Makindo Medical Notes.com

Clozapine: reminder of potentially fatal risk of intestinal obstruction, faecal impaction, and paralytic ileus (October 2017)

About: Always check the BNF link here

• Check BNF or equivalent for UpToDate prescribing advice
• Check ECG
• Warn patients signs of neutropenia including sustained temperature elevation with flu-like symptoms or a sore throat

Mode of action

• dopamine D1, dopamine D2, 5-HT2A, alpha1-adrenoceptor, and muscarinic-receptor antagonist.

Indication/Dose

• Patients with psychosis in Parkinson's disease: Clozapine 12.5 mg taken at bedtime. Increased in steps of 12.5 mg up to twice weekly. Usual dose 25 (37.5 mg) once daily, dose to be taken at bedtime; increased in steps of 12.5 mg once weekly, this applies only in exceptional cases, increased if necessary up to 100 mg daily in 2 divided doses; Usual maximum 50mg/24 hours

Interactions

• See BNF

Cautions

• Blood dyscrasias, heart disease, risk of seizures
• Depression; diabetes, jaundice, myasthenia gravis
• Parkinson's disease (may be exacerbated) (in adults); photosensitisation (may occur with higher dosages)
• Prostatic hypertrophy (in adults); severe respiratory disease; susceptibility to angle-closure glaucoma

Contraindications

• See BNF

Haematological Side effects

• Neutropenia and potentially fatal agranulocytosis reported. Ensure DWCC normal before starting. Check FBC every week for 18 weeks then at least every 2 weeks and if clozapine continued and blood count stable after 1 year at least every 4 weeks (and 4 weeks after discontinuation)
• if leucocyte count < 3000/mm3 or if absolute neutrophil count below 1500/mm3 discontinue permanently and refer to haematologist.
• Patients who have a low white blood cell count because of benign ethnic neutropenia may be started on clozapine with the agreement of a haematologist.
• Avoid drugs that depress leucopoiesis; patients should report immediately symptoms of infection, especially influenza-like illness.

Side effects

• Ileus: Impairment of intestinal peristalsis
• Fatal myocarditis (most commonly in the first 2 months) and cardiomyopathy reported.

References

• Clozapine in BNF

Revisions