Liver function tests methotrexate

Prior to initiating methotrexate therapy, obtain complete blood count, serum creatinine, liver function tests, chest x-ray, and pregnancy test (if female). Monitor blood counts weekly for 1 month, then monthly thereafter. 

Methotrexate Monitor complete blood cell count and liver function tests at baseline and regularly, and consider liver biopsy prior to treatment and at a cumulative dose of 1.5 g. If available, monitor PIIINP at least three times yearly. 

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. 

Transient liver function test abnormalities are observed frequently after methotrexate administration and are usually not cause for modification of therapy. Persistent liver function test abnormalities and/or depression of serum albumin may be indicators of serious liver toxicity and require evaluation. 

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. 

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. 

Leflunomide can cause abnormal liver function tests, but the risk of serious and non-serious hepatic adverse events is not higher than with methotrexate (71). In the MN301, US301, and MN302 trials, there were abnormal liver enzymes in 6-10% (9,10,12). The co-administration of methotrexate is a risk factor (18,72-74). According to the National Cancer Institute Common Toxicity Criteria, 8.9% of patients developed grade 2 or 3 hepato-toxicity within the first year, mainly within 6 months and in combination with methotrexate, after the start of leflunomide therapy based on liver enzyme determinations (72). The use of folate was also associated with less... 

Routine liver function tests do not rehably indicate hver damage, and they may not become abnormal until there is already considerable hver damage. It is therefore common practice to monitor patients by conducting annual liver biopsies. Measurement of the serum amino-terminal propeptide of type III procoUagen (PHI PI) has been used as an alternative to hver biopsy high concentrations correlate with fibrosis on liver biopsy (49). No patient with a normal serum concentration had an abnormal biopsy. An increase in the plasma phenylalanine/tjrosine ratio in children and adolescents can provide chnical evidence of liver damage before the appearance of symptoms in patients who have taken high doses of methotrexate (50). 

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. ... 

Methotrexate exerts significant antiproliferative effects on the bone marrow therefore, complete blood counts should be monitored. Folinic acid (leucovorin) can be used to rescue patients with hematologic crises caused by methotrexate-induced bone marrow suppression. Careful monitoring of liver function tests is necessary but may not be adequate to identify early hepatic fibrosis in patients receiving chronic methotrexate therapy. Liver biopsy is recommended when the cumulative dose reaches 1-1.5 g. A baseline hver biopsy also is recommended for patients with increased... 

Liver In a retrospective study in 30 patients with Crohn s disease who had failed treatment with thiopurines with or without methotrexate, thioguanine 40 mg/ day was used instead [156 ]. Seven stopped taking it because of adverse reactions seven developed abnormal liver function tests during treatment, mostly transient and mild, and one developed portal hypertension, which resolved after withdrawal. Of 11 liver biopsies, none showed nodular regenerative hyperplasia. 

Low-dose methotrexate, 10 to 25 mg a week, is used for the treatment of cutaneous sarcoidosis (42). Cutaneous improvement may be noted within one month, but maximal therapeutic benefit often does not occur until at least six months after the initiation of treatment. The drug requires careful monitoring of liver function tests and blood cell counts. Folic acid is recommended to be given in conjunction with methotrexate. Approximately 10% of sarcoidosis patients taking methotrexate develop hepatic fibrosis, even if their serum liver function tests are normal (43). Therefore liver biopsies should be considered after two grams of total therapy (usually after two years) (43). 

Granulomatous hepatitis from sarcoidosis may require treatment if patients develop fever, nausea, vomiting, pruritus weight loss, or right upper-quadrant abdominal pain (67). Corticosteroids are usually effective in alleviating these symptoms (67,93). Many patients require a daily dose of prednisone in the 10 to 15 mg range. Therapy is often required for more than one year (67). Despite the potential risk of hepatic toxicity from methotrexate, it has been shown to be effective, reduce liver function test abnormalities, and to be corticosteroid sparing (67,95). 

Methotrexate is an antimetabolite, which is metabolised by the renal and hepatic systems and may lead to renal and hepatic toxicities. Liver and renal function tests are therefore carried out for patients who are administered the drug. Methotrexate can lead to myelosuppression and therefore full blood counts must be monitored for patients taking it. 

Monitoring Periodic monitoring for toxicity, including CBC with differential and platelet counts, and liver and renal function testing is mandatory. Periodic liver biopsies may be indicated in some situations. Monitor patients at increased risk for impaired methotrexate elimination (eg, renal dysfunction, pleural effusions, ascites) more frequently (see Precautions). 

METHOTREXATE ANTIMALARIALS -PYRIMETHAMINE t antifolate effect of methotrexate Pyrimethamine should not be used alone and is combined with sulfadoxine. Pyrimethamine and methotrexate synergistically induce folate deficiency Although the toxic effects of methotrexate are more frequent with high doses of methotrexate, it is necessary to do an FBC, liver and renal function tests before starting treatment even with low doses, repeating these tests weekly until therapy is stabilized and thereafter every 2-3 months. Patients should be advised to report symptoms such as sore throat and fever immediately, and also any gastrointestinal discomfort. A profound drop in white cell count or platelet count warrants immediate stoppage of methotrexate therapy and initiation of supportive therapy... 

Baughman RP, Koehler A, Bejarano PA, et al. Role of hver function tests in detecting methotrexate-induced liver damage in sarcoidosis. Arch Intern Med 2003 163 615-620. 

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