Table 2.
Summary of clozapine titration schedules based on ancestry and clozapine metabolism [82]
| Patient characteristics | Expected dosage, (concentration/ dosage ratio, ng per mL/mg per d) | First Week | Second week | Third week | Fourth and subsequent weeks |
|---|---|---|---|---|---|
| Asia/Amerindian with lower clozapine metabolisma |
75–150 mg/day (4.7 to 2.3) |
First dose 6.25 mg at nightb Increase daily dosage by 6.25 mg Target 25 mg/day |
2 dose increases of 12.5 mg/day Target 50 mg/day TDM < 118 ng/mL on day 7 |
2 dose increases of 12.5 mg/day Target 75 mg/day TDM < 235 ng/mL on day 14 |
Target dosage from 75 mg/day for female non-smokers to 75 to 150 mg/day for male smokersc TDM < 353 ng/mL on day 21 |
| Asia/Amerindian with average clozapine metabolism |
175–300 mg/day (2.1 to 1.3) |
First dose 12.5 mg at night Increase daily dosage by 12.5 mg Target 50 mg/day |
2 dose increases of 12.5 mg/day Target 100 mg/day TDM < 105 ng/mL on day 7 |
2 dose increases of 25 mg/day Target 150 mg/day TDM < 210 ng/mL on day 14 |
Target dosage from 175 mg/day for female non-smokers to 300 mg/day for male smokers TDM < 315 ng/mL on day 21 |
| European/Western Asiand ancestry with lower clozapine metabolism |
100–200 mg/day (3.5 to 1.75) |
First dose 12.5 mg at night Increase daily dosage by 12.5 mg Target 50 mg/day |
2 dose increases of 50 mg/day Target 75 mg/day TDM < 175 ng/mL on day 7 |
2 dose increases of 25 mg/day Target 100 mg/day for female non-smokers; 150 mg/day for others TDM < 263 ng/mL on day 14 |
Target dosage from 100 mg/day for female non-smokers to 200 mg/day for male smokers TDM < 350 ng/mL on day 21 |
| European/Western Asiand ancestry with average clozapine metabolism |
250–400 mg/day (1.4 to 0.88) |
First dose 25 mg at night Increase daily dosage by 25 mg Target 100 mg/day |
2 dose increases of 50 mg/day Target 200 mg/day at the end of the second week. TDM < 140 ng/mL on day 7 |
2 dose increases of 25 mg/day Target 250 mg/day for female non-smokers; 300 mg/day for others TDM < 280 ng/mL on day 14 |
Target dosage from 250 mg/day for female non-smokers to 400 mg/day for male smokers TDM < 350 ng/mL on day 21 |
| US patients with non-European ancestries other than Asia/Amerindian with lower clozapine metabolism |
150–300 mg/day (2.33 to 1.17) |
First dose 12.5 mg at night Increase daily dosage by 12.5 mg Target 50 mg/day |
2 dose increases of 25 mg/day Target 100 mg/day at the end of the second week. TDM < 117 ng/mL on day 7 |
2 dose increases of 25 mg/day Target 125 mg/day for female non-smokers; 150 mg/day for others TDM < 233 ng/mL on day 14 |
Target dosage from 150 mg/day for female non-smokers to 300 mg/day for male smokers TDM < 291 ng/mL on day 21 |
| US patients with non-European ancestries other than Asia/Amerindian with average clozapine metabolism |
300–600 mg/day (1.17 to 0.58) |
First dose of 25 mg at night Increase daily dosage by 25 mg Target 100 mg/day |
2 dose increases of 50 mg/day Target 200 mg/day TDM < 117 ng/mL on day 7 |
2 dose increases of 25 mg/day Target 300 mg/day TDM < 234 ng/mL on day 14 |
Target dosage from 300 mg/day for female non-smokers to 600 mg/day for male smokers TDM < 351 ng/mL on day 21 |
TDM therapeutic drug monitoring of clozapine concentration, which may be useful for personalizing titration rates
aLower clozapine metabolism, e.g., obesity, oral contraceptives, valproate, use of caffeine (for caffeine-containing beverages, see https://www.caffeineinformer.com/the-caffeine-database)
bAdminister most of dosage at night to avoid daytime sedation and orthostatic hypotension
cIncreased clozapine metabolism by cigarette smoking
dWestern Asians are those whose ancestry is from Asian countries west of Pakistan
Drawn from information in reference [82], permission not required