cyp1a2
14 interactions related to cyp1a2
propranolol + st. john's wort
St. John's Wort potently induces CYP1A2 and CYP2C19 along with CYP3A4 and P-glycoprotein, accelerating the metabolism of propranolol and reducing its plasma levels. Documented cases include loss of intraocular pressure control in glaucoma patients on topical beta-blockers, and the mechanism predicts similar loss of antihypertensive and antiarrhythmic effect with systemic propranolol.
caffeine + ciprofloxacin
Ciprofloxacin is a potent CYP1A2 inhibitor. Co-administration increases caffeine's area-under-the-curve by 50-100% and prolongs its half-life, producing exaggerated central nervous system and cardiovascular stimulation.
caffeine + theophylline
Caffeine and theophylline are closely related methylxanthines that share the CYP1A2 metabolic pathway and compete for the same adenosine receptors. Concurrent use can raise theophylline levels and add pharmacodynamically to cause tachycardia, tremor, nausea, seizures or arrhythmias.
caffeine + sertraline
Sertraline and caffeine can each contribute to anxiety, insomnia, tremor and GI upset, and sertraline may modestly slow caffeine clearance via CYP1A2 inhibition. The pharmacokinetic effect is small but the additive symptomatic effect can be uncomfortable.
smoking + clozapine
Polycyclic aromatic hydrocarbons in tobacco smoke (not nicotine) potently induce CYP1A2, the enzyme responsible for roughly 70% of clozapine metabolism, lowering clozapine plasma levels by up to 50% in smokers. Sudden smoking cessation can cause clozapine levels to rise 50-72% within 3-5 days, risking sedation, seizures, and toxicity.
smoking + olanzapine
Polycyclic aromatic hydrocarbons in cigarette smoke induce CYP1A2, the primary enzyme that metabolizes olanzapine, increasing olanzapine clearance by roughly 37-48% in smokers. Meta-analysis data suggest olanzapine doses should be 30% lower in non-smokers than in smokers to reach the same plasma levels.
smoking + theophylline
Polycyclic aromatic hydrocarbons in tobacco smoke induce CYP1A2, increasing theophylline clearance by 58-100% and shortening its half-life by roughly 63%. Smokers often need 1.5-2 times the usual theophylline dose, and abrupt cessation can rapidly produce toxic levels.
smoking + propranolol
Cigarette smoking induces hepatic metabolism of propranolol via CYP1A2 and accelerated glucuronidation, increasing apparent oral clearance and reducing propranolol plasma concentrations in smokers compared with non-smokers. Nicotine also independently raises heart rate, blood pressure, and circulating catecholamines, partially counteracting propranolol's beta-blocking effect.
smoking + caffeine
Polycyclic aromatic hydrocarbons in tobacco smoke induce CYP1A2, the enzyme that performs about 95% of caffeine demethylation, raising caffeine clearance by 40-65% and shortening its half-life from roughly 6 hours to 3.5 hours in smokers. Quitting smoking can cause caffeine levels to rise sharply, contributing to jitters, anxiety, palpitations, and insomnia.
coffee + sertraline
Sertraline modestly inhibits CYP1A2-mediated caffeine metabolism, raising caffeine plasma levels and prolonging its half-life. Caffeine can also worsen the anxiety, insomnia, jitteriness, and palpitations that sertraline is often prescribed to treat, blunting the clinical response.
caffeine + clozapine
Caffeine inhibits CYP1A2, the main enzyme that metabolizes clozapine. High caffeine intake (especially energy drinks) can dramatically raise clozapine levels, with case reports of life-threatening toxicity including multiorgan failure.
caffeine + oral contraceptives
Ethinyl estradiol in oral contraceptives inhibits CYP1A2, the enzyme that metabolizes caffeine. This roughly doubles caffeine's area-under-the-curve and prolongs its half-life, intensifying jitteriness, insomnia and palpitations.
coffee + ciprofloxacin
Ciprofloxacin is a potent inhibitor of CYP1A2, the enzyme that metabolizes caffeine. Co-administration can reduce caffeine clearance by 30% to 50% and prolong its half-life, leading to higher plasma caffeine levels, jitteriness, insomnia, palpitations, tremor, and (rarely) seizures.
coffee + antidepressants
Many antidepressants (especially fluvoxamine, fluoxetine, sertraline, duloxetine) inhibit CYP1A2 to varying degrees and slow caffeine clearance, while caffeine itself can worsen the anxiety, insomnia, tremor, and tachycardia that antidepressants are often prescribed to treat. MAOIs add a risk of caffeine-induced hypertensive episodes.