CLOZAPINE

( kloe' za peen)
Clozaril
PREGNANCY CATEGORY B

Drug classes
Therapeutic actions
Indications
Contraindications and cautions
Available forms
Dosages
  Adults
  Pediatric patients
Pharmacokinetics
Adverse effects
Interactions
  Drug-drug
Nursing considerations
CLINICAL ALERT!
Assessment
Interventions
Teaching points

 

Drug classes

Antipsychotic
Dopaminergic blocking agent

Therapeutic actions

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.

Indications

• 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.

Available forms

Tablets—25, 100 mg

Dosages

Adults

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.

Pediatric patients

Safety and efficacy in patients < 16 yr not established.

Pharmacokinetics


Route Onset Peak Duration
Oral Varies 1–6 hr Weeks

Metabolism: Hepatic; T ½: 4–12 hr

Distribution: Crosses placenta; enters breast milk

Excretion: Urine and feces

Adverse effects

Adverse effects in Italics are most common; those in Bold are life-threatening.

•  CNS: Drowsiness, sedation, seizures, dizziness, syncope, headache, tremor, disturbed sleep, nightmares, restlessness, agitation, increased salivation, sweating, tardive dyskinesia, neuroleptic malignant syndrome
•  CV: Tachycardia, hypotension, ECG changes, hypertension
•  GI: Nausea, vomiting, constipation, abdominal discomfort, dry mouth
•  GU: Urinary abnormalities
•  Hematologic: Leukopenia, granulocytopenia, agranulocytopenia
•  Other: Fever, weight gain, rash

Interactions

Drug-drug

• Increased therapeutic and toxic effects with cimetidine
• Decreased therapeutic effect with phenytoin, mephenytoin, ethotoin

Nursing considerations

CLINICAL ALERT!

Name confusion has occurred with Clozaril (clozapine) and Colazal (balsalazide); dangerous effects could occur. Use extreme caution.

Assessment

•  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

Interventions

• 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.

Teaching points

• 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.


Copyright © 2004 Lippincott Williams & Wilkins
Amy M. Karch
2004 Lippincott's Nursing Drug Guide