Clozapine Titration Planner
For more information, see de Leon et al., 2022
This tool was built specifically to align with the internal medication guidelines of the CA Department of State Hospitals and is intended for their use only. This tool is an interactive, browser-based calculator designed to provide information for clinicians in planning an inpatient clozapine titration, based on ancestry-informed titration rules and aligned with current DSH clinical policy. It can be used to generate a proposed day-by-day dosing schedule and general monitoring reminders according to clinician-entered patient factors. The tool does not make clinical decisions, does not account for individual medical complexity, and does not replace clinical judgment, institutional protocols, or direct patient evaluation.
Patient factors & settings
If a patient’s ancestry is unknown or falls outside the listed categories, this tool has not been developed or validated for that scenario and should not be used as the primary basis for titration decisions. In such cases, clinicians should follow local protocols and use their clinical judgment when planning clozapine initiation.
Initial work up
- Baseline ANC, WBC, platelets, and eosinophils.
- Electrocardiogram (ECG), if there is a positive history of unstable cardiovascular disease.
- Fasting blood sugar and hemoglobin A1c.
- Lipid panel or total cholesterol and triglycerides.
- For patients exhibiting BEN, at least two ANC measurements to establish the patient’s baseline.
- Physical assessment including blood pressure, BMI, abdominal girth, and AIMS.
- Pregnancy test in premenopausal women.
-
KUB if indicated clinically, such as history or findings of:
- Constipation, paralytic ileus, or partial bowel obstruction.
- Bowel or related surgery.
- Abdominal adhesions.
- Diverticulitis or diverticulosis.
- Dehydration or anorexia.
- Unreliability in reporting bowel movements.
Complete vital signs, including orthostatic blood pressure measurements, are recommended at least twice, with one set obtained within 24 hours before beginning clozapine treatment. Measurements should be separated by at least one hour.
Monitoring
On days 7, 14, 21, and 28, ANC monitoring is recommended. Weight, hemoglobin A1c, and a lipid panel (including triglycerides and cholesterol) support ongoing metabolic risk monitoring.
In patients known to be at elevated risk of inflammatory responses (for example, those with known inflammatory diseases or with positive family histories of inflammatory diseases), it is recommended, but not required, that weekly measurements of troponin-I, CRP, and serum creatinine be obtained during the first eight weeks of clozapine treatment.
Titration plan
| Day | Date | AM (mg) | PM (mg) | Total (mg/day) | Monitoring / notes |
|---|
Titration notes
Dose increases should be made only when clinically appropriate (orthostasis acceptable, sedation tolerable). Gradual titration is recommended to minimize risk for neutropenia, myocarditis, DRESS, seizures, and other adverse effects.
QHS-only dosing is recommended initially due to the approximately 24-hour half-life in average metabolizers, unless patients are intolerant (for example, due to nightly orthostatic hypotension symptoms).
Pathway & start/target
Tip: The rate and/or incremental dose size may need to be adjusted based on the presence or absence of inducers or inhibitors of clozapine metabolism. Inducers, e.g., smoking, carbamazepine, or barbiturates, may call for an increase in the frequency or size of dose changes, while inhibitors of clozapine metabolism, e.g. fluvoxamine, bupropion, fluoxetine, or paroxetine, may call for reductions in titration frequency or incremental dose size. The best means to assess the need for adjustments based on the presence of inducers or inhibitors is to measure a trough clozapine plasma concentration 5 to 7 days after a dose change to calculate the plasma concentration to dose ratio. For adult male nonsmokers this ratio averages about 1.08, while for adult nonsmoking women it averages about 1.32. Smaller ratios reflect faster metabolism while larger ratios reflect slower metabolism. Consider slower dose titration in elderly or medically fragile individuals and in those with an intellectual disability, as they may be more sensitive to clozapine side effects.
Disclaimer: This tool provides information which may support clinical decision-making. It does not serve as a guideline for individual patient management and does not replace clinical judgment or local protocols. Ultimate treatment decisions must be made by the treating clinician considering individual patient factors and clinical data and relying upon their professional judgment. For complex cases or nuanced questions, please place a consult with SMI CalAdviser.
Some information presented within this tool was created in collaboration with the California Department of State Hospitals (DSH). This includes that the content has been specifically aligned to the DSH’s medication guidelines (DSH Psychotropic Medication Operational Procedures, appended to DSH Policy Directive 3400). These medication guidelines are applicable only to the DSH settings and inclusion within this resource does not necessarily indicate that they should be followed in any non-DSH settings. The medication guidelines included in this resource are those of DSH and do not necessarily represent the views, policy(ies), and/or position(s) of the American Psychiatric Association (APA).