Does Keytruda (pembrolizumab) interact with statins (HMG-CoA reductase inhibitors)?

Keytruda (Pembrolizumab) Does Not Have Significant Interactions with Statins

There is no evidence of clinically significant drug interactions between Keytruda (pembrolizumab) and statins (HMG-CoA reductase inhibitors).

Mechanism and Metabolism Considerations

Keytruda (pembrolizumab) is a monoclonal antibody that works as an immune checkpoint inhibitor, specifically targeting PD-1 receptors. Unlike small molecule drugs such as tyrosine kinase inhibitors, Keytruda has a different metabolic pathway:

• Pembrolizumab is not metabolized through the cytochrome P450 (CYP) enzyme system that metabolizes most statins
• Monoclonal antibodies like pembrolizumab are primarily eliminated through proteolytic degradation into peptides and amino acids
• Statins are primarily metabolized by the liver through various CYP enzymes (particularly CYP3A4 for atorvastatin, simvastatin, and lovastatin)

Evidence Assessment

The available guidelines do not specifically address interactions between pembrolizumab and statins. However:

• The British Journal of Pharmacology guideline on drug-drug interactions with tyrosine kinase inhibitors 1 documents various interactions between TKIs and statins (particularly pazopanib with simvastatin causing transaminase elevations), but does not mention any interactions with monoclonal antibodies like pembrolizumab
• The American Heart Association guideline 1 extensively discusses statin interactions with various drug classes but does not identify immune checkpoint inhibitors like pembrolizumab as having significant interactions with statins

Clinical Management Approach

When managing patients on both Keytruda and statins:

1. Continue statin therapy as indicated for cardiovascular risk reduction in patients receiving pembrolizumab
2. No dose adjustments are necessary for either medication based on this combination
3. Monitor liver function tests as part of routine care for both medications independently (both can rarely cause hepatotoxicity on their own)
4. Be aware of statin interactions with other medications that may be part of the patient's regimen:
   • Avoid gemfibrozil with lovastatin, pravastatin, and simvastatin 1
   • Use caution with CYP3A4 inhibitors and statins metabolized by this pathway

Important Considerations

• While pembrolizumab itself doesn't interact with statins, cancer patients often receive multiple medications that might interact with statins
• If a patient on pembrolizumab requires a statin but has concerns about drug interactions with other medications, consider pravastatin, rosuvastatin, or pitavastatin which have fewer CYP-mediated drug interactions
• Routine monitoring of muscle symptoms is recommended for all patients on statins regardless of concurrent pembrolizumab therapy

In conclusion, patients can safely receive both Keytruda and statin therapy without concerns about pharmacokinetic drug interactions between these specific agents.