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Naproxen / EsomeprazolePronunciation: nay-PROX-en/ES-oh-MEP-ra-zole
Class: Nonsteroidal anti-inflammatory drug/proton pump inhibitor combination
- Tablets, delayed-release, oral naproxen 375 mg/esomeprazole 20 mg
- Tablets, delayed-release, oral naproxen 500 mg/esomeprazole 20 mg
Naproxen decreases inflammation and pain, probably through inhibition of cyclooxygenase activity and prostaglandin synthesis. Esomeprazole suppresses gastric acid secretion by blocking proton pump within gastric parietal cells.
Indications and Usage
Relief of signs and symptoms of ankylosing spondylitis, osteoarthritis, and rheumatoid arthritis, and to decrease the risk of developing gastric ulcers in patients at risk of developing NSAID-associated gastric ulcers.
History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs; use during the perioperative period in the setting of coronary artery bypass graft (CABG) surgery; late stages of pregnancy; hypersensitivity to any component of the product or substituted benzimidazoles.
Dosage and AdministrationAnkylosing spondylitis, osteoarthritis, and rheumatoid arthritis
PO 1 tablet twice daily. Use the lowest effective dose.Hepatic Function Impairment
Consider naproxen dosage reduction in mild to moderate hepatic impairment; not recommended in severe hepatic impairment (Child-Pugh class C).
- Tablets should be swallowed whole; tablets should not be split, chewed, crushed, or dissolved.
- Advise patient to take at least 30 min before meals.
Store between 59° and 86°F. Protect from moisture.
Drug InteractionsACE inhibitors (eg, captopril)
The hypotensive effects of ACE inhibitors may be diminished. Closely monitor BP. If BP control deteriorates, consider stopping naproxen/esomeprazole.Alcohol
The risk of bleeding may be increased. Use with caution.Anticoagulants (eg, fondaparinux, heparin, warfarin)
The effects of naproxen and warfarin on GI bleeding are synergistic, increasing the risk of serious GI bleeding. Coadministration may prolong prothrombin time. If coadministration cannot be avoided, use with extreme caution. Closely monitor prothrombin time and the patient.Aspirin
The risk of serious bleeding may be increased. Naproxen/esomeprazole can be used with low-dose aspirin (325 mg/day or less). In addition, aspirin (greater than 1 g/day) may displace naproxen from its protein binding site. Concurrent use of aspirin and NSAIDs is not generally recommended.Atazanavir, nelfinavir
Atazanavir and nelfinavir AUC, C max , and C min may be reduced, decreasing their efficacy. Coadministration is not recommended.Azole antifungal agents (eg, ketoconazole)
Because ketoconazole absorption is altered by gastric pH, inhibition of gastric acid secretion by esomeprazole may decrease ketoconazole bioavailability. If coadministration cannot be avoided, consider increasing the dose of the azole antifungal agent or administering with hydrochloric acid 0.1 to 0.2 normal or an acidic beverage (eg, Coca-Cola, Pepsi).Beta-blockers (eg, propranolol)
The antihypertensive effect of the beta-blocker may be reduced, but this does not appear to be clinically significant. Closely monitor BP and adjust the beta-blocker dose as needed.Bisphosphonates (eg, alendronate)
GI adverse effects may be increased.Cholestyramine
The absorption of naproxen may be delayed. If an interaction is suspected and the naproxen dose cannot be adjusted, it may be necessary to use alternative therapy for one of the agents.Cilostazol
Coadministration of esomeprazole and cilostazol is expected to increase concentrations of cilostazol and its active metabolite. The risk of adverse reactions may be increased. A cilostazol dose reduction should be considered.Clopidogrel
The risk of bleeding may be increased. Concomitant therapy may reduce the antiplatelet effect of clopidogrel and cause adverse CV outcomes; data are conflicting.Corticosteroids, oral (eg, prednisone)
The risk of bleeding may be increased. Use with caution; closely monitor patients.Cyclosporine
May increase risk and severity of renal impairment. Monitor renal function and cyclosporine levels; adjust dose as needed.Diazepam
Coadministration may reduce diazepam Cl. Diazepam concentrations and risk of adverse reactions may be increased. Monitor the clinical response and adjust the diazepam dose as needed.Digoxin
Because digoxin absorption is altered by gastric pH, inhibition of gastric acid secretion by esomeprazole may increase digoxin bioavailability. A clinically important interaction is unlikely; however, because digoxin has a narrow therapeutic index, monitor digoxin concentrations and adjust the digoxin dose as needed.Fluoroquinolones (eg, levofloxacin)
Coadministration may increase the risk of CNS stimulation and seizures.Food
Administration of naproxen/esomeprazole with a high-fat meal decreases naproxen C max and prolongs the T max . In addition, esomeprazole T max is delayed and the AUC and C max are reduced, decreasing the extent of absorption. Give naproxen/esomeprazole at least 30 min before a meal.Iron salts (eg, ferrous sulfate)
Because absorption of iron salts is altered by gastric pH, inhibition of gastric acid secretion by esomeprazole may decrease bioavailability of the iron salt. If coadministration cannot be avoided, consider giving parenteral iron as an alternative.Lithium
Lithium concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Monitor lithium plasma concentrations, the clinical response, and for signs of lithium toxicity. Adjust the lithium dose as needed.Loop diuretics (eg, furosemide), thiazide diuretics (eg, hydrochlorothiazide)
The diuretic effects may be reduced. In addition, renal toxicity has been reported. Closely observe patients for diuretic efficacy and signs of renal failure.Methotrexate
The risk of methotrexate toxicity may be increased. Use with caution. Avoid high-dose methotrexate therapy.Mycophenolate
Mycophenolate plasma concentration and pharmacologic effects may be decreased.NSAIDs (eg, ibuprofen)
Because of the potential increased risk of adverse reactions, naproxen/esomeprazole should not be used with other naproxen-containing products or any dose of nonaspirin NSAID.Probenecid
Probenecid may increase naproxen plasma concentrations and prolong its half-life. Closely monitor for signs of naproxen toxicity. If the naproxen dose cannot be adjusted, it may be necessary to use alternative therapy for one of the agents.Protein-bound drugs (eg, hydantoins [eg, phenytoin], sulfonylureas [eg, chlorpropamide])
Because naproxen is highly bound to plasma albumin, there is a theoretical potential for interaction with other albumin-bound agents. Use with caution. Monitor the clinical response and adjust the dose of either agent as needed.Saquinavir
Saquinavir AUC, C max , and C min may be elevated, increasing the risk of adverse reactions. Consider dose reduction of saquinavir.Serotonin reuptake inhibitors (eg, fluoxetine), serotonin and norepinephrine reuptake inhibitors (eg, venlafaxine)
The risk of upper GI bleeding may be increased. Use with caution and closely monitor for signs of GI bleeding.Smoking
The risk of bleeding may be increased. Use with caution; closely monitor the patient.Tyrosine kinase receptor inhibitors (eg, dasatinib, erlotinib, nilotinib)
The solubility and bioavailability of the tyrosine kinase inhibitor may be reduced. Dosage or administration adjustments may be needed.Voriconazole
Esomeprazole exposure may be increased. An esomeprazole dose adjustment is not usually required. Monitor the clinical response and if an interaction is suspected, adjust the naproxen/esomeprazole dose or use alternative therapy.
Laboratory Test Interactions
Naproxen may decrease platelet aggregation and prolong bleeding time, which should be considered when bleeding times are determined. Naproxen administration may increase urinary values for 17-ketogenic steroids because of an interaction between naproxen and/or its metabolites with m-di-nitrobenzene used in the assay. It is suggested that naproxen therapy be temporarily discontinued 72 h prior to adrenal function tests using the Porter-Silber test. Naproxen may interfere with some urinary assays of 5-hydroxy indoleacetic acid.
Dizziness, headache (3%).
Erosive gastritis (19%); dyspepsia (18%); gastritis (17%); diarrhea, gastric ulcer, upper abdominal pain (6%); nausea (5%), abdominal distention, constipation, esophagitis, flatulence, hiatus hernia (4%); abdominal pain, dysgeusia, erosive duodenitis, lower abdominal pain (2%); duodenitis, hemorrhagic gastritis (1%).
Liver function test elevations.
Peripheral edema (3%); fluid retention, edema.
Renal papillary necrosis.
Upper respiratory tract infection (5%), bronchitis, cough, sinusitis (2%); nasopharyngitis (1%).
NSAIDs may cause an increased risk of serious CV thrombotic events, MI, and stroke, which can be fatal. This risk may increase with length of therapy. Patients with CV disease or risk factors for CV disease may be at greater risk. NSAIDs cause an increased risk of serious GI adverse reactions, including bleeding, inflammation, perforation of the stomach or intestines, and ulceration, which can be fatal. These events can occur any time during use and without warning symptoms. Elderly patients are at greater risk of serious GI events.
Monitor for signs and symptoms of GI ulcerations and bleeding. Closely monitor BP. Periodically check CBC and chemistry profile during prolonged therapy. If used in patients with advanced renal disease, monitor renal function.
Category C prior to 30 wk gestation; Category D starting at 30 wk gestation. Contraindicated in late stages of pregnancy.
Excreted in small amounts. Manufacturer recommends avoiding use.
Safety and efficacy not established.
Increased risk of adverse reactions. Use with caution.
May occur. Do not give NSAIDs to patients with the aspirin triad.
Not recommended in moderate to severe renal impairment (CrCl less than 30 mL/min).
Consider naproxen dosage reduction in mild to moderate hepatic impairment; not recommended in severe hepatic impairment (Child-Pugh class C).
Special Risk Patients
Use with caution in patients with preexisting asthma, hypovolemia, salt depletion, hypertension, fluid retention, heart failure, known CV disease, or risk factors for CV disease.
Do not use in patients with aspirin-sensitive asthma. Use with caution in patients with preexisting asthma.
Withdraw treatment when active and clinically significant bleeding from any source occurs.
Proton pump inhibitor therapy is associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine.
May cause an increased risk of serious CV thrombotic events, MI, and stroke, which can be fatal. Hypertension may develop or worsen.
Fluid retention, edema, and peripheral edema may occur. Use with caution in patients with fluid retention or heart failure.
Anemia and prolonged bleeding time have occurred with NSAIDs.
Borderline elevations of 1 or more liver tests may occur in up to 15% of NSAID users. Rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis, and hepatic failure, have occurred. Discontinue therapy if clinical signs or symptoms of liver disease develop, or if systemic manifestations occur (eg, eosinophilia, rash).
Renal papillary necrosis and other renal injury have occurred with long-term administration of NSAIDs.
NSAIDs can cause serious skin adverse reactions, such as exfoliative dermatitis, Stevens-Johnson syndrome, and TEN, which can be fatal.
Abdominal discomfort, acute renal failure, apnea, blurred vision, coma, confusion, diaphoresis, disorientation, dizziness, drowsiness, dry mouth, epigastric pain, flushing, GI bleeding, headache, heartburn, hypertension, hypoprothrombinemia, indigestion, lethargy, metabolic acidosis, nausea, renal dysfunction, respiratory depression, tachycardia, transient alterations in liver function, vomiting.
- Advise patients to swallow tablets whole, and not to split, chew, crush. or dissolve tablets. Instruct patients to take at least 30 min before meals.
- Advise patients that antacids may be used while taking naproxen/esomeprazole.
- Explain that this drug combination may cause serious CV effects, such as MI or stroke, which may result in hospitalization and even death. Although serious CV events can occur without warning symptoms, advise patients to be alert for the signs and symptoms of chest pain, shortness of breath, slurring of speech, and weakness, and advise them to ask for medical advice when observing any indicative sign or symptoms.
- Advise patients that NSAIDs can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, advise patients to be alert for the signs and symptoms of bleeding and ulcerations, and to ask for medical advice when observing any indicative signs or symptoms, including dyspepsia, epigastric pain, hematemesis, and melena.
- Advise patients that NSAIDs can cause serious skin side effects, such as exfoliative dermatitis, Stevens-Johnson syndrome, and TEN, which may result in hospitalizations and even death. Although serious skin reactions may occur without warning, advise patients to be alert for the signs and symptoms of fever, skin rash and blisters, or other signs of hypersensitivity, such as itching, and to ask for medical advice when observing any indicative signs or symptoms. Advise patients to stop the drug immediately if they develop any type of rash and to contact their health care provider as soon as possible.
- Advise patients to promptly report signs or symptoms of unexplained weight gain or edema to their health care provider.
- Advise patients of the warning signs and symptoms of hepatotoxicity (eg, fatigue, flu-like symptoms, jaundice, lethargy, nausea, pruritus, right upper quadrant tenderness). If these occur, instruct patients to stop therapy and seek immediate medical therapy.
- Advise patients of the signs of an anaphylactoid reaction (eg, difficulty breathing, swelling of the face or throat). If these occur, instruct patients to seek immediate emergency help.
- Advise pregnant patients to avoid this drug combination during late pregnancy because it may cause premature closure of the ductus arteriosus.
- Advise patients to exercise caution when performing activities that require alertness if they experience depression, dizziness, drowsiness, or vertigo during drug therapy.
- Advise patients to alert the health care provider if they have a history of asthma or aspirin-sensitive asthma because the use of NSAIDs in patients with aspirin-sensitive asthma has been associated with severe bronchospasm, which can be fatal. Instruct patients with this form of aspirin sensitivity not to take naproxen/esomeprazole. Instruct patients with preexisting asthma to seek immediate medical attention if their asthma worsens after taking naproxen/esomeprazole.
- Advise patients that alcohol use may increase the risk of GI bleeding.
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