Published November 4, 2024
Methotrexate is a medicine used to treat certain types of cancer. Doctors also prescribe methotrexate to treat other conditions such as severe rheumatoid arthritis and psoriasis (a skin condition). However, the dose and frequency of taking the medicine are different based on the condition being treated. For example, when used to treat cancer, methotrexate is often taken daily for 5 days or more at a higher dose. When used to treat rheumatoid arthritis or psoriasis, methotrexate is usually taken just once or twice a week at a lower dose. People often begin by taking a single 7.5 mg tablet once a week, or three 2.5 mg tablets per week, each taken 12 hours apart. The doctor may increase the weekly dose up to about 25 mg if needed. But if you take methotrexate every day by accident, you could be harmed. There are reports of this type of error probably because most people are more familiar with taking medicines every day rather than once a week. Some of these errors have even resulted in death.
Since early 1996, harmful or fatal errors with low-dose oral methotrexate have been reported to the Institute for Safe Medication Practices (ISMP). One example of an event involved an elderly woman with rheumatoid arthritis. Her doctor had prescribed 15 mg of methotrexate once every week. The pharmacy provided the woman with a 3-month supply of the medicine. Unfortunately, the directions on the prescription bottle were wrong. The label instructed the woman to take 15 mg daily instead of weekly. The woman took the medicine daily until the 3-month supply was finished. The error was discovered when the woman tried to refill the prescription just 3weeks after first filling it. She developed severe toxic effects and had to be treated in the hospital for several weeks.
Serious harm or death can also happen when taking methotrexate along with some other medicines. Examples include prescription and over-the-counter (OTC) pain medicines called nonsteroidal anti-inflammatory drugs (NSAIDs), such as Motrin or Advil (ibuprofen); medicines used to treat stomach acid associated with gastric reflux or stomach ulcers; and certain antibiotics. A serious reaction can occur because these medicines increase the toxic effects of methotrexate. When one medicine affects another medicine, it is called a drug-drug interaction. Two fatal events caused by drug-drug interactions with low-dose methotrexate were reported.
In the first case, an elderly man with kidney disease doubled his weekly methotrexate dose from 10 mg to 20 mg without his doctor’s approval because his rheumatoid arthritis symptoms were getting worse. The man was also taking the antibiotic amoxicillin to treat an infection. The next day, his doctor also gave him a prescription for leflunomide, another medicine to treat rheumatoid arthritis. Within a week, the man was hospitalized with a very low blood count. Despite all efforts to treat him, the man died. His kidney disease, doubling of the methotrexate dose without his doctor’s knowledge, and the drug interactions from taking amoxicillin and leflunomide together with methotrexate all contributed to his death.
In the other case, an elderly man with rheumatoid arthritis was hospitalized with a fractured leg caused by a fall. While in the hospital, his weekly dose of methotrexate 20 mg was continued. He was also receiving the pain medicine, diclofenac, as needed every 6 hours. Diclofenac is an NSAID, much like Advil and Motrin but only available with a prescription. The man’s doctor, pharmacists, and nurses failed to address the potentially serious drug-drug interaction that occurs when taking diclofenac and methotrexate together. The man developed kidney failure and extremely low blood counts, and died.
Even when low-dose methotrexate is taken correctly, severe side effects can occur that can lead to hospitalization or death. Methotrexate primarily affects the blood cell counts causing them to become low. If blood cell counts are not regularly checked, people can quickly become very sick and possibly die. Some of the more common side effects include nausea, vomiting, and diarrhea. The medicine can also cause stomach, kidney, liver, brain, and spinal cord problems. Because the kidneys and liver help eliminate methotrexate from the body, kidney or liver problems may increase the risk of developing serious side effects even when taking low-dose methotrexate. But when methotrexate is taken daily or with certain medicines that cause serious drug interactions, these life-threatening side effects may become difficult or impossible to treat.
Here’s what you can do: To avoid mistakes or serious drug-drug interactions with oral methotrexate, consider the following:
When receiving a prescription
When dropping off a prescription
When picking up your prescription
When taking your medicine
