Can Eliquis (apixaban) cause rhabdomyolysis?

Apixaban (Eliquis) and Rhabdomyolysis

Apixaban (Eliquis) is not known to cause rhabdomyolysis based on current medical evidence and guidelines. Unlike statins which have a well-documented association with myopathy and rhabdomyolysis, direct oral anticoagulants (DOACs) like apixaban have not been linked to muscle breakdown.

Mechanism of Action and Known Side Effects

• Apixaban is a direct factor Xa inhibitor that works by inhibiting both free and prothrombinase-bound factor Xa, thereby preventing thrombin formation and clot development 1
• The primary adverse effect profile of apixaban centers around bleeding risk, not muscle toxicity 2
• Major clinical guidelines for apixaban use focus on bleeding complications rather than muscle-related adverse events 3

Medications Known to Cause Rhabdomyolysis

• Statins are well-documented to cause myopathy and rhabdomyolysis in 5-10% of patients, particularly when used with certain interacting medications 3
• Fibric acid derivatives (such as gemfibrozil and bezafibrate) have been associated with rhabdomyolysis, especially in patients with underlying renal impairment 4
• Drug-induced rhabdomyolysis typically occurs with medications that have high affinity for muscle tissue, which is not a characteristic of apixaban 5

Apixaban Safety Profile

• In major clinical trials evaluating apixaban (ARISTOTLE, ADVANCE-1, ADVANCE-2, ADVANCE-3), rhabdomyolysis was not reported as a significant adverse event 2, 6
• The primary safety concerns with apixaban are related to bleeding risk, with clinical trials showing lower rates of intracranial hemorrhage compared to warfarin 2
• Apixaban's metabolism occurs primarily through the liver via CYP3A4-dependent pathways with approximately 27% renal elimination 7

Drug Interactions to Consider

• The main concern with apixaban is drug interactions that may increase bleeding risk, not muscle toxicity 7
• Medications that inhibit CYP3A4 or P-glycoprotein could potentially increase apixaban levels, leading to increased bleeding risk, but not rhabdomyolysis 7
• Table 17 from the European guidelines lists medications that increase myopathy risk with statins, but apixaban is not included in these interactions 3

Monitoring Recommendations

• Routine monitoring for signs of rhabdomyolysis is not recommended for patients taking apixaban alone 3
• Patients should be monitored for signs of bleeding, which is the primary safety concern with apixaban 3
• If a patient on apixaban develops unexplained muscle pain, weakness, or dark urine, other causes should be investigated rather than assuming it's related to apixaban 5

Special Populations

• Patients with renal impairment require dose adjustments of apixaban due to increased bleeding risk, not due to muscle toxicity concerns 3
• Elderly patients (>75 years) may require closer monitoring for bleeding complications with apixaban, but not specifically for rhabdomyolysis 7

In conclusion, while drug-induced rhabdomyolysis is a serious condition that can lead to acute renal failure and electrolyte imbalances 5, there is no substantial evidence in current medical literature or guidelines linking apixaban to rhabdomyolysis. Clinicians should focus on monitoring for bleeding complications, which are the established adverse effects of this medication.