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Answer: CYP1A2 interaction
- 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, hereby causing symptoms of toxicity in non-smoking patients.
- Thus, this patient needs to be advised to limit his caffeine intake.
- Clozapine has low CYP2D6 interaction.
- Clozapine has been shown to reduce the incidence of suicide and does not affect cognitive function.
- Hagg, S., Spigset, O., Mjorndal, T., Dahlqvist, R. (2000). Effect of caffeine on clozapine pharmacokinetics in healthy volunteers. Br J Clin Pharmacol
⇒ Read course chapter for details of following 12 medications interactions with clozapine:
(1) Proton pump inhibitors, Antacids, and Histamine receptor antagonists.
(2) Antibiotics and Infections.
(3) Anti-tuberculosis medications.
(4) Oral contraceptive pills.
(5) Smoking (nicotine)
(7) St John’s Wort
(8) Amiodarone and Lisinopril
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