Methotrexate monitoring treatment with

Therapy with leucovorin/5-FU must not be initiated or continued in patients who have symptoms of Gl toxicity of any severity, until those symptoms have completely resolved. Patients with diarrhea must be monitored with particular care until the diarrhea has resolved, as rapid clinical deterioration leading to death can occur. Methotrexate concentrations Monitoring of the serum methotrexate concentration is essential in determining the optimal dose and duration of treatment with leucovorin. Delayed methotrexate excretion may be caused by a third space fluid accumulation, renal insufficiency, or inadequate hydration. Under such circumstances, higher doses of leucovorin or prolonged administration may be indicated. Doses higher than those recommended for oral use must be given IV. 

METHOTREXATE PENICILLINS t plasma concentrations of methotrexate and risk of toxic effects of methotrexate, e.g. myelosuppression, liver cirrhosis, pulmonary toxicity Penicillins 1 renal elimination of methotrexate by renal tubular secretion, which is the main route of elimination of methotrexate. Penicillins compete with methotrexate for renal elimination. Displacement from proteinbinding sites may occur and is only a minor contribution to the interaction Avoid concurrent use. If concurrent use is necessary, monitor clinically and biochemically for blood dyscrasia, liver toxicity and pulmonary toxicity. Do FBCs and LFTs prior to concurrent treatment... 

Pleural effusions or ascites In patients with significant third space accumulations, evacuate the fluid before treatment and monitor plasma methotrexate levels. Psoriasis lesions Lesions of psoriasis may be aggravated by concomitant exposure to ultraviolet radiation. Radiation dermatitis and sunburn may be recalled by the use of methotrexate. 

METHOTREXATE CISPLATIN t methotrexate levels, with t risk of pulmonaiy toxicity Cisplatin is the most common anticancer drug associated with renal proximal and distal tubular damage. Cisplatin could significantly l renal elimination of methotrexate It would be best to start with lower doses of methotrexate. It is necessary to assess renal function prior to and during concurrent treatment until stability is achieved. Monitor clinically and with pulmonary function tests... 

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... 

A comprehensive review discusses the therapeutic management of RA (Turesson and Matteson, 2004). Epidemiological studies link extra-articular rheumatoid arthritis manifestations with premature mortality and support aggressive anti rheumatoid therapies for those patients. Cyclophosphamide is favored in patients with systemic rheumatoid vasculitis and methotrexate in those cases with other manifestations of extra-articular rheumatoid arthritis (Turesson and Matteson, 2004). Cyclophosphamide and TNFa inhibitors such as infliximab have some positive success in treatment resistant vasculitis associated with RA (Unger et al., 2003). However, TNFa inhibitors have also been associated with the opposite effect, an induction of extra articular rheumatoid arthritis so their use should be used only in specific cases when close monitoring is in place. 

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. 

In rheumatoid arthritis, cyclosporine is used in severe cases that have not responded to methotrexate. Cyclosporine can be combined with methotrexate, but the levels of both drugs must be monitored closely. In psoriasis, cyclosporine is indicated for treatment of adult immunocompetent patients with severe and disabling disease for whom other systemic therapies have failed. Because of its mechanism of action, cyclosporine also has been used successfully in inflammatory bowel disease see Chapter 38). 

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). 

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