Table 1.

Summary of international clozapine titration guideline for adult inpatients according to ancestry groups with updates*

	Asians/Native Americans		Europeans/Western Asians		Blacks (US extrapolation)†
	PMs*	Non-PMs	PMs*	Non-PMs	PMs*	Non-PMs
Target	75–150 mg/day	175–300 mg/day	100–200 mg/day	250–400 mg/day	150–300 mg/day	300–600 mg/day
Week 1
Day 1	6.25 mg/day	12.5 mg/day	12.5 mg/day	25 mg/day	12.5 mg/day	25 mg/day
↑ D by	6.25 mg/day	12.5 mg/day	12.5 mg/day	25 mg/day	12.5 mg/day	25 mg/day
Day 7	25 mg/day	50 mg/day	50 mg/day	100 mg/day	50 mg/day	100 mg/day
Alert C	<118 ng/mL	<105 ng/mL	<175 ng/mL	<140 ng/mL	<117 ng/mL	<117 ng/mL
Week 2
↑ D by	12.5 mg	12.5 mg/day	12.5 mg/day	25 mg/day	25 mg/day	50 mg/day
Day 14	50 mg/day	100 mg/day	75 mg/day	200 mg/day	100 mg/day	200 mg/day
Alert C	<235 ng/mL	<210 ng/mL	<263 ng/mL	<280 ng/mL	<233 ng/mL	<234 ng/mL
Week 3
↑ D by	12.5 mg	25 mg/day	25 mg/day	25/50 mg/day	25 mg/day	50 mg/day
Day 21	75 mg/day	150 mg/day			150 mg/day	300 mg/day
NS ♀			100 mg/day	250 mg/day
Other			125 mg/day	300 mg/day
Alert C	<353 ng/mL	<315 ng/mL	<350 ng/mL	<350 ng/mL	<291 ng/mL	<351 ng/mL
Week 4
NS ♀	75 mg/day	150 mg/day	100 mg/day	250 mg/day	150 mg/day	300 mg/day
C	C 1 week later	C 1 week later	C 1 week later	C 1 week later	C 1 week later	C 1 week later
Other	75–150 mg/day	175–300 mg/day	100–200 mg/day	250–400 mg/day	150–300 mg/day	300 mg/day
↑ D by	25 mg/day	25/50 mg/day	25/50 mg/day	25/50 mg/day	25/50 mg/day	25/100 mg/day
C	C 1 week later	C 1 week later	C 1 week later	C 1 week later	C 1 week later	C 1 week later
Interpreting clozapine C
Cs before week 4 are not at a steady state but are used in order not to delay titrations. They are alert signs.‡
Titrations try to reach the target dose for an NS ♀ at day 21 so that 1 week later a steady state C is measured at week 4.
At week 4, the prescriber needs to decide on a target dose for other patients who are not NS ♀. Ranges include two extremes: NS ♀ and S ♂. The prescriber chooses a target dose and continues it for 1 week to obtain the C, to determine the final dose.
Published information suggests that 5 days on the same clozapine dose may be enough to reach a steady state. We use 1 week.§
In S ♂ who continue to smoke during hospitalisation, an additional 1–3 weeks may be needed to reach the final dosage.
If the patient did not smoke during hospitalisation, further increases may be needed after discharge if smoking is restarted.

*The international clozapine titration guideline⁴ recommended considering those taking oral contraceptives or valproate or who are obese to be clozapine PMs. The update³⁰ added those taking flupentixol, olanzapine, perphenazine or quetiapine to the list of those who should be titrated as clozapine PMs and provided recommendations for how to stop these antipsychotics once the minimum clozapine therapeutic dose has been reached.

†This table provides a one-page summary of six prior titration schedules described in the already published supplemental tables S9–S14 of the international clozapine titration guideline.⁴ The titration schedules for black patients are extrapolated from the US titration schedules. It includes corrections of errors that the guideline had. The table is an update and modification from the table published in the update³⁰ of the guideline.

‡Cs provided at the end of weeks 1, 2 and 3 are alert signs that the titration may be too fast for that patient. These Cs are estimated in each group using clozapine C/D ratios.

§One week for a steady state, which is easier to remember and implement (in many hospitals, Cs cannot be collected during weekends) than 5 days. Some clozapine PMs may need 2 weeks to reach a steady state; thus, allotting 1 week to reach a steady state is a practical compromise. It may be wise in clozapine PMs to get another C 2 weeks after the maintenance dosage has been selected.

C, concentration; C/D, concentration-to-dose; D, dose; NS, non-smoking; PM, poor metabolizer; S, smoking; US, United States.