Drug Interaction Report

MONITOR CLOSELY: Concomitant administration of corticosteroids may potentiate the risk of tendinitis and tendon rupture associated with fluoroquinolone treatment. The mechanism is unknown. Tendinitis and tendon rupture have most frequently involved the Achilles tendon, although cases involving the rotator cuff (the shoulder), the hand, the biceps, and the thumb have also been reported. Some have required surgical repair or resulted in prolonged disability. Tendon rupture can occur during or up to several months after completion of fluoroquinolone therapy.

MANAGEMENT: Caution is recommended if fluoroquinolones are prescribed in combination with corticosteroids, particularly in patients with other concomitant risk factors (e.g., age over 60 years; recipient of kidney, heart, and/or lung transplant). Patients should be advised to stop taking the fluoroquinolone, avoid exercise and use of the affected area, and promptly contact their physician if they experience pain, swelling, or inflammation of a tendon. In general, fluoroquinolones should only be used to treat conditions that are proven or strongly suspected to be caused by bacteria and only if the benefits outweigh the risks.

MONITOR: Coadministration with CYP450 inducers may decrease the plasma concentrations of zolpidem, which is primarily metabolized by CYP450 3A4 and, to a lesser extent, by CYP450 1A2. In eight healthy female volunteers, administration of a single 20 mg dose of zolpidem following pretreatment with the potent CYP450 inducer rifampin (600 mg/day for 5 days) decreased mean zolpidem peak plasma concentration (Cmax) and systemic exposure (AUC) by 58% and 73%, respectively, compared to administration following placebo. These changes were associated with significant reductions in the pharmacodynamic effects of zolpidem. In another study with 18 healthy volunteers, administration of a single 5 mg dose of zolpidem following daily dosing of carbamazepine 400 mg for 15 days resulted in a 41% decrease in mean Cmax and 57% decrease in mean AUC of zolpidem compared to administration of zolpidem alone.

MANAGEMENT: The potential for diminished pharmacologic effects of zolpidem should be considered during coadministration with CYP450 inducers, particularly potent ones like carbamazepine, enzalutamide, lumacaftor, mitotane, phenobarbital, phenytoin, rifamycins, and St. John's wort. Alternative treatments or a dosage adjustment for zolpidem may be required if an interaction is suspected.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of zolpidem. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Administration of zolpidem with food may delay the onset of hypnotic effects. In 30 healthy subjects, administration of zolpidem 20 minutes after a meal resulted in decreased mean peak plasma drug concentration (Cmax) and area under the concentration-time curve (AUC) by 25% and 15%, respectively, compared to fasting. The time to reach peak plasma drug concentration (Tmax) was prolonged by 60%, from 1.4 to 2.2 hours.

MANAGEMENT: Patients receiving zolpidem should be advised to avoid the consumption of alcohol. For faster sleep onset, zolpidem should not be administered with or immediately after a meal.