Why Terbinafine Cannot Be Sent with Rifampin
Rifampin is a potent inducer of hepatic cytochrome P450 enzymes (particularly CYP3A4) and will dramatically reduce terbinafine plasma concentrations, leading to therapeutic failure of the antifungal treatment. 1, 2
Mechanism of the Interaction
Rifampin induces multiple drug-metabolizing pathways including CYP1A2, 2B6, 2C8, 2C9, 2C19, 3A4, UDP-glucuronyltransferases, sulfotransferases, carboxylesterases, and transporters (P-glycoprotein and MRP2) 2
Terbinafine is metabolized through these hepatic enzyme systems that rifampin induces, resulting in accelerated clearance and subtherapeutic drug levels 1, 3
The FDA label explicitly identifies rifampin as having a significant effect on terbinafine metabolism, listing it among the key interacting drugs 1
This enzyme induction develops gradually during rifampin treatment and persists for weeks after discontinuation, making timing adjustments ineffective 4
Clinical Consequences
Suboptimal or failed antifungal treatment is the primary concern, as terbinafine concentrations will be reduced to ineffective levels 3, 5
Mycological cure rates exceeding 80% with terbinafine monotherapy cannot be achieved when rifampin co-administration reduces drug exposure 6
The fungicidal activity of terbinafine against dermatophytes requires adequate tissue concentrations that rifampin induction prevents 6
Management Approach
Complete rifampin-based tuberculosis treatment before initiating terbinafine whenever clinically feasible 7
If antifungal treatment is urgent, use topical terbinafine formulations (1% cream/gel applied once or twice daily), which achieve local tissue concentrations independent of systemic metabolism and are highly effective for superficial mycoses 6
Consider alternative systemic antifungals such as itraconazole or fluconazole if systemic therapy is required during rifampin treatment, though these also have interactions requiring dose adjustments 3, 5
Do not attempt dose escalation of terbinafine to overcome the interaction, as the magnitude of enzyme induction makes this approach ineffective and potentially dangerous 7
Important Clinical Context
Rifampin causes "potentially serious consequences" through enzyme induction affecting numerous common medications including oral contraceptives, methadone, and warfarin 8
Terbinafine has a relatively low potential for drug interactions overall and is generally well-tolerated in older and multimorbid patients, making this rifampin interaction particularly notable as one of the few clinically significant concerns 9, 6
The interaction is bidirectional but asymmetric: while rifampin dramatically reduces terbinafine levels, terbinafine (a CYP2D6 inhibitor) has minimal effect on rifampin metabolism 1, 3