Hepatotoxicity methotrexate

Methods of monitoring patients for possible methotrexate hepatotoxicity and guidelines have been reviewed (48,51,52). It should be mentioned that the frequent rise in serum transaminases (involving 30-80% of patients) after the start of treatment is transient and does not predict liver damage only persistently abnormal transaminases are potential indicators of methotrexate hepatotoxicity. 

Kaplan MM. Methotrexate hepatotoxicity and the premature reporting of Mark Twain s death both greatly exaggerated. Hepatology 1990 12(4 Pt l) 784-6. 

West SG. Methotrexate hepatotoxicity. Rheum Dis Clin North Am 1997 23(4) 883-915. 

Zachariae H, Schroder H, Foged E, Sogaard H. Methotrexate hepatotoxicity and concentrations of methotrexate and folate in erythrocytes—relation to hver fibrosis and cirrhosis. Acta Dermatol Venereol 1987 67(4) 336-40. 

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... 

Methotrexate -antifolate antimetabolite cell cycle dependent -bone marrow suppression -nausea and vomiting—mild to moderate -mucocutaneous effects (mucositis, stomatitis, diarrhea) -hepatotoxicity—more common in high-dose therapy -CNS toxicity—dizziness, malaise, blurred vision, encephalopathy -nephrotoxicity—including acute renal failure, particularly at high doses... 

Thioguanine is a purine analog that has been used as an alternative treatment for psoriasis when conventional therapies have failed. The typical dose is 80 mg twice weekly, increased by 20 mg every 2 to 4 weeks the maximum dose is 160 mg three times a week. Adverse effects include bone marrow suppression, GI complications (e.g., nausea, diarrhea), and elevation of liver fimction tests. 6-Thioguanine may be less hepatotoxic and therefore more useful than methotrexate in hepatically compromised patients with severe psoriasis. 

Methotrexate, given as a weekly injection of 5 to 25 mg, has demonstrated efficacy for induction of remission in Crohn s disease as well as for maintenance therapy. The risks are bone marrow suppression, hepatotox-icity, and pulmonary toxicity. 

Liver Methotrexate causes hepatotoxicity, fibrosis, and cirrhosis, but generally only after prolonged use. Acutely, liver enzyme elevations are frequent, usually transient and asymptomatic, and also do not appear predictive of subsequent hepatic disease. Liver biopsy after sustained use often shows histologic changes, and fibrosis and cirrhosis have occurred these latter lesions often are not preceded by symptoms or abnormal liver function tests (see Precautions). For this reason, periodic liver biopsies are usually recommended for psoriatic patients who are under long-term treatment. Persistent abnormalities in liver function tests may precede appearance of fibrosis or cirrhosis in the RA population. 

Hepatic - Methotrexate has the potential for acute (elevated transaminases) and chronic (fibrosis and cirrhosis) hepatotoxicity. Chronic toxicity is potentially fatal it generally occurs after prolonged use (generally 2 years or more) and after a total dose of at least 1.5 g. 

RA In RA, first use of methotrexate and duration of therapy have been reported as risk factors for hepatotoxicity. Persistent abnormalities in liver function tests may precede appearance of fibrosis or cirrhosis in this population. 

For immunosuppressive effects methotrexate is most frequently used in RA but also azathioprine and cyclosporin are employed. Methotrexate doses for this indication can be lower than those used for cancer chemotherapy but significant toxicity such as nausea, cytopenias and mucosal lesions, and with longterm therapy slowly progressive hepatotoxicity may still be seen. 

The principal advantage of MMF over alternative systemic immunosuppressive agents (e.g., methotrexate, cyclosporine) is its relative lack of hepatotoxicity and nephrotoxicity. Adverse effects produced by MMF most commonly include nausea, abdominal cramps, diarrhea, and possibly an increased incidence of viral and bacterial infections. Whether MMF may be associated with an increased long-term risk of lymphoma or other malignancies is controversial however, any such risk is likely to be lower in patients treated for skin disease with MMF monotherapy than in transplant patients treated with combination immunosuppressive therapy. 

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. 

Purine analogs and antimetabolites, eg, 6-mercaptopurine, methotrexate Mechanism uncertain may promote apoptosis of immune cells Generalized suppression of immune processes Moderately severe to severe Crohn s disease and ulcerative colitis GI upset, mucositis myelosuppression purine analogs may cause hepatotoxicity, but rare with methotrexate at the low doses used... 

Methotrexate (Rheumatrex Dose Pack, Trexall) [Antineoplastic, Antirheumatic (DMARDs), Immunosuppressant/ Antimetabolite] WARNING Administration only by experienced healthcare provider do not use in women of childbearing age unless absolutely necessary (teratogenic) impaired elimination w/ impaired renal Fxn, ascites, pleural effusion severe myelosuppression if used w/ NSATDs hepatotox can induce lung Dz ... 

Methotrexate Generic (when used for cancer] Acute lymphocytic leukemia meningeal leukemia carcinoma of head and neck region, lung non-Flodgkin lymphomas Blood disorders (anemia, leukopenia, thrombocytopenia] Gl distress (including ulceration of Gl tract] skin disorders (rashes, photosensitivity, hair loss] hepatotoxicity CNS effects (headaches, drowsiness, fatigue]... 

Tetracycline Tetracycline injections have an acid pH. Incompatibility may reasonably be expected with alkaline preparations or with drugs unstable at low pH. Care should be taken when administering tetracyclines, since chelation takes place with metal ions. Tetracyclines interact with inorganic metal ions. They should not be used with drugs that cause hepatotoxicity and nephrotoxicity (e.g., digoxin, theophylline, ergot alkaloids, methotrexate, oral contraceptives, and penicillins). 

Pre-existing liver disease In general patients with pre-existing liver disease are not at increased risk of drug-induced hepatotoxicity exceptions to this include methotrexate and sodium valproate... 

METHOTREXATE AMINOSALICYLATES-SULFASALAZINE t risk of hepatotoxicity with sulfasalazine Additive hepatotoxic effects. Sulfasalazine also competes with methotrexate for renal elimination Monitor closely for symptoms of liver failure. Check LFTs at the beginning of treatment then weekly until stable, and repeat if there is clinical suspicion of liver disease... 

METHOTREXATE RETINOIDS - ACITRETIN t risk of hepatotoxicity Additive hepatotoxic effects Avoid co-administration... 

Echinacea 1. Hepatotoxic drugs, e.g. anabolic steroids 2. amiodarone 3. Methotrexate 4. Ketoconazole Risk of additive hepatotoxicity Use of echinacea for over 8 weeks can cause hepatotoxicity Be aware and use drugs with a potential to cause hypertonicity cautiously, monitoring clinically and biochemically for any early signs of hepatic dysfunction... 

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