Methotrexate Toxicity

by on May 11, 2012

Methotrexate is a powerful drug that can cause harmful side effects when taken correctly, and deadly toxicity when taken incorrectly. Anyone prescribed methotrexate must be aware of the potential hazards, and should take care to fully understand the doctor’s instructions while taking this drug.

How does Methotrexate Toxicity Occur?

Some patients can develop a heightened susceptibility to methotrexate during treatment. This means that continuation of the prescribed dosage may in reality be overdosing. Cases of unintentional overdosing may also include misunderstanding the dosing directions.

A patient could accidentally take the medication daily instead of the prescribed weekly dose. Taking non-steroidal anti-inflammatory drugs (NSAIDS) together with methotrexate can cause the content of methotrexate in the blood to increase and concentrate, causing an overdose.

Symptoms of Toxicity

Overdosing produces toxicity which can be recognized from the following symptoms:

  • dry cough
  • vomiting
  • diarrhea
  • kidney failure
  • seizures
  • depression
  • tachycardia
  • low blood pressure
  • stroke-like symptoms
  • frequent infections
  • anemia
  • cirrhosis of the liver

Although some of these symptoms can also be normal side effects of the drug, any increase in severity should be investigated thoroughly with blood tests and even liver biopsy or bone marrow biopsy in those patients who have taken methotrexate for prolonged periods.

Toxic Levels of Methotrexate

Since methotrexate changes the way a body uses folic acid, all levels are toxic. A healthy person would not have any methotrexate in his or her body. Prescribed doses of methotrexate are usually 7.5 mg once each week; however, in some patients the dose may go as high as 20 mg to 30 mg per week, with 30 being the maximum.

Depending on the disease that is being treated, and the individual patient, dosages will vary. But any dosage higher than 30 mg would be considered toxic.

Treating and Preventing Toxicity

Renal failure or other kidney problems can cause an inability to eliminate methotrexate from the body. In these cases glucarpidase is administered to the patient. Glucarpidase inactivates methotrexate and is sometimes followed with leucovorin, a folic acid derivative.

Leucovorin is an effective methotrexate antidote and is used in cases of accidental overdose also. In cases where methotrexate was prescribed as a chemotherapy drug, leucovorin can be used to protect healthy cells while still allowing the cancer cells to be killed.


Since methotrexate concentrates in the liver, gall bladder, spleen and kidneys, patients taking it should be routinely monitored by their doctors. Tests should be performed to verify that serum albumin levels and AST (aspartate amenotransferese) levels are stable. Elevated levels of AST can indicate liver damage; low albumin levels can indicate kidney problems.

Taking supplements of folic acid may be recommended by some doctors since its use has been shown to keep some of the side effects of methotrexate in check. In prolonged-use patients, biopsies may be used as a preventative measure to insure the health of the liver, kidneys and bone marrow.

Whether prescribed to treat psoriasis, rheumatoid arthritis, Crohn’s disease or cancer, methotrexate use must be carefully monitored to insure prevention of toxicity.