Naproxen and esomeprazole interactions

• Gastric Acid Reducing Agents: Avoid co-administration with proton pump inhibitors (PPIs). (Acalabrutinib label, Drug interactions)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

…risk of developing epidural or spinal hematomas in these patients include: • use of indwelling epidural catheters • concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants • a history of traumatic or repeated epidural or spinal punctures • a history of spinal deformity… (Apixaban label, Boxed warning)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

In HIV-treatment-experienced adult patients: Coadministration of REYATAZ with PPIs is not recommended. (Atazanavir label, Drug interactions)

Intervention: The concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with other NSAIDs or salicylates is not recommended. (Naproxen and esomeprazole label, Drug interactions)

Intervention: The concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with other NSAIDs or salicylates is not recommended. (Naproxen and esomeprazole label, Drug interactions)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

Histamine-2 (H 2 ) antagonists and proton pump inhibitors should be avoided. (Cefuroxime label, Drug interactions)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

Nephrotoxic agents Concomitant administration of cidofovir injection and agents with nephrotoxic potential [e.g., intravenous aminoglycosides (e.g., tobramycin, gentamicin, and amikacin), amphotericin B, foscarnet, intravenous pentamidine, vancomycin, and nonsteroidal anti-inflammatory agents] is contraindicated. (Cidofovir label, Drug interactions)

Avoid use of Citalopram Capsules in CYP2C19 poor metabolizers, patients receiving concomitant cimetidine or another CYP2C19 inhibitor, patients with hepatic impairment, and patients who are greater than 60 years of age, because Citalopram Capsules are only available in a 30 mg dose strength and dosage adjustments are not possible [see Drug Interactions ( 7 ),… (Citalopram label, Warnings and precautions)

Interaction with Clopidogrel : Avoid concomitant use. (Naproxen and esomeprazole label, Warnings and precautions)

…the risk of developing epidural or spinal hematomas in these patients include: use of indwelling epidural catheters concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants a history of traumatic or repeated epidural or spinal punctures a history of spinal deformity… (Dabigatran label, Boxed warning)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

…the risk of developing epidural or spinal hematomas in these patients include: use of indwelling epidural catheters concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants a history of traumatic or repeated epidural or spinal punctures a history of spinal deformity… (Edoxaban label, Boxed warning)

Avoid SYMFI with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.3) ] . (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

• Proton pump inhibitors (PPIs), including esomeprazole magnesium, are contraindicated in patients receiving rilpivirine-containing products [see Drug Interactions ( 7 ) ]. (Naproxen and esomeprazole label, Contraindications)

…the risk of developing epidural or spinal hematomas in these patients include: Use of indwelling epidural catheters Concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, and other anticoagulants A history of traumatic or repeated epidural or spinal punctures A history of spinal deformity… (Enoxaparin label, Boxed warning)

For proton pump inhibitors, avoid concomitant use if possible. (Erlotinib label, Drug interactions)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

…risk of developing epidural or spinal hematomas in these patients include: • use of indwelling epidural catheters • concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, or other anticoagulants • a history of traumatic or repeated epidural or spinal puncture • a history of spinal deformity… (Fondaparinux label, Boxed warning)

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)]. (Fosamprenavir label, Drug interactions)

• Drugs Affecting Gastric pH: Avoid concomitant use of IRESSA with proton pump inhibitors, if possible. (Gefitinib label, Drug interactions)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

Intervention: The concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with other NSAIDs or salicylates is not recommended. (Naproxen and esomeprazole label, Drug interactions)

Intervention: The concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with other NSAIDs or salicylates is not recommended. (Naproxen and esomeprazole label, Drug interactions)

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] . (Methotrexate label, Warnings and precautions)

Intervention Concomitant use of methylphenidate extended-release orally disintegrating tablets with a gastric pH modulator (i.e., a H2-blocker or a proton pump inhibitor) is not recommended. (Methylphenidate label, Drug interactions)

MISOPROSTOL SHOULD NOT BE TAKEN BY PREGNANT WOMEN TO REDUCE THE RISK OF ULCERS INDUCED BY NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs) (see CONTRAINDICATIONS , WARNINGS , and PRECAUTIONS ). (Misoprostol label, Boxed warning)

Patients with known aspirin sensitivity should continue to avoid aspirin or non-steroidal anti-inflammatory agents while taking SINGULAIR ( 5.4 ). (Montelukast label, Warnings and precautions)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

It should not be used with other naproxen-containing products since they all circulate in the plasma as the naproxen anion. (Naproxen and esomeprazole label, Warnings and precautions)

Naproxen and esomeprazole magnesium delayed-release tablets are contraindicated in the following patients: • Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to naproxen, esomeprazole magnesium, substituted benzimidazoles, or to any components of the drug product, including omeprazole. (Naproxen and esomeprazole label, Contraindications)

Naproxen and esomeprazole magnesium delayed-release tablets are contraindicated in the following patients: • Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to naproxen, esomeprazole magnesium, substituted benzimidazoles, or to any components of the drug product, including omeprazole. (Naproxen and esomeprazole label, Contraindications)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

Concomitant Use With Gastric Acid-Reducing Agents : Avoid concomitant use of VOTRIENT with gastric acid-reducing agents. (Pazopanib label, Drug interactions)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

Prevention or Management Avoid concomitant use of Noxafil oral suspension with cimetidine or esomeprazole unless the benefit outweighs the risks. (Posaconazole label, Drug interactions)

Avoid coadministration with probenecid or nonsteroidal anti-inflammatory drugs. (Pralatrexate label, Drug interactions)

Additional risk factors for bleeding include: body weight <60 kg, propensity to bleed, concomitant use of medications that increase the risk of bleeding (e.g . , warfarin, heparin, fibrinolytic therapy, chronic use of nonsteroidal anti-inflammatory drugs [NSAIDs]) [see Warnings and Precautions (5.1) ] . (Prasugrel label, Boxed warning)

John’s Wort or Rifampin : Avoid concomitant use. (Naproxen and esomeprazole label, Warnings and precautions)

• Proton pump inhibitors (PPIs), including esomeprazole magnesium, are contraindicated in patients receiving rilpivirine-containing products [see Drug Interactions ( 7 ) ]. (Naproxen and esomeprazole label, Contraindications)

Concomitant administration of Risedronate sodium delayed-release and H 2 blockers or PPIs is not recommended. (Risedronate label, Drug interactions)

…risk of developing epidural or spinal hematomas in these patients include: • use of indwelling epidural catheters • concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants • a history of traumatic or repeated epidural or spinal punctures • a history of spinal deformity… (Rivaroxaban label, Boxed warning)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

Intervention: The concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with other NSAIDs or salicylates is not recommended. (Naproxen and esomeprazole label, Drug interactions)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

It should not be used with other naproxen-containing products since they all circulate in the plasma as the naproxen anion. (Naproxen and esomeprazole label, Warnings and precautions)

VIREAD should be avoided with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.1) ] . (Tenofovir label, Warnings and precautions)

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. (Naproxen and esomeprazole label, Contraindications)

Intervention : Voriconazole : Avoid concomitant use with naproxen and esomeprazole magnesium delayed-release tablets. (Naproxen and esomeprazole label, Drug interactions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

• Strong Inhibitors of CYP2C19 : The recommended dosage is 50 mg once daily or 100 mg once daily for those patients who are not responding to 50 mg once daily. (Abrocitinib label, Drug interactions)

Intervention : • During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. (Naproxen and esomeprazole label, Drug interactions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

However, this is of special importance in patients at risk of or having underlying renal dysfunction and patients taking concomitant nephrotoxic agents such as cyclosporine, tacrolimus, aminoglycosides, vancomycin and non-steroidal anti-inflammatory drugs [See Adverse Reactions (6.2) and Clinical Pharmacology (12.3) ]. (Adefovir label, Warnings and precautions)

Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (Afatinib label, Warnings and precautions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Use caution when co-prescribing aspirin/nonsteroidal anti- inflammatory drugs that may worsen gastrointestinal irritation. (Alendronate label, Drug interactions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Proton Pump Inhibitors Clinical Impact Time to maximum concentration (T max ) of amphetamine is decreased compared to when administered alone. (Amphetamine and dextroamphetamine label, Drug interactions)

Monitor patients for bleeding, including those receiving concomitant therapy with other drugs known to cause bleeding (e.g., anticoagulants, PDE3 inhibitors, NSAIDs, antiplatelet agents, selective serotonin reuptake inhibitors) [see Drug Interactions (7.3) , Clinical Pharmacology (12.3) ] . (Anagrelide label, Warnings and precautions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Intervention : • During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. (Naproxen and esomeprazole label, Drug interactions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Co-morbid conditions such as coagulation disorders or concomitant use of warfarin and other anticoagulants, antiplatelet agents (e.g., aspirin), and serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk. (Naproxen and esomeprazole label, Warnings and precautions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Intervention : • During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. (Naproxen and esomeprazole label, Drug interactions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. (Naproxen and esomeprazole label, Warnings and precautions)

Intervention : • During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. (Naproxen and esomeprazole label, Drug interactions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Proton Pump Inhibitors (PPI) As an alternative to PPIs, use short-acting antacids or H2 blockers and separate dosing by more than 2 hours from BOSULIF dosing. (Bosutinib label, Drug interactions)

Intervention : • During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. (Naproxen and esomeprazole label, Drug interactions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Co-morbid conditions such as coagulation disorders or concomitant use of warfarin and other anticoagulants, antiplatelet agents (e.g., aspirin), and serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. (Naproxen and esomeprazole label, Warnings and precautions)

Co-administration of CYP2C19 inhibitors, such as omeprazole or fluvoxamine, with carisoprodol could result in increased exposure of carisoprodol and decreased exposure of meprobamate. (Carisoprodol label, Drug interactions)

Intervention : • During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. (Naproxen and esomeprazole label, Drug interactions)

Drug Interactions As with other cephalosporins, cefotaxime may potentiate the nephrotoxic effects of nephrotoxic drugs such as aminoglycosides, NSAIDs and furosemide. (Cefotaxime label, Drug interactions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Cilostazol Clinical Impact : Increased exposure of cilostazol and one of its active metabolites (3,4-­dihydro-cilostazol) when coadministered with omeprazole magnesium, the racemate of esomeprazole [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

NSAIDs Use with caution Non-steroidal anti-inflammatory drugs (but not acetyl salicylic acid) in combination of very high doses of quinolones have been shown to provoke convulsions in pre-clinical studies and in postmarketing. (Ciprofloxacin label, Drug interactions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

Cyclosporine Clinical Impact : Concomitant use of naproxen and cyclosporine may increase cyclosporine’s nephrotoxicity. (Naproxen and esomeprazole label, Drug interactions)

…↔ ↔ Valsartan (320 mg) 20 mg ↓12% [↓3%, ↓20%] ↔ Simvastatin (40 mg) 20 mg ↔ ↔ Anti-infective Agent Rifampin (600 mg once daily for 6 days) 10 mg ↓7% [↓22%, ↑11%] ↓22% [↓27%, ↓17%] Nonsteroidal Anti-inflammatory Agent Mefenamic Acid (loading dose of 500 mg followed by 14 doses of 250 mg every 6 hours) 10 mg ↑13% [↑3%, ↑24%] ↑51% [↑44%, ↑58%] ↔ = no change (geometric… (Dapagliflozin label, Drug interactions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, mycophenoloate mofetil, ketoconazole) Clinical Impact: Esomeprazole magnesium 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 magnesium is an enantiomer,… (Naproxen and esomeprazole label, Drug interactions)

Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, mycophenoloate mofetil, ketoconazole) Clinical Impact: Esomeprazole magnesium 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 magnesium is an enantiomer,… (Naproxen and esomeprazole label, Drug interactions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

…Hyponatremia Concomitant administration of DESMODA with other drugs that may increase the risk of water intoxication with hyponatremia, (e.g., tricyclic antidepressants, selective serotonin re-uptake inhibitors, chlorpromazine, opiate analgesics, thiazide diuretics, NSAIDs, lamotrigine, sulfonylureas, particularly chlorpropamide, oxybutynin and carbamazepine). (Desmopressin label, Drug interactions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Co-morbid conditions such as coagulation disorders or concomitant use of warfarin and other anticoagulants, antiplatelet agents (e.g., aspirin), and serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk. (Naproxen and esomeprazole label, Warnings and precautions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Bone Fracture : Long-term and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. (Naproxen and esomeprazole label, Warnings and precautions)

Proton Pump Inhibitors Time to maximum concentration (T max ) of amphetamine is decreased compared to when administered alone. (Dextroamphetamine label, Drug interactions)

Diazepam Clinical Impact: Increased exposure of diazepam [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse Reactions (6.2) ]. (Naproxen and esomeprazole label, Warnings and precautions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. (Naproxen and esomeprazole label, Warnings and precautions)

Co-morbid conditions such as coagulation disorders or concomitant use of warfarin and other anticoagulants, antiplatelet agents (e.g., aspirin), and serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk. (Naproxen and esomeprazole label, Warnings and precautions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Therefore, patients should be monitored closely for symptoms of active or occult gastrointestinal bleeding, especially those at increased risk for developing ulcers, e.g., those with a history of ulcer disease or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs). (Donepezil label, Warnings and precautions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Intervention : • During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. (Naproxen and esomeprazole label, Drug interactions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Medications that may increase serum potassium concentration include ACE inhibitors, angiotensin-II receptor antagonists, potassium-sparing diuretics, potassium supplementation, heparin, aldosterone antagonists, and NSAIDS. (Drospirenone and ethinyl estradiol label, Warnings and precautions)

Co-morbid conditions such as coagulation disorders or concomitant use of warfarin and other anticoagulants, antiplatelet agents (e.g., aspirin), and serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk. (Naproxen and esomeprazole label, Warnings and precautions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. (Naproxen and esomeprazole label, Warnings and precautions)

Co-morbid conditions such as coagulation disorders or concomitant use of warfarin and other anticoagulants, antiplatelet agents (e.g., aspirin), and serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk. (Naproxen and esomeprazole label, Warnings and precautions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Intervention : • During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. (Naproxen and esomeprazole label, Drug interactions)

Bone Fracture : Long-term and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

In order to prevent gout flares when ULORIC is initiated, concurrent prophylactic treatment with an NSAID or colchicine is recommended [see Dosage and Administration (2.4) ]. (Febuxostat label, Warnings and precautions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, mycophenoloate mofetil, ketoconazole) Clinical Impact: Esomeprazole magnesium 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 magnesium is an enantiomer,… (Naproxen and esomeprazole label, Drug interactions)

Strong CYP2C19 Inhibitors Examples Proton pump inhibitors, selective serotonin reuptake inhibitors, benzodiazepines, antifungals Clinical Implications The concomitant use of ADDYI with strong CYP2C19 inhibitors may increase flibanserin exposure which may increase the risk of hypotension, syncope, and CNS depression. (Flibanserin label, Drug interactions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Naproxen Coadministration (N=18) of naproxen sodium capsules (250 mg) with NEURONTIN (125 mg) appears to increase the amount of gabapentin absorbed by 12% to 15%. (Gabapentin label, Drug interactions)

Therefore, patients should be monitored closely for symptoms of active or occult gastrointestinal bleeding, especially those with an increased risk for developing ulcers, e.g., those with a history of ulcer disease or patients using concurrent nonsteroidal anti-inflammatory drugs (NSAIDS). (Galantamine label, Warnings and precautions)

…steroids and androgens, cyclophosphamide, phenyramidol, guanethidine, fluconazole, sulfinpyrazone, tetracyclines, clarithromycin, disopyramide, quinolones, and those drugs that are highly protein-bound, such as fluoxetine, nonsteroidal anti-inflammatory drugs, salicylates, sulfonamides, chloramphenicol, coumarins, probenecid and monoamine oxidase inhibitors. (Glimepiride label, Drug interactions)

…angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, propoxyphene, salicylates, somatostatin analogs (e.g., octreotide), sulfonamide antibiotics, nonsteroidal anti-inflammatory agents, chloramphenicol, probenecid, coumarins, voriconazole, H2 receptor antagonists, and quinolones. (Glipizide label, Drug interactions)

Glipizide: The hypoglycemic action of sulfonylureas may be potentiated by certain drugs, including nonsteroidal anti-inflammatory agents, some azoles, and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, and beta-adrenergic blocking agents. (Glipizide and metformin label, Precautions)

Drug Interactions The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents, ACE inhibitors, disopyramide, fluoxetine, clarithromycin, and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, monoamine oxidase inhibitors, and beta adrenergic blocking… (Glyburide label, Drug interactions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Use caution when co-prescribing aspirin/nonsteroidal anti-inflammatory drugs that may worsen gastrointestinal irritation. (Ibandronate label, Drug interactions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, mycophenoloate mofetil, ketoconazole) Clinical Impact: Esomeprazole magnesium 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 magnesium is an enantiomer,… (Naproxen and esomeprazole label, Drug interactions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, mycophenoloate mofetil, ketoconazole) Clinical Impact: Esomeprazole magnesium 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 magnesium is an enantiomer,… (Naproxen and esomeprazole label, Drug interactions)

Intervention : • During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. (Naproxen and esomeprazole label, Drug interactions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Bone Fracture : Long-term and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. (Naproxen and esomeprazole label, Warnings and precautions)

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. (Lapatinib label, Drug interactions)

Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. (Naproxen and esomeprazole label, Warnings and precautions)

Concomitant Drug Class: Drug Name Effect on Concentration ↓ = decrease, ↑ = increase Clinical Comment tenofovir DF = tenofovir disoproxil fumarate Acid Reducing Agents: ↓ ledipasvir Ledipasvir solubility decreases as pH increases. (Ledipasvir and sofosbuvir label, Drug interactions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Non-Steroidal Anti-Inflammatory Drugs The concomitant administration of a non-steroidal anti-inflammatory drug with a fluoroquinolone, including Levofloxacin in 5% Dextrose Injection, may increase the risk of CNS stimulation and convulsive seizures [see Warnings and Precautions (5.4) ]. (Levofloxacin label, Drug interactions)

Co-morbid conditions such as coagulation disorders or concomitant use of warfarin and other anticoagulants, antiplatelet agents (e.g., aspirin), and serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Lithium Clinical Impact : NSAIDs have produced elevations of plasma lithium levels and reductions in renal lithium clearance. (Naproxen and esomeprazole label, Drug interactions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

Patients treated with NAMZARIC should be monitored closely for symptoms of active or occult gastrointestinal bleeding, especially those at increased risk for developing ulcers, e.g., those with a history of ulcer disease or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs). (Memantine and donepezil label, Warnings and precautions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Intervention : • During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. (Naproxen and esomeprazole label, Drug interactions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Co-morbid conditions such as coagulation disorders or concomitant use of warfarin and other anticoagulants, antiplatelet agents (e.g., aspirin), and serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk. (Naproxen and esomeprazole label, Warnings and precautions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Although not observed with moxifloxacin in preclinical and clinical trials, the concomitant administration of a nonsteroidal anti-inflammatory drug with a quinolone may increase the risks of CNS stimulation and convulsions [see Warnings and Precautions ( 5.4 ), and Patient Counseling Information ( 17 )]. (Moxifloxacin label, Drug interactions)

…mycophenoloate mofetil, ketoconazole) Clinical Impact: Esomeprazole magnesium 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 magnesium is an enantiomer, in healthy subjects and in transplant patients receiving MMF has been… (Naproxen and esomeprazole label, Drug interactions)

Intervention : • During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. (Naproxen and esomeprazole label, Drug interactions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Table 2: Clinically Significant Drug Interactions with Nateglinide Drugs That May Increase the Blood-Glucose-Lowering Effect of Nateglinide and Susceptibility to Hypoglycemia Drugs: Nonsteroidal anti-inflammatory drugs (NSAIDs), salicylates, monoamine oxidase inhibitors, non-selective beta-adrenergic-blocking agents, anabolic hormones (e.g., methandrostenolone),… (Nateglinide label, Drug interactions)

Intervention : • During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. (Naproxen and esomeprazole label, Drug interactions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

Use OFEV with caution when treating patients with recent abdominal surgery, previous history of diverticular disease or receiving concomitant corticosteroids or NSAIDs. (Nintedanib label, Warnings and precautions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

Proton Pump Inhibitors, H2-receptor Antagonists, or Antacids: may decrease bioavailability of MYCAPSSA and the MYCAPSSA dose may need to be increased (‎ 7 ). (Octreotide label, Drug interactions)

Non Steroidal Anti-Inflammatory Drugs The concomitant administration of a non-steroidal anti-inflammatory drug with a quinolone, including ofloxacin, may increase the risk of CNS stimulation and convulsive seizures (see WARNINGS and PRECAUTIONS , General ). (Ofloxacin label, Drug interactions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Bone Fracture : Long-term and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. (Naproxen and esomeprazole label, Warnings and precautions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Pemetrexed Clinical Impact : Concomitant use of naproxen and esomeprazole magnesium delayed-release tablets and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity (see the pemetrexed prescribing information). (Naproxen and esomeprazole label, Drug interactions)

DRUG INTERACTIONS Bleeding has been reported in patients treated with pentoxifylline extended-release tablets with or without concomitant NSAIDs, anticoagulants, or platelet aggregation inhibitors. (Pentoxifylline label, Drug interactions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Intervention : • During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. (Naproxen and esomeprazole label, Drug interactions)

…steroids and androgens, cyclophosphamide, phenyramidol, guanethidine, fluconazole, sulfinpyrazone, tetracyclines, clarithromycin, disopyramide, quinolones, and those drugs that are highly protein-bound, such as fluoxetine, nonsteroidal anti-inflammatory drugs, salicylates, sulfonamides, chloramphenicol, coumarins, probenecid and monoamine oxidase inhibitors. (Pioglitazone and glimepiride label, Drug interactions)

Nonsteroidal anti-inflammatory drugs: Monitor for hyperkalemia ( 7.3 ) (Potassium chloride label, Drug interactions)

Nonsteroidal Anti-inflammatory drugs (NSAIDs) monitor for hyperkalemia (7.4) (Potassium citrate label, Drug interactions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Intervention : • During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. (Naproxen and esomeprazole label, Drug interactions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Bone Fracture : Long-term and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. (Naproxen and esomeprazole label, Warnings and precautions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Monitor patients using rivastigmine tartrate for symptoms of active or occult gastrointestinal bleeding, especially those at increased risk for developing ulcers, e.g., those with a history of ulcer disease or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs). (Rivastigmine label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Clinical Effect/Recommendation Acid Reducing Agents: ↓ velpatasvir Velpatasvir solubility decreases as pH increases. (Sofosbuvir and velpatasvir label, Drug interactions)

Co-morbid conditions such as coagulation disorders or concomitant use of warfarin and other anticoagulants, antiplatelet agents (e.g., aspirin), and serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk. (Naproxen and esomeprazole label, Warnings and precautions)

Intervention : • During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. (Naproxen and esomeprazole label, Drug interactions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Tacrolimus Clinical Impact : Concomitant use of esomeprazole magnesium and tacrolimus may increase exposure of tacrolimus Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets and tacrolimus, monitor tacrolimus whole blood concentrations. (Naproxen and esomeprazole label, Drug interactions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

Co-morbid conditions such as coagulation disorders or concomitant use of warfarin and other anticoagulants, antiplatelet agents (e.g., aspirin), and serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk. (Naproxen and esomeprazole label, Warnings and precautions)

Intervention : • During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. (Naproxen and esomeprazole label, Drug interactions)

Co-morbid conditions such as coagulation disorders or concomitant use of warfarin and other anticoagulants, antiplatelet agents (e.g., aspirin), and serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk. (Naproxen and esomeprazole label, Warnings and precautions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (Tofacitinib label, Warnings and precautions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), other antiplatelet drugs, warfarin, and other anticoagulants may increase this risk ( 5.5 ). (Trazodone label, Warnings and precautions)

Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. (Naproxen and esomeprazole label, Warnings and precautions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Monitor RINVOQ/RINVOQ LQ-treated patients who may be at risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis and those taking concomitant medications including NSAIDs or corticosteroids). (Upadacitinib label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. (Naproxen and esomeprazole label, Warnings and precautions)

Co-morbid conditions such as coagulation disorders or concomitant use of warfarin and other anticoagulants, antiplatelet agents (e.g., aspirin), and serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk. (Naproxen and esomeprazole label, Warnings and precautions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (Naproxen and esomeprazole label, Drug interactions)

Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. (Naproxen and esomeprazole label, Warnings and precautions)

Co-morbid conditions such as coagulation disorders or concomitant use of warfarin and other anticoagulants, antiplatelet agents (e.g., aspirin), and serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk. (Naproxen and esomeprazole label, Warnings and precautions)

This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed. (Naproxen and esomeprazole label, Warnings and precautions)

• Increased Risk of Bleeding : Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, other antiplatelet drugs, warfarin, or other drugs that affect coagulation may increase risk ( 5.3 ). (Vortioxetine label, Warnings and precautions)

Esomeprazole Magnesium • Increased INR and prothrombin time in patients treated with PPIs, including esomeprazole, and warfarin concomitantly. (Naproxen and esomeprazole label, Drug interactions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Nephrotoxic Drugs Caution is indicated when Reclast is used with other potentially nephrotoxic drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs). (Zoledronic acid label, Drug interactions)

The selective serotonin reuptake inhibitors sertraline (weak CYP3A4 inducer) and fluoxetine (CYP2D6 inhibitor), and the anti-epileptic drug felbamate (CYP2C19 inhibitor and CYP3A4 inducer) do not affect the pharmacokinetics of clonazepam. (Clonazepam label, Drug interactions)

…angiotensin-converting enzyme (ACE) inhibitors, analgesics, anti-convulsants, beta-adrenergic blocking agents, diuretics, calcium channel blockers, cardiac nitrates, HMG-CoA reductase inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), benzodiazepines, H 2 antagonists and quinolone anti-infectives without evidence of clinically significant adverse interactions. (Finasteride label, Drug interactions)

Examples: Nonsteroidal anti-inflammatory agents and other highly protein-boind drugs, salicylcates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, beta-adrenergic blocking agents; potentially with ciprofloxacin, micronazole. (Glyburide and metformin label, Drug interactions)

In RA, concomitant medications besides MTX were nonsteroidal anti-inflammatory agents (NSAIDs), folic acid, corticosteroids and/or narcotics. (Infliximab label, Drug interactions)

Patients with Grade 1 and 2 TFR may also be treated with corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) and/or narcotic analgesics for management of TFR symptoms. (Lenalidomide label, Warnings and precautions)

Other drugs: Carbamazepine Furosemide (> 80 mg IV) Heparin Hydantoins Non-Steroidal Anti-Inflammatory Drugs - Fenamates These drugs may cause protein-binding site displacement. (Levothyroxine label, Drug interactions)

Other drugs: Carbamazepine Furosemide (>80 mg IV) Heparin Hydantoins Non-Steroidal Anti-inflammatory Drugs Fenamates These drugs may cause protein binding site displacement. (Liothyronine label, Drug interactions)

Proton pump inhibitors taken for a year or longer can cause low magnesium; supplements may not correct it while the PPI continues. (NIH Office of Dietary Supplements, Magnesium)

…performed, the following concomitant drugs were used in at least 10% of patients in either or both Sjogren's efficacy studies: acetylsalicylic acid, artificial tears, calcium, conjugated estrogens, hydroxychloroquine sulfate, ibuprofen, levothyroxine sodium, medroxyprogesterone acetate, methotrexate, multivitamins, naproxen, omeprazole, paracetamol, and prednisone. (Pilocarpine label, Drug interactions)

These include agents such as indomethacin, acetaminophen, naproxen, ketoprofen, meclofenamate, lorazepam, and rifampin. (Probenecid label, Drug interactions)

These include agents such as indomethacin, acetaminophen, naproxen, ketoprofen, meclofenamate, lorazepam, and rifampin. (Probenecid and colchicine label, Drug interactions)

Examples: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, nonsteroidal anti-inflammatory agents (NSAIDs), pentoxifylline, pramlintide, propoxyphene, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics. (Repaglinide label, Drug interactions)

Concomitant Drugs for Treatment of Adult Indications In RA patients, population pharmacokinetic analyses did not detect any effect of methotrexate (MTX), non-steroidal anti-inflammatory drugs or corticosteroids on tocilizumab clearance. (Tocilizumab label, Drug interactions)

Drug-drug interaction studies in healthy subjects have been conducted with zileuton immediate-release tablets and digoxin, phenytoin, sulfasalazine, and naproxen. (Zileuton label, Drug interactions)

Effects of Concomitant Acid Blockers or Antibiotics A population pharmacokinetic analysis suggests that the pharmacokinetics of alvimopan were not affected by concomitant administration of acid blockers (proton pump inhibitors (PPIs), histamine-2 (H 2 ) receptor antagonists) or antibiotics. (Alvimopan label, Drug interactions)

Effect of Other Drugs on Micafungin in Sodium Chloride Injection CYP3A4, CYP2C9 and CYP2C19 Inhibitors Co-administration of Micafungin in Sodium Chloride Injection with cyclosporine, itraconazole, voriconazole and fluconazole did not alter the pharmacokinetics of micafungin. (Micafungin label, Drug interactions)