Major
fluvoxamine × Theophylline
SSRI×Methylxanthine
Mechanism
Fluvoxamine is the most potent CYP1A2 inhibitor among SSRIs, and CYP1A2 is the main theophylline metabolic route. Theophylline plasma levels rise 3-fold. Theophylline has a narrow therapeutic window.
Symptoms
Nausea, tachycardia, tremor, insomnia, agitation. At levels above 30 mg/L: seizures and ventricular arrhythmias. Older patients and chronic kidney disease: earlier symptoms.
Management
Avoid the combination. Alternative antidepressants without CYP1A2 effect: sertraline, escitalopram, or agomelatine. If fluvoxamine is needed, reduce theophylline 3-fold and check level at 3–5 days.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.