What is the target blood level for Clozaril (clozapine)?

Target Blood Level for Clozapine

The target therapeutic trough blood level for clozapine is ≥350 ng/mL, with an optimal therapeutic range of 350-550 ng/mL. 1, 2

Therapeutic Target Levels

• The minimum therapeutic threshold is 350 ng/mL, which should be measured as a trough level (drawn just before the next dose). 1, 2
• The optimal therapeutic range is 350-550 ng/mL, where the best balance of efficacy and safety is achieved. 1, 2
• Levels above 550 ng/mL show diminishing therapeutic benefit (number needed to treat = 17) and significantly increased seizure risk. 1

Timing and Frequency of Measurement

• Measure trough levels on at least two occasions separated by at least one week at a stable dose to establish both therapeutic adequacy and medication adherence. 1
• Trough sampling (just before the next dose) provides the most consistent and reliable measurement for assessing therapeutic adequacy. 1

Dose-Level Relationship

• If blood level monitoring is not feasible, a minimum dose of 500 mg/day is recommended (unless limited by tolerability), as doses over 400 mg/day show superior efficacy. 1
• However, blood level monitoring is strongly preferred because clozapine has an unpredictable dose-concentration relationship between patients due to factors like smoking status, caffeine consumption, genetic polymorphisms (CYP2D6), and drug interactions. 3, 4

Clinical Application Algorithm

For patients not responding at lower levels:

• If therapeutic response is inadequate at 350 ng/mL after 12 weeks, increase the dose to achieve concentrations up to 550 ng/mL. 1, 2
• Consider prophylactic lamotrigine if using concentrations above 550 ng/mL due to increased seizure risk. 1, 2

For monitoring adherence:

• Trough measurements help identify covert non-adherence; for suspected non-adherence, unannounced blood tests may be more representative. 1

Important Caveats

• Older literature cited lower therapeutic ranges (200-350 ng/mL or 400 mcg/L), but current evidence strongly supports the ≥350 ng/mL threshold. 4, 5
• The risk of seizures increases with rising plasma concentrations, particularly with rapid dose changes and levels above 550 ng/mL. 1
• Clozapine therapy should be tried for at least 3 months after attaining therapeutic plasma levels before determining treatment failure. 1