Lansoprazole Methotrexate

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... 

Naproxen had no significant effect on the AUC, half-life, or clearance of methotrexate and its major metabolite 7-hydroxymethotrexate in 18 patients with rheumatoid arthritis given intravenous methotrexate 15 mg weekly. Other studies have found that naproxen did not affect the pharmacokinetics of methotrexate. In a study in 27 patients with rheumatoid arthritis who had taken oral methotrexate 7.5 to 15 mg weekly for at least 3 months, the concurrent use of naproxen 600 mg twice daily with lansoprazole did not affect the pharmacokinetics of methotrexate or 7-hydroxymethotrexate. Another study in patients with rheumatoid arthritis with normal renal function found that no toxicity was caused when naproxen 500 mg twice daily was given with methotrexate 15 mg given orally or intravenously, nor was the methotrexate clearance altered. ... 

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 a study in 76 patients with solid tumours treated with high-dose methotrexate infusions (300 mg/m to 12 g/m over 1 to 24 hours), the clearance of methotrexate and its metabolite 7-hydroxymethotrexate was significantly decreased and plasma levels significantly increased in the 3 patients who were also given lansoprazole 30 mg daily. ... 

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. 

VaMly M, Amer F, KukuUca MJ, et al. Coadministration of lansoprazole and naproxen does not affect the pharmacokinetic profile of methotrexate in adult patients with rheumatoid arthritis. J Chn Pharmacol 2005 45 1179-1186. 

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