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Side Effects of Methotrexate (Anti-Rheumatic) Oral

Written by
Dr. Saumya Mittal
and medically reviewed by iCliniq medical review team.

Published on Nov 29, 2013 and last reviewed on Sep 07, 2018   -  2 min read


This article speaks about the side effects of the drug methotrexate which is used to treat 'Rheumatoid Arthritis'

Side Effects of Methotrexate (Anti-Rheumatic) Oral

Methotrexate, an antifolate agent, synthesized in 1948, is a commonly used medicine for certain cancers and rheumatoid arthritis (since 1970, after it was realized that it prevents joint deformity and by precluding the progression of bony erosion).The drug, in low doses as well as high doses is known to cause numerous side effects.

Methotrexate, a teratogenic drug, affects multiple systems. The side effects include :

Renal Failure - Acute renal failure is commonly known. The cause behind this is the tubular necrosis associated with the accumulation of the drug and its metabolites in the tubules, possibly due to their insoluble nature in acidic urine. Alternatively, methotrexate may be directly toxic to tubules. This may cause the rise in the serum methotrexate levels.

Neurological Manifestations - Despite the occurrence of acute, subacute and chronic neuropathy, the mechanisms of neurotoxicity are not well established. Manifestations of acute neuropathy are in the form of aseptic meningitis, leucoencephalopathy (This affects the brain and spinal cord), headache, nausea and vomiting. Subacute neuropathy presents as seizure, paraplegia, or cerebellar dysfunction. Necrotic leucoencephalopathy is amongst the most common manifestations of chronic neuropathy.

Pancytopenia or reduction in any one of the three cell line lineages is frequently seen in the methotrexate toxicity affecting the hematopoietic system. Megaloblastic anemia, leukopenia (especially neutropenia), thrombocytopenia may all be seen individually or in combinations. An elderly patient, with folate deficiency or hypoalbuminemia, dehydration and renal dysfunction are more predisposed to developing these haematological manifestations. In such cases, even an accidental overdose may lead to pancytopenia.

Hypersensitivity reactions : Methotrexate, in low as well as high doses, may cause expression of drug derived antigens on keratinocytes. These, when detected by cytotoxic-T lymphocytes and mononuclear cells can result in keratinocyte apoptosis. Hypersensitivity reactions may be considered in both, mucocutaneous as well as haematological manifestations. Ulcers of the oral mucosa and skin, with erythema and urticaria are frequently seen.

Abdominal pain is a constant feature of methotrexate toxicity. This may occasionally be associated with vomiting and diarrhoea. Hepatotoxicity, with raised aminotransferases is frequently seen. Liver damage may be seen with fatty infiltration to fibrosis to frank cirrhosis. Diabetic patients and alcohol users are prone to more severe hepatic involvement.

Pneumonitis - The patients present with non productive cough. This may be associated with fever, dyspnea or malaise. The patient may be found to have a pneumonitis (activated T cells induce a hypersensitivity reaction), or diffuse interstitial disease (lung fibroblasts induced eosinophils, occasionally with peripheral eosinophilia).

Frequently Asked Questions


What Are the Uses of Methotrexate?

Methotrexate is a medication that is given for controlling cancer cells. It is also helpful in treating psoriasis. It prevents the formation of scales in the skin. The activity of the immune system is reduced, and so it can treat rheumatoid arthritis.


How Can the Effectiveness of Methotrexate Be Identified?

The effectiveness of Methotrexate can be identified by measuring the levels of polyglutamate. It might usually take a few months for Methotrexate to show its action. If the polyglutamate levels are low, then the drug is not a suitable one. You should ask your doctor to suggest some alternative medicines.


Is Methotrexate a Steroid Drug?

Methotrexate is a steroid. It is a safe drug that is widely used for treating any inflammatory conditions. It is necessary to avoid alcohol consumption while consuming this drug as it might cause damage to the liver. You should get recommendations from your doctor before taking these medications.


Can Weight Increase After Using Methotrexate?

In a study that calculated the range of weight changes in patients, weight gain was seen in patients after six months of usage. This was highly noted in patients who lost weight due to the condition of rheumatoid arthritis.


It Is Necessary to Drink a Larger Amount of Water Along With Methotrexate?

Yes, you should take plenty of water along with Methotrexate. It can be approximately around seven to eight cups of water. It is not necessary to take all eight cups of water at once. You can increase the water content throughout the day.


How Long Should a Person Take Methotrexate for the Treatment of Rheumatoid Arthritis?

For the treatment of rheumatoid arthritis, the patient should consume this drug for a prolonged period of 20 years. If the condition is not perfectly cured, the patient will be asked to continue the medication or will be advised of any other treatment option. The duration of the dosage is decided based on the health status of the individual.


Can I Consume Vitamin D Along With Methotrexate?

Reports suggest that there are no drug interactions identified to date. So it might be safe to consume vitamin D along with Methotrexate. It is necessary to look for the actual purpose of consuming vitamin D. If it is required only for poor nutrition, then you can try to supplement it in other ways.


What Are the Foods to Be Avoided While Consuming Methotrexate?

While you are taking Methotrexate drugs, you have to avoid foods that are rich in folic acid. This is due to the fact that folic acid can interfere with the mechanism of action of Methotrexate. The efficiency of Methotrexate medications is also known to reduce when folic acid levels are increased.


What Are the Drugs to Be Avoided Along With Methotrexate?

Below are the medicines that should be avoided while consuming
- Methotrexate.
- Celecoxib.
- Duloxetine.
- Etanercept.
- Cyclobenzaprine.
- Adalimumab.
- Pregabalin.
- Esomeprazole.
- Acetaminophen.


Can Coffee Be Consumed Along With Methotrexate?

Yes, you can drink coffee along with Methotrexate. The intolerance to Methotrexate drugs can be greatly reduced in patients who drank coffee. You can get help from your doctor before drinking coffee along with Methotrexate.


What Are the Alternative Drugs to Methotrexate?

The alternate drugs for Methotrexate are:
- Leflunomide.
- Azathioprine.
- Mycophenolate.


Do the Side Effects of Methotrexate Subside?

Most of the patients do not have any side effects at all. The patients who have side effects need reduction in the dosage of the drugs. After the reduction of dosage, the side effects are gradually reduced. If you experience any severe abnormal symptoms, then you have to consult the doctor immediately.


What Are the Side Effects of Methotrexate?

The side effects of Methotrexate are:
- Hair loss.
- Headaches.
- Rashes.
- Vomiting.
- Diarrhea.
- Feeling sick.
- Shortness of breath.
- Mouth ulcers.

Last reviewed at:
07 Sep 2018  -  2 min read




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