Methotrexate contraindications

Methotrexate, an antimetabolite, is indicated for moderate to severe psoriasis. It is particularly beneficial for psoriatic arthritis. It is also indicated for patients refractory to topical or UV therapy. Methotrexate can be administered orally, subcutaneously, or intramuscularly. The starting dose is 7.5 to 15 mg per week, increased incrementally by 2.5 mg every 2 to 4 weeks until response maximal doses are approximately 25 mg/wk. Adverse effects include nausea, vomiting, mucosal ulceration, stomatitis, malaise, headache, macrocytic anemia, and hepatic and pulmonary toxicity. Nausea and macrocytic anemia can be ameliorated by giving oral folic acid 1 to 5 mg/day. Methotrexate should be avoided in patients with active infections and in those with liver disease. It is contraindicated in pregnancy because it is teratogenic. 

Methotrexate is an antimetabolite drug that is excreted primarily by the kidney. It is contraindicated in significant renal impairment and in hepatic impairment. It is nephrotoxic and accumulation may occur in renal impairment. Dose should be reduced in renal impairment that is not severe and drug should be avoided if creatinine clearance is less than 20 mL/minute. 

Psoriasis Neoral and Gengraf are indicated for the treatment of adult, nonimmunocompromised patients with severe (ie, extensive and/or disabling), recalcitrant, plaque psoriasis who have failed to respond to at least 1 systemic therapy (eg, PUVA, retinoids, methotrexate) or in patients for whom other systemic therapies are contraindicated or cannot be tolerated. While rebound rarely occurs, most patients will experience relapse with Neoral or Gengraf as with other therapies upon cessation of treatment. 

Pregnancy Fetal death and/or congenital anomalies have occurred do not use in women of childbearing potential unless benefits outweigh possible risks. Pregnant women with psoriasis or RA should not receive methotrexate (see Contraindications). 

Lactation - Because of the potential for serious adverse reactions from methotrexate in breastfed infants, it is contraindicated in nursing mothers. 

Contraindications Severely impaired liver or kidney function, chronic abnormal elevated lipid levels, concomitant use of methotrexate ortetracyclines, hypersensitivity to acitretin, etretinate, or other retinoids, sensitivity to parabenz (used as preservative in gelatin capsule)... 

Nausea and mucosal ulcers are the most common toxicities. Progressive dose-related hepatotoxicity in the form of enzyme elevation occurs frequently, but cirrhosis is rare (< 1%). Liver toxicity is not related to serum methotrexate concentrations, and liver biopsy follow-up is only recommended every 5 years. A rare hypersensitivity-like lung reaction with acute shortness of breath is documented, as are pseudolymphomatous reactions. The incidence of gastrointestinal and liver function test abnormalities can be reduced by the use of leucovorin 24 hours after each weekly dose or by the use of daily folic acid, although this may decrease the efficacy of the methotrexate. This drug is contraindicated in pregnancy. 

Methotrexate Probably all NSAIDs Reduced clearance of methotrexate (mechanism unclear), increasing plasma concentration and risk of severe toxicity Simultaneous dosing is contraindicated use of NSAIDs between cycles of chemotherapy is probably safe... 

Methotrexate is now considered the DMARD of choice by many rheumatologists for treating rheumatoid arthritis. In psoriatic arthritis it not only treats the joint symptoms, but also improves the skin disease for most patients. Methotrexate is contraindicated in pregnant and nursing women. It is also contraindicated in patients with chronic liver disease, immunodeficiency, pleural or peritoneal effusions, leukopenia, thrombocytopenia, pre-existing blood disorders, and a creatinine clearance of less than 40 mL/min. 

Leflunomide has efficacy similar to that of methotrexate for treating rheumatoid arthritis. The drug may cause liver toxicity and is contraindicated in patients with pre-existing liver disease. Patients taking the drug should have ALT monitored monthly initially, and periodically thereafter as long as they continue treatment. 

Malignant lymphomas have been reported in several patients treated with methotrexate. In some cases, lymphomas regressed when methotrexate was discontinued, strongly suggesting a causal relationship. Methotrexate is contraindicated in pregnant women because it is teratogenic. ... 

Methotrexate, cisplatin Renal impairment In proportion to lowered creatinine clearance (normal = 60 mL/min per m ) CIcr <10 mL/min, contraindicated... 

Methotrexate distributes readily into third space fluids (ascites, pleural effusions), prolonging exposure and increasing toxicity. May be contraindication for use. 

Probenecid but not cidofovir alters zidovudine pharmacokinetics such that zidovudine doses should be reduced when probenecid is present, as should the doses of drugs similarly affected by probenecid fe.g., /i-lactam antibiotics, nonsteroidal anti-inflammatory drugs [NSAIDs], acyclovir, lorazepam, furosemide, methotrexate, theophylline, and rifampin). Concurrent nephrotoxic agents are contraindicated, and an interval of 1 week before beginning cidofovir treatment is recommended after prior exposure to aminoglycosides, intravenous pentamidine, amphotericin foscamet, NSAIDs, or contrast dye. Cidofovir and oral ganciclovir in combination are poorly tolerated at full doses. 

Methotrexate therapy requires monitoring of liver enzymes and is contraindicated in those with hepatic disease and in women considering pregnancy. 

It has been claimed that alcohol can increase the hepatotoxic effects of methotrexate. Two reports of patients treated for psoriasis indicate that this may be so in one, 3 out of 5 patients with methotrexate-induced cirrhosis were reported to have taken alcohol concurrently (2 patients greater than 85 g, one patient 25 to 85 g of alcohol per week), and in the other, the subject was known to drink excessively. The evidence is by no means conclusive and no direct causal relationship has been established. However, the manufacturers of methotrexate advise the avoidance of drugs, including alcohol, which have hepatotoxic potential, and contraindicate its use in patients with alcoholism or alcoholic liver disease. ... 

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