No Clinically Significant Drug-Drug Interaction Between Eliquis and Clindamycin
There is no clinically significant drug-drug interaction between apixaban (Eliquis) and clindamycin, and they can be safely co-prescribed without dose adjustment. 1
Pharmacokinetic Rationale
Clindamycin does not affect the critical metabolic pathways for apixaban. Apixaban is metabolized primarily through CYP3A4 and is a substrate for P-glycoprotein (P-gp) transport. 1, 2
Only strong dual inhibitors or inducers of both CYP3A4 AND P-gp require dose adjustment or avoidance with apixaban. 1 Clindamycin does not significantly inhibit or induce either of these pathways.
Clindamycin is classified as a low-risk antibiotic for anticoagulant interactions. In a large cohort study of warfarin users, clindamycin was specifically identified as a low-risk antibiotic that did not increase bleeding risk, unlike high-risk antibiotics such as trimethoprim/sulfamethoxazole, ciprofloxacin, levofloxacin, metronidazole, and azithromycin. 3
Clinical Evidence on Antibiotic-Anticoagulant Interactions
The antibiotics that DO interact with anticoagulants work through different mechanisms than clindamycin. High-risk antibiotics like trimethoprim/sulfamethoxazole (HR 2.09), ciprofloxacin (HR 1.87), and clarithromycin (HR 2.40) significantly increase bleeding risk with warfarin through CYP450 inhibition or disruption of vitamin K-producing gut flora. 3
Clindamycin was used as a control "low-risk" antibiotic in major studies examining antibiotic-anticoagulant interactions. This designation confirms its safety profile when combined with anticoagulants. 3
Even with DOACs like apixaban, the antibiotics that increase bleeding risk are those with CYP3A4/P-gp effects. A retrospective study of 115,362 DOAC users found that NSAIDs, antiplatelet agents, diltiazem, and amiodarone were the most common drugs associated with bleeding—not clindamycin. 4
Important Clinical Caveats
Monitor for general bleeding signs as with any anticoagulant therapy. While clindamycin doesn't interact pharmacokinetically, all patients on apixaban should be counseled to watch for unusual bruising, blood in urine or stool, or prolonged bleeding. 2
The infection itself may affect bleeding risk more than the antibiotic. Acute illness, fever, and decreased oral intake can affect anticoagulant levels through mechanisms unrelated to drug interactions. 1
Avoid combining apixaban with NSAIDs during the antibiotic course. If additional pain relief is needed during clindamycin therapy, use acetaminophen rather than NSAIDs, as NSAIDs significantly increase bleeding risk with apixaban independent of any antibiotic effect. 2, 4
Practical Management
No dose adjustment of apixaban is needed when starting clindamycin. Continue the standard apixaban dose (typically 5 mg twice daily, or 2.5 mg twice daily if dose-reduction criteria are met). 1
No additional INR or anti-Xa monitoring is required. Unlike warfarin, apixaban does not require routine monitoring, and clindamycin does not necessitate any special laboratory surveillance. 1
Ensure adequate renal function assessment. While unrelated to the clindamycin interaction, verify that apixaban dosing remains appropriate for the patient's current renal function, as acute illness may affect kidney function. 5