Esomeprazole

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. See Drug Interactions in prescribing information for amoxicillin.

Co-administration substantially decreases atazanavir plasma concentrations (AUC decreased by 94%, Cmax by 96%, Cmin by 95%), resulting in loss of therapeutic effect and potential drug resistance development.

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

Avoid concomitant use. Esomeprazole significantly reduces the antiplatelet activity of clopidogrel bisulfate when given concomitantly.

Proton pump inhibitors: e.g., Esomeprazole Lansoprazole Omeprazole Pantoprazole Rabeprazole ↓Rilpivirine Coadministration is contraindicated with JULUCA due to decreased rilpivirine concentrations [see Contraindications ( 4 )] .

Proton Pump Inhibitors: e.g., dexlansoprazole esomeprazole lansoprazole omeprazole pantoprazole rabeprazole ↓ RPV Coadministration is contraindicated due to potential for loss of virologic response and development of resistance.

Proton Pump Inhibitors: e.g., dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole ↓ RPV Coadministration is contraindicated due to potential for loss of virologic response and development of resistance.

Proton Pump Inhibitors: e.g., dexlansoprazole esomeprazole lansoprazole omeprazole pantoprazole rabeprazole ↓ RPV Coadministration is contraindicated due to potential for loss of virologic response and development of resistance.

Proton pump inhibitors: Esomeprazole a , lansoprazole, omeprazole, pantoprazole, rabeprazole Fosamprenavir calcium: ↔ Amprenavir ↑ Esomeprazole Proton pump inhibitors can be administered at the same time as a dose of fosamprenavir calcium with no change in plasma amprenavir concentrations. Fosamprenavir calcium/ritonavir: ↔ Amprenavir ↔ Esomeprazole Sedative/hypnotics: Midazolam, triazolam ↑Midazolam ↑Triazolam Coadministration is contraindicated due to potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression [see Contraindications (4)].

Concomitant use is not recommended. Co-administration decreases nelfinavir serum levels (AUC decreased by 92%, Cmax by 89%, Cmin by 75%) and active metabolite M8 levels.

Proton Pump Inhibitors: e.g., esomeprazole lansoprazole omeprazole pantoprazole rabeprazole ↓ rilpivirine Coadministration is contraindicated with rilpivirine tablets [see Contraindications (4) ] In addition to the drugs included in Table 6, the interaction between rilpivirine tablets and the following drugs was evaluated in clinical studies and no dose adjustment is needed for either drug [see Clinical Pharmacology ( 12.3 )] : acetaminophen, atorvastatin, chlorzoxazone, cabotegravir, ethinylestradiol, norethindrone, raltegravir, sildenafil, simeprevir and tenofovir disoproxil fumarate.

Proton Pump Inhibitors: e.g., esomeprazole lansoprazole omeprazole pantoprazole rabeprazole ↓ rilpivirine Coadministration is contraindicated with EDURANT or EDURANT PED [see Contraindications (4) ] .

Omeprazole or Esomeprazole Avoid concomitant use of clopidogrel with omeprazole or esomeprazole. A similar reduction in antiplatelet activity was observed with esomeprazole when given concomitantly with clopidogrel. Dexlansoprazole, lansoprazole, and pantoprazole had less effect on the antiplatelet activity of clopidogrel than did omeprazole or esomeprazole [ see Warnings and Precautions ( 5.1 ) and Clinical Pharmacology ( 12.3 ) ].

Concomitant use with high-dose methotrexate may elevate and prolong serum methotrexate and hydroxymethotrexate levels, possibly leading to toxicity. Use caution with high-dose methotrexate.

Interaction Drug Interaction Rifabutin, phenytoin, efavirenz, cimetidine, esomeprazole* Avoid coadministration unless the benefit outweighs the risks ( 7.6 , 7.7 , 7.8 , 7.9 ) Other drugs metabolized by CYP3A4 Consider dosage adjustment and monitor for adverse effects and toxicity ( 7.1 , 7.10 , 7.11 ) Digoxin Monitor digoxin plasma concentrations ( 7.12 ) Fosamprenavir, metoclopramide* Monitor for breakthrough fungal infections ( 7.6 , 7.13 ) *The drug interactions with esomeprazole and metoclopramide do not apply to posaconazole tablets.

Co-administration increases saquinavir concentrations (AUC increased by 82%, Cmax by 75%, Cmin by 106%), which may increase toxicity. Clinical and laboratory monitoring recommended; dose reduction should be considered.

Concomitant use increases INR and prothrombin time, potentially leading to abnormal bleeding and death.

CYP2C19 substrate; potential for interaction with esomeprazole.

CYP2C19 substrate; potential for interaction with esomeprazole.

Increases digoxin concentrations; magnitude unclear. Requires monitoring and dose adjustment.

Esomeprazole can reduce erlotinib absorption due to effects on gastric acid secretion.

7 DRUG INTERACTIONS • May affect plasma levels of antiretroviral drugs - use with atazanavir and nelfinavir is not recommended; if saquinavir is used with esomeprazole magnesium delayed-release capsules, monitor for toxicity and consider saquinavir dose reduction. Patients treated with esomeprazole magnesium delayed-release capsules and digoxin may need to be monitored for digoxin toxicity. (7.2) • Combined inhibitor of CYP2C19 and 3A4 may raise esomeprazole levels.

7 DRUG INTERACTIONS May affect plasma levels of antiretroviral drugs – use with atazanavir and nelfinavir is not recommended; if saquinavir is used with esomeprazole magnesium, monitor for toxicity and consider saquinavir dose reduction. Patients treated with esomeprazole magnesium and digoxin may need to be monitored for digoxin toxicity. ( 7.2 ) Combined inhibitor of CYP 2C19 and 3A4 may raise esomeprazole levels.( 7.3 ) Clopidogrel: esomeprazole magnesium decreases exposure to the active metabolite of clopidogrel.

Esomeprazole can reduce iron salt absorption due to effects on gastric acid secretion.

Esomeprazole can reduce ketoconazole absorption due to effects on gastric acid secretion.

Esomeprazole can reduce mycophenolate mofetil absorption due to effects on gastric acid secretion.

Concomitant administration decreases bioavailability of octreotide; may require increased octreotide dose.

Co-administration with esomeprazole increased risedronate Cmax by 60% and AUC by 22%. Not recommended concomitantly.

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.

Co-administration of esomeprazole 30 mg and diazepam, a CYP2C19 substrate, resulted in a 45% decrease in clearance of diazepam.

7 DRUG INTERACTIONS Tables 5 and 6 include drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with esomeprazole and instructions for preventing or managing them. Table 5: Clinically Relevant Interactions Affecting Drugs Co-Administered with Esomeprazole 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 esomeprazole may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ].

Omeprazole, of which esomeprazole is an enantiomer, has been reported to interact with some antiretroviral drugs. Therefore, clinical and laboratory monitoring for saquinavir toxicity is recommended during concurrent use with esomeprazole. 7.2 Drugs for Which Gastric pH Can Affect Bioavailability Due to its effects on gastric acid secretion, esomeprazole can reduce the absorption of drugs where gastric pH is an important determinant of their bioavailability.

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.

However, esomeprazole, a proton pump inhibitor, administered at a dose of 40 mg once daily for 7 days, did not result in a clinically meaningful reduction in lapatinib steady-state exposure.

7.13 Proton Pump Inhibitors, H 2 Blockers, Antacids ORKAMBI may reduce the exposure and effectiveness of proton pump inhibitors such as omeprazole, esomeprazole, and lansoprazole, and may alter the exposure of ranitidine.

7 DRUG INTERACTIONS See Table 3 and Table 4 for clinically significant drug interactions and interactions with diagnostics with naproxen and esomeprazole magnesium. Table 3: Clinically Significant Drug Interactions with Naproxen and Esomeprazole Magnesium – Affecting Drugs Co-Administered with Naproxen and Esomeprazole magnesium delayed-release tablets and Interactions with Diagnostics Clinical Impact: Naproxen • Naproxen and anticoagulants such as warfarin have a synergistic effect on bleeding. Esomeprazole Magnesium • Increased INR and prothrombin time in patients treated with PPIs, including esomeprazole, and warfarin concomitantly.

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.

Omeprazole, of which esomeprazole is an enantiomer, has been reported to interact with some antiretroviral drugs. Increased gastric pH during omeprazole treatment may change the absorption of the antiretroviral drug. Reduced concentrations of atazanavir and nelfinavir For some antiretroviral drugs, such as atazanavir and nelfinavir, decreased serum levels have been reported when given together with omeprazole.

7.4 Concomitant Use With Gastric Acid-Reducing Agents Concomitant use of pazopanib tablets with esomeprazole, a PPI, decreased the exposure of pazopanib.

7.4 Concomitant Use With Gastric Acid-Reducing Agents Concomitant use of pazopanib tablets with esomeprazole, a PPI, decreased the exposure of pazopanib.

Increased concentrations of saquinavir For other antiretroviral drugs, such as saquinavir, elevated serum levels have been reported, with an increase in AUC by 82%, in Cmax by 75%, and in Cmin by 106%, following multiple dosing of saquinavir/ritonavir (1,000/100 mg) twice daily for 15 days with omeprazole 40 mg daily co-administered days 11 to 15.

Concomitant administration of esomeprazole and a combined inhibitor of CYP2C19 and CYP3A4, such as voriconazole, may result in more than doubling of the esomeprazole exposure.