Is there an interaction between Keytruda (pembrolizumab) and gabapentin?

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No Significant Interaction Between Keytruda (Pembrolizumab) and Gabapentin

There is no documented clinically significant interaction between Keytruda (pembrolizumab) and gabapentin, making this combination safe to use without dose adjustments.

Mechanism of Action and Metabolism

Keytruda (Pembrolizumab)

  • Pembrolizumab is a monoclonal antibody that targets PD-1 (programmed death-1) receptors
  • Unlike small molecule drugs, monoclonal antibodies:
    • Are not metabolized through cytochrome P450 enzyme systems
    • Are eliminated through proteolytic degradation
    • Have minimal potential for drug-drug interactions with medications metabolized by hepatic enzymes

Gabapentin

  • Gabapentin binds to voltage-gated calcium channels at the α-δ subunit
  • Has a favorable drug interaction profile:
    • Not metabolized by the liver
    • Excreted unchanged by the kidneys
    • Does not induce or inhibit hepatic enzymes
    • Has few documented drug interactions 1

Clinical Evidence

The absence of interaction between pembrolizumab and gabapentin is supported by:

  1. No specific warnings or contraindications regarding this combination in clinical guidelines
  2. Different metabolic and elimination pathways:
    • Pembrolizumab: proteolytic degradation (immune system)
    • Gabapentin: renal excretion (unchanged)

Considerations for Clinical Use

Dosing

  • No dose adjustments are required when using these medications together
  • Standard dosing can be maintained for both medications:
    • Gabapentin: Starting at 100-300 mg at bedtime or 100-300 mg three times daily, titrated as needed 1
    • Pembrolizumab: Standard oncology protocols based on indication

Monitoring

While no specific interaction exists, monitor for:

  • Expected side effects of each medication individually
  • Gabapentin side effects: dizziness, sedation, peripheral edema
  • Pembrolizumab side effects: fatigue, pruritus, diarrhea, rash, immune-mediated adverse events 1

Special Populations

Renal Impairment

  • Gabapentin requires dose adjustment in renal impairment as it is eliminated by the kidneys 1
  • Pembrolizumab does not require dose adjustment for renal impairment

Hepatic Impairment

  • Neither medication requires significant dose adjustment for mild hepatic impairment
  • Pembrolizumab has been studied in patients with various cancer types and comorbidities without specific hepatic dose adjustments

Conclusion

The combination of pembrolizumab and gabapentin can be safely administered without concerns for pharmacokinetic or pharmacodynamic interactions. This is particularly beneficial for cancer patients who may require gabapentin for neuropathic pain management, which is common in cancer treatment.

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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