Clozapine

Antipsychotic — atypical (treatment-resistant)

Indications

Treatment-resistant schizophrenia (after ≥2 antipsychotic trials, one atypical)Psychosis in Parkinson's disease

Adult dose

Start 12.5 mg OD day 1, 25 mg OD day 2, then increase by 25–50 mg/day to 300 mg over 2–3 weeks. Usual 200–450 mg/day in divided doses; max 900 mg.

Common side effects

HypersalivationSedationWeight gainConstipationTachycardiaHypotensionHyperthermia (early)

Serious side effects

Agranulocytosis / neutropeniaMyocarditis (esp. weeks 2–4)CardiomyopathyBowel obstruction (lethal — review constipation)Seizures (dose-related)DVT/PENMS

Contraindications

Previous neutropenia (non-clozapine related — relative)Bone marrow diseaseUncontrolled epilepsyParalytic ileusActive myocarditis/cardiomyopathy

Monitoring

CPMS/Denzapine/ZTAS registration mandatory
FBC weekly for 18 weeks, fortnightly to week 52, then 4-weekly
Troponin & CRP weekly for first 4 weeks (myocarditis screen)
Weight, BMI, BP, lipids, glucose, ECG
Plasma level for efficacy/toxicity (target 350–600 ng/mL)

Notable interactions

Smoking induces CYP1A2 — abrupt cessation can double levels
Fluvoxamine, ciprofloxacin raise levels significantly
Carbamazepine — AVOID (additive marrow suppression)
Benzodiazepines (respiratory depression)

Notes

Restart titration from scratch if doses missed >48 hours.

Curated reference based on BNF, Maudsley Prescribing Guidelines and NICE. Verify against current BNF and local guidelines before prescribing.