Drug Interactions between Synalgos-DC and terbinafine

MONITOR: Coadministration with terbinafine may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity by terbinafine, which is expected to occur in patients who are CYP450 2D6 extensive metabolizers (approximately 93% of Caucasians and more than 98% of Asians and individuals of African descent). A case of nortriptyline (a CYP450 2D6 substrate) intoxication corresponding to significantly increased serum drug concentrations was reported in a patient shortly after the addition of terbinafine. Rechallenge in the patient produced similar results.

MANAGEMENT: Caution is advised if terbinafine must be used concurrently with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever terbinafine is added to or withdrawn from therapy. Due to the long elimination half-life of terbinafine, especially following prolonged use, such interactions may be observed for several months after discontinuation of terbinafine therapy.

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

Terbinafine may decrease the clearance of intravenously administered caffeine by 19% to 21%. The mechanism of the interaction has not been delineated. Although this interaction is unlikely to be of clinical significance, it may be appropriate to monitor the patient for increased caffeine effects.