Drug Interactions Between Thiocholchicoside and Methotrexate/Tofacitinib
There are no documented clinically significant drug interactions between thiocholchicoside (a muscle relaxant) and either methotrexate or tofacitinib based on available evidence, though theoretical considerations warrant monitoring for additive central nervous system effects.
Evidence Review
Methotrexate Interactions
The FDA drug label for methotrexate provides comprehensive interaction warnings but does not list thiocholchicoside or muscle relaxants as contraindicated or requiring dose adjustment 1. The primary methotrexate interactions of concern involve:
- NSAIDs (particularly with high-dose methotrexate, though lower doses used in RA appear safer) 1
- Drugs affecting renal tubular secretion (probenecid, penicillins, salicylates) 1
- Hepatotoxic agents (azathioprine, retinoids, sulfasalazine) requiring close monitoring 1
- Folate antagonists (trimethoprim/sulfamethoxazole) 1
Notably, a study specifically examining methotrexate with NSAIDs (ibuprofen and flurbiprofen) found no significant pharmacokinetic interactions at low doses used in arthritis 2, suggesting that concerns about drug interactions with methotrexate may be overstated for non-mechanistically related compounds.
Tofacitinib Interactions
Current guidelines and FDA labeling for tofacitinib focus on:
- CYP3A4 inhibitors requiring dose reduction to 5 mg once daily 3
- Immunosuppressants (contraindicated with azathioprine, cyclosporine, or biologics) 3
- Methotrexate combination is explicitly approved and commonly used 4, 3
Neither the EULAR consensus statement on JAK inhibitors 4 nor the ACR guidelines 4 mention muscle relaxants or thiocholchicoside as problematic combinations.
Clinical Considerations
Theoretical Concerns
- CNS depression: Thiocholchicoside has muscle relaxant properties that could theoretically add to any CNS effects, though methotrexate and tofacitinib are not primarily CNS-active drugs
- Hepatic metabolism: All three drugs undergo hepatic metabolism, but there is no evidence of competitive inhibition or clinically relevant interactions
Monitoring Recommendations
While no specific interactions are documented, prudent monitoring includes:
- Standard methotrexate monitoring: CBC, liver enzymes, and renal function every 1-2 months as per guidelines 4, 1
- Standard tofacitinib monitoring: CBC at baseline and periodically, liver enzymes, lipids at 4-12 weeks 4, 3
- Clinical assessment: Monitor for excessive sedation or dizziness if thiocholchicoside is initiated, though this is not a documented concern
Bottom Line
Thiocholchicoside can be safely used with methotrexate and tofacitinib in RA patients, as there are no documented pharmacokinetic or pharmacodynamic interactions requiring dose adjustment or contraindication. Standard monitoring protocols for methotrexate 4, 1 and tofacitinib 3 should be maintained regardless of thiocholchicoside use. The combination of methotrexate with tofacitinib itself is well-established and recommended in guidelines 4, with superior efficacy compared to either agent alone in many patients 5, 6, 7.