A possible interaction between favipiravir and methotrexate: Drug-induced hepatotoxicity in a patient with...

Area of Science:

• Pharmacology
• Hepatology
• Oncology

Background:

• Favipiravir is an antiviral medication increasingly used for SARS-CoV-2 infections.
• The potential for drug-drug interactions between favipiravir and chemotherapy agents remains largely uncharacterized.
• Patients with malignancy undergoing chemotherapy may be at risk for unknown adverse events when treated with novel antivirals.

Observation:

• A patient with metastatic osteosarcoma received high-dose methotrexate chemotherapy.
• Favipiravir was initiated due to suspected SARS-CoV-2 infection.
• The patient developed Grade 3 hepatotoxicity within 12 hours of starting favipiravir.

Findings:

• Hepatotoxicity was diagnosed as toxic hepatitis, likely resulting from a drug interaction between favipiravir and methotrexate.
• Viral and autoimmune liver disease panels were negative, ruling out other common causes of hepatitis.
• Liver enzymes normalized after discontinuation of favipiravir, and treatment with methylprednisolone was initiated.

Implications:

• Favipiravir may inhibit methotrexate elimination, potentially via aldehyde oxidase inhibition.
• Sequential administration of favipiravir and methotrexate can lead to significant hepatotoxicity.
• Clinicians must consider potential drug interactions when prescribing favipiravir alongside chemotherapy agents, especially in vulnerable patient populations.