Makindo Medical Notes

⚠️ Clozapine can cause severe gastrointestinal hypomotility → constipation, faecal impaction, intestinal obstruction, and paralytic ileus (rare but potentially fatal). Treat constipation as a medical priority.

About

• 📚 Always confirm indication, dosing, monitoring requirements, interactions, and counselling in the BNF clozapine monograph.
• 🩺 Specialist initiation only; ensure the patient is registered with the clozapine monitoring service (UK).
• ❤️ Baseline: BP (postural), pulse, weight/BMI/waist, glucose/HbA1c, lipids, LFTs; consider baseline ECG (local policy).
• 🦠 Counsel on neutropenia red flags: fever, flu-like symptoms, sore throat, mouth ulcers — seek urgent assessment and blood count.
• 🚽 Ask about bowels at every review: frequency, stool consistency, abdominal pain, vomiting, bloating — escalate urgently if red flags (no flatus, severe pain, persistent vomiting).

Mode of action

• 🧠 Atypical antipsychotic with broad receptor antagonism: D2 (relatively weak/fast dissociation), 5-HT2A, plus α1 and muscarinic effects (drives hypotension, sedation, anticholinergic GI hypomotility).

Indication

• 🧩 Primary licensed use: treatment-resistant schizophrenia (specialist care).
• 🧓 In some settings, used at low dose for psychosis in Parkinson’s disease under specialist supervision (very cautious titration).

Dose (Parkinson’s disease psychosis – specialist, low-dose approach)

• 🌙 Start 12.5 mg at bedtime.
• ⬆️ Increase by 12.5 mg increments (often no more than twice weekly initially; slower if frail/PD autonomic symptoms).
• 🎯 Typical effective dose is often 25–50 mg/day (usually at night); keep dose as low as possible.
• ⛔ Max is commonly kept to 50 mg/day in PD (higher doses only in exceptional specialist cases).

Key prescribing advice

• 🩸 Blood monitoring is non-negotiable: clozapine cannot be supplied without compliant FBC/ANC monitoring.
• 🚬 Smoking matters: cigarette smoke induces CYP1A2 → lowers clozapine levels; sudden smoking cessation can raise levels and toxicity risk.
• ☕ Caffeine changes can also affect levels (advise consistent intake).
• 🧠 Seizure risk rises with dose and rapid titration; avoid abrupt dose jumps.

Haematology monitoring (typical UK schedule)

• 📅 Weekly FBC for the first 18 weeks, then fortnightly up to 1 year, then 4-weekly if stable (and continue monitoring for 4 weeks after stopping).
• 🚨 If significant neutropenia occurs, stop clozapine and follow the monitoring service / haematology pathway (thresholds depend on the service and whether BEN applies).
• 🌍 Benign ethnic neutropenia (BEN): initiation/continuation may be possible under agreed specialist criteria.

GI hypomotility / constipation prevention

• 🧻 Record baseline bowel habit and start a proactive plan (often stool softener + stimulant laxative per local policy).
• 💧 Encourage fluids and mobility where feasible; review constipating co-meds (opioids, antimuscarinics, iron).
• 🚑 Red flags needing urgent same-day assessment: severe/colicky abdominal pain, persistent vomiting, abdominal distension, no stool/flatus, fevers.

Cautions

• ❤️ Cardiac disease, history of myocarditis/cardiomyopathy, QTc concerns (risk–benefit + monitoring plan).
• ⚡ Seizure disorder, dementia/frailty (sedation/falls), autonomic dysfunction (postural hypotension).
• 🍬 Diabetes/metabolic risk (weight gain, dysglycaemia, lipids).
• 👁️ Glaucoma risk, prostatic symptoms/urinary retention (anticholinergic effects).

Contraindications

• ⛔ See BNF for full list (including prior clozapine-associated agranulocytosis and situations where monitoring cannot be assured).

Interactions (high-yield)

• 📚 Full list: see BNF.
• 🚫 Avoid/add extreme caution with other drugs that affect white cells (e.g. carbamazepine).
• 🧪 CYP interactions: inhibitors (e.g. fluvoxamine, ciprofloxacin) can ↑ levels; inducers (incl. smoking) ↓ levels.
• 💤 Additive sedation/hypotension with CNS depressants, benzodiazepines, alcohol.

Notable adverse effects

• 🦠 Neutropenia/agranulocytosis (potentially fatal) → strict monitoring + urgent response to infection symptoms.
• 🚨 Myocarditis (often early weeks) and cardiomyopathy (later) — watch for chest pain, dyspnoea, tachycardia, fever.
• 🚽 Constipation/ileus from GI hypomotility (treat proactively).
• 😴 Sedation, hypersalivation, postural hypotension, seizures (dose/titration related), weight gain/metabolic syndrome.

References

• BNF: Clozapine

Revisions