Drug Interactions between Flomax and quinine

ADJUST DOSING INTERVAL: Food may delay the gastrointestinal absorption of tamsulosin. The time to maximum plasma concentration (Tmax) is reached by 4 to 5 hours under fasted conditions and by 6 to 7 hours when tamsulosin is administered with food. The delay in Tmax has the desirable effect of smoothing the tamsulosin plasma concentration profile, thereby reducing fluctuation of the plasma peak and trough concentrations with multiple dosing. Food may also affect the extent of absorption of tamsulosin. It has been reported that taking tamsulosin under fasted conditions results in a 30% increase in bioavailability (AUC) and 40% to 70% increase in peak plasma concentration (Cmax) compared to fed conditions. The effects of food on the pharmacokinetics of tamsulosin are consistent regardless of whether tamsulosin is taken with a light meal or a high-fat meal.

MANAGEMENT: To ensure uniformity of absorption, tamsulosin should be administered approximately one-half hour following the same meal each day.

Coadministration with grapefruit juice does not appear to affect the pharmacokinetics of quinine in a clinically relevant manner. Although grapefruit juice is an inhibitor of CYP450 3A4 and quinine is metabolized by this pathway to its major metabolite, 3-hydroxyquinine, a study of ten healthy volunteers found no significant differences in quinine peak plasma concentration (Cmax), time to reach Cmax (Tmax), terminal elimination half-life, systemic exposure (AUC), or apparent oral clearance (Cl/F) when a single 600 mg oral dose of quinine sulfate was administered in combination with 200 mL of orange juice (control), half-strength grapefruit juice, and full-strength grapefruit juice twice daily for 6 days each, separated by a 2-week washout period. Relative to the control period, the apparent renal clearance of quinine was markedly increased by 81% during treatment with half-strength grapefruit juice. However, since renal clearance accounts for approximately 6% of the total clearance of quinine, this change would likely have minimal clinical impact. The lack of a significant interaction is probably due to the fact that grapefruit juice primarily inhibits intestinal rather than hepatic CYP450 3A4, and quinine is not known to undergo significant presystemic metabolism as evidenced by its relatively high oral bioavailability (76% to 88%). Nevertheless, excessive consumption of grapefruit juice and tonic water (which contains quinine) was suspected as the cause of torsade de pointes arrhythmia in a patient with a history of asymptomatic long QT syndrome. Treatment with magnesium sulfate and metoprolol had no effect, but the arrhythmia resolved spontaneously 48 hours after discontinuation of the drinks. Based on current data, moderate grapefruit juice consumption is probably safe for the majority of patients taking quinine.