Perampanel and Methotrexate Interactions
There are no documented pharmacokinetic or pharmacodynamic interactions between perampanel and methotrexate, and these medications can be safely co-administered in patients requiring both antiepileptic therapy and methotrexate for conditions such as rheumatoid arthritis or malignancy. 1
Evidence for Safety of Concurrent Use
A comprehensive review of drug interactions with newer antiepileptic drugs specifically examined perampanel and found only three pharmacodynamic interactions described across all newer AEDs, with perampanel associated with minimal interaction potential overall. 1
Perampanel does not induce or inhibit hepatic enzymes in a clinically significant manner, which is the primary mechanism by which drug interactions with methotrexate typically occur. 1
The review of 68 pharmacokinetic interactions involving newer antiepileptic drugs and non-epilepsy medications did not identify any interactions between perampanel and methotrexate or other antifolate/antineoplastic agents. 1
Standard Methotrexate Monitoring Remains Essential
Regardless of perampanel co-administration, maintain standard methotrexate monitoring protocols:
Complete blood count (CBC) and platelet counts every 2-4 weeks for the first few months, then every 1-3 months thereafter. 2
Liver function tests at monthly intervals. 2
BUN and creatinine every 2-3 months. 2
Folic acid supplementation at 1-5 mg daily (except on methotrexate dosing days) to reduce methotrexate side effects. 2
Clinically Relevant Drug Interactions to Avoid with Methotrexate
While perampanel is safe, be vigilant about other medications that DO interact with methotrexate:
High-dose trimethoprim-sulfamethoxazole (800 mg/160 mg twice daily) should be avoided entirely due to risk of severe pancytopenia, mucositis, and renal toxicity. 2
NSAIDs require caution as they interfere with renal secretion of methotrexate, though concurrent use appears safe with appropriate monitoring in rheumatoid arthritis patients. 2, 3
Anti-inflammatory doses of aspirin (≥2 g daily) should be avoided due to adverse effects on liver and renal function. 3
Other hepatotoxic drugs require increased monitoring frequency when combined with methotrexate. 2
Warning Signs Requiring Immediate Attention
Educate patients to report immediately:
Fever or flu-like illness. 4
Mouth ulceration or unusual bruising/bleeding of gums. 4
Severe nausea, vomiting, or abdominal pain. 4
Dark urine, breathlessness, or persistent cough. 4
Special Populations Requiring Closer Monitoring
Patients with renal impairment require more cautious methotrexate dosing and monitoring due to reduced drug elimination. 2
Elderly patients may need closer monitoring due to age-related changes in drug metabolism and elimination. 2
Maintain adequate hydration in all patients on methotrexate to ensure proper drug elimination. 2
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