Proton pump inhibitors Phenytoin

PROTON PUMP INHIBITORS PHENYTOIN Possible t efficacy and adverse effects of phenytoin Unclear possible altered metabolism via CYP2C19 1 dose may be required. Use the proton pump inhibitor regularly, not PRN. Monitor phenytoin levels when starting or stopping treatment. Patients have received omeprazole for 3-5 weeks without altered phenytoin levels. Not reported with pantoprazole or rabeprazole... 

Azathioprine, chloramphenicol, colchicine, cyclophosphamide, cytarabine, 5-fluorodeoxyuridine, 5-fluorouracil, hydroxyurea, mercaptopurine, metformin, methotrexate, phenobarbital, phenytoin, primidone, proton pump inhibitors, pyrimethamine, sulfasalazine, and vinblastine... 

Omeprazole is classified as a proton pump inhibitor, as it acts by blocking the hydrogen-potassium adenosine triphosphate enzyme system of the gastric parietal cells. Omeprazole therefore inhibits gastric acid release. Common side-effects associated with omeprazole include diarrhoea, headache, nausea and vomiting. Concurrent administration of omeprazole and phenytoin results in enhanced effects of phenytoin, which may lead to phenytoin toxicity. 

Drugs that may be affected by proton pump inhibitors include azole antifungal agents (eg, itraconazole, ketoconazole), benzodiazepines, cilostazol, clarithromycin, digoxin, phenytoin, salicylates, sulfonylureas, and warfarin. Drugs that may affect proton pump inhibitors include sucralfate and clarithromycin. 

Drugs that affect voriconazole include the following barbiturates (long acting), cimetidine, nonnucleoside reverse transcriptase inhibitors (NNRIs), phenytoin, protease inhibitors, proton pump inhibitors, rifampin, rifabutin. 

Drugs affected by voriconazole include the following benzodiazepines, calcium channel blockers, cisapride, coumarin anticoagulants, cyclosporine, ergot alkaloids, HMG-CoA reductase inhibitors, NNRTIs, phenytoin, protease inhibitors, pimozide, proton pump inhibitors, quinidine, prednisolone, rifabutin, sirolimus, sulfonylureas, tacrolimus, vinca alkaloids. 

Il.b.l.1. Adverse effects of anti-secretory treatment. Histamine H2 antagonists and proton pump inhibitors are very safe as well as effective treatments. Cimetidine has small effects on hepatic drug metabolism which are only of clinical signiflcance with drugs used in doses close to toxic levels, notably phenytoin, aminophylline and warfarin. Other adverse effects such as headache, rash and thrombocytopenia are rare. 

Itraconazole has significant interactions with a number of commonly prescribed drugs, such as rifampin, phenytoin, and carbamazepine. Itraconazole raises serum digoxin and cyclosporine levels and may affect the metabolism of oral hypoglycemic agents and coumadin. Absorption of itraconazole is impaired by antacids, Hj blockers, proton pump inhibitors, and drugs that contain buffers, such as the antiretroviral agent didanosine. 

Omeprazole is a proton pump inhibitor. Headache, skin rash, and diarrhea have all been recorded by adverse event registries sufficiently often to suggest causal relations (1). Omeprazole is a modest inhibitor of CYP isoforms. Interactions are less likely than with cimetidine and are probably of no practical importance. However, omeprazole reduces the absorption of drugs that require a low gastric pH (ketoconazole, iron salts, ampicilhn) and can inhibit the hepatic clearance of some drugs (diazepam, warfarin, phenytoin) (2). 

Delavirdine Due to its shorter tj, d rapid emergence of resistance, delavirdine is the least used of the NNRTIs. Its absorption is best at acid pH and may be decreased by histamine Hj receptor antagonists or proton pump inhibitors. It is cleared predominantly by CYP3A4 and has an elimination tj 6 hours. It should be avoided with CYP3A4 substrates with a narrow therapeutic index and not combined with potent inducers of CYP3A4 (e.g., carbamazepine, phenobarbital, phenytoin, rifabutin, and rifampin). 

A4 Barbiturates, carbamazepine, corticosteroids, efavirenz, phenytoin, rifampin, troglitazone Antiarrhythmics, antidepressants, azole antifungals, benzc iazepines, calcium channel blockers, cyclosporine, delavirdine, doxorubicin, efavirenz, erythromycin, estrogens, HIV protease inhibitors, nefazodone, paclitaxel, proton pump inhibitors, HMG-CoA reductase inhibitors, rifabutin, rifampin, sildenafil, SSRIs, tamoxifen, trazodone, vinca anticancer agents... 

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