From the Guidelines
Patients taking omeprazole should be aware of potential drug interactions, particularly with clopidogrel, and consult their healthcare provider before starting any new medications, as omeprazole may reduce the effectiveness of clopidogrel, an antiplatelet medication, and alternative acid-reducing medications like famotidine or pantoprazole may be recommended 1.
Key Interactions
- Clopidogrel: Omeprazole may reduce the effectiveness of clopidogrel, an antiplatelet medication, by inhibiting the cytochrome P450 2C19 enzyme, which is involved in the metabolism of clopidogrel, and alternative acid-reducing medications like famotidine or pantoprazole may be recommended 1.
- Warfarin: Omeprazole can increase the blood-thinning effect of warfarin, and more frequent INR monitoring may be necessary when starting or stopping omeprazole 1.
- Methotrexate: Omeprazole may increase methotrexate levels, and patients on high-dose methotrexate should avoid omeprazole if possible 1.
- Digoxin: Omeprazole can increase digoxin levels, and monitoring of digoxin levels and adjustment of dosage may be necessary 1.
- HIV medications (e.g., atazanavir, nelfinavir): Omeprazole may decrease the absorption of these drugs, and alternative acid-reducing medications should be considered 1.
Mechanism of Interactions
These interactions occur because omeprazole affects stomach pH and can inhibit or induce certain liver enzymes involved in drug metabolism, such as cytochrome P450 2C19, which is involved in the metabolism of clopidogrel 1.
Management of Interactions
To manage these interactions, healthcare providers may adjust dosages, increase monitoring, or recommend alternative medications, and patients should always inform their healthcare providers about all medications they are taking, including over-the-counter drugs and supplements 1.
From the FDA Drug Label
- Drug Interactions Tables 3 and 4 include drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with omeprazole and instructions for preventing or managing them. Table 3: 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. • 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 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. 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. 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
The potential drug interactions with omeprazole include:
- Antiretrovirals: decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) and increased exposure of other antiretroviral drugs (e.g., saquinavir)
- Warfarin: increased INR and prothrombin time, which may lead to abnormal bleeding and even death
- Methotrexate: elevated and prolonged serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities
- CYP2C19 Substrates (e.g., clopidogrel, citalopram, cilostazol, phenytoin, diazepam): reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition 2
From the Research
Potential Drug Interactions with Omeprazole
Omeprazole, a proton pump inhibitor (PPI), has been found to interact with various drugs, leading to adverse consequences. Some of the potential drug interactions with omeprazole include:
- Increased plasma concentrations of venlafaxine and its active metabolite O-desmethylvenlafaxine when co-administered with omeprazole 3
- Increased risk of drug interactions due to omeprazole's inhibition of cytochrome P450 enzymes, particularly CYP2C19 4
- Adverse influences on the pharmacokinetics of medications such as diazepam, carbamazepine, clozapine, indinavir, nelfinavir, atazanavir, rilpivirine, methotrexate, tacrolimus, mycophenolate mofetil, clopidogrel, digoxin, itraconazole, posaconazole, and oral iron supplementation 5
- Concomitant use with warfarin, ibuprofen, and serotonergic drugs such as tramadol, citalopram, and escitalopram may increase the risk of bleeding in patients treated with oral antiplatelets 6
- Decreased absorption of mycophenolate mofetil in newly transplanted patients, leading to rejection of transplanted organs 7
- Increased risk of cardiac problems, such as cardiovascular death, myocardial infarction, and stroke, when used concomitantly with antiplatelet agents such as clopidogrel 7
Factors Influencing Drug Interactions
The degree of drug interactions associated with omeprazole depends on various factors, including:
- Genotype status of CYP2C19 and CYP1A2 5
- Ethnicity 5
- Dose and treatment course of omeprazole 5
- Pharmaceutical formulation of the object drug 5
- Other concomitant medications 5
- Administration schedule 5
Clinical Risk Management
To minimize the risk of adverse drug interactions, clinical professionals should: