Safety of Desmodium with Eliquis (Apixaban)
The combination of Desmodium adscendens with apixaban should be avoided or used with extreme caution due to documented CYP enzyme induction by Desmodium, which can significantly reduce apixaban levels and increase thrombotic risk.
Critical Drug Interaction Mechanism
Desmodium adscendens induces CYP enzymes, which directly threatens apixaban's efficacy. Research demonstrates that Desmodium extract causes induction of CYP enzymes in animal studies, evidenced by decreased zoxazolamine paralysis time and prevention of thiopentone-induced sleep 1. This CYP induction represents a serious concern because:
- Apixaban is metabolized through CYP3A4 pathways and is also a substrate of P-glycoprotein (P-gp) and BCRP transporters 2, 3
- Strong CYP3A4 inducers should be avoided with apixaban according to expert consensus 2
- Rifampin, a strong CYP3A4 inducer, significantly reduces apixaban levels and increases thrombotic risk, serving as a clear precedent for avoiding CYP inducers 4
Evidence-Based Risk Assessment
The magnitude of CYP induction by Desmodium is concerning:
- The study authors explicitly warn of "possible drug interaction when the plant extract is co-administered with other drugs" due to CYP enzyme induction 1
- Moderate CYP3A4 inducers can reduce apixaban exposure by 50% or more, as demonstrated with rifampin 2
- Any reduction in apixaban exposure increases the risk of stroke or systemic embolization in patients requiring anticoagulation 2
Clinical Implications
The risk-benefit analysis strongly favors avoiding this combination:
- Desmodium's CYP-inducing properties could reduce apixaban plasma concentrations to subtherapeutic levels 2, 1
- Unlike dose-adjustable interactions, there is no established safe dosing strategy for apixaban when combined with CYP inducers 2
- Patients taking apixaban typically have serious indications (atrial fibrillation, VTE treatment/prevention) where loss of anticoagulant effect could be catastrophic 2
Alternative Recommendations
If Desmodium use is deemed essential, consider these alternatives:
- Switch to low molecular weight heparin (LMWH) during Desmodium therapy, as LMWH is not affected by CYP enzyme induction 4
- Edoxaban may be a safer DOAC alternative as it is minimally metabolized by CYP3A4 compared to apixaban 4
- Warfarin with INR monitoring could allow detection of any interaction effects, though warfarin itself has CYP-related interactions 2
Critical Monitoring if Combination Cannot Be Avoided
If the combination must be used despite these warnings:
- Monitor closely for signs of thromboembolism including stroke symptoms, leg swelling, chest pain, or shortness of breath 2
- Consider measuring anti-Xa levels if available, though clinical correlation with apixaban is not well-established 2
- Assess renal function, as impaired clearance could partially compensate for reduced absorption, though this is unpredictable 2
- Avoid any additional medications that induce CYP3A4 or P-gp to prevent compounding the interaction 2
Additional Safety Concerns
Beyond the CYP interaction, other considerations include:
- The LD50 of Desmodium extract was 1122 mg/kg in rats, indicating potential toxicity at high doses 1
- Desmodium at 100 mg/ml significantly decreased cell viability by 40% in hepatocyte studies 5
- Many patients on apixaban also take other medications or supplements that could interact, with 33% taking potentially interacting products daily 6