Bone marrow depression methotrexate

At higher dosage, methotrexate may cause bone marrow depression, megaloblastic anemia, alopecia, and mucositis. At the doses used in the treatment of inflammatory bowel disease, these events are uncommon but warrant dose reduction if they do occur. Folate supplementation reduces the risk of these events without impairing the antiinflammatory action. 

Cyclophosphamide (Cytoxan and Endoxan) is used in the treatment of Hodgkin s disease, lymphosarcoma, and other lymphomas. It is employed as a secondary drug in patients with acute leukemia and in combination with doxorubicin in women with breast cancer. A drug combination effective in the treatment of breast cancer is cyclophosphamide, methotrexate, fluorouracil, and prednisone (CMFP). Cyclophosphamide is also an immunosuppressive agent. The toxicity of cyclophosphamide causes alopecia, bone marrow depression, nausea and vomiting, and hemorrhagic cystitis. 

Mercaptopurine is used in the treatment of acute lymphoid leukemia. Maintenance therapy makes use of both methotrexate and 6-mercaptopurine. Mercaptopurine is absorbed well from the gastrointestinal tract. It is metabolized through (1) methylation of the sulfhydryl group and subsequent oxidation, and (2) conversion to 6-thiouric acid with the aid of xanthine oxidase, which is inhibited by allopurinol. Mercaptopurine may cause hyperuricemia. Its chief toxicities are hepatic damage and bone marrow depression. 

Methotrexate 2.5-5 mg/d orally (Rheumatrex) 10 mg intrathecally (Folex) once or twice weekly Mucositis, diarrhea, bone marrow depression with leukopenia and thrombocytopenia... 

Antimetabolites cause gastrointestinal toxicity including stomatitis and diarrhoea as well as bone marrow depression renal impairment potentiates the toxicity of methotrexate. Active excreHon of methotrexate by the renal tubule is blocked by salicylate, which also displaces it from plasma protein, increasing the risk of toxicity. Hepatic dysfunction potentiates the toxicity of 5-fluorouracil, since it is primarily metabolised by the liver. 

Methotrexate Nausea and vomiting diarrhoea fever anaphylaxis hepatic necrosis Oral and gastrointestinal ulceration, perforation may occur bone marrow depression hepatic toxicity including cirrhosis renal toxicity pulmonary infiltrates and fibrosis osteoporosis conjunctivFtis alopecia depigmentation menstrual dysfunction encephalopathy infertility lymphoma teratogenesis... 

Dactinomycin is used against ihabdomyasarcoma and Wilms tumor in children. It can be liicsaving for women with choriocarcinoma resistant to methotrexate. In combination with vincristine and cyclophosphamide, it has received some use in. solid tumors in children. Toxic reaction.s include anorexia, nausea, and vomiting. Bone marrow depression, resulting in pancytopenia, may occur within a week after therapy. Alopecia, erythema, and tissue injury may ixtcur at the injection site. 

The toxicity of antimetabolites is, as expected, due to their incorporation into the metabolism of normal cells, which is nearly identical to that of the malignant cells that they were designed to injure. The normal cells injured most severely are the rapidly proliferating cells of the bone marrow, the lymphoid system, and the GI epithelium. Thus, the common toxicities are bone marrow depression, nausea and vomiting, diarrhea, and mucositis. Cytarabine and pentostatin can cause conjunctivitis. Capecitabine and prolonged use of fluorouracil or cytarabine can cause cerebellar ataxia and the hand-foot syndrome, that is, palmar-plantar erythrodysesthesia or acral erythema. Pentostatin and high-dose methotrexate can cause renal toxicity. 

Methotrexate is prescribed for oral administration once a week and it is extremely important the patients understand this. Bone marrow depression and hepatotoxicity are... 

Methotrexate (e.g., Mexate) Inhibits dihydrofolate reductase, an enzyme that catalyzes the synthesis of thymidine. DNA synthesis is thus impaired. Prevention of organ transplant rejection, severe psoriasis. Bone marrow depression, Gl ulceration, nephrotoxicity, hepatotoxicity, pulmonary infiltration, skin toxicity. 

Eleven cases of severe bone marrow depression have been reported, three of them fatal, caused by the concurrent use of low-dose methotrexate and treatment doses of trimethoprim or co-trimox-azole (sulfamethoxazole and trimethoprim). Panc3d openia has also been reported in a few patients given treatment doses of co-trimoxazole shortly after stopping methotrexate. 

Two patients taking methotrexate for psoriasis developed methotrexate toxicity and skin ulceration shortly after starting to take phenylbutazone 200 to 600 mg daily. One of them died from septicaemia following bone marrow depression. ... 

Probenecid inhibits the renal excretion of methotrexate in both monkeys and rat and this probably also happens in man. Changes in the protein binding of methotrexate may also have some part to play. The increased methotrexate levels increase the risk of serious bone marrow depression. 

In view of the well-documented inhibition of dihydrofolate reductase by aminopterin (325), methotrexate (326) and related compounds it is generally accepted that this inhibitory effect constitutes the primary metabolic action of folate analogues and results in a block in the conversion of folate and dihydrofolate (DHF) to THF and its derivatives. As a consequence of this block, tissues become deficient in the THF derivatives, and this deficiency has many consequences similar to those resulting from nutritional folate deficiency. The crucial effect, however, is a depression of thymidylate synthesis with a consequent failure in DNA synthesis and arrest of cell division that has lethal results in rapidly proliferating tissues such as intestinal mucosa and bone marrow (B-69MI21604, B-69MI21605). 

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