Clozapine


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plasma clozapine level


Is a plasma clozapine level of 1.36 mg/L using the GC/FID method from a IIiac blood specimen an acceptable safe level?
by Jeffrey Bukowiecki in Milwaukee, Wisconsin/ USA, 06/04/2007

Clozapine
Clozapine (Clozaril)
Clozapine
( KLOH-zah-peen)
Pregnancy Category: B Clozaril (Rx)

Classification: Antipsychotic

Action/Kinetics: Interferes with the binding of dopamine to both D-1 and D-2 receptors; more active at limbic than at striatal dopamine receptors. Thus, is relatively free from extrapyramidal side effects and does not induce catalepsy. Also acts as an antagonist at adrenergic, cholinergic, histaminergic, and serotonergic receptors. Increases the amount of time spent in REM sleep. Food does not affect the bioavailability of clozapine. Peak plasma levels: 2.5 hr. Average maximum concentration at steady state: 122 ng/mL plasma after 100 mg b.i.d. Highly bound to plasma proteins. t 1/2: 12 hr. Metabolized in the liver to inactive compounds and excreted through the urine (50%) and feces (30%).

Uses: Severely ill schizophrenic clients who do not respond adequately to conventional antipsychotic therapy, either because of ineffectiveness or intolerable side effects from other drugs. Due to the possibility of development of agranulocytosis and seizures, avoid continued use in clients failing to respond.

Contraindications: Myeloproliferative disorders. Use in those with a history of clozapine-induced agranulocytosis or severe granulocytopenia; use with other agents known to suppress bone marrow function . Severe CNS depression or coma due to any cause. Lactation.

Special Concerns: Use with caution in clients with known CV disease, prostatic hypertrophy, narrow angle glaucoma, hepatic or renal disease.

Side Effects: Hematologic: Agranulocytosis leukopenia, neutropenia, eosinophilia. CNS: Seizures (appear to be dose dependent), drowsiness or sedation, dizziness, vertigo, headache, tremor, restlessness, nightmares, hypokinesia, akinesia, agitation, akathisia, confusion, rigidity, fatigue, insomnia, hyperkinesia, weakness, lethargy, slurred speech, ataxia, depression, anxiety, epileptiform movements. CV: Orthostatic hypotension (especially initially), tachycardia, syncope, hypertension, angina, chest pain, cardiac abnormalities changes in ECG. Neuroleptic malignant syndrome: Hyperpyrexia muscle rigidity, altered mental status, irregular pulse or BP, tachycardia, diaphoresis, cardiac dysrhythmias. GI: Constipation, nausea, heartburn, abdominal discomfort, vomiting, diarrhea, anorexia. GU: Urinary abnormalities, incontinence, abnormal ejaculation, urinary frequency or urgency, urinary retention. Musculoskeletal: Muscle weakness, pain (back, legs, neck), muscle spasm, muscle ache. Respiratory: Dyspnea, SOB, throat discomfort, nasal congestion. Miscellaneous: Salivation, sweating, visual disturbances, fever (transient), dry mouth, rash, weight gain, numb or sore tongue.

Laboratory Test Alterations: Hyperprolactinemia.

Overdose Management: Symptoms: Drowsiness, delirium, tachycardia, respiratory depression hypotension, hypersalivation, seizures, coma. Treatment: Establish an airway and maintain with adequate oxygenation and ventilation. Give activated charcoal and sorbitol. Monitor cardiac status and VS. General supportive measures.

Drug Interactions: Anticholinergic drugs / Additive anticholinergic effects Antihypertensive drugs / Additive hypotensive effects Benzodiazepines / Possible respiratory depression and collapse Digoxin / Digoxin effect R/T binding to plasma protein Epinephrine / Clozapine may reverse effects when given for hypotension Phenobarbital / Clozapine plasma levels due to liver breakdown St. John's wort / Possible clozapine plasma levels R/T metabolism Warfarin / Warfarin effect R/T binding to plasma protein

How Supplied: Tablet: 25 mg, 100 mg

Dosage
?Tablets Schizophrenia.
Adults, initial: 25 mg 1-2 times/day; then, if drug is tolerated, the dose can be increased by 25-50 mg/day to a dose of 300-450 mg/day at the end of 2 weeks. Subsequent dosage increments should occur no more often than once or twice a week in increments not to exceed 100 mg. Usual maintenance dose: 300-600 mg/day (although doses up to 900 mg/day may be required in some clients). Total daily dose should not exceed 900 mg.

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