Clozapine Unit Converter
Clozapine Unit Converter
Convert clozapine trough levels between ng/mL and nmol/L, with the response and seizure thresholds and why stopping smoking is the interaction to watch for.
Clozapine converter
Mass ⇄ molarClozapine trough 420 ng/mL
Formula and conversion factor
ng/mL = nmol/L ÷ 3.0598
- 3.0598
- derived from the molecular weight of clozapine, 326.82 Da (1000 ÷ 326.82)
- µg/L
- numerically identical to ng/mL
- norclozapine
- the major metabolite; the clozapine-to-norclozapine ratio helps separate non-adherence from poor metabolism
Worked example
Clozapine trough 420 ng/mL
420 × 3.0598 = 1285 nmol/L
= 420 µg/L
Response and toxicity thresholds
| Level (ng/mL) | Interpretation |
|---|---|
| < 350 | Response unlikely |
| 350 – 600 | Usual target range for treatment resistance |
| > 1000 | Substantially increased seizure risk |
What moves clozapine levels
| Factor | Effect |
|---|---|
| Smoking (CYP1A2 induction) | Lower levels — stopping smoking can double the level within days |
| Caffeine | Raises levels |
| Fluvoxamine | Markedly raises levels (potent CYP1A2 inhibitor) |
| Acute infection / inflammation | Raises levels |
The interaction that matters most: smoking
The threshold generally quoted for antipsychotic response is around 350 ng/mL, and levels are usually kept below roughly 1000 ng/mL, above which the risk of seizures rises substantially. Between those figures the dose is titrated to clinical response and tolerability rather than to a single target number.
Smoking is the single most important modifier of clozapine levels, and it is under-recognised. Tobacco smoke — not nicotine itself — induces the CYP1A2 enzyme that metabolises clozapine, so smokers typically need considerably higher doses than non-smokers to reach the same level. The clinically important corollary is what happens when smoking stops: because induction reverses over days, a patient who stops smoking, including simply on admission to a smoke-free hospital ward, can see their clozapine level double within days, producing toxicity — sedation, hypotension, seizures — in someone whose dose has not changed at all. This is a common and entirely avoidable clinical event, and it should be stated plainly: every admission of a patient on clozapine should include an explicit question about smoking status and a plan to reduce the dose if smoking is expected to stop.
Caffeine intake, fluvoxamine — a potent CYP1A2 inhibitor sometimes used deliberately to raise clozapine levels in poor responders — and any acute inflammatory response, infection in particular, also raise levels, the last through cytokine-mediated suppression of CYP1A2 activity.
Measuring norclozapine, the major metabolite, alongside clozapine gives the clozapine-to-norclozapine ratio, a useful adjunct: a low ratio suggests non-adherence, while a high ratio suggests poor metabolism rather than a missed dose.
Frequently asked questions
How do I convert clozapine from ng/mL to nmol/L?
Multiply by 3.0598. A trough of 420 ng/mL is 1285 nmol/L. The factor comes from clozapine’s molecular weight of 326.82 Da.
What clozapine level is needed for response?
Response becomes likely at around 350 ng/mL, with a usual target range of 350 – 600 ng/mL for treatment-resistant schizophrenia.
Why can stopping smoking cause clozapine toxicity?
Tobacco smoke induces CYP1A2, the enzyme that clears clozapine. When smoking stops, that induction reverses within days and the level can double, causing toxicity in a patient whose dose has not changed.
What does the clozapine-to-norclozapine ratio show?
It helps distinguish non-adherence (a low ratio, or an unexpectedly low clozapine level relative to norclozapine) from poor metabolism (a high ratio).
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References
- Hiemke C et al. AGNP consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017. Pharmacopsychiatry. 2018;51(1-2):9–62.
- Clark SR et al. Elevated clozapine levels associated with cigarette smoking cessation and other environmental changes. J Clin Psychopharmacol. 2018;38(3):200–5.