Atypical antipsychotic (treatment-resistant schizophrenia) Pregnancy: Neonates exposed during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Published epidemiologic data over decades have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal/fetal outcomes. A pregnancy exposure registry exists (National Pregnancy Registry for Atypical Antipsychotics).

Clozapine

Brand names: Clozaril, Denzapine, Zaponex

Clozapine is an atypical antipsychotic used for treatment-resistant schizophrenia, where it can be uniquely effective; its use requires registration with a monitoring service.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Starting dosage 12.5 mg once or twice daily; if well-tolerated, increase in increments of 25-50 mg/day to a target of 150-225 mg twice per day by the end of two weeks

Route: Oral (orally disintegrating tablet)

Frequency: Once or twice daily; subsequently may increase in increments of up to 100 mg once or twice weekly

Max: 450 mg twice daily

US labelling (orally disintegrating tablet). Starting dose is much lower than target to reduce risk of orthostatic hypotension, bradycardia and syncope. Obtain baseline absolute neutrophil count (ANC) before initiation; initiation not recommended if ANC <1500/uL (or <1000/uL in documented Benign Ethnic Neutropenia). Dosage must be modified based on ANC results (see full label Tables 1-2). Can be taken with or without food; ODT may be allowed to disintegrate or chewed, with or without water. Reduce dose to one-third when coadministered with strong CYP1A2 inhibitors. See full prescribing information for dosing in renal/hepatic impairment and CYP2D6 poor metabolizers, and for discontinuation/re-initiation. Verify against UK SPC — no eMC posology available in this bundle.

Dose adjustments

Renal

See full prescribing information for dosage recommendations in patients with renal or hepatic impairment

Dose auto-extracted from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

US labelling (FDA)

Reference — US labelling, may differ from UK

Recommended starting oral dosage is 12.5 mg once daily or twice daily. ( 2.2 ) If well-tolerated, increase the total daily dosage in increments of 25 mg to 50 mg per day at target dosage of 150 mg to 225 mg twice per day by the end of two weeks. ( 2.2 ) Subsequently may increase the doage in increments up to 100 mg, once or twice weekly. ( 2.2 ) Maximum daily dosage is 450 mg twice daily. ( 2.2 ) Administer with or without food. Clozapine ODT may be allowed to disintegrate or chewed, and may be taken with or without water. See additional administration instructions in the full prescribing information. ( 2.2 ) See dosage modification based on ANC results. ( 2.3 , 2.4 ) See recommendations …

Source: US FDA prescribing information (openFDA / DailyMed), label dated 2026-03-13. Accessed 2026-06-12. US dosing and indications can differ from UK practice — use UK sources for prescribing decisions.

Contraindications

History of hypersensitivity to clozapine (e.g. photosensitivity, vasculitis, erythema multiforme, or Stevens-Johnson Syndrome) or any other component of the product

Side effects

Severe neutropenia
Orthostatic hypotension, bradycardia, and syncope
Seizures
Gastrointestinal hypomotility with severe complications; anticholinergic toxicity
Metabolic changes (hyperglycemia/diabetes, dyslipidemia, weight gain); myocarditis; QT interval prolongation

Interactions

Strong CYP1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin, enoxacin) — reduce clozapine dose to one-third
Strong CYP3A4 inducers — concomitant use not recommended
Discontinuation of CYP1A2 (e.g. tobacco smoke) or CYP3A4 (e.g. carbamazepine) inducers — consider reducing clozapine dose
Anticholinergic drugs — increased risk of anticholinergic toxicity

Clinical monograph

How it works

It antagonises multiple receptors (including dopamine D2 and serotonin 5-HT2) with a distinctive receptor profile.

Prescribing in practice

Agranulocytosis is a defining risk — mandatory regular full-blood-count monitoring through a patient-monitoring scheme, and immediate review/stop for neutropenia or signs of infection.
Myocarditis and cardiomyopathy (especially in the first weeks), severe constipation/ileus (which can be fatal), seizures, sedation, hypersalivation and metabolic effects all occur.
Smoking affects clozapine levels (stopping smoking can raise them); after any break of more than 48 hours it must be re-titrated from a low dose.

Monitoring

Mandatory scheduled FBC monitoring; monitor for myocarditis (early), bowel function (constipation), seizures, weight, glucose and lipids, and levels where relevant.

Counselling the patient

You must have your regular blood tests — the medicine cannot be supplied without them.
Report fever, sore throat or feeling unwell, chest pain or breathlessness, and any difficulty opening your bowels.
Tell your team if you change your smoking, and never miss doses for more than a day or two without advice.

Evidence & guidelines

The most effective option for treatment-resistant schizophrenia (NICE NG178), used within a strict monitoring framework.

Reference: NICE CG178; Clozapine CPMS SPC; Maudsley Prescribing Guidelines 14th ed.; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways