Medications Affecting Clozapine Level?

Clozapine is indicated for the management of treatment resistant schizophrenia and hence it is likely that patient will also be taking other psychotropic and non-psychotropic medications.

It is clinically relevant to have the knowledge of these interactions, as certain medication can lower clozapine level (thereby causing relapse & worsening of schizophrenia symptoms) or increase clozapine level (thereby causing toxicity and increasing clozapine’s side effects)

Let’s begin by discussing this hypothetical case:

Q: A 23-year-old man was admitted to the inpatient psychiatry unit after a suicide attempt 3 weeks ago. This was his second suicide attempt this year. He has a 2-year history of schizophrenia and has been tried on 3 different antipsychotic agents with breakthrough symptoms. While on the ward, he is pleasant and cooperative with, though continues to hear voices which instruct him to kill himself. The patient is a creative writer and has been coping with these voices by immersing himself in his work. He spends all day on his laptop writing and will have 8-10 cups of coffee daily to fuel his writing streak.

Welcome to your Clozapine Nicotine

You would like to start the patient on clozapine but should to be mindful of which of the following?

Answer: CYP1A2 Interaction (Inhibition)

  • Clozapine is extensively metabolized in the liver via the cytochrome P450 system.

  • Cytochrome P450 isoenzyme 1A2 (CYP1A2) is mainly responsible for the metabolism of clozapine.

  • Caffeine is another CYP1A2 substrate.

  • Daily caffeine doses of 400-1000 mg have been shown to inhibit the metabolism of clozapine to an extent of clinical significance –> causing increase in clozapine levels. (Br J Clin Pharmacol. 2000 Jan;49(1):59-63)

  • Thus, this patient needs to be advised to limit his caffeine intake.

We have summarized the clinically relevant drug interaction between clozapine and both psychotropics and non-psychotropic medications in our following academy chapter:

CLOZAPINE & CAFFEINE:

This chapter will summarize the interactions of the following medications on clozapine level:

(1) ANTIDEPRESSANTS:

  • Which antidepressants can increase clozapine level?

(2) MOOD STABILIZERS:

  • Which mood stabilizers can increase & decrease clozapine level?

(3) ANTIPSYCHOTICS:

  • Which antipsychotics can increase clozapine level?

(4) ANTIBIOTICS:

  • Which antibiotics can increase clozapine level?

(5) ANTI-TUBERCULOSIS MEDICATIONS:

  • Which anti-TB medications can increase & decrease clozapine level?

(6) GERD MEDICATIONS:

  • Which GERD can increase & decrease clozapine level?
  • Which GERD medications is preferred with clozapine?

(7) ANTIHYPERTENSIVE MEDICATIONS:

  • Which antihypertensive medications can increase decrease clozapine level?

(8) CAFFEINE

(9) NICOTINE SMOKINE

(10) HERBAL MEDICATIONS

MEDICATIONS AFFECTING CLOZAPINE LEVELS

INTERESTED IN LEARNING MORE?

JOIN PSYCHIATRY EDUCATION FORUM ACADEMY MEMBERSHIP

This is a closed membership for medical professionals only.

  • 30+ Courses/Sections: Each chapter within these sections is of direct clinical relevance for your daily practice. 
  • Journal Club: we will post the most recently published psychiatry articles relevant to your daily clinical practice.
  • Coffee Club: contain short discussions with clinical experts in the field of psychiatry.
  • Essentials of Inpatient Psychiatry Book: All chapters from this book are included in the academy sections. 
  • Discussion Forum & Community: Connect with other medical professionals and discuss your difficult-to-treat clinical cases.
  • Conference Discounts: Academy members get discounted access at our conferences. 
  • Goal: is to have all important clinically relevant topics in one place for ease of access.

Related Articles