How do I interpret clozapine or norclozapine blood, serum or plasma levels, what do these mean?

Blood levels of medications (serum or plasma) are used because, compared with oral dosage, they correlate more closely with medication concentration in the brain. They also assess medication adherence. With regard to clozapine, blood levels are available for clozapine, and for norclozapine, the major active clozapine metabolite. Levels should be a steady state, trough level. Levels are usually drawn more than 3 days after a patient is stable on a dose. Levels should be drawn roughly 12 hours after the last dose. Clozapine blood levels are correlated with both clozapine effectiveness and side effects. However, there is large variation between patients in blood levels.  There is also substantial variation within patients (plus or minus 30% in some studies). Given the inter-patient variability, there is no minimum effective clozapine level, no therapeutic range, and no maximum safe level. On average, efficacy starts above 250 ng/ml, is substantial above 350 ng/ml, and the risk of seizures increases with levels above 1000 ng/ml. However, levels should not be the primary determinant of dosage. Clinician assessment of symptoms and side effects guides clozapine treatment. There are situations when a clozapine level can be useful: to assess medication adherence, when clozapine is less effective than expected, when there are more side effects than expected, or when medication interactions are suspected. Levels can be useful when there are changes that might be affecting P450 metabolism, such as stopping or starting smoking around hospital admissions. Norclozapine levels are often performed at the same time as clozapine levels. Norclozapine is an active metabolite that differs from clozapine in efficacy and side effects and has a longer half-life. The interpretation of norclozapine levels is unclear, and of limited use clinically. Most agree that clozapine levels provide the most value, while others suggest norclozapine levels should also be considered.  When interpreting blood levels, low clozapine levels can result from low dose, non-adherence, or rapid metabolism. If a clozapine level is high, check the patient for dose-related side effects. If there is clozapine toxicity, the patient should obtain urgent care that includes symptomatic treatment and assessment for serious problems such as cardiac arrhythmias or seizure activity. If the patient has no signs of toxicity, possibilities include lab error, a non-trough blood draw, a safe level for this patient, or inhibition of P450 metabolic enzymes from changes in other medications or smoking. Evaluate and consider whether to recheck the level.

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