Drug Interaction Report

MONITOR: Coadministration with strong CYP450 3A4 inducers may decrease plasma concentrations and antimicrobial effects of clindamycin, which is metabolized predominantly by the isoenzyme. In a pharmacokinetic analysis among patients (n=34) with staphylococcal osteoarticular infection receiving treatment with clindamycin (600 mg 3 times a day) and either rifampin (a strong CYP450 3A4 inducer; 600 mg twice a day) or levofloxacin (500 mg twice a day), clindamycin mean trough concentrations and Cmax values for patients treated with levofloxacin were 4.7 and 10.2 mcg/mL, respectively, compared to 0.79 and 3.48 mcg/mL, respectively, for patients treated with rifampin. However, while these findings confirm rifampin is an effective inducer of clindamycin, this combination has been used clinically with some success. The extent of the interaction or clinical use with other 3A4 inducers has not been established.

MANAGEMENT: Monitor closely for diminished therapeutic response to clindamycin during coadministration with strong CYP450 3A4 inducers. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever a strong CYP450 3A4 inducer is added to or withdrawn from therapy with clindamycin. An alternative agent with no or minimal CYP450 3A4-inducing activity may also be considered.

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.