Indications for: CLOZARIL
Treatment resistant schizophrenia. To reduce risk of recurrent suicidal behavior in schizophrenia or schizoaffective disorders.
See full labeling. Initially 12.5mg 1–2 times daily; then usually given in divided doses; may increase by 25–50mg/day to 300–450mg/day by the end of 2 weeks. Then may increase once or twice weekly in increments of up to 100mg; max 900mg/day. Reevaluate periodically. Reduce gradually over 1–2 weeks if discontinuing; can discontinue abruptly if necessary (eg, severe neutropenia, others); monitor for psychotic symptom recurrences or cholinergic rebound. Retitrate if stopped for ≥2 days. Caution when rechallenging. Concomitant strong CYP1A2 inhibitors (eg, fluvoxamine, ciprofloxacin, enoxacin): reduce Clozaril dose to ⅓. Concomitant strong CYP3A4 inducers: not recommended; if use necessary, may need to increase Clozaril dose and monitor. If CYP1A2 (eg, tobacco smoke) or CYP3A4 (eg, carbamazepine) inducers discontinued, consider reducing Clozaril dose.
Severe neutropenia. Orthostatic hypotension, bradycardia, and syncope. Seizures. Myocarditis and cardiomyopathy. Increased mortality in elderly patients with dementia-related psychosis.
See full labeling. Risk of severe neutropenia; obtain CBC and confirm baseline ANC ≥1500/μL (≥1000/μL if benign ethnic neutropenia) prior to initiation. Monitor ANC weekly for 1st 6 months; if acceptable ANC maintained, may reduce monitoring to every 2 weeks from 6–12 months, then monthly after 12 months. Cardio- or cerebrovascular disease. Conditions that would predispose to hypotension (eg, concomitant antihypertensives, dehydration, hypovolemia). Perform fall risk assessments when initiating and recurrently on long-term therapy. Reevaluate periodically. History of seizures or head trauma. Monitor for myocarditis and cardiomyopathy esp. during the first 2 months of therapy; discontinue and evaluate if suspected. Increased mortality in elderly with dementia-related psychosis (not approved use). Increased risk of QT prolongation; discontinue if interval >500msec. Significant cardiac arrhythmia. Recent MI. Uncompensated heart failure. Consider obtaining baseline ECG and serum chemistry panel. Correct electrolyte abnormalities prior to starting; obtain baseline serum potassium and magnesium levels; monitor periodically thereafter. Monitor for hepatotoxicity; consider permanently discontinuing if clozapine-associated hepatitis or elevated transaminases occur. Monitor for hyperglycemia, diabetes or risk factors thereof, dyslipidemia, weight, cholinergic rebound. Glaucoma. Constipation (screen and treat prior to initiation). GI hypomotility with severe complications. Urinary retention. Significant prostatic hypertrophy. Exclude severe neutropenia, infection, or neuroleptic malignant syndrome if fever occurs. Pulmonary disease. Renal or hepatic impairment, CYP2D6 poor metabolizers: may need to reduce dose. Elderly or hospice patients. Neonates: risk of extrapyramidal and/or withdrawal symptoms post delivery (due to exposure during 3rd-trimester pregnancy). Pregnancy (Cat.B). Nursing mothers: not recommended.
Caution with general anesthetics, benzodiazepines, psychotropics (possible respiratory/cardiac arrest), fluvoxamine, paroxetine, sertraline. Caution with concomitant drugs known to prolong the QT interval (eg, quinidine, procainamide, amiodarone, sotalol), certain antipsychotics (eg, ziprasidone, iloperidone, chlorpromazine, thioridazine, mesoridazine, droperidol, pimozide), antibiotics (eg, gatifloxacin, moxifloxacin, sparfloxacin), and others (eg, pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol, tacrolimus). Caution with drugs that can cause electrolyte imbalance (eg, diuretics). Caution with drugs that affect or are affected by CYP2D6, 3A4, 1A2; clozapine levels increased by CYP450 inhibitors (eg, bupropion, cimetidine, erythromycin); clozapine levels decreased by CYP450 inducers (eg, rifampin, phenytoin, St. John's wort). Increased risk for anticholinergic toxicity, severe GI hypomotility effects when concomitant other anticholinergic drugs (eg, benztropine, cyclobenzaprine, diphenhydramine); avoid use when possible. May potentiate CNS drugs, antihypertensives. May potentiate or be potentiated by protein-bound drugs. Neuroleptic malignant syndrome possible with concomitant lithium.
Sedation, dizziness/vertigo, headache, tremor, hypersalivation, sweating, dry mouth, visual disturbances, seizures, tachycardia, orthostatic hypotension, bradycardia, syncope, cardiac arrest, constipation, nausea, weight gain, fever; myocarditis (can be fatal), cardiomyopathy, mitral valve incompetence, eosinophilia, tardive dyskinesia, CHF, neuroleptic malignant syndrome, DVT, pulmonary embolism, interference with cognitive and motor performance, hepatotoxicity, GI hypomotility with severe complications.
To register patients call National Registry at (800) 448-5938.
Renal (~50%), fecal (~30%). Half-life: 8 hours (75mg dose).