Omeprazoleinteractions

Tables 6 and 7 include drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with omeprazole and instructions for preventing or managing them. Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs.

Table 6: Clinically Relevant Interactions Affecting Drugs Co-Administered with Omeprazole and Interaction with Diagnostics Antiretrovirals Clinical Impact: The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known. Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir and nelfinavir) when used concomitantly with omeprazole may reduce antiviral effect and promote the development of drug resistance. Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with omeprazole may increase toxicity. There are other antiretroviral drugs which do not result in clinically relevant interactions with omeprazole.

Intervention: Rilpivirine-containing products: Concomitant use with omeprazole and sodium bicarbonate is contraindicated.

Atazanavir: Avoid concomitant use with omeprazole and sodium bicarbonate. See prescribing information for atazanavir for dosing information.

Nelfinavir: Avoid concomitant use with omeprazole and sodium bicarbonate. See prescribing information for nelfinavir.

Saquinavir: See the prescribing information for saquinavir for monitoring of potential saquinavir-related toxicities.

Other antiretrovirals: See prescribing information for specific antiretroviral drugs.

Warfarin Clinical Impact: Increased INR and prothrombin time in patients receiving PPIs, including omeprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death.

Intervention: Monitor INR and prothrombin time and adjust the dose of warfarin, if needed, to maintain target INR range.

Methotrexate Clinical Impact: Concomitant use of omeprazole with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted.

Intervention: A temporary withdrawal of omeprazole and sodium bicarbonate may be considered in some patients receiving high-dose methotrexate. CYP2C19 Substrates (e.g., clopidogrel, citalopram, cilostazol, phenytoin, diazepam) Clopidogrel Clinical Impact: Concomitant use of omeprazole 80 mg results in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition. There are no adequate combination studies of a lower dose of omeprazole or a higher dose of clopidogrel in comparison with the approved dose of clopidogrel.

Intervention: Avoid concomitant use with omeprazole and sodium bicarbonate. Consider use of alternative anti-platelet therapy.

Citalopram Clinical Impact: Increased exposure of citalopram leading to an increased risk of QT prolongation.

Intervention: Limit the dose of citalopram to a maximum of 20 mg per day. See prescribing information for citalopram.

Cilostazol Clinical Impact: Increased exposure of one of the active metabolites of cilostazol (3,4-dihydro­cilostazol).

Intervention: Reduce the dose of cilostazol to 50 mg twice daily. See prescribing information for cilostazol.

Phenytoin Clinical Impact: Potential for increased exposure of phenytoin.

Intervention: Monitor phenytoin serum concentrations. Dose adjustment may be needed to maintain therapeutic drug concentrations. See prescribing information for phenytoin.

Diazepam Clinical Impact: Increased exposure of diazepam.

Intervention: Monitor patients for increased sedation and reduce the dose of diazepam as needed.

Digoxin Clinical Impact: Potential for increased exposure of digoxin.

Intervention: Monitor digoxin concentrations. Dose adjustment may be needed to maintain therapeutic drug concentrations. See digoxin prescribing information. Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole) Clinical Impact: Omeprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity.

Intervention: Mycophenolate mofetil (MMF): Co-administration of omeprazole in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving omeprazole and sodium bicarbonate and MMF. Use omeprazole and sodium bicarbonate with caution in transplant patients receiving MMF. See the prescribing information for other drugs dependent on gastric pH for absorption.

Tacrolimus Clinical Impact: Potential for increased exposure of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19.

Intervention: Monitor tacrolimus whole blood concentrations. Dose adjustment may be needed to maintain therapeutic drug concentrations. See prescribing information for tacrolimus. Interactions with Investigations of Neuroendocrine Tumors Clinical Impact: Serum chromogranin A (CgA) levels increase secondary to PPI-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors.

Intervention: Temporarily stop PRILOSEC treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g., for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary. Interaction with Secretin Stimulation Test Clinical Impact: Hyper-response in gastrin secretion in response to secretin stimulation test, falsely suggesting gastrinoma.

Intervention: Temporarily stop omeprazole and sodium bicarbonate treatment at least 14 days before assessing to allow gastrin levels to return to baseline. False Positive Urine Tests for THC Clinical Impact: There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs.

Intervention: An alternative confirmatory method should be considered to verify positive results.

Other Clinical Impact: There have been clinical reports of interactions with other drugs metabolized via the cytochrome P450 system (e.g., cyclosporine, disulfiram).

Intervention: Monitor patients to determine if it is necessary to adjust the dosage of these other drugs when taken concomitantly with omeprazole and sodium bicarbonate.

Table 7: Clinically Relevant Interactions Affecting Omeprazole When Co-Administered with Other Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact: Decreased exposure of omeprazole when used concomitantly with strong inducers.

Intervention: St. John’s wort, rifampin: Avoid concomitant use with omeprazole and sodium bicarbonate.

Ritonavir-containing products: See prescribing information for specific drugs. CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of omeprazole.

Intervention: Voriconazole: Dosage adjustment of omeprazole and sodium bicarbonate is not required. See full prescribing information for a list of clinically important drug interactions.