Does Aricept (donepezil) interact with methotrexate?

Donepezil (Aricept) and Methotrexate Interaction

There is no documented significant interaction between donepezil (Aricept) and methotrexate, and they can generally be used concurrently without specific concerns about direct drug interactions.

Pharmacology and Metabolism Considerations

• Donepezil is a reversible acetylcholinesterase inhibitor that is well absorbed orally, reaches peak plasma concentrations in 3-4 hours, and has a long elimination half-life of approximately 70 hours 1, 2
• Donepezil is primarily metabolized by the liver and excreted unchanged in urine, with minimal potential for significant drug interactions 1, 2
• Methotrexate is primarily eliminated through renal excretion, with some metabolism occurring in the liver 3
• The metabolic pathways of these medications are distinct, reducing the likelihood of pharmacokinetic interactions 1, 2, 3

Safety Profile

• Donepezil is generally well-tolerated with minimal liver toxicity and few significant drug interactions 1, 2
• Common side effects of donepezil include nausea, vomiting, diarrhea, insomnia, muscle cramps, fatigue, anorexia, and syncope 1, 2
• Methotrexate can cause hepatotoxicity, bone marrow suppression, and other adverse effects that require regular monitoring 4
• There is no evidence in the literature suggesting that donepezil increases methotrexate toxicity or vice versa 1, 2

Monitoring Recommendations

• When using methotrexate, standard monitoring includes:
  • Complete blood count (CBC) and platelet counts initially every 2-4 weeks for the first few months, then every 1-3 months 4
  • Liver function tests (LFTs) at monthly intervals 4
  • BUN and creatinine every 2-3 months 4
• No additional monitoring is specifically required when adding donepezil to methotrexate therapy 1, 2

Important Considerations for Methotrexate

• Methotrexate does have documented interactions with other medications that should be avoided, including:
  • Hepatotoxic drugs (though donepezil is not in this category) 4
  • Drugs that interfere with renal secretion of methotrexate (e.g., NSAIDs, penicillins, sulfamethoxazole) 4, 5, 6
  • Folic acid antagonists (e.g., trimethoprim) 4, 3
• Folic acid supplementation (1-5 mg daily except on methotrexate dosing days) is recommended to reduce methotrexate side effects 4, 5

Special Precautions

• In patients with renal impairment, both medications should be used with caution as both have some degree of renal elimination 5, 1, 2
• Elderly patients may require closer monitoring due to age-related changes in drug metabolism and elimination 5, 2
• Maintain adequate hydration in patients on methotrexate to ensure proper drug elimination 5

Clinical Approach

• No dosage adjustments are necessary when using donepezil and methotrexate concurrently 1, 2
• Continue standard monitoring protocols for methotrexate as recommended in guidelines 4
• Educate patients about the side effect profiles of each medication individually, as there are no specific combined effects to watch for 1, 2