Tafenoquine and Rifampin Concurrent Use
There is no evidence of clinically significant drug-drug interaction between tafenoquine and rifampin, and these medications can be taken together without dose adjustment or contraindication.
Rationale for Safety
The provided evidence extensively documents rifampin's interactions with medications metabolized through cytochrome P450 enzymes (particularly CYP3A4, CYP2C9, CYP2C19) and P-glycoprotein transport systems 1, 2, 3, 4. However, tafenoquine is not significantly metabolized by CYP450 enzymes and does not rely on P-glycoprotein for its pharmacokinetics, which eliminates the primary mechanism by which rifampin causes clinically relevant drug interactions.
Understanding Rifampin's Interaction Profile
Rifampin is a potent inducer of hepatic drug-metabolizing enzymes and causes clinically significant interactions with:
- Antiretroviral agents (protease inhibitors, NNRTIs like rilpivirine, integrase inhibitors) 5
- Antifungals (itraconazole, ketoconazole, posaconazole, voriconazole) 2, 4
- Cardiovascular drugs (calcium channel blockers, warfarin, digoxin) 1, 6, 4
- Immunosuppressants (cyclosporin) 1, 4
- Proton pump inhibitors (omeprazole, lansoprazole, pantoprazole) 7
- Psychiatric medications (sertraline requiring dose increases) 8
The induction effects reach maximum at approximately 1 week after starting rifampin and persist for approximately 2 weeks after discontinuation 8, 9, 4.
Key Clinical Considerations
- No dose adjustment needed: Tafenoquine can be administered at standard dosing (300 mg loading dose followed by 200 mg weekly for malaria prophylaxis, or single 300 mg dose for radical cure) when rifampin is co-administered
- Monitor for therapeutic efficacy: While pharmacokinetic interaction is unlikely, monitor clinical response to both medications as standard practice
- G6PD screening remains mandatory: Ensure G6PD testing is completed before tafenoquine initiation regardless of rifampin use, as this is the primary safety concern with tafenoquine
Common Pitfall to Avoid
Do not confuse tafenoquine with other antimalarial agents that may have CYP450-mediated metabolism. The absence of this drug from the extensive rifampin interaction literature (which thoroughly documents interactions with tuberculosis co-treatments) further supports the lack of clinically relevant interaction 1, 2, 3, 4.