What is the interaction between terbinafine and rifampicin in a patient with a history of cutaneous sporotrichosis and tuberculosis?

Interaction Between Terbinafine and Rifampicin

Rifampicin significantly reduces terbinafine blood levels by approximately 100% through potent enzyme induction, requiring either a doubled terbinafine dose or consideration of alternative antifungal agents, though no formal dosing guidelines exist for this specific combination. 1

Mechanism of Drug Interaction

• Rifampicin is a potent inducer of cytochrome P450 enzymes and increases terbinafine clearance by 100%, effectively cutting terbinafine exposure in half 1
• This enzyme induction occurs through the same hepatic pathways that rifampicin uses to interact with numerous other medications metabolized via CYP450 2
• The interaction is unidirectional—terbinafine does not significantly affect rifampicin levels or tuberculosis treatment efficacy 1

Clinical Management Strategy

For Concurrent Sporotrichosis and Tuberculosis Treatment

The tuberculosis regimen must never be compromised or modified due to drug interactions, as this significantly worsens TB treatment outcomes and mortality. 3

• Prioritize completing tuberculosis treatment with full-dose rifampicin as the first-line agent 3
• Consider doubling the terbinafine dose from 250 mg/day to 500 mg/day, though this approach lacks formal validation in the literature 1, 4
• Higher terbinafine doses (500-1000 mg/day) have demonstrated efficacy and safety in sporotrichosis treatment, with the 1000 mg/day dose showing 87% cure rates versus 52% with 500 mg/day 4

Alternative Sequencing Approach

• Delay sporotrichosis treatment until tuberculosis therapy is completed (typically 6 months for drug-susceptible TB), as sporotrichosis is rarely life-threatening and can be safely deferred 5, 6
• If sporotrichosis requires immediate treatment due to extensive disease, consider using itraconazole instead of terbinafine, though itraconazole also has significant interactions with rifampicin requiring dose adjustments 6, 2
• Standard terbinafine 250 mg/day achieves 92-96% cure rates for cutaneous sporotrichosis when used without interacting medications, with mean treatment duration of 11-14 weeks 5, 6

Critical Clinical Pitfalls

• Never discontinue or reduce rifampicin dosing to accommodate terbinafine therapy—tuberculosis treatment takes absolute priority for mortality reduction 3
• Do not assume standard terbinafine 250 mg/day dosing will be effective during concurrent rifampicin therapy, as the 100% increase in clearance renders this dose likely subtherapeutic 1
• Rifampicin's enzyme-inducing effects persist for approximately 2 weeks after discontinuation, so terbinafine levels will remain reduced during this washout period 3
• Monitor clinical response closely if treating both conditions simultaneously—lack of sporotrichosis improvement may indicate inadequate terbinafine exposure requiring further dose escalation 4

Practical Treatment Algorithm

Step 1: Assess urgency of both conditions

• Active tuberculosis always requires immediate treatment 3
• Cutaneous sporotrichosis can typically be deferred unless extensive or rapidly progressive 5, 6

Step 2: If tuberculosis is active:

• Initiate standard rifampicin-based TB regimen without modification 3
• Defer sporotrichosis treatment until TB therapy completion if clinically feasible 5

Step 3: If sporotrichosis requires concurrent treatment:

• Consider terbinafine 500-1000 mg/day (off-label dosing based on sporotrichosis studies showing efficacy at these doses) 4
• Monitor for adverse effects, though terbinafine is generally well-tolerated even at 1000 mg/day 4
• Assess clinical response at 4-6 weeks; if inadequate, further increase terbinafine dose or switch to alternative antifungal 4

Step 4: After TB treatment completion:

• Wait 2 weeks for rifampicin enzyme induction to resolve 3
• Reduce terbinafine to standard 250 mg/day dosing if continuing treatment 1, 5