infection, and consult physician for comfort measures.
Monitor elderly patients for dehydration. Institute remedial measures promptly; sedation and decreased thirst related to CNS effects can lead to dehydration.
Encourage voiding before taking drug to decrease anticholinergic effects of urinary retention.
Follow guidelines for discontinuation or reinstitution of the drug.
Weekly blood tests will be taken to determine safe dosage; dosage will be increased gradually to achieve most effective dose. Only 1 wk of medication can be dispensed at a time. Do not take more than your prescribed dosage. Do not make up missed doses, instead contact care provider. Do not stop taking this drug suddenly; gradual reduction of dosage is needed to prevent side effects.
These effects may occur as a result of drug therapy: drowsiness, dizziness, sedation, seizures (avoid driving or performing tasks that require concentration); dizziness, faintness
on arising (change positions slowly); increased salivation (reversible); constipation (consult care provider for correctives); fast heart rate (rest, take your time).
This drug cannot be taken during pregnancy. If you think you are pregnant or wish to become pregnant, contact your care provider.
Report lethargy, weakness, fever, sore throat, malaise, mouth ulcers, and flu-like symptoms.
© 2004 Lippincott Williams & Wilkins
Amy M. Karch
2004 Lippincott's Nursing Drug Guide