Methotrexate monitoring therapy 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. 

Biologic response modifiers (BRMs) are indicated in patients who have failed an adequate trial of DMARD therapy.1 BRMs may be added to DMARD monotherapy (i.e., methotrexate) or replace ineffective DMARD therapy.22 The decision to select a particular agent generally is based on the prescriber s comfort level with monitoring the safety and efficacy of the medications, the frequency and route of administration, the patient s comfort level or manual dexterity to self-administer subcutaneous injections, the cost, and the availability of insurance coverage.23 In general, BRMs should be avoided in patients with serious infections, demyelinating disorders (e.g., multiple sclerosis or optic neuritis) or heart failure.21... 

Severe reactions Because of the possibility of severe toxic reactions (which can be fatal), fully inform patients of the risks involved and assure constant supervision. Deaths Use methotrexate only in life-threatening neoplastic diseases, or in patients with psoriasis or rheumatoid arthritis (RA) with severe, recalcitrant, disabling disease that is not adequately responsive to other forms of therapy. Deaths have occurred with the use of methotrexate in malignancy, psoriasis, and RA. Closely monitor patients for bone marrow, liver, lung, and kidney toxicities. 

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. 

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). 

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... 

Methotrexate therapy requires monitoring of liver enzymes and is contraindicated in those with hepatic disease and in women considering pregnancy. 

The picture is not totally clear but it seems possible that the previous use of cisplatin causes kidney damage that may not necessarily be detectable with the usual creatinine clearance tests, llie effect is to cause a marked reduction in the clearance of the methotrexate. The serum methotrexate levels of such patients should be closely monitored so that any delay in its clearance is detected early and folinic acid rescue therapy can be given. This appears to prevent serious toxicity. " ... 

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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