Methotrexate Toxicity

What is Methotrexate Toxicity?

Methotrexate is a medication that is utilized in the treatment of several medical conditions. This drug is very potent and should only be given in its recommended dose in order to prevent any unintended effects. If the serum level exceeds the therapeutic range, it will lead to toxicity and is harmful to the body [1, 2].

What is Methotrexate?

Methotrexate is a drug that disturbs the development of rapidly-producing cells such as cells of the skin, bone marrow and neoplastic cells. In low doses, methotrexate is used in the treatment of rheumatologic conditions. A higher formulation of this drug is used in the treatment of malignancies of the head, neck, skin, lungs and breast. The therapeutic regimen with methotrexate involves taking the drug taking one or two times per week.

The correct dose of this drug must be received in accordance of the condition because receiving a high dose of methotrexate can be fatal. A patient who have a pre-existing liver condition, disorder in their bone marrow, a lack of red blood cells and white blood cells are contraindicated to receive this drug for their rheumatologic disorders. Methotrexate are only given to these patients as a management for their malignancy especially if the benefits outweigh the risks [1, 2, 3, 4].

How much is Methotrexate Toxicity?

The therapeutic dose of this drug depends on the intended action to the patient. Those who have rheumatoid arthritis should receive low doses of methotrexate while individuals who are receiving this drug for their malignancies are given with relatively higher doses. The toxic serum level of methotrexate is a dose greater than 10 mcmol/L over a 24-hour period [1, 2].

What are Methotrexate Toxicity symptoms?

Individuals who have received toxic levels of methotrexate may present with GI bleeding, diarrhea and vomiting. Severe suppression of the bone marrow and alteration of liver and renal function may also occur. Patients who have a pre-existing liver condition are at increased risk for this effect.

The injury of the liver is accompanied by elevations of liver enzymes Alanine transaminase (ALT) and Aspartate transaminase (AST). Acute pneumonitis may also occur in these patients and this can be fatal if it is not managed on time. Symptoms associated with the pneumonitis include dry and persistent cough, fever and shortness of breath [1, 2, 3, 4].

Methotrexate toxicity symptoms

What are Methotrexate Toxicity management?

Management of the toxicity in methotrexate involves measuring the serum drug level of the patient. If the drug was taken orally, activated charcoal may be given to the patient in order to bind the drug and facilitate urinary excretion. Antidotes that are used for this condition are thymidine, leucovorin and glucarpidase.

These drugs are given until the levels of the drug return to normal. Failure of the kidneys may be prevented by ensuring adequate hydration and alkalinization of the urine through the use of bicarbonates. If these drugs are not successful, a hemodialysis may be performed to the patient [1, 2, 3, 4, 5].

How to prevent Methotrexate Toxicity?

A majority of fatality associated with methotrexate toxicity are due to dosage frequency errors. Patients should be reminded that this drug is only taken weekly and not daily. Carers of the patients should be included in consultations in order to be taught the correct administration of the drug.

Adverse effects experienced after taking the drug should be reported immediately to the physician. Laboratory tests such as a full blood count, kidney and liver function tests must be performed in regular intervals in order to monitor the condition of the patient while taking methotrexate [1, 2, 3, 4, 5].

This condition can be fatal if it is not corrected immediately. If you got more information about the toxicity of methotrexate, feel free to share it in the comments section.


  1. (2015, August 4). Methotrexate. Retrieved from
  2. Greco, F. A. (2015, April 27). Therapeutic drug levels. Retrieved from Medline Plus:
  3. Harrison, A., & Jones, P. (2014). Safer prescribing of high-risk medicines – Methotrexate: potentially fatal in overdose. Best Practice Journal.
  4. Jariwala, P., Kumar, V., Kothari, K., Thakkar, S., & Umrigar, D. D. (2014). Acute Methotrexate Toxicity: A Fatal Condition in Two Cases of Psoriasis. Case Reports in Dermatological Medicine, 1-3.
  5. Maryland Poison Center. (2009, January). Methotrexate Toxicity. Retrieved from Maryland Poison Center:

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