What to Know About Methotrexate Weekly Dosing

The reason behind the weekly dose

The methotrexate dosage for rheumatoid arthritis and other inflammatory types of arthritis is to be taken weekly, not daily like most other medications. Because it is unlike the typical medication schedule, it may be confusing at first, unless your healthcare provider takes the time to thoroughly explain.

Mistakes have been made by patients who thought "weekly" was a mere typographical error on the label of their methotrexate prescription bottle. If you are ever in doubt, call your pharmacist and your healthcare provider. Double-check or triple-check the directions if need be. It is incredibly important to get your dosage right. Too often, the Institute for Safe Medication Practices receives reports of oral methotrexate overdose due to accidental daily dosing.

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Weekly Dose of Methotrexate

Methotrexate was a cancer drug before it was approved for rheumatoid arthritis. The dosage used for rheumatoid arthritis and other inflammatory diseases is small compared to that used for cancer. Typically, people with rheumatoid arthritis are initially prescribed three 2.5 milligram methotrexate pills (7.5 milligrams total) to be taken together once weekly, on the same day of the week (e.g., every Saturday). As needed, the healthcare provider may increase the dose, but it still is taken weekly, not daily.

There is the potential for severe toxic effects, especially hepatoxicity, if methotrexate is mistakenly taken daily. You must never increase the prescribed dose of methotrexate or change the dosing schedule on your own.

Optimal Methotrexate Dose for Rheumatoid Arthritis

The usual adult dose of methotrexate for rheumatoid arthritis is, as mentioned above, 7.5 milligrams as a single weekly dose. It can be taken as a divided dose: 2.5 milligrams taken orally every 12 hours for 3 divided doses over 36 hours once a week. The usual maximum weekly adult dose for oral methotrexate is 20 milligrams (due to increased risk of bone marrow suppression). The usual oral pediatric dose of methotrexate for rheumatoid arthritis is 5 to 15 milligrams once weekly.

According to research, the optimal evidence-based dose recommendation for adults with rheumatoid arthritis involves a starting dose of 15 milligrams of oral methotrexate once a week. That dose may be gradually increased to 25-30 milligrams per week or the highest tolerable dose. A switch to injectable methotrexate can be made by people with rheumatoid arthritis who achieve an insufficient response with oral methotrexate or for those who cannot tolerate the oral formulation. No matter what adjustments are made, it must remain as a weekly dose.

Other Warnings for Methotrexate

Methotrexate is associated with increased toxicity if taken with certain other medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), acid reflux medications, and some antibiotics. Such drug interactions may cause harmful toxicity, and possibly even death. Make sure your healthcare provider has a complete list of all medications that you take and discuss possible interactions with methotrexate.

Methotrexate should not be taken by people who have liver disease, significant kidney disease, alcoholism, blood disorders (e.g., anemia, leukopenia) or a bone marrow disorder. Methotrexate should also not be used by women who are pregnant or who are breastfeeding. It also should be stopped by both women and men who are planning a pregnancy.

If you experience signs of an allergic reaction while taking methotrexate, seek emergency medical attention. Such signs would include hives, skin reactions, difficulty breathing, swelling of face, lips, tongue, or throat. You should discontinue methotrexate and call your healthcare provider if you develop a dry cough, shortness of breath, diarrhea, vomiting, white patches or sores inside your mouth, blood in urine or stool, rapid weight gain, decreased urine production, seizure, fever, chills, flu symptoms, weakness, lightheadedness, or any other unusual symptom.

The most common side effects associated with methotrexate are nausea, headache, dizziness, fatigue, and blurry vision. To avoid nausea, divide the dose throughout the day, or another option would be to give methotrexate by subcutaneous injection.

A Word From Verywell

Methotrexate can be a safe and effective medication for rheumatoid arthritis if taken properly. It must be taken according to directions, with no deviation from those directions. Never take more than is prescribed and do not switch the weekly schedule. Be aware of potential side effects, especially serious adverse events, and notify your healthcare provider immediately if anything worrisome develops.

You will be required to have laboratory tests periodically to monitor blood cell counts, liver enzymes, and kidney function. Do not drink alcohol while taking methotrexate. Let your healthcare provider know if you develop an active infection. Ask your practitioner about taking antibiotics for the infection. It is also important to discuss vaccinations with your healthcare provider. People who are taking higher doses of methotrexate should avoid live vaccines. Bottom line—for safe use of methotrexate, you must strictly follow directions and pay attention to warnings and precautions. Talk openly with your healthcare provider about anything that remains unclear, or anything that is concerning to you.

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7 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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