Omeprazole Methotrexate

METHOTREXATE PROTON PUMP INHIBITORS -OMEPRAZOLE Likely t plasma concentration of methotrexate and t risk of toxic effects, e.g. blood dyscrasias, liver cirrhosis, pulmonary toxicity, renal toxicity Attributed to omeprazole decreasing the renal elimination of methotrexate Monitor clinically and biochemically for blood dyscrasias and liver, renal and pulmonary toxicity... 

E)rug5 that influence nutrient metabolism are discussed in various sections. These drugs include lovastatin, pravastatin, omeprazole, dilantin, methotrexate, allopurinol, warfarin, furosemide, thiouracil, and diphosphonatc. Alcohol is also discussed in this context because, depending on its intake, it functions as a food, drug, or toxin. 

A 74-year-old woman with seronegative rheumatoid arthritis was given sulfasalazine followed by methotrexate, both of which were withdrawn because of adverse effects. She also took prednisone 10 mg/day. She developed acute abdominal pain and fever (38.7 C) with no chills. Her serum amylase was 269 IU/1, serum lipase 300 IU/1, and urinary amylase 2895 IU/1. There was no evidence of tumor, hypertriglyceridemia, or lithiasis. In addition to prednisone, she was taking amlodipine, bromazepam, and omeprazole, none of which have been reported to cause pancreatitis. A marked improvement was noted after prednisone withdrawal. 

Clinically important, potentially hazardous interactions with aluminum, aminophylline, aspirin, chlorambucil, cimetidine, clarithromycin, cyclophosphamide, cyclosporine, dicumarol, diuretics, docetaxel, estrogens, grapefruit juice, indomethacin, influenza vaccines, itraconazole, ketoconazole, lansoprazole, live vaccines, methotrexate, montelukast, omeprazole, oral contraceptives, pancuronium, phenobarbital, phenytoin, ranitidine, rifampicin, rifampin, timolol, tolbutamide, vitamin A... 

The excretion of methotrexate is reported to have been reduced in twelve patients given omeprazole and three patients given lansoprazole. However, similar elevations in methotrexate levels in another patient were independent of omeprazole use. One patient had myalgia and elevated 7-hydroxymethotrexate levels when given methotrexate with pantoprazole. 

In eontrast to these findings, a ease is reported in whieh a man with chon-droblastie osteosareoma, who had been taking omeprazole, was treated with high-dose methotrexate 20 g over 6 hours with hydration, urinary al-kalinisation and, after 24 hours, folinie aeid reseue. The folinic acid dose was adjusted in response to elevated methotrexate levels and omeprazole was stopped. A second dose of methotrexate 2 weeks later, this time without omeprazole, resulted in similar elevated methotrexate levels. Thus the elevated methotrexate levels in this patient could not be attributed to coadministered omeprazole. ... 

Proton pump inhibitors may affect renal, and possibly hepatic, clearance of methotrexate by inhibition of methotrexate transporter proteins. It has been suggested that omeprazole may inhibit the activity of a hydrogen-ion dependent mechanism in the kidney, on which methotrexate depends for its excretion, so that its loss is diminished. It has also been suggested that the situation with lansoprazole may be similar, but that pantoprazole may differ since at about the pH found in the renal tubules (pH 5), pantoprazole is more slowly activated than omeprazole. However, a case of an interaction with pantoprazole has also been reported. ... 

Information seems to be limited to these few reports and with the exception of one case report, they all found that proton pump inhibitors reduced the clearance of methotrexate. Any changes in methotrexate kinetics are important in terms of the potential for increased toxicity. Further study is required. The authors of one study in which the levels of methotrexate and its active metabolite were increased during the concurrent use of omeprazole or lansoprazole advise against concurrent use. Further, the authors of one report recommend that if omeprazole is necessary for a patient about to receive methotrexate, then omeprazole should be discontinued 4 to 5 days before methotrexate administration. The situation with other proton pump inhibitors may be similar. Ranitidine was found to be a suitable alternative in two of the cases.Note that the risks would appear to be most significant with high-dose methotrexate, but the case report involving a 15 mg weekly dose of methotrexate introduces a note of caution in all patients. 

Reid T, Yuen A, Catolico M, Carlson RW. Impact of omeprazole on the plasma clearance of methotrexate. Cancer ChemotherPharmacol 993) 33, 82-4. 

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