CLOZAPINE

(clo'za-pin)

Clozaril, Fazaclo
Classifications: psychotherapeutic agent; antipsychotic, atypical;
Therapeutic: atypical antipsychotic
Pregnancy Category: B

Availability

25 mg, 50 mg, 100 mg tablets and 12.5 mg, 25 mg, 50 mg, 100 mg orally disintegrating tablets

Action

Interferes with binding of dopamine to D₁ and D₂ receptors in the limbic region of brain. It binds primarily to nondopaminergic sites (e.g., alpha-adrenergic, serotonergic, and cholinergic receptors).

Therapeutic Effect

Limited to treatment of schizophrenia uncontrolled by other agents.

Uses

Management of severely ill schizophrenic patients who have failed to respond to other neuroleptic agents.

Unlabeled Uses

Schizo-affective disorder, severe obsessive-compulsive disorder, bipolar disorder, dementia-related behavioral disorders.

Contraindications

Severe CNS depression, blood dyscrasia, history of bone marrow depression; patients with myeloproliferative disorders, uncontrolled epilepsy; clozapine-induced agranulocytosis, severe granulocytosis, chemotherapy, coma, leukemia, leukopenia, neutropenia, myocarditis, concurrent administration of benzodiazepines or other psychotropic drugs; renal failure, dialysis, hepatitis, jaundice; infants, lactation.

Cautious Use

Arrhythmias, GI disorders, narrow-angle glaucoma, hepatic and renal impairment, prostatic hypertrophy, history of seizures; patients with cardiovascular and/or pulmonary disease; cerebrovascular disease, cardiac arrhythmias, tachycardia, dehydration, neurological disease, tardive dyskinesia, previous history of agranulocytosis; surgery, glaucoma, infection, pregnancy (category B); older adults. Safety and efficacy in children <9 y have not been established.

Route & Dosage

Schizophrenia
Adult (>16 y): PO Initiate at 12.5 mg q.d. or b.i.d. then increase by 25–50 mg/d and titrate to a target dose of 350–450 mg/d in 3 divided doses, further increases (not more than twice weekly) can be made if necessary, max of 900 mg/d

Administration

Oral

Drug is usually withdrawn gradually over 1–2 wk if therapy must be discontinued.
Store the drug away from heat or light.

Adverse Effects (≥1%)

CV: Orthostatic hypotension, tachycardia, ECG changes, increased risk of myocarditis especially during first month of therapy, pericarditis, pericardial effusion, cardiomyopathy, heart failure, MI, mitral insufficiency. GI: Nausea, dry mouth, constipation, hypersalivation. Hematologic: Agranulocytosis. CNS: Seizures, transient fever, sedation, neuroleptic malignant syndrome (rare), dystonic reactions (rare). Metabolic: Hyperglycemia, diabetes mellitus. Urogenital: Urinary retention. Other: Increased mortality from severe hematologic, cardiovascular, and respiratory adverse effects.

Interactions

Drug: Alcohol and other cns depressants compound depressant effects; anticholinergic agents potentiate anticholinergic effects; antihypertensive agents may potentiate hypotension. Herbal: St. John's wort and kava may increase sedation.

Pharmacokinetics

Absorption: Readily absorbed from GI tract. Onset: 2–4 wk. Peak: 2.5 h. Distribution: Possibly distributed into breast milk. Metabolism: In liver. Elimination: 50% in urine, 30% in feces. Half-Life: 8–12 h.

Nursing Implications

Assessment & Drug Effects

Lab tests: Baseline WBC and absolute neutrophil count must be made before initial treatment, every week for first 6 mo, then every 2 wk for next 6 mo, then every 4 wk, and weekly for 4 wk after the drug is discontinued. Periodically monitor blood glucose.
Monitor diabetics for loss of glycemic control.
Monitor for seizure activity; seizure potential increases at the higher dose level.
Closely monitor for recurrence of psychotic symptoms if the drug is being discontinued.
Monitor cardiovascular and respiratory status, especially during the first month of therapy. Report promptly S&S of CHF and other potential cardiac problems.
Monitor for development of tachycardia or hypotension, which may pose a serious risk for patients with compromised cardiovascular function.
Monitor daily temperature and report fever. Transient elevation above 38° C (100.4° F), with peak incidence during first 3 wk of drug therapy, may occur.

Patient & Family Education

Carefully monitor blood glucose levels if diabetic.
Do not engage in any hazardous activity until response to the drug is known. Drowsiness and sedation are common adverse effects.
Due to the risk of agranulocytosis (see Appendix F) it is important to comply with blood test regimen. Report flulike symptoms, fever, sore throat, lethargy, malaise, or other signs of infection.
Rise slowly to avoid orthostatic hypotension.
Report immediately any of the following: unexplained fatigue, especially with activity; shortness of breath, sudden weight gain or edema of the lower extremities.
Take drug exactly as ordered.
Do not use OTC drugs or alcohol without permission of physician.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

(115)