Reasons to Avoid MTX

Use is contraindicated in patients with a nonmalignant diagnosis who are pregnant, breast-feeding or who have alcoholism, alcoholic liver disease, or chronic liver disease; immunodeficiency syndromes; or pre-existing blood dyscrasias.

There are medical conditions and histories that may disqualify some patients from using MTX:

  • Women who are pregnant
  • Men or women who are trying to conceive a child 
  • People who have blood disorders, including HIV/AIDS
  • People with an active peptic ulcer
  • People with severe anemia
  • People with cirrhosis of the liver
  • People with active hepatitis
  • People with significant liver or kidney abnormalities
  • People with active infectious disease
  • People who consume alcohol (beer, wine, liquor)
  • Patients who are unreliable

Drugs to avoid with MTX

PPI

Diuretics

NSAIDs

Amiodarone

Sulfonyureas

Oral antibiotics (PCN,FLQ,BACTRIM)

https://www.pfizermedicalinformation.ca/en-ca/methotrexate/drug-interactions#

In women of reproductive potential, methotrexate use is not recommended unless the benefits of therapy are expected to outweigh the considered risks. Advise females of reproductive potential to avoid pregnancy while taking methotrexate; counsel these patients on the fetal risk if pregnancy occurs. Methotrexate is contraindicated in pregnancy in women who are being treated for nonmalignant diseases (e.g., psoriasis, rheumatoid arthritis, polyarticular juvenile idiopathic arthritis). Methotrexate can cause intrauterine fetal death and/or congenital anomalies when administered to a pregnant woman.  Methotrexate may cause infertility; and menstrual irregularity/dysfunction have been reported in patients during methotrexate therapy and for a short period after stopping therapy.

Additionally, male patients with a female partner of reproductive potential should use effective contraception during methotrexate therapy and for at least 3 months after therapy due to the risk of male-mediated teratogenicity. 

Reactivation of HSV

Patients with a history of varicella zoster, other herpes infection (e.g., herpes simplex), or other viral infection are at risk for reactivation of the infection when treated with chemotherapy. 

Use is contraindicated in patients with preexisting immunosuppression.

  • preexisting bone marrow suppression such as:

leukopenia, 

thrombocytopenia,

significant anemia should not receive methotrexate.

  • Methotrexate should be used only in life threatening neoplastic diseases or in patients with psoriasis or rheumatoid arthritis with severe, recalcitrant, disabling disease that is not adequately responsive to other forms of therapy.

Methotrexate therapy can produce potentially fatal pulmonary toxicity, including acute or chronic interstitial pneumonitis and pulmonary fibrosis.

The following are risk factors for pulmonary toxicity in rheumatoid arthritis patients treated with methotrexate: 

  • diabetes mellitus
  • older age
  • rheumatoid pleuropulmonary involvement
  • previous use of the disease modifying drugs sulfasalazine, gold or penicillamine
  • hypoalbuminemia

In nondiabetic patients the most important risk factors are:

  • hypoalbuminemia 
  • previous use of disease modifying drugs (DMARD’s)

 Risk factors for hepatotoxicity include while using MTX are:

  • alcoholism
  • obesity
  • diabetes mellitus
  • hyperlipidemia
  • duration of therapy
  • advanced age

The National Psoriasis Foundation suggests 3 options in patients without risk factors for hepatic toxicity who reach a cumulative dose of 3.5 to 4 g oral methotrexate with normal LFTs: perform a liver biopsy, continue to monitor without a biopsy, or switch to an alternative agent if possible.

Methotrexate should be used only in:

  • life threatening neoplastic diseases 
  • or in patients with psoriasis or rheumatoid arthritis with severe, recalcitrant, disabling disease that is not adequately responsive to other forms of therapy.

Methotrexate is eliminated primarily by the kidney and clearance is dependent on dosage and route of administration. Patients who have renal impairment or renal disease or are receiving concurrent nephrotoxic drugs (e.g., nonsteroidal anti-inflammatory drugs (NSAIDs), salicylates) are at risk for increased toxicity due to prolonged elevated methotrexate serum concentrations.  

Methotrexate should be used with extreme caution in patients with GI disease such as peptic ulcer disease or ulcerative colitis.