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 esomeprazole 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 esomeprazole may increase toxicity [see Clinical Pharmacology (12.3)].
• There are other antiretroviral drugs which do not result in clinically relevant interactions with esomeprazole.

Intervention:

Rilpivirine-containing products: Concomitant use with esomeprazole magnesium is contraindicated [see Contraindications (4)].
Atazanavir: See prescribing information for atazanavir for dosing information.
Nelfinavir: Avoid concomitant use with esomeprazole magnesium. 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 esomeprazole, 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 the target INR range.

Methotrexate

Clinical Impact:

Concomitant use of esomeprazole 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 (5.12)].

Intervention:

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

2C19 Substrates (e.g., clopidogrel, citalopram, cilostazol)

Clopidogrel

Clinical Impact:

Concomitant use of esomeprazole 40 mg resulted 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 esomeprazole or a higher dose of clopidogrel in comparison with the approved dose of clopidogrel.

Intervention:

Avoid concomitant use with esomeprazole magnesium Consider use of alternative anti-platelet therapy [see Warnings and Precautions (5.7)].

Citalopram

Clinical Impact:

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

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 cilostazol and one of its active metabolites (3,4-dihydro-cilostazol) [see Clinical Pharmacology (12.3)].

Intervention:

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

Digoxin

Clinical Impact:

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

Intervention:

Monitor digoxin concentrations and adjust the dose, if needed, to maintain therapeutic drug concentrations. See prescribing information for digoxin.

Combination Therapy with Clarithromycin and Amoxicillin

Clinical Impact:

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.

Intervention:

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

Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole)

Clinical Impact:

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

Intervention:

Mycophenolate mofetil (MMF): Co-administration of omeprazole, of which esomeprazole is an enantiomer, 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 esomeprazole magnesium and MMF. Use esomeprazole magnesium 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.

Tacrolimus

Clinical Impact:

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

Intervention:

Monitor tacrolimus whole blood concentrations and consider reducing the dose, if 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 [see Warnings and Precautions (5.11), Clinical Pharmacology (12.2)].

Intervention:

Discontinue esomeprazole magnesium 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:

Discontinue esomeprazole magnesium 4 weeks prior to testing [see Clinical Pharmacology (12.2)]

False Positive Urine Tests for THC

Clinical Impact:

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

Intervention:

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

CYP2C19 or CYP3A4 Inducers

Clinical Impact:

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

Intervention:

St. John’s Wort, rifampin: Avoid concomitant use with [see Warnings and Precautions (5.10)]. Ritonavir-containing products: see prescribing information for specific drugs

Voriconazole

Clinical Impact:

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

Intervention:

Dose adjustment of esomeprazole magnesium is not normally required. However, in patients with Zollinger-Ellison syndrome, who may require higher doses, dosage adjustment may be considered. See prescribing information for voriconazole.