Clozapine & GERD Medications: Drug Interaction

It is clinically relevant to have the knowledge of drug interactions between clozapine and medications used for common medical conditions, 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 answering this hypothetical case:

A 32-year-old female with history of schizophrenia is admitted for a recent worsening of command auditory hallucinations and negative symptoms of schizophrenia. She was initiated on clozapine and gradually titrated to 250 mg bedtime dose with a good response. The patient later reports worsening of GERD symptoms and was initiated on her home medication for GERD. This resulted in sudden deterioration and worsening of underlying psychotic symptoms.  Which of the following GERD medication can result in a decrease in clozapine levels?

Proton pump inhibitors, Antacids, and Histamine receptor antagonists

Omeprazole:

  • DECREASE in plasma clozapine levels.
  • Mechanism: mixed inducer of CYP450 1A2 and 3A4.

Esomeprazole:

  • mixed results.
  • Studies with esomeprazole found NO potential interaction with drugs metabolized by CYP1A2, 2A6, 2C9, 2D6, or 2E1 isoenzymes.
  • one study found an INCREASE in plasma clozapine level after substituting omeprazole to esomeprazole: likely result from the removal of omeprazole induction.

Cimetidine:

  • INCREASE in plasma clozapine levels.
  • Mechanism: Pan-inhibitor of P450.

Ranitidine:

  • NO effect on plasma clozapine levels.

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

Here is the slide from this presentation on important drug interactions with Clozapine & GERD medications:

CLOZAPINE & GERD MEDICATIONS:

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

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