Safety Profile for NEXIUM

Demonstrated Safety Profile for NEXIUM1

NEXIUM has a demonstrated safety and tolerability profile.
  • The safety of NEXIUM was evaluated in over 15,000 patients (aged 18 to 84 years) in clinical trials worldwide, including over 8500 patients in the United States and over 6500 patients in Europe and Canada. NEXIUM has a demonstrated safety and tolerability profile
  • The safety of NEXIUM was evaluated in 316 pediatric patients and adolescent patients aged 1 to 17 years in 4 clinical trials for the treatment of symptomatic GERD. No new safety concerns were identified in pediatric patients
  • Acute interstitial nephritis has been observed in patients taking PPIs including NEXIUM. Discontinue NEXIUM if acute interstitial nephritis develops
  • Daily treatment with any acid-suppressing medications over a long period of time (eg, longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B12). Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature
  • Proton Pump Inhibitor (PPI) therapy may be associated with increased risk of Clostridium difficile-associated diarrhea
  • 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
  • Hypomagnesemia has been reported rarely with prolonged treatment with PPI therapy and may require discontinuing PPI therapy
  • In over 1000 patients treated with NEXIUM for up to 6 to 12 months, the prevalence of Enterochromaffin-like (ECL) cell hyperplasia increased with time and dose. No patient developed ECL cell carcinoids, dysplasia, or neoplasia in the gastric mucosa

Drug Interactions1

Drug interaction studies have shown that NEXIUM does not have any clinically significant interactions with1:

  • phenytoin
  • warfarin
  • quinidine
  • clarithromycin
  • amoxicillin

Postmarketing reports of changes in prothrombin measures have been received among patients on concomitant warfarin and esomeprazole therapy. Patients treated with PPIs and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time.

Avoid concomitant use of NEXIUM with clopidogrel, due to a reduction in plasma concentrations of the active metabolite of clopidogrel. When using NEXIUM consider alternative anti-platelet therapy.

Esomeprazole may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (eg, ketoconazole, iron salts, erlotinib, and digoxin).

Combined inhibitor of CYP2C19 and 3A4 may raise esomeprazole levels.

Concomitant use of NEXIUM and St. John's wort or rifampin can substantially decrease NEXIUM concentrations. Avoid concomitant use.

Concomitant use of NEXIUM and atazanavir or nelfinavir is not recommended because the plasma concentrations and therapeutic effects of those antiretroviral drugs may be reduced.

NEXIUM may increase the plasma levels of saquinavir. Dose reduction of saquinavir should be considered.

Concomitant use of NEXIUM and methotrexate may increase and prolong the serum levels of methotrexate and/or its metabolite. In high-dose methotrexate administration, a temporary withdrawal of NEXIUM may be considered in some patients.

Important Safety Information for NEXIUM

  • NEXIUM is contraindicated in patients with known hypersensitivity to any component of the formulation or to substituted benzimidazoles
  • Symptomatic response to therapy does not rule out the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with a proton pump inhibitor (PPI). In older patients, also consider an endoscopy
  • Acute interstitial nephritis has been observed in patients taking PPIs including NEXIUM. Discontinue NEXIUM if acute interstitial nephritis develops
  • PPI therapy may be associated with increased risk of Clostridium difficile-associated diarrhea. This diagnosis should be considered for diarrhea that does not improve
  • PPI therapy may be associated with an increased risk of osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose (multiple daily doses) and long-term (a year or longer) therapy
  • Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including esomeprazole. These events included both new onset and exacerbations. If signs or symptoms consistent with CLE or SLE are noted with NEXIUM, discontinue and refer the patient to a specialist. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks
  • Avoid concomitant use of NEXIUM with clopidogrel, due to a reduction in plasma concentrations of the active metabolite of clopidogrel. When using NEXIUM consider alternative anti-platelet therapy
  • Daily treatment with any acid-suppressing medications over a long period of time (eg, longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B12). Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature
  • Hypomagnesemia has been reported rarely with prolonged treatment with PPI therapy and may require discontinuing PPI therapy and magnesium replacement
  • Concomitant use of NEXIUM and St. John’s wort or rifampin can substantially decrease NEXIUM concentrations. Avoid concomitant use
  • Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration, a temporary withdrawal of the PPI may be considered in some patients
  • PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use, especially beyond one year. Use shortest duration of PPI therapy appropriate to the condition being treated
  • Concomitant use of NEXIUM and atazanavir or nelfinavir is not recommended due to decreased plasma levels of these anti-retroviral drugs. NEXIUM is expected to increase the plasma levels of saquinavir. Consider dose reduction of saquinavir
  • Patients treated with PPIs and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time. Esomeprazole may interfere with the absorption of drugs for which gastric pH affects bioavailability (eg, ketoconazole, iron salts, and digoxin)
  • NEXIUM may increase systemic exposure of cilostazol and one of its active metabolites. Consider dose reduction of cilostazol
  • NEXIUM I.V. should be used only when oral therapy with NEXIUM is not possible or appropriate
  • In adults, the most frequently reported (≥1%) adverse reactions (ARs) with oral NEXIUM include headache, diarrhea, nausea, flatulence, abdominal pain, constipation, and dry mouth
  • In pediatric patients 1 to 17 years of age, the most frequently reported (≥2%) ARs with oral NEXIUM include headache, diarrhea, abdominal pain, nausea, and somnolence
  • In pediatric patients 1 to 11 months the most frequently reported (1%) ARs with oral NEXIUM include abdominal pain, regurgitation, tachypnea, and increased ALT
  • The ARs reported at a frequency of 1% or greater with NEXIUM I.V. in clinical trials were headache, flatulence, nausea, abdominal pain, injection site reaction, diarrhea, dry mouth, dizziness/vertigo, constipation, and pruritus

Approved Uses

NEXIUM 40 mg and 20 mg are indicated for short-term treatment (4 to 8 weeks) in healing and symptomatic resolution of diagnostically confirmed erosive esophagitis (EE). NEXIUM 20 mg is indicated to maintain symptom resolution and healing of EE (controlled studies did not extend beyond 6 months), and for short-term treatment (4 to 8 weeks) of heartburn and other symptoms associated with GERD.

Prescribing Information (PDF - 303 KB)