Methotrexate Alcohol

Folate antagonists (eg, methotrexate and certain antiepileptics) are used ia treatment for various diseases, but their adininistration can lead to a functional folate deficiency. Folate utilization can be impaired by a depletion of ziac (see Zinc compounds). In humans, the intestinal bmsh border folate conjugase is a ziac metaHoenzyme (72). One study iadicates that the substantial consumption of alcohol, when combiaed with an iaadequate iatake of folate and methionine, may iacrease the risk of colon cancer (73). Based on this study, it is recommended to avoid excess alcohol consumption and iacrease folate iatake to lower the risk of colon cancer. 

Hepatotoxicity is a higher risk when methotrexate is given to those who chronically drink large amounts of alcohol avoid methotrexate in this group if possible otherwise monitor LFTs. 

Methotrexate 7.S-20 mg once weekly Oral or IM 4-8 weeks N, D, hepatotoxicity, alopecia, new-onset cough or SOB, MYL CBC, creatinine, LFTs q 4-8 weeks Monitor for signs of infection Concomitant use of folic acid Avoid alcohol Use contraception if childbearing potential... 

Megaloblastic anemia results from insufficient active THF to support cell division in the bone marrow. Methotrexate inhibits DHF reductase, making it a useful antineoplastic drug. Folate deficiencies may be seen during pregnancy and in alcoholism. 

Concomitant administration of methotrexate and Voltarol, a proprietary preparation of diclofenac, a non-steroidal anti-inflammatory drug, may result in accumulation of methotrexate as its excretion is reduced. The use of diclofenac and diuretics such as bendroflumethiazide may increase the risk of nephrotoxicity. Concomitant use of alcohol and an angiotensin-converting enzyme inhibitor such as lisinopril (Zestril) may result in an enhanced hypotensive effect. Alcohol and the benzodiazepine diazepam (Valium) may result in enhanced sedation. 

Drugs that may affect aspirin include activated charcoal, ammonium chloride, ascorbic acid or methionine, antacids and urinary alkalinizers, carbonic anhydrase inhibitors, corticosteroids, and nizatidine. Drugs that may be affected by aspirin include alcohol, ACE inhibitors, anticoagulants (oral), beta-adrenergic blockers, heparin, loop diuretics, methotrexate, nitroglycerin, NSAIDs, probenecid and sulfinpyrazone, spironolactone, sulfonylureas and exogenous insulin, and valproic acid. 

Folate deficiency Folate deficiency states may increase methotrexate toxicity. Benzyl alcohol Methotrexate sodium for injection contains the preservative benzyl alcohol and is not recommended for use in neonates. 

Avoid alcohol, salicylates, and overexposure to sun or ultraviolet light during methotrexate therapy... 

ALCOHOL METHOTREXATE t risk of liver damage/toxicity Additive liver toxicity Be aware advocate abstinence. Monitor liver function... 

Liver. Methotrexate may cause liver damage and hepatic fibrosis (see also alcohol p. 184). 

Drugs known to be teratogenic include cytotoxics, warfarin, alcohol, lithium, methotrexate, phenytoin, valproate, ACE inhibitors and isotretinoin. Selective interference can produce characteristic anatomical abnormalities, and the phocomelia (flipper-Uke) limb defect was one factor that caused thalidomide to be so readily recognised. (For an account of thalidomide see p. 81.)... 

Hepatic fibrosis or cirrhosis may be caused by therapeutic use of methotrexate, e.g. for psoriasis in the latter case the risk is lessened by giving a large dose weekly rather than a smaller dose daily and by monitoring progress by liver biopsy after every 1.5-2 g of methotrexate. Chronic exposure to amiodarone may lead to cirrhosis this drug can also cause an alcoholic hepatitis-like picture. 

E)rug5 that influence nutrient metabolism are discussed in various sections. These drugs include lovastatin, pravastatin, omeprazole, dilantin, methotrexate, allopurinol, warfarin, furosemide, thiouracil, and diphosphonatc. Alcohol is also discussed in this context because, depending on its intake, it functions as a food, drug, or toxin. 

The data on reported cases of neurological disorders after intrathecal chemotherapy with methotrexate or cytosine arabinoside that could be attributed to benzyl alcohol or to other preservatives have been reviewed in the context of a case of flaccid paraplegia after intrathecal administration of cytosine arabinoside diluted in bacteriostatic water containing 1.5% benzyl alcohol (1). Most commonly, flaccid paraparesis, with absent reflexes, developed rapidly, often with pain and anesthesia. Very often there was full recovery. The prognosis depended mainly on the concentration of the preservative and on the time of exposure. In some cases, the paralysis ascended to cause respiratory distress, cardiac arrest, and death. Only preservative-free sterile CSF substitute or saline, or preferably the patient s own CSF, should be used to dilute chemotherapeutic agents (SEDA-11, 475). 

Strong association Previous or concurrent heavy alcohol use Pre-existing liver disease Daily methotrexate administration Renal insufficiency... 

In a meta-analysis of 636 patients from 15 studies, who took chronic low-dose methotrexate for rheumatoid arthritis or psoriasis, the risk of liver toxicity increased with cumulative dose and heavy alcohol intake (56). 

Concomitant use of heparin and oral anticoagulants can increase the risk for bleeding due to the antiplatelet effect of aspirin. In addition, use with alcohol can increase the risk of Gl bleeding. / spirin displaces a number of drugs (e.g., tolbutamide, nonsteroidal anti-inflammatory drugs [NSAIDs], methotrexate, phenytoin, and probenecid) from protein binding sites in the blood. Corticosteroid use can reduce serum salicylate levels by increasing the clearance of aspirin. 

Folic acid is a nutritional supplement frequently used during periods of deficiency. Folic acid needs increase during chronic diseases, such as malabsorption liver disease, alcoholism, and anticonvulsant or oral contraceptive use. Folic acid supplementation during pregnancy is strongly recommended to prevent neural tube defects to the unborn child. The active form of folic acid, folinic acid, is used in the management of certain medical diseases (e.g., patients taking methotrexate, and 5-fluorouracil). 

Clinically important, potentially hazardous interactions with alcohol, bexarotene, chloroquine, cholestyramine, corticosteroids, danazol, ethanolamine, isotretinoin, lithium, medroxyprogesterone, methotrexate, minocycline, progestins,... 

Drugs and toxins Alcohol, methotrexate, isoniazid, methyidopa, organic hydrocarbons... 

Elevated liver enzymes may occur in up to 15% of patients cirrhosis is rare. Liver function tests, aspartate aminotransferase (AST) or alanine aminotransferase (ALT), should be performed periodically. Methotrexate should be discontinued if these test values show sustained results greater than twice the upper limits of normal. Serum albumin levels also should be checked periodically, as signs of liver toxicity in some patients may not have liver inflammation manifested by AST or ALT elevation. Liver biopsy is now recommended before beginning methotrexate therapy only for patients with a history of excessive alcohol use, ongoing hepatitis B or C infection, or recurring elevation of AST. Biopsies during methotrexate therapy are recommended only for patients who develop consistently abnormal liver function tests. ... 

Bone marrow toxicity that leads to leukopenia, anemia, and thrombocytopenia has been shown to be induced by methotrexate. A serious long-term adverse effect is hepatotoxicity. Consequently, methotrexate should typically be avoided in patients with liver disease. Risk factors for hepatotoxicity include a history of excessive alcohol consumption, hepatitis, persistent elevated liver function tests, and family history of inheritable liver disease. ... 

FOLATE DEFICIENCY Folate deficiency is a common complication of diseases of the small intestine, which interfere with the absorption of dietary folate and the recirculation of folate through the enterohepatic cycle. In acute or chronic alcohohsm, daily intake of dietary folate may be severely restricted, and the enterohepatic cycle of the vitamin may be impaired by toxic effects of alcohol on hepatic parenchymal cells this is the most common cause of folate-deficient megaloblastic erythropoiesis. However, it also is the most amenable to therapy, inasmuch as the reinstitution of a normal diet is sufficient to overcome the effect of alcohol. Disease states characterized by a high rate of cell turnover, such as hemolytic anemias, also may be complicated by folate deficiency. Additionally, drugs that inhibit dihydrofolate reductase (e.g., methotrexate and trimethoprim) or that interfere with the absorption and storage of folate in tissues (e.g., certain anticonvulsants and oral contraceptives) can lower the concentration of folate in plasma and may cause a megaloblastic anemia. 

Lipophilic prodrugs can also be derived from a carboxylic function, the most commonly used derivatives being carboxylic esters. Simple esters of aliphatic alcohols are attractive as they are cheap to prepare, chemically stable, and yield harmless hydrolysis products." Typical representatives of such prodrugs are tyrosine methyl ester," levodopa ethyl ester," nipecotic acid ethyl ester," enala-prilat ethyl ester," " " trandolapril," y-aminobutyric acid cetyl ester" " and methotrexate cetyl ester." ... 

Increased risk of bleeding with anticoagulants. Increased risk of Gl ulceration with alcohol, corticosteroids, phenylbutazone, oxyphenbutazone. Decreases uricosurea effects of probenecid and sulfinpyrazone and diuretic effects of spironolactone. Decreases absorption of tetracycline. Increases plasma levels of methotrexate. 

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