Why Rifampicin and Tofacitinib Cannot Be Combined
Rifampicin is a potent CYP3A4 inducer that dramatically reduces tofacitinib blood levels, leading to loss of therapeutic efficacy and treatment failure—coadministration is not recommended. 1
Mechanism of the Drug Interaction
Rifampicin induces hepatic cytochrome P450 enzymes, particularly CYP3A4, which is the primary metabolic pathway for tofacitinib (responsible for approximately 70% of its metabolism). 2, 1 This enzyme induction causes:
- Accelerated metabolism of tofacitinib, resulting in substantially decreased plasma concentrations 1, 3
- Full enzyme induction occurs within approximately 1 week of starting rifampicin and persists for roughly 2 weeks after discontinuation 3
- Loss of clinical response due to subtherapeutic tofacitinib levels 1
Clinical Evidence of Treatment Failure
Real-world data demonstrates the clinical significance of this interaction:
- Discontinuation rates within 6 months were dramatically higher in rheumatoid arthritis patients receiving tofacitinib with rifampicin for latent tuberculosis compared to those without rifampicin (38.9% vs. 11.2% for all causes; 24.7% vs. 5.1% for lack of efficacy, P<0.01) 4
- Uncontrolled disease activity was the primary reason for early tofacitinib discontinuation in patients co-treated with rifampicin 4
Official Contraindication
The FDA drug label explicitly states that coadministration with strong CYP3A4 inducers like rifampicin is not recommended due to decreased tofacitinib exposure and potential loss of clinical response. 1
Critical Clinical Pitfalls to Avoid
When Treating Latent Tuberculosis in Patients Requiring JAK Inhibitors
- Complete rifampicin-based latent TB treatment BEFORE initiating tofacitinib whenever possible 5
- If tofacitinib must be started urgently, use alternative TB prophylaxis regimens that avoid rifampicin (such as isoniazid monotherapy for 9 months) 2
- Never assume dose escalation of tofacitinib will overcome the interaction—the magnitude of enzyme induction makes this approach ineffective and potentially dangerous 2
The "Washout Period" Problem
- After discontinuing rifampicin, wait at least 2 weeks before expecting full tofacitinib efficacy, as enzyme induction persists during this period 3
- Conversely, if rifampicin must be added to a patient already on tofacitinib, expect rapid loss of disease control within 1 week as enzyme induction reaches maximum effect 3
Alternative Management Strategies
For Tuberculosis Treatment
- Rifabutin has fewer CYP450 interactions than rifampicin and may be considered as an alternative rifamycin, though specific dosing guidance for use with tofacitinib is not established 2
- Non-rifamycin regimens for latent TB (such as 9-month isoniazid) should be strongly considered in patients requiring JAK inhibitor therapy 2
For JAK Inhibitor Selection
- Baricitinib (70% renal excretion) has minimal CYP450 metabolism and may be a safer alternative if a JAK inhibitor is essential during rifampicin therapy, though formal interaction studies are lacking 2
- Filgotinib is metabolized by hepatic carboxylesterases rather than CYP450 and theoretically has lower interaction potential 2
Broader Context of Rifampicin Interactions
Rifampicin is notorious for causing clinically significant interactions with numerous drug classes beyond JAK inhibitors, including oral contraceptives, corticosteroids, anticoagulants, immunosuppressants (cyclosporin), HIV protease inhibitors, and many others. 6, 7, 3, 8 The interaction with tofacitinib follows this well-established pattern of rifampicin rendering orally administered CYP3A4 substrates therapeutically ineffective. 3