PRILOSEC - Interactions Omeprazole magnesium

•   Antiretrovirals

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 [see Clinical Pharmacology (12.3)].
• Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with omeprazole may increase toxicity [see Clinical Pharmacology (12.3)].
• There are other antiretroviral drugs which do not result in clinically relevant interactions with omeprazole.

Rilpivirine-containing products: Concomitant use with PRILOSEC is contraindicated [see Contraindications (4)].

Atazanavir: Avoid concomitant use with PRILOSEC. See prescribing information for atazanavir for dosing information.

Nelfinavir: Avoid concomitant use with PRILOSEC. 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.

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.

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

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 [see Warnings and Precautions (5.11)].

A temporary withdrawal of PRILOSEC may be considered in some patients receiving high-dose methotrexate.

Concomitant use of omeprazole 80 mg results in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition [see Clinical Pharmacology (12.3)].

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.

Avoid concomitant use with PRILOSEC. Consider use of alternative anti-platelet therapy [see Warnings and Precautions (5.6)].

Increased exposure of citalopram leading to an increased risk of QT prolongation [see Clinical Pharmacology (12.3)].

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

Increased exposure of one of the active metabolites of cilostazol (3,4-dihydro-cilostazol) [see Clinical Pharmacology (12.3) ].

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

Potential for increased exposure of phenytoin.

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

Increased exposure of diazepam [see Clinical Pharmacology (12.3)].

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

Potential for increased exposure of digoxin [see Clinical Pharmacology (12.3) ].

Monitor digoxin concentrations. Dose adjustment may be needed to maintain therapeutic drug concentrations. See digoxin prescribing information.

Omeprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity.

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 PRILOSEC and MMF. Use PRILOSEC with caution in transplant patients receiving MMF [see Clinical Pharmacology (12.3)].

See the prescribing information for other drugs dependent on gastric pH for absorption.

Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions, including potentially fatal arrhythmias, and are contraindicated.

Amoxicillin also has drug interactions.

See Contraindications, Warnings and Precautions in prescribing information for clarithromycin.

See Drug Interactions in prescribing information for amoxicillin.

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

Monitor tacrolimus whole blood concentrations. Dose adjustment may be needed to maintain therapeutic drug concentrations. See prescribing information for tacrolimus.

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 [see Warnings and Precautions (5.10), Clinical Pharmacology (12.2)].

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.

Hyper-response in gastrin secretion in response to secretin stimulation test, falsely suggesting gastrinoma.

Temporarily stop PRILOSEC treatment at least 14 days before assessing to allow gastrin levels to return to baseline [see Clinical Pharmacology (12.2)].

There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs.

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

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 PRILOSEC.

CYP2C19 or CYP3A4 Inducers

Decreased exposure of omeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ].

St. John’s Wort, rifampin: Avoid concomitant use with PRILOSEC [see Warnings and Precautions (5.9)].

Ritonavir-containing products: see prescribing information for specific drugs.

Increased exposure of omeprazole [see Clinical Pharmacology (12.3) ].

Intervention:

Voriconazole: Dose adjustment of PRILOSEC is not normally required. However, in patients with Zollinger-Ellison syndrome, who may require higher doses, dose adjustment may be considered.

See prescribing information for voriconazole.