Methotrexate: three tablets daily or weekly?
A 68-year-old woman with rheumatoid arthritis brings a handwritten prescription to a community pharmacy. It reads: 'Methotrexate 2.5 mg tablets - 3 tablets daily for 7 days, then review.' The prescription is dated, signed, and stamped by a rheumatology clinic, and the quantity is 21 tablets. The pharmacy's medication record shows she has filled methotrexate 2.5 mg before, with directions '3 tablets once weekly', plus folic acid 5 mg once weekly and ibuprofen 400 mg as needed. Her estimated glomerular filtration rate is 55 mL/min/1.73 m². The rheumatology clinic is closed for a public holiday; an on-call physician is reachable by phone. The patient says, 'I have always taken three tablets once a week.' She has not yet started this new supply. She has no mouth ulcers, fever, or dyspnea today. The pharmacy has no electronic prescribing link.
1. Identify the dosing discrepancy and quantify the risk. What is the correct weekly dose and what would the prescribed daily course deliver? What should the technician do before dispensing?
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The discrepancy. The correct regimen for rheumatoid arthritis is 7.5 mg once weekly (three 2.5 mg tablets). The new prescription says 7.5 mg daily for 7 days: 52.5 mg in a week, seven times the intended weekly dose. Methotrexate is a folate antagonist cleared renally; daily dosing causes prolonged intracellular polyglutamation and can produce severe myelosuppression, mucositis, hepatotoxicity, renal impairment, and pneumonitis. This is a recognized fatal medication error, so the prescription must not be dispensed as written.
Immediate action. Call the on-call physician, read the exact prescription, state the discrepancy with the old record, and ask for a corrected order. If the prescriber confirms weekly dosing, document the name, time, advice, and corrected directions, and amend the label. If the prescriber cannot be reached, do not dispense; explain to the patient that the directions look unsafe and arrange contact the next working day. Do not give an emergency supply of methotrexate. If the patient had already taken any daily doses, send her for same-day clinical assessment with CBC, liver enzymes, and creatinine; leucovorin may be needed.
Other issues. eGFR 55 means reduced renal clearance, so any dose increase or interacting drug matters. Ibuprofen can reduce methotrexate clearance and add GI and renal risk; this should be raised with the prescriber. Folic acid 5 mg weekly is consistent with the record but should be confirmed.
2. Describe the counseling and documentation, including what to tell the patient about folic acid and ibuprofen and what to do if the prescriber cannot be reached.
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Counseling. Explain that methotrexate is taken once a week, on the same day, and never daily; the daily instruction was a prescribing error. Use a written schedule and a pill calendar. Tell her to report mouth ulcers, fever, sore throat, unusual bruising or bleeding, breathlessness, nausea, or dark urine immediately. Avoid alcohol and unprescribed NSAIDs; paracetamol may be acceptable for pain but check the total daily dose and liver status. Continue folic acid only as prescribed, usually on a different day from methotrexate, and do not double doses.
Documentation. Record the original prescription, the old medication record, the call to the on-call physician, the corrected order, the pharmacist's approval, the label change, and the counseling points. Keep the erroneous prescription in the file according to policy. File an internal incident report so the clinic and pharmacy can review the handwriting or electronic prescribing problem.
If no prescriber is reachable. Do not dispense methotrexate on a 'daily' label. Explain the risk, give the patient a written note of the concern, and arrange urgent contact. The patient should not take any of the new supply until the directions are confirmed.