Renal dysfunction methotrexate

Adverse reactions may include renal dysfunction tremor infectious complications hirsutism hypertension gum hyperplasia cramps acne convulsions paresthesia. Methotrexate... 

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). 

Renal use Use methotrexate in patients with impaired renal function with extreme caution, and at reduced dosages, because renal dysfunction will prolong elimination. Gl Diarrhea and ulcerative stomatitis require interruption of therapy hemorrhagic enteritis and death from intestinal perforation may occur. 

The mechanism differs from that underlying the sulfamethoxazole/trimethoprim interaction. Sulphonamides such as co-trimoxazole and sulfadiazine are known to cause renal dysfunction - interstitial nephritis and renal failure, which may -L excretion of methotrexate. Sulphonamides are also known to compete with methotrexate for renal elimination. Displacement from protein-binding sites of methotrexate is a minor contribution to the interaction... 

Comparative studies In 20 patients with high-dose methotrexate-induced renal dysfunction, who received one to three doses of carboxypeptidase G2, 50 U/kg intravenously, thymidine 8 g/rr /day by... 

Urinary tract Methotrexate-induced renal damage appears to be physicochemical in nature. Both the parent compound and its major metabolite, 7-hydroxymethotrexate, are less soluble at acidic pH values, increasing the risk of precipitation in the kidneys, particularly at high dosages. An amorphous yellow material—very probably methotrexate—has been isolated in the kidneys of patients who died as a result of methotrexate-induced renal dysfunction. For physicochemical reasons, it is recommended that the urine be alkalinized (target urinary pH above 7.5) before intensive methotrexate regimens are started. Supportive agents include sodium bicarbonate orally or intravenously, acetazolamide 500 mg qds, or both in combination [1805, 18F, 182 ]. If there is acute renal insufficiency despite appropriate urinary alkalinization, one may need to use carboxypeptidase G2 as an antidote, which is also appropriate in cases of accidental intrathecal overdose of methotrexate [183", 184 ]. 

Widemann BC, Balis FM, Murphy RF, Sorensen JM, Montello MJ, O Brien M, Adamson PC. Carboxypeptidase-G2, thymidine, and leucovorin rescue in cancer patients with methotrexate-induced renal dysfunction. J Clin Oncol 1997 15(5) 2125-34. 

In studies of the neurotoxic effects of low-dose methotrexate treatment, dizziness, headache, visual disturbances or hallucinations, lack of concentration, cognitive dysfunction, and depression-like symptoms were detected in 1-35% of patients (527,528). Advanced age and mild renal insufficiency were possible susceptibility factors (529). 

Antimetabolites cause gastrointestinal toxicity including stomatitis and diarrhoea as well as bone marrow depression renal impairment potentiates the toxicity of methotrexate. Active excreHon of methotrexate by the renal tubule is blocked by salicylate, which also displaces it from plasma protein, increasing the risk of toxicity. Hepatic dysfunction potentiates the toxicity of 5-fluorouracil, since it is primarily metabolised by the liver. 

Methotrexate Nausea and vomiting diarrhoea fever anaphylaxis hepatic necrosis Oral and gastrointestinal ulceration, perforation may occur bone marrow depression hepatic toxicity including cirrhosis renal toxicity pulmonary infiltrates and fibrosis osteoporosis conjunctivFtis alopecia depigmentation menstrual dysfunction encephalopathy infertility lymphoma teratogenesis... 

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