These strategies can prevent accidental daily methotrexate dosing
Institute for Safe Medication Practices
Methotrexate is a folic acid antagonist that was originally approved to treat a variety of cancers. For oncologic indications, methotrexate is administered in cyclical frequencies and in variable doses based on body surface area and the type of cancer being treated. The labeled indications for methotrexate later expanded to include treatment of nononcologic conditions, including psoriasis and rheumatoid arthritis. Methotrexate also is prescribed for other nononcologic off-label uses (e.g., Crohn’s disease, multiple sclerosis). For most nononcologic indications, a low dose of methotrexate is administered just once or twice weekly (e.g., 7.5 mg/wk when treating rheumatoid arthritis).
A high-alert medication
Relatively few medications are dosed weekly; thus, accidental daily dosing of oral methotrexate has occurred all too frequently. This type of wrong frequency error has originated in all stages of the medication use process, from prescribing to self-administration. These errors have resulted in serious overdoses that have led to vomiting, mouth sores, stomatitis, skin lesions, liver and renal failure, severe myelosuppression, GI bleeding, life-threatening pulmonary symptoms, and in some cases, death.
Since early 1996, harmful or fatal errors with daily oral methotrexate for nononcologic use have been reported to the Institute for Safe Medication Practices (ISMP). ISMP has designated oral methotrexate for nononcologic use as a high-alert medication since 2003. Although the risk of errors with oral methotrexate for nononcologic use has been known for a long time, harmful and fatal errors are still occurring today.
Fatal error
The most recent event involved an error that was caught during hospitalization but continued upon discharge when an incorrect entry for daily methotrexate on a patient’s home medication list was not corrected. An older adult with rheumatoid arthritis was admitted to a hospital with renal failure. At home, he had been taking oral methotrexate 2.5 mg twice weekly. When completing the list of the patient’s home medications, the admitting physician mistakenly documented that the patient had been taking 2.5 mg of oral methotrexate twice daily instead of twice weekly. He then made this an active order during the patient’s hospitalization.
Noticing the daily order for methotrexate, a pharmacist contacted the physician to let him know that he must prescribe daily methotrexate on a hospital-mandated chemotherapy order template. However, the pharmacist did not verify that the patient had an appropriate oncologic indication for the order. The physician then prescribed the daily methotrexate via a chemotherapy order template. Fortunately, an oncology pharmacist identified the error after talking to the patient and corrected the active order to twice weekly. However, it never occurred to the pharmacist to correct the methotrexate entry on the patient’s home medication list.
The patient received the correct dose during his hospital stay before being transferred to a skilled nursing facility. The physician reconciled the patient’s list of home medications for continuation upon discharge. In doing so, he pulled the erroneous methotrexate entry from the patient’s home medication list and prescribed oral methotrexate 2.5 mg twice daily. The patient received twice-daily methotrexate at the skilled nursing facility for more than a week before he was rehospitalized with a change in mental status, severe neutropenia, and mucositis.
Sadly, he died in the hospital about a week later.
Strategies
Most of the wrong frequency errors with methotrexate could be prevented by fully implementing long-standing risk reduction strategies, including the following:
■Defaulting to a weekly dosing schedule in prescriber and pharmacy order entry systems
■Requiring verification and entry of an appropriate oncologic indication in order entry systems for daily orders
■Educating patients and providing them with verbal and written instructions that specify the weekly dosing schedule, and emphasizing the danger with taking daily or extra doses
■Asking patients to repeat back the instructions for taking oral methotrexate to validate understanding
■Verifying the dose and frequency of all medication lists and discharge instructions
■Limiting the prescription quantity to a 30-day supply (e.g., dispensing just eight 2.5-mg tablets for a 5-mg/wk dose would reduce the risk of a serious overdose)
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