Drug Interactions between Choledyl SA and Luvox

GENERALLY AVOID: Coadministration with fluvoxamine may significantly increase the serum concentrations of theophylline and the associated risk of toxicity. The mechanism is fluvoxamine inhibition of theophylline metabolism via CYP450 1A2. Case reports and pharmacokinetic studies indicate that fluvoxamine 50 to 100 mg/day can reduce the clearance of theophylline by 50% to 70%, resulting in toxic theophylline levels and/or clinical toxicity in some patients. Two- to fourfold increases in theophylline serum levels or systemic exposure (AUC) and half-life have been reported, with onset of clinical toxicity as early as two to three days and typically within a week of initiating fluvoxamine. Patients with liver dysfunction may be less susceptible to the interaction. In a study consisting of 10 healthy subjects, 10 subjects with mild hepatic impairment (Child class A) and 10 subjects with severe hepatic impairment (Child class C), fluvoxamine-induced inhibition of theophylline clearance was reduced from 62% in healthy subjects to 52% and 12% in subjects with mild and severe cirrhosis, respectively. These differences may be due to reduced hepatic uptake of fluvoxamine as well as reduced hepatic expression of CYP450 1A2 in the cirrhotic liver.

MANAGEMENT: The use of theophylline or its salts in combination with fluvoxamine should generally be avoided. If coadministration is required, a reduction of theophylline dosage by one-half to two-thirds should be considered. Pharmacologic response and serum levels should be closely monitored following initiation, discontinuation or change of dosage of fluvoxamine, and the theophylline dosage adjusted accordingly. Patients should be advised to contact their physician if they experience signs and symptoms suggestive of theophylline toxicity such as nausea, vomiting, diarrhea, anorexia, headache, tremor, irritability, confusion, insomnia, seizure, palpitation, and arrhythmia. Other selective serotonin reuptake inhibitors including citalopram, escitalopram, fluoxetine, paroxetine, and sertraline do not significantly inhibit CYP450 1A2 and may be safer alternatives in theophylline-treated patients.

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