Choose an inpatient or outpatient base schedule, enter the patient's ancestry, sex, smoking status, age and poor-metabolizer risk factors, and the calculator produces a day-by-day 21-day clozapine titration schedule with a target dose capped by the de Leon 2022 international guideline. Copy it into the chart or print it as a PDF. Built for prescribers by the psychiatrists at TelepsychHealth; for clinician reference only. Always confirm against current prescribing information and local protocols.
Key facts about clozapine titration
- Start low: 12.5 mg (half of a 25 mg tablet) on day 1. The manufacturer's example inpatient schedule reaches 300 mg a day by day 13; a typical outpatient schedule reaches 300 mg a day by day 21.
- One pace does not fit everyone. The de Leon 2022 international guideline describes six inpatient titrations: three ancestry groups, each with an average-metabolism and a lower-metabolism version. Minimum therapeutic doses range from 75–150 mg a day (Asian or Indigenous American ancestry with obesity or valproate) to 300–600 mg a day (US patients of other ancestries with average metabolism). Outpatient titration should be slower still.
- Slower and lower when clearance is lower. The guideline's reasons for the slower schedule are an inhibitor (an oral contraceptive, and valproate treated as one), obesity, or inflammation with a raised CRP; such patients need about half the dose of their sex and smoking group. Non-smoking women get the lowest target in every ancestry group and male smokers the highest. The calculator also slows the first week and lowers the target for age 65 and over, a known poor-metabolizer biomarker, and several co-prescribed antipsychotics.
- Check CRP at baseline and weekly for at least the first four weeks, with weekly troponin where resources allow. A fever or a rising CRP during titration means hold the dose until it settles: clozapine-induced inflammation precedes myocarditis, and inflammation also slows clozapine clearance.
- Measure a trough clozapine level once the target dose has been held for at least five days (and whenever response or tolerability is unexpected). The response threshold is 350 ng/mL; the clozapine plasma level calculator interprets the result.
- Before starting: no fluvoxamine (the guideline offers no titration for it) and no potent inducer such as rifampin, phenytoin or phenobarbital; taper benzodiazepines where possible; rule out baseline inflammation; and avoid stopping smoking during the titration. Do not taper the previous antipsychotic before week 4 and a clozapine level of at least 350 ng/mL.
How to use the calculator
- Pick the base schedule: the manufacturer's inpatient schedule (faster, with daily monitoring) or the UK NHS outpatient schedule (slower, for community starts).
- Set the current dose (0 mg for a new start) and the dose you want to reach by day 21. The calculator allows up to 300 mg above the current dose.
- Enter ancestry, sex, smoking status and age, then tick any poor-metabolizer criteria.
- Read the 21-day table. If the guideline's cap is lower than the target you chose, the calculator says so and uses the cap. Use "Copy Schedule to Clipboard" for the chart or "Print or save as PDF" for the ward or the patient's file.
The calculator scales the chosen base schedule to the target dose, halves the pace of the first week for poor metabolizers and patients aged 65 and over, rounds every step to 12.5 mg, and never exceeds the ancestry- and sex-specific target in the table below. For a patient already on clozapine it moves in a straight line from the current dose to the target over 20 days.
Standard clozapine titration schedules
Both base schedules are total daily doses in milligrams. Divide the daily dose per local protocol, usually with the larger portion at night once the dose exceeds 25 to 50 mg.
| Day | Manufacturer inpatient schedule (faster) | UK NHS outpatient schedule (slower) |
|---|---|---|
| 1 | 12.5 | 12.5 |
| 2 | 25 | 12.5 |
| 3 | 50 | 25 |
| 4 | 75 | 25 |
| 5 | 100 | 37.5 |
| 6 | 125 | 37.5 |
| 7 | 150 | 50 |
| 8 | 175 | 50 |
| 9 | 200 | 75 |
| 10 | 225 | 75 |
| 11 | 250 | 100 |
| 12 | 275 | 100 |
| 13 | 300 | 125 |
| 14 | 300 | 125 |
| 15 | 300 | 150 |
| 16 | 300 | 150 |
| 17 | 300 | 175 |
| 18 | 300 | 200 |
| 19 | 300 | 225 |
| 20 | 300 | 250 |
| 21 | 300 | 300 |
The inpatient schedule follows the example in the Teva clozapine prescribing information; the outpatient schedule follows the Oxford Health NHS Foundation Trust outpatient titration protocol (2024). The calculator scales either one up or down to the target dose you choose.
Personalized clozapine target doses by ancestry (de Leon 2022)
The guideline's central idea is that clozapine clearance differs by ancestry, sex and smoking, so the dose that produces a therapeutic level differs too. Patients of Asian or Indigenous American ancestry clear clozapine most slowly; patients of European or Western Asian ancestry sit in the middle; and the guideline's US group of other ancestries, which the calculator labels as a US extrapolation, tends to need the highest doses. Within each group, non-smoking women need less than men who smoke, and "lower metabolism" patients (obesity, valproate and the other criteria above) need less still.
| Ancestry group | Guideline minimum therapeutic dose, average metabolism | Guideline minimum therapeutic dose, lower metabolism | Calculator's day-21 cap: standard / poor metabolizer | Calculator's cap for a non-smoking woman: standard / poor metabolizer |
|---|---|---|---|---|
| Asian or Indigenous American | 175–300 mg/day | 75–150 mg/day | 300 / 200 mg | 175 / 75 mg |
| European or Western Asian | 250–400 mg/day | 100–200 mg/day | 400 / 200 mg | 250 / 100 mg |
| US patients of other ancestries (extrapolated) | 300–600 mg/day | 150–300 mg/day | 400 / 300 mg | 300 / 150 mg |
These are targets for the end of the titration, not maximum doses. The trough level measured once the target has been held for at least five days decides whether to go further; clozapine follows linear kinetics at therapeutic doses, so that single level estimates the dose that reaches 350 ng/mL, and the mean of several levels estimates it better.
Monitoring during a clozapine titration
- CRP at baseline and weekly for at least the first four weeks, with weekly troponin where resources allow. Do not start if the baseline CRP is abnormal until the cause is found. A CRP rise during titration means rule out a concurrent infection, do not increase the dose, and hold the titration; consider daily CRP and troponin, and if they do not normalize, reduce or stop clozapine. CRP rises several days before troponin.
- Absolute neutrophil count per the current US prescribing information before starting and on the labeled schedule.
- Orthostatic blood pressure, pulse and sedation at each step. Slow the titration if the patient develops orthostatic hypotension, tachycardia or severe sedation.
- A trough clozapine level once the target dose has been held for at least five days; the response threshold is 350 ng/mL.
- Keep the previous antipsychotic until at least week 4 and a level of 350 ng/mL or more.
For clinicians
TelepsychHealth is a psychiatrist-led telepsychiatry practice that sees adults by video in Arizona, California, Connecticut, Florida, Georgia, Illinois, Michigan, Minnesota, New York and Texas, including patients who need clozapine-level monitoring and treatment-resistant care coordinated with their local team. We also run a free biweekly webinar for practice owners.
Frequently asked questions
What is the starting dose of clozapine?
12.5 mg once or twice on the first day, which is half of a 25 mg tablet. The dose then rises in steps of 12.5 to 25 mg a day (inpatient) or every two days (outpatient), guided by blood pressure, pulse, sedation and CRP.
How fast can clozapine be titrated?
The manufacturer's example reaches 300 mg a day by day 13 and is meant for inpatients under daily observation. Community starts usually take three weeks or more to reach 300 mg. The de Leon 2022 guideline, written for inpatients, slows the titration and lowers the target for patients who clear clozapine slowly: non-smoking women, patients of Asian or Indigenous American ancestry, patients with obesity, and patients taking valproate or hormonal contraceptives. Faster titrations are associated with more myocarditis, syncope, sedation and, through sedation and hypersalivation, aspiration pneumonia, which worldwide kills more clozapine patients than agranulocytosis or myocarditis.
Why does ancestry matter for clozapine dosing?
Because the enzyme that clears clozapine, CYP1A2, works at different average rates in different populations. Patients of Asian or Indigenous American ancestry typically need lower doses, about 175 to 300 mg a day against 250 to 400 mg a day for patients of European ancestry, to reach the same level. Ancestry is a proxy for metabolism, not a rule: the measured level at the end of the titration is what confirms the dose.
What are the six de Leon clozapine titrations?
Three ancestry groups (Asian or Indigenous American; European or Western Asian; other ancestries in the US), each with an average-metabolism schedule and a lower-metabolism schedule for patients with obesity, valproate or other poor-metabolizer criteria. Each schedule has its own minimum therapeutic dose, from 75–150 mg a day up to 300–600 mg a day, and all six are paired with CRP monitoring and a clozapine level.
Should outpatients be titrated more slowly than inpatients?
Yes. Outpatients are not observed daily, so the UK NHS outpatient schedule rises every second day rather than every day and reaches 300 mg a day on day 21 rather than day 13. The calculator uses it as the default base schedule.
When should a clozapine level be checked during titration?
Once the target dose has been held for at least five days, as a 12-hour trough, and earlier if the patient is unexpectedly sedated, tachycardic or hypotensive. The response threshold is 350 ng/mL. Use the clozapine plasma level calculator on this site to interpret the result and to see how smoking, caffeine, infection and interacting drugs change it.
What is the maximum dose of clozapine?
The US prescribing information allows up to 900 mg a day, but most patients respond well below that, and the right ceiling is set by the plasma level and tolerability rather than by milligrams. Doses above 600 mg a day carry a higher seizure risk and call for a level before any further increase.
Why check CRP during clozapine titration?
Clozapine can cause an inflammatory reaction in the first weeks, and myocarditis, its most dangerous early complication, is usually preceded by a rise in CRP and often by fever. Weekly CRP during the first four weeks catches it early, and holding the dose while CRP is raised is the single most protective step. Inflammation also slows clozapine clearance, so a level drawn during an infection reads high.
Can I print the schedule?
Yes. "Print or save as PDF" prints the 21-day table with the patient's settings; choose "Save as PDF" in the print dialog to keep a copy. The schedule is total daily dose in milligrams and is intended for the prescriber's chart or the ward, not as patient instructions on its own.
References
- de Leon J, Schoretsanitis G, Smith RL, et al. An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels. Pharmacopsychiatry. 2022;55(2):73-86.
- Teva Pharmaceuticals. Clozapine tablets: prescribing information and example titration schedule. TevaClozapine.com.
- Oxford Health NHS Foundation Trust. Clozapine outpatient titration protocol. January 2024.
- Hiemke C, Bergemann N, Clement HW, et al. Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017. Pharmacopsychiatry. 2018;51(1-02):9-62.