Nexium
Esomeprazole magnesium · Granule, Delayed Release · Oral
Uses
1 INDICATIONS AND USAGE NEXIUM is a proton pump inhibitor (PPI). NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension are indicated for the:
• Short-term treatment in the healing of erosive esophagitis (EE) in adults and pediatric patients 12 years to 17 years of age. ( 1.1 )
• Maintenance of healing of EE in adults. ( 1.2 )
• Short-term treatment of heartburn and other symptoms associated GERD in adults and pediatric patients 12 years to 17 years of age. ( 1.3 )
• Risk reduction of nonsteroidal anti-inflammatory drugs (NSAID)-associated gastric ulcer in adults at risk for developing gastric ulcers due to age (60 years and older) and/or documented history of gastric ulcers. ( 1.4 )
• Helicobacter pylori eradication in adult patients to reduce the risk of duodenal ulcer recurrence in combination with amoxicillin and clarithromycin. ( 1.5 )
• Long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome in adults. ( 1.6 ) NEXIUM for delayed-release oral suspension is indicated for the:
• Short-term treatment in the healing of EE in pediatric patients 1 year to 11 years of age and of EE due to acid-mediated GERD in pediatric patients 1 month to less than 1 year of age. ( 1.1 )
• Short-term treatment of heartburn and other symptoms associated with GERD in pediatric patients 1 year to 11 years of age. ( 1.3 ) 1.1 Healing of Erosive Esophagitis (EE) Adults NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension are indicated for the short-term treatment (4 to 8 weeks) in the healing and symptomatic resolution of diagnostically confirmed EE in adults. For those patients who have not healed after 4 to 8 weeks of treatment, an additional 4- to 8- week course of NEXIUM may be considered. Pediatric Patients 12 Years to 17 Years of Age NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension are indicated for the short-term treatment (4 to 8 weeks) for the healing of EE in pediatric patients 12 years to 17 years of age. Pediatric Patients 1 Year to 11 Years of Age NEXIUM for delayed-release oral suspension is indicated for the short-term treatment (8 weeks) for the healing of EE in pediatric patients 1 year to 11 years of age. Pediatric Patients 1 Month to Less Than 1 Year of Age NEXIUM for delayed-release oral suspension is indicated for short-term treatment (up to 6 weeks) of EE due to acid-mediated GERD in pediatric patients 1 month to less than 1 year of age. 1.2 Maintenance of Healing of EE NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension are indicated for the maintenance of healing of EE in adults. Controlled studies do not extend beyond 6 months. 1.3 Treatment of Symptomatic GERD Adults NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension are indicated for short-term treatment (4 to 8 weeks) of heartburn and other symptoms associated with GERD in adults. Pediatric Patients 12 Years to 17 Years of Age NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension are indicated for short-term treatment (4 weeks) of heartburn and other symptoms associated with GERD in pediatric patients 12 years to 17 years of age. Pediatric Patients 1 Year to 11 Years of Age NEXIUM for delayed-release oral suspension is indicated for short-term treatment (up to 8 weeks) of heartburn and other symptoms associated with GERD in pediatric patients 1 year to 11 years of age. 1.4 Risk Reduction of Nonsteroidal Anti-Inflammatory Drugs (NSAID)-Associated Gastric Ulcer NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension are indicated for the reduction in the occurrence of gastric ulcers associated with continuous NSAID therapy in adult patients at risk for developing gastric ulcers. Patients are considered to be at risk due to their age (60 years and older) and/or documented history of gastric ulcers. Controlled studies do not extend beyond 6 months. 1.5 Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence. Triple Therapy NEXIUM delayed-release capsules or NEXIUM for delayed-release oral suspension in combination with amoxicillin and clarithromycin is indicated for the treatment of adult patients with H. pylori infection and duodenal ulcer disease (active or history of within the past 5 years) to eradicate H. pylori . In patients who fail therapy, susceptibility testing should be done. If resistance to clarithromycin is demonstrated or susceptibility testing is not possible, alternative antimicrobial therapy should be instituted [see Clinical Pharmacology (12.4) and the prescribing information for clarithromycin]. 1.6 Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension are indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison Syndrome, in adults.
Dosage and administration
Population Recommended Adult (2.1) and Pediatric Dosage (2.2) Healing of EE (1 year and older) EE due to Acid-Mediated GERD (1 month to less than 1 year) Adults 20 mg or 40 mg A maximum dosage of 20 mg once daily is recommended for patients with severe liver impairment (Child-Pugh Class C). once daily for 4 to 8 weeks; some patients may require an additional 4 to 8 weeks 12 years to 17 years 20 mg or 40 mg once daily for 4 to 8 weeks 1 month to 11 years see full prescribing information for weight-based dosing and duration of treatment ( 2.2 ) Maintenance of Healing of EE Adults 20 mg once daily. Controlled studies do not extend beyond 6 months Treatment of Symptomatic GERD Adults 20 mg once daily once daily for 4 weeks some patients may require an additional 4 weeks 12 years to 17 years 20 mg once daily for 4 weeks 1 year to 11 years 10 mg once daily for up to 8 weeks Risk Reduction of NSAID-Associated Gastric Ulcer Adults 20 mg or 40 mg once daily for up to 6 months Controlled studies do not extend beyond 6 months. H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence Adults NEXIUM 40 mg once daily for 10 days Amoxicillin 1000 mg twice daily for 10 days Refer to the amoxicillin and clarithromycin prescribing information for dosage adjustments in elderly and renally-impaired patients. Clarithromycin 500 mg twice daily for 10 days Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome Adults Starting dosage is 40 mg twice daily A starting dosage of 20 mg twice daily is recommended for patients with severe liver impairment (Child-Pugh Class C). (varies with the individual patient) as long as clinically indicated. Preparation and Administration Information
• Swallow capsules whole; do not crush or chew. For patients who cannot swallow intact capsule, the capsule can be opened, and the contents mixed with applesauce. ( 2.3 )
• Mix packets with water to create an oral suspension. ( 2.3 )
• Opened capsules can be administered through a nasogastric tube and oral suspension can be administered through a nasogastric or gastric tube. ( 2.3 ) 2.1 Recommended Dosage in Adults by Indication Table 1 shows the recommended adult dosage of NEXIUM by indication. The duration of NEXIUM treatment should be based on available safety and efficacy data specific to the defined indication and dosing frequency and individual patient medical needs. NEXIUM should only be initiated and continued if the benefits outweigh the risks of treatment. Table 1: Recommended Dosage of NEXIUM in Adults by Indication Adult Indication Recommended Dosage of NEXIUM d elayed-release capsules and NEXIUM for delayed-release oral suspension Treatment Duration Healing of EE 20 mg or 40 mg A maximum dosage of 20 mg once daily is recommended for patients with severe liver impairment (Child-Pugh Class C) [see Use in Specific Populations (8.6) ] . once daily 4 to 8 weeks Most patients are healed within 4 to 8 weeks. For patients who do not heal after 4 to 8 weeks, an additional 4 to 8 weeks of treatment may be required to achieve healing [see Clinical Studies (14.1) ] . Maintenance of Healing of EE 20 mg once daily Controlled studies do not extend beyond 6 months Treatment of Symptomatic GERD 20 mg once daily 4 weeks; if symptoms do not resolve completely, consider an additional 4 weeks Risk Reduction of NSAID-Associated Gastric Ulcer 20 mg or 40 mg once daily Controlled studies do not extend beyond 6 months H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence (Triple Therapy) NEXIUM 40 mg once daily 10 days Amoxicillin 1000 mg twice daily Refer to the amoxicillin and clarithromycin prescribing information for dosage adjustments in elderly and renally-impaired patients. 10 days Clarithromycin 500 mg twice daily 10 days Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome Starting dosage is 40 mg twice daily A starting dosage of 20 mg twice daily is recommended for patients with severe liver impairment (Child-Pugh Class C) [see Use in Specific Populations (8.6) ] . ; individualize the regimen to patient needs. Dosages of up to 240 mg/day have been administered [see Clinical Studies (14.7) ] . As long as clinically indicated 2.2 Recommended Dosage in Pediatric Patients by Indication Table 2 shows the recommended dosage of NEXIUM in pediatric patients by indication. Table 2: Recommended Dosage of NEXIUM in Pediatric Patients by Indication Indication Patient Age Recommended Dosage Duration Healing of EE 12 years to 17 years NEXIUM delayed-release capsules or NEXIUM for delayed-release oral suspension: 20 mg or 40 mg once daily 4 to 8 Weeks 1 year to 11 years Dosages over 1 mg/kg/day have not been studied NEXIUM for delayed-release oral suspension: Less than 20 kg 10 mg once daily 20 kg and greater 10 mg or 20 mg once daily 8 weeks Treatment of EE due to Acid-Mediated GERD 1 month to less than 1 year Dosages over 1.33 mg/kg/day have not been studied NEXIUM for delayed-release oral suspension: 3 kg to 5 kg 2.5 mg once daily Greater than 5 kg to 7.5 kg 5 mg once daily Greater than 7.5 kg to 12 kg 10 mg once daily Up to 6 weeks Treatment of Symptomatic GERD 12 years to 17 years NEXIUM delayed-release capsules or NEXIUM for delayed-release oral suspension: 20 mg once daily 4 weeks 1 year to 11 years NEXIUM for delayed-release oral suspension: 10 mg once daily 1 Up to 8 weeks 2.3 Preparation and Administration Instructions
• Take NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension at least one hour before meals [see Clinical Pharmacology (12.3) ].
• Antacids may be used concomitantly with NEXIUM.
• Take a missed dose as soon as possible. If it is almost time for the next dose, skip the missed dose and take the next dose at the regular scheduled time. Do not take 2 doses at the same time. NEXIUM Delayed-Release Capsules Administer NEXIUM delayed-release capsules orally or via a nasogastric tube, as described below.
Dosage forms and strengths
Delayed-Release Capsules
• 20 mg esomeprazole in opaque, hard gelatin, amethyst colored capsules with two radial bars in yellow on the cap and NEXIUM 20 mg in yellow on the body.
• 40 mg esomeprazole in opaque, hard gelatin, amethyst colored capsules with three radial bars in yellow on the cap and NEXIUM 40 mg in yellow on the body. NEXIUM For Delayed-Release Oral Suspension
• 2.5 mg, 5 mg, 10 mg, 20 mg or 40 mg esomeprazole in unit dose packets containing a fine yellow powder, consisting of white to pale brownish esomeprazole granules and pale-yellow inactive granules.
• Delayed-Release Capsules: 20 mg and 40 mg esomeprazole. ( 3 )
• For Delayed-Release Oral Suspension: 2.5 mg, 5 mg, 10 mg, 20 mg, and 40 mg esomeprazole. ( 3 )
Contraindications
• NEXIUM is contraindicated in patients with known hypersensitivity to substituted benzimidazoles or to any component of the formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see Warnings and Precautions (5.2) , Adverse Reactions (6.2) ].
• For information about contraindications of amoxicillin and clarithromycin, indicated in combination with NEXIUM for H. pylori eradication to reduce the risk of duodenal ulcer recurrence, refer to the Contraindications section of the respective prescribing information.
• Proton pump inhibitors (PPIs), including NEXIUM, are contraindicated in patients receiving rilpivirine-containing products [see Drug Interactions (7) ] .
• Known hypersensitivity to substituted benzimidazoles or any component of the formulation. ( 4 )
• Patients receiving rilpivirine-containing products. ( 4 , 7 )
• Refer to the Contraindications section of the prescribing information for amoxicillin and clarithromycin, when administered in combination with NEXIUM. ( 4 )
Warnings and precautions
• Gastric Malignancy: In adults, symptomatic response does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing. (5.1)
• Acute Tubulointerstitial Nephritis : Discontinue treatment and evaluate patients. (5.2)
• Clostridium difficile- Associated Diarrhea: PPI therapy may be associated with increased risk. (5.3)
• 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. (5.4)
• Severe Cutaneous Adverse Reactions: Discontinue at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation. ( 5.5 )
• Cutaneous and Systemic Lupus Erythematosus: Mostly cutaneous; new onset or exacerbation of existing disease; discontinue NEXIUM and refer to specialist for evaluation. (5.6)
• Interaction with Clopidogrel: Avoid concomitant use of NEXIUM. (5.7)
• Cyanocobalamin (Vitamin B-12) Deficiency: Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin. (5.8)
• Hypomagnesemia and Mineral Metabolism: Reported rarely with prolonged treatment with PPIs. (5.9)
• Interaction with St. John’s Wort or Rifampin: Avoid concomitant use of NEXIUM. (5.10 , 7 )
• Interactions with Diagnostic Investigations for Neuroendocrine Tumors: Increased chromogranin A (CgA) levels may interfere with diagnostic investigations for neuroendocrine tumors, temporarily stop NEXIUM at least 14 days before assessing CgA levels. (5.11 , 12.2)
• Interaction with Methotrexate : Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity. With high dose methotrexate administration, consider temporary withdrawal of NEXIUM. (5.12 , 7)
• Fundic Gland Polyps : Risk increases with long-term use, especially beyond one year. Use the shortest duration of therapy. (5.13) 5.1 Presence of Gastric Malignancy In adults, symptomatic response to therapy with NEXIUM does not preclude 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 PPI. In older patients, also consider an endoscopy. 5.2 Acute Tubulointerstitial Nephritis Acute tubulointerstitial nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy. Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function (e.g., malaise, nausea, anorexia). In reported case series, some patients were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia). Discontinue NEXIUM and evaluate patients with suspected acute TIN [see Contraindications (4) ]. 5.3 Clostridium difficile- Associated Diarrhea Published observational studies suggest that PPI therapy like NEXIUM may be associated with an increased risk of Clostridium difficile- associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve [see Adverse Reactions (6.2) ] . Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Clostridium difficile- associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents. For more information specific to antibacterial agents (clarithromycin and amoxicillin) indicated for use in combination with NEXIUM, refer to Warnings and Precautions section of the corresponding prescribing information. 5.4 Bone Fracture Several published observational studies suggest that proton pump inhibitor (PPI) therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines [see Dosage and Administration (2) and Adverse Reactions (6.2) ] . 5.5 Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use of PPIs [see Adverse Reactions (6.2) ]. Discontinue NEXIUM at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation. 5.6 Cutaneous and Systemic Lupus Erythematosus Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including esomeprazole. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematosus cases were CLE. The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. Generally, histological findings were observed without organ involvement. Systemic lupus erythematosus (SLE) is less commonly reported than CLE in patients receiving PPIs. PPI associated SLE is usually milder than non-drug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The majority of patients presented with rash; however, arthralgia and cytopenia were also reported.
Side effects
The following serious adverse reactions are described below and elsewhere in labeling:
• Acute Tubulointerstitial Nephritis [see Warnings and Precautions (5.2) ]
• Clostridium difficile-Associated Diarrhea [see Warnings and Precautions (5.3) ]
• Bone Fracture [see Warnings and Precautions (5.4) ]
• Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.5) ]
• Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions (5.6) ]
• Cyanocobalamin (Vitamin B-12) Deficiency [see Warnings and Precautions (5.8) ]
• Hypomagnesemia and Mineral Metabolism [see Warnings and Precautions (5.9) ]
• Fundic Gland Polyps [see Warnings and Precautions (5.13) ] Most common adverse reactions (6.1) :
• Adults (≥ 18 years) ( > 1%) are: headache, diarrhea, nausea, flatulence, abdominal pain, constipation, and dry mouth.
• Pediatrics (1 to 17 years) ( > 2%) are: headache, diarrhea, abdominal pain, nausea, and somnolence.
• Pediatrics (1 month to less than 1 year) (>1%) are: abdominal pain, regurgitation, tachypnea, and increased ALT. To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adults The safety of NEXIUM delayed-release capsules was evaluated in over 15,000 patients (aged 18 to 84 years) in clinical trials worldwide including over 8,500 patients in the United States and over 6,500 patients in Europe and Canada. Over 2,900 patients were treated in long-term studies for up to 6 to 12 months. The safety in the treatment of healing of EE in adults was assessed in four randomized comparative clinical trials, which included 1,240 patients who received NEXIUM 20 mg once daily, 2,434 patients on NEXIUM 40 mg once daily, and 3,008 patients on omeprazole 20 mg once daily. The most frequently occurring adverse reactions (at least 1%) in all three groups were headache (5.5%, 5%, and 3.8%, respectively) and diarrhea (no difference among the three groups). Nausea, flatulence, abdominal pain, constipation, and dry mouth occurred at similar rates among patients taking NEXIUM or omeprazole. Less common adverse reactions with an incidence of less than 1% are listed below by body system: Body as a Whole: abdomen enlarged, allergic reaction, asthenia, back pain, chest pain, substernal chest pain, facial edema, peripheral edema, hot flushes, fatigue, fever, flu-like disorder, generalized edema, leg edema, malaise, pain, rigors; Cardiovascular: flushing, hypertension, tachycardia; Endocrine: goiter; Gastrointestinal: bowel irregularity, constipation aggravated, dyspepsia, dysphagia, dysplasia GI, epigastric pain, eructation, esophageal disorder, frequent stools, gastroenteritis, GI hemorrhage, GI symptoms not otherwise specified, hiccup, melena, mouth disorder, pharynx disorder, rectal disorder, serum gastrin increased, tongue disorder, tongue edema, ulcerative stomatitis, vomiting; Hearing: earache, tinnitus; Hematologic: anemia, anemia hypochromic, cervical lymphadenopathy, epistaxis, leukocytosis, leukopenia, thrombocytopenia; Hepatic: bilirubinemia, hepatic function abnormal, SGOT increased, SGPT increased; Metabolic/Nutritional: glycosuria, hyperuricemia, hyponatremia, increased alkaline phosphatase, thirst, vitamin B12 deficiency, weight increase, weight decrease; Musculoskeletal: arthralgia, arthritis aggravated, arthropathy, cramps, fibromyalgia syndrome, hernia, polymyalgia rheumatica; Nervous System/Psychiatric: anorexia, apathy, appetite increased, confusion, depression aggravated, dizziness, hypertonia, nervousness, hypoesthesia, impotence, insomnia, migraine, migraine aggravated, paresthesia, sleep disorder, somnolence, tremor, vertigo, visual field defect; Reproductive: dysmenorrhea, menstrual disorder, vaginitis; Respiratory: asthma aggravated, coughing, dyspnea, larynx edema, pharyngitis, rhinitis, sinusitis; Skin and Appendages: acne, angioedema, dermatitis, pruritus, pruritus ani, rash, rash erythematous, rash maculo-papular, skin inflammation, sweating increased, urticaria; Special Senses: otitis media, parosmia, taste loss, taste perversion; Urogenital: abnormal urine, albuminuria, cystitis, dysuria, fungal infection, hematuria, micturition frequency, moniliasis, genital moniliasis, polyuria; Visual: conjunctivitis, vision abnormal. The following potentially clinically significant laboratory changes in clinical trials, irrespective of relationship to NEXIUM, were reported in 1% or less of patients: increased creatinine, uric acid, total bilirubin, alkaline phosphatase, ALT, AST, hemoglobin, white blood cell count, platelets, serum gastrin, potassium, sodium, thyroxine and thyroid stimulating hormone [see Clinical Pharmacology (12.2) ] . Decreases were seen in hemoglobin, white blood cell count, platelets, potassium, sodium, and thyroxine. Endoscopic findings that were reported as adverse reactions include: duodenitis, esophagitis, esophageal stricture, esophageal ulceration, esophageal varices, gastric ulcer, gastritis, hernia, benign polyps or nodules, Barrett’s esophagus, and mucosal discoloration. The incidence of adverse reactions during 6-month trials for the maintenance of healing of EE with NEXIUM 20 mg once daily was similar to placebo. There were no differences in types of adverse reactions seen during maintenance treatment up to 12 months compared to short-term treatment. Two placebo-controlled studies were conducted in 710 adult patients for the treatment of symptomatic GERD. The most common adverse reactions that were reported were: diarrhea (4%), headache (4%), and abdominal pain (4%). Combination Treatment with NEXIUM, Amoxicillin and Clarithromycin In clinical trials of H.
Drug interactions
Tables 3 and 4 include drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with esomeprazole and instructions for preventing or managing them. Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs. Table 3: Clinically Relevant Interactions Affecting Drugs Co-Administered with Esomeprazole and Interaction with Diagnostics Antiretrovirals Clinical Impact: The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known.
• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine atazanavir, and nelfinavir) when used concomitantly with esomeprazole may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ] .
• Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with esomeprazole may increase toxicity [see Clinical Pharmacology (12.3) ] .
• There are other antiretroviral drugs which do not result in clinically relevant interactions with esomeprazole. Intervention: Rilpivirine-containing products: Concomitant use with NEXIUM is contraindicated [see Contraindications (4) ] . Atazanavir: See prescribing information for atazanavir for dosing information. Nelfinavir: Avoid concomitant use with NEXIUM. See prescribing information for nelfinavir. Saquinavir: See the prescribing information for saquinavir for monitoring of potential saquinavir-related toxicities. Other antiretrovirals: See prescribing information for specific antiretroviral drugs Warfarin Clinical Impact: Increased INR and prothrombin time in patients receiving PPIs, including esomeprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Intervention: Monitor INR and prothrombin time and adjust the dose of warfarin, if needed, to maintain the target INR range. Methotrexate Clinical Impact: Concomitant use of esomeprazole with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted [see Warnings and Precautions (5.12) ] . Intervention: A temporary withdrawal of NEXIUM may be considered in some patients receiving high-dose methotrexate. 2C19 Substrates (e.g., clopidogrel, citalopram, cilostazol) Clopidogrel Clinical Impact: Concomitant use of esomeprazole 40 mg resulted in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition [see Clinical Pharmacology (12.3) ] . There are no adequate combination studies of a lower dose of esomeprazole or a higher dose of clopidogrel in comparison with the approved dose of clopidogrel. Intervention: Avoid concomitant use with NEXIUM Consider use of alternative anti-platelet therapy [see Warnings and Precautions (5.7) ] . Citalopram Clinical Impact: Increased exposure of citalopram leading to an increased risk of QT prolongation [see Clinical Pharmacology (12.3) ]. Intervention: Limit the dose of citalopram to a maximum of 20 mg per day. See prescribing information for citalopram. Cilostazol Clinical Impact: Increased exposure of cilostazol and one of its active metabolites (3,4-dihydro-cilostazol) [see Clinical Pharmacology (12.3) ]. Intervention: Consider reducing the dose of cilostazol to 50 mg twice daily. See prescribing information for cilostazol. Digoxin Clinical Impact: Potential for increased exposure of digoxin [see Clinical Pharmacology (12.3) ]. Intervention: Monitor digoxin concentrations and adjust the dose, if needed, to maintain therapeutic drug concentrations. See prescribing information for digoxin. Combination Therapy with Clarithromycin and Amoxicillin Clinical Impact: Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions, including potentially fatal arrhythmias, and are contraindicated. Amoxicillin also has drug interactions. Intervention: See Contraindications, Warnings and Precautions in prescribing information for clarithromycin. See Drug Interactions in prescribing information for amoxicillin. Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole) Clinical Impact: Esomeprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity Intervention: Mycophenolate mofetil (MMF): Co-administration of omeprazole, of which esomeprazole is an enantiomer, in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving NEXIUM and MMF. Use NEXIUM with caution in transplant patients receiving MMF [ see Clinical Pharmacology (12.3) ]. See the prescribing information for other drugs dependent on gastric pH for absorption. Tacrolimus Clinical Impact: Potentially increased exposure of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19. Intervention: Monitor tacrolimus whole blood concentrations and consider reducing the dose, if needed, to maintain therapeutic drug concentrations. See prescribing information for tacrolimus. Interactions with Investigations of Neuroendocrine Tumors Clinical Impact: Serum chromogranin A (CgA) levels increase secondary to PPI-induced decreases in gastric acidity.
Use in specific populations
Pediatrics : Use is not recommended for the treatment of symptomatic GERD in patients 1 month to less than 1 year of age; efficacy was not demonstrated. ( 8.4 ) 8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies with esomeprazole in pregnant women. Esomeprazole is the S-isomer of omeprazole. Available epidemiologic data fail to demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use (see Data) . Reproduction studies in rats and rabbits resulted in dose-dependent embryo-lethality at omeprazole doses that were approximately 3.4 to 34 times an oral human dose of 40 mg (based on a body surface area for a 60 kg person). Teratogenicity was not observed in animal reproduction studies with administration of oral esomeprazole magnesium in rats and rabbits with doses about 68 times and 42 times, respectively, an oral human dose of 40 mg (based on a body surface area basis for a 60 kg person). Changes in bone morphology were observed in offspring of rats dosed through most of pregnancy and lactation at doses equal to or greater than approximately 34 times an oral human dose of 40 mg. When maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age ( see Data). The estimated background risks of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data Esomeprazole is the S-isomer of omeprazole. Four epidemiological studies compared the frequency of congenital abnormalities among infants born to women who used omeprazole during pregnancy with the frequency of abnormalities among infants of women exposed to H 2 -receptor antagonists or other controls. A population-based retrospective cohort epidemiological study from the Swedish Medical Birth Registry, covering approximately 99% of pregnancies, from 1995 to 1999, reported on 955 infants (824 exposed during the first trimester with 39 of these exposed beyond first trimester, and 131 exposed after the first trimester) whose mothers used omeprazole during pregnancy. The number of infants exposed in utero to omeprazole that had any malformation, low birth weight, low Apgar score, or hospitalization was similar to the number observed in this population. The number of infants born with ventricular septal defects and the number of stillborn infants was slightly higher in the omeprazole-exposed infants than the expected number in this population. A population-based retrospective cohort study covering all live births in Denmark from 1996 to 2009, reported on 1,800 live births whose mothers used omeprazole during the first trimester of pregnancy and 837,317 live births whose mothers did not use any proton pump inhibitor. The overall rate of birth defects in infants born to mothers with first trimester exposure to omeprazole was 2.9% and 2.6% in infants born to mothers not exposed to any proton pump inhibitor during the first trimester. A retrospective cohort study reported on 689 pregnant women exposed to either H2-blockers or omeprazole in the first trimester (134 exposed to omeprazole) and 1,572 pregnant women unexposed to either during the first trimester. The overall malformation rate in offspring born to mothers with first trimester exposure to omeprazole, an H2-blocker, or were unexposed was 3.6%, 5.5%, and 4.1% respectively. A small prospective observational cohort study followed 113 women exposed to omeprazole during pregnancy (89% with first trimester exposures). The reported rate of major congenital malformations was 4% in the omeprazole group, 2% in controls exposed to non-teratogens, and 2.8% in disease paired controls. Rates of spontaneous and elective abortions, preterm deliveries, gestational age at delivery, and mean birth weight were similar among the groups. Several studies have reported no apparent adverse short-term effects on the infant when single dose oral or intravenous omeprazole was administered to over 200 pregnant women as premedication for cesarean section under general anesthesia. Animal Data Omeprazole Reproductive studies conducted with omeprazole in rats at oral doses up to 138 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis) and in rabbits at doses up to 69.1 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis) during organogenesis did not disclose any evidence for a teratogenic potential of omeprazole. In rabbits, omeprazole in a dose range of 6.9 to 69.1 mg/kg/day (about 3.4 to 34 times an oral human dose of 40 mg on a body surface area basis) administered during organogenesis produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy disruptions. In rats, dose-related embryo/fetal toxicity and postnatal developmental toxicity were observed in offspring resulting from parents treated with omeprazole at 13.8 to 138.0 mg/kg/day (about 3.4 to 34 times an oral human dose of 40 mg on a body surface area basis), administered prior to mating through the lactation period. Esomeprazole No effects on embryo-fetal development were observed in reproduction studies with esomeprazole magnesium in rats at oral doses up to 280 mg/kg/day (about 68 times an oral human dose of 40 mg on a body surface area basis) or in rabbits at oral doses up to 86 mg/kg/day (about 41 times an oral human dose of 40 mg on a body surface area basis) administered during organogenesis.
Pregnancy
8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies with esomeprazole in pregnant women. Esomeprazole is the S-isomer of omeprazole. Available epidemiologic data fail to demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use (see Data) . Reproduction studies in rats and rabbits resulted in dose-dependent embryo-lethality at omeprazole doses that were approximately 3.4 to 34 times an oral human dose of 40 mg (based on a body surface area for a 60 kg person). Teratogenicity was not observed in animal reproduction studies with administration of oral esomeprazole magnesium in rats and rabbits with doses about 68 times and 42 times, respectively, an oral human dose of 40 mg (based on a body surface area basis for a 60 kg person). Changes in bone morphology were observed in offspring of rats dosed through most of pregnancy and lactation at doses equal to or greater than approximately 34 times an oral human dose of 40 mg. When maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age ( see Data). The estimated background risks of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data Esomeprazole is the S-isomer of omeprazole. Four epidemiological studies compared the frequency of congenital abnormalities among infants born to women who used omeprazole during pregnancy with the frequency of abnormalities among infants of women exposed to H 2 -receptor antagonists or other controls. A population-based retrospective cohort epidemiological study from the Swedish Medical Birth Registry, covering approximately 99% of pregnancies, from 1995 to 1999, reported on 955 infants (824 exposed during the first trimester with 39 of these exposed beyond first trimester, and 131 exposed after the first trimester) whose mothers used omeprazole during pregnancy. The number of infants exposed in utero to omeprazole that had any malformation, low birth weight, low Apgar score, or hospitalization was similar to the number observed in this population. The number of infants born with ventricular septal defects and the number of stillborn infants was slightly higher in the omeprazole-exposed infants than the expected number in this population. A population-based retrospective cohort study covering all live births in Denmark from 1996 to 2009, reported on 1,800 live births whose mothers used omeprazole during the first trimester of pregnancy and 837,317 live births whose mothers did not use any proton pump inhibitor. The overall rate of birth defects in infants born to mothers with first trimester exposure to omeprazole was 2.9% and 2.6% in infants born to mothers not exposed to any proton pump inhibitor during the first trimester. A retrospective cohort study reported on 689 pregnant women exposed to either H2-blockers or omeprazole in the first trimester (134 exposed to omeprazole) and 1,572 pregnant women unexposed to either during the first trimester. The overall malformation rate in offspring born to mothers with first trimester exposure to omeprazole, an H2-blocker, or were unexposed was 3.6%, 5.5%, and 4.1% respectively. A small prospective observational cohort study followed 113 women exposed to omeprazole during pregnancy (89% with first trimester exposures). The reported rate of major congenital malformations was 4% in the omeprazole group, 2% in controls exposed to non-teratogens, and 2.8% in disease paired controls. Rates of spontaneous and elective abortions, preterm deliveries, gestational age at delivery, and mean birth weight were similar among the groups. Several studies have reported no apparent adverse short-term effects on the infant when single dose oral or intravenous omeprazole was administered to over 200 pregnant women as premedication for cesarean section under general anesthesia. Animal Data Omeprazole Reproductive studies conducted with omeprazole in rats at oral doses up to 138 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis) and in rabbits at doses up to 69.1 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis) during organogenesis did not disclose any evidence for a teratogenic potential of omeprazole. In rabbits, omeprazole in a dose range of 6.9 to 69.1 mg/kg/day (about 3.4 to 34 times an oral human dose of 40 mg on a body surface area basis) administered during organogenesis produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy disruptions. In rats, dose-related embryo/fetal toxicity and postnatal developmental toxicity were observed in offspring resulting from parents treated with omeprazole at 13.8 to 138.0 mg/kg/day (about 3.4 to 34 times an oral human dose of 40 mg on a body surface area basis), administered prior to mating through the lactation period. Esomeprazole No effects on embryo-fetal development were observed in reproduction studies with esomeprazole magnesium in rats at oral doses up to 280 mg/kg/day (about 68 times an oral human dose of 40 mg on a body surface area basis) or in rabbits at oral doses up to 86 mg/kg/day (about 41 times an oral human dose of 40 mg on a body surface area basis) administered during organogenesis. A pre- and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone development was performed with esomeprazole magnesium at oral doses of 14 to 280 mg/kg/day (about 3.4 to 68 times an oral human dose of 40 mg on a body surface area basis).
Pediatric use
8.4 Pediatric Use Healing of EE Pediatric Patients 1 Year to 17 Years of Age The safety and effectiveness of NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension have been established in pediatric patients 12 years to 17 years for short-term treatment (4 to 8 weeks) for healing of EE. The safety and effectiveness of NEXIUM for delayed-release oral suspension have been established in pediatric patients 1 year to 11 years for short-term treatment (up to 8 weeks) for healing of EE. Use of NEXIUM for this indication is supported by evidence from adequate and well-controlled studies in adults with additional safety and pharmacokinetic data in pediatric patients 1 year to 17 years of age. The safety profile in pediatric patients 1 year to 17 years of age was similar to adults [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , Clinical Studies (14.4) ]. Pediatric Patients 1 Month to Less Than 1 Year of Age The safety and effectiveness of NEXIUM for delayed-release oral suspension have been established in pediatric patients 1 month to less than 1 year of age for short-term treatment (up to 6 weeks) of EE due to acid-mediated GERD. Use of NEXIUM for this indication is supported by evidence from adequate and well-controlled studies in adults with additional safety, pharmacokinetic, and pharmacodynamic data in pediatric patients 1 month to less than 1 year of age. The safety profile in pediatric patients 1 month to less than 1 year of age was similar to adults [see Adverse Reactions (6.1) , Clinical Pharmacology (12.2 , 12.3 )] . The safety and effectiveness of NEXIUM for the treatment of EE due to acid-mediated GERD in pediatric patients less than 1 month of age have not been established. Symptomatic GERD Pediatric Patients 1 Year to 17 Years of Age The safety and effectiveness of NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension have been established in pediatric patients 12 years to 17 years of age for the short-term treatment (4 weeks) of heartburn and other symptoms associated with GERD. The safety and effectiveness of NEXIUM for delayed-release oral suspension have been established in pediatric patients 1 year to 11 years of age for the short-term treatment (up to 8 weeks) of heartburn and other symptoms associated with GERD. Use of NEXIUM for this indication is supported by evidence from adequate and well-controlled studies in adults with additional safety and pharmacokinetic data in pediatric patients 1 year to 17 years of age. The safety profile in pediatric patients 1 year to 17 years of age was similar to adults [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , Clinical Studies (14.4) ]. The safety and effectiveness of NEXIUM for the treatment of symptomatic GERD in pediatric patients less than 1 year of age have not been established. Infants 1 Month to Less Than 1 Year of Age NEXIUM was not found to be effective in a multicenter, randomized, double-blind, controlled, treatment-withdrawal study of 98 infants aged 1 month to 11 months for the treatment of symptomatic GERD. Patients were enrolled if they had either a clinical diagnosis of suspected GERD, symptomatic GERD, or endoscopically proven GERD. Twenty of 98 enrolled patients underwent endoscopy, and 6 patients were found to have EE on endoscopy at baseline. All patients received NEXIUM for delayed-release oral suspension once daily during a two-week, open-label phase of the study. There were 80 patients who attained a pre-specified level of symptom improvement and who entered the double-blind phase, in which they were randomized in equal proportions to receive NEXIUM or placebo for the next four weeks. Efficacy was assessed by observing the time from randomization to study discontinuation due to symptom worsening during the four-week, treatment-withdrawal phase. There was no statistically significant difference between NEXIUM and placebo in the rate of discontinuation due to symptom worsening; therefore, these results do not support the use of NEXIUM for the treatment of symptomatic GERD in infants 1 month to less than 1 year of age. Other Conditions The safety and effectiveness of NEXIUM for the risk reduction of NSAID-associated gastric ulcer, H. pylori eradication to reduce the risk of duodenal ulcer recurrence and treatment of pathological hypersecretory conditions have not been established in pediatric patients. Juvenile Animal Toxicity Studies In a juvenile rat toxicity study, esomeprazole was administered with both magnesium and strontium salts at oral doses about 34 to 68 times a daily human dose of 40 mg based on body surface area. Increases in death were seen at the high dose, and at all doses of esomeprazole, there were decreases in body weight, body weight gain, femur weight and femur length, and decreases in overall growth [see Nonclinical Toxicology (13.2) ].
Geriatric use
8.5 Geriatric Use Of the total number of patients who received NEXIUM in clinical trials, 1459 were 65 to 74 years of age and 354 patients were 75 years of age and older. No overall differences in safety and efficacy were observed between the elderly and younger individuals, and other reported clinical experience has not identified differences in responses between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Overdosage
Manifestations in patients exposed to omeprazole, the racemic mixture, at doses up to 2,400 mg (120 times the usual recommended clinical dose) include confusion, drowsiness, blurred vision, tachycardia, nausea, diaphoresis, flushing, headache, dry mouth, and other adverse reactions similar to those seen at recommended dosages. See the full prescribing information for omeprazole for complete safety information. No specific antidote for esomeprazole is known. Since esomeprazole is extensively protein bound, it is not expected to be removed by dialysis. In the event of overdosage, treatment should be symptomatic and supportive. If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.
Description
The active ingredient in NEXIUM ® (esomeprazole magnesium) delayed-release capsules for oral administration and NEXIUM (esomeprazole magnesium) for delayed-release oral suspension is bis(5-methoxy-2-[(S)-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1 H -benzimidazole-1-yl) magnesium trihydrate, a PPI. Esomeprazole is the S-isomer of omeprazole, which is a mixture of the S- and R- isomers. (Initial U.S. approval of esomeprazole magnesium: 2001). Its molecular formula is (C 17 H 18 N 3 O 3 S) 2 Mg x 3 H 2 O with molecular weight of 767.2 as a trihydrate and 713.1 on an anhydrous basis. The structural formula is: The magnesium salt is a white to slightly colored crystalline powder. It contains 3 moles of water of solvation and is slightly soluble in water. The stability of esomeprazole magnesium is a function of pH; it rapidly degrades in acidic media, but it has acceptable stability under alkaline conditions. At pH 6.8 (buffer), the half-life of the magnesium salt is about 19 hours at 25°C and about 8 hours at 37°C. NEXIUM is supplied in delayed-release capsules and in packets for a delayed-release oral suspension. Each NEXIUM delayed-release capsule contains 20 mg of esomeprazole (equivalent to 22.3 mg esomeprazole magnesium trihydrate) or 40 mg of esomeprazole (equivalent to 44.5 mg esomeprazole magnesium trihydrate) in the form of enteric-coated granules with the following inactive ingredients: glyceryl monostearate 40-55, hydroxypropyl cellulose, hypromellose, magnesium stearate, methacrylic acid copolymer type C, polysorbate 80, sugar spheres, talc, and triethyl citrate. The capsule shells have the following inactive ingredients: D&C Red #28, D&C Yellow #10, ethyl alcohol, FD&C Blue #1, FD&C Red #40, gelatin, isopropyl alcohol, n-butyl alcohol, polyvinyl pyrrolidone, propylene glycol, shellac, sodium hydroxide, and titanium dioxide. Each packet of NEXIUM for delayed-release oral suspension contains esomeprazole, in the form of same enteric-coated granules used in NEXIUM delayed-release capsules, and also inactive granules:
• 2.5 mg esomeprazole (equivalent to 2.8 mg esomeprazole magnesium trihydrate)
• 5 mg esomeprazole (equivalent to 5.6 mg esomeprazole magnesium trihydrate)
• 10 mg esomeprazole (equivalent to 11.1 mg esomeprazole magnesium trihydrate)
• 20 mg esomeprazole (equivalent to 22.3 mg esomeprazole magnesium trihydrate)
• 40 mg esomeprazole (equivalent to 44.5 mg esomeprazole magnesium trihydrate) The inactive granules are composed of the following ingredients: citric acid, crospovidone, dextrose, hydroxypropyl cellulose, iron oxide, and xanthan gum. The esomeprazole granules and inactive granules are constituted with water to form a suspension and are given by oral, nasogastric, or gastric administration. Structural Formula
Mechanism of action
12.1 Mechanism of Action Esomeprazole belongs to a class of antisecretory compounds, the substituted benzimidazoles, that suppress gastric acid secretion by specific inhibition of the H+/K+ ATPase enzyme system at the secretory surface of the gastric parietal cell. Esomeprazole is protonated and converted in the acidic compartment of the parietal cell forming the active inhibitor, the achiral sulphenamide. Because this enzyme system is regarded as the acid (proton) pump within the gastric mucosa, esomeprazole has been characterized as a gastric acid-pump inhibitor, in that it blocks the final step of acid production. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus.
How supplied
Delayed-Release Capsules, 20 mg esomeprazole, are opaque, hard gelatin, amethyst colored capsules with two radial bars in yellow on the cap and NEXIUM 20 mg in yellow on the body. They are supplied as follows: NDC 0186-5020-31 unit of use bottles of 30 NDC 0186-5020-54 bottles of 90 NEXIUM Delayed-Release Capsules, 40 mg esomeprazole, are opaque, hard gelatin, amethyst colored capsules with three radial bars in yellow on the cap and NEXIUM 40 mg in yellow on the body. They are supplied as follows: NDC 0186-5040-31 unit of use bottles of 30 NDC 0186-5040-54 bottles of 90 NEXIUM For Delayed-Release Oral Suspension is supplied as a unit dose packet containing a fine yellow powder, consisting of white to pale brownish esomeprazole granules and pale yellow inactive granules. NEXIUM unit dose packets are supplied as follows: NDC 0186-4025-01 unit dose packages of 30: 2.5 mg esomeprazole packets NDC 0186-4050-01 unit dose packages of 30: 5 mg esomeprazole packets NDC 0186-4010–01 unit dose packages of 30: 10 mg esomeprazole packets NDC 0186-4020–01 unit dose packages of 30: 20 mg esomeprazole packets NDC 0186-4040–01 unit dose packages of 30: 40 mg esomeprazole packets Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature]. Keep NEXIUM delayed-release capsules container tightly closed. Dispense in a tight container if the NEXIUM delayed-release capsules product package is subdivided.
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Acute Tubulointerstitial Nephritis Advise the patient or caregiver to call the patient’s healthcare provider immediately if they experience signs and/or symptoms associated with suspected acute TIN [see Warnings and Precautions (5.2) ]. Clostridium difficile -Associated Diarrhea Advise the patient or caregiver to immediately call the patient’s healthcare provider if they experience diarrhea that does not improve [see Warnings and Precautions (5.3) ]. Bone Fracture Advise the patient or caregiver to report any fractures, especially of the hip, wrist or spine, to the patient’s healthcare provider [see Warnings and Precautions (5.4) ] . Severe Cutaneous Adverse Reactions Advise the patient or caregiver to discontinue NEXIUM and immediately call the patient’s healthcare provider for at first appearance of a severe cutaneous adverse reaction or other sign of hypersensitivity signs or symptoms associated with Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.5) ] . Cutaneous and Systemic Lupus Erythematosus Advise the patient or caregiver to immediately call the patient’s healthcare provider for any new or worsening of symptoms associated with cutaneous or systemic lupus erythematosus [see Warnings and Precautions (5.6) ] . Cyanocobalamin (Vitamin B-12) Deficiency Advise the patient or caregiver to report any clinical symptoms that may be associated with cyanocobalamin deficiency to the patient’s healthcare provider if they have been receiving NEXIUM for longer than 3 years [see Warnings and Precautions (5.8) ] . Hypomagnesemia and Mineral Metabolism Advise the patient or caregiver to report any clinical symptoms that may be associated with hypomagnesemia, hypocalcemia, and/or hypokalemia to the patient’s healthcare provider, if they have been receiving NEXIUM for at least 3 months [see Warnings and Precautions (5.9) ] . Drug Interactions Advise the patient or caregiver to report to their healthcare provider if starting treatment with rilpivirine-containing products, clopidogrel, St. John’s Wort or rifampin; or, if they take high-dose methotrexate [see Contraindications (4) , Warnings and Precautions (5.7 , 5.10 , 5.12 ) ]. Administration
• Take NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension at least one hour before meals.
• Antacids may be used concomitantly with NEXIUM.
• Swallow NEXIUM delayed-release capsules whole; do not chew or crush the capsules.
• For patients who have difficulty swallowing capsules, NEXIUM delayed-release capsules can be opened, and the contents sprinkled on applesauce. Use with other foods is not recommended. 1. Add one tablespoon of applesauce to an empty bowl. The applesauce used should not be hot and should be soft enough to be swallowed without chewing. 2. Open the NEXIUM delayed-release capsule and carefully empty the granules inside the capsule onto the applesauce. 3. Mix the granules with the applesauce. 4. Administer the mixture immediately. Do not chew or crush the granules. 5. Discard any remaining mixture. Do not store the mixture for future use.
• NEXIUM delayed-release capsules can also be administered via a nasogastric tube, as described in the Instructions for Use.
• Administer NEXIUM for delayed-release oral suspension orally or via a nasogastric or gastric tube, as described in the Instructions for Use. Distributed by: AstraZeneca Pharmaceuticals LP Wilmington, DE 19850 NEXIUM and the color purple as applied to the capsule are registered trademarks of the AstraZeneca group of companies. ©AstraZeneca 2023
Label text from the FDA structured product label by AstraZeneca Pharmaceuticals LP (revised Dec 19, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Esomeprazole Magnesium Trihydrate in 7 products
Nexium NDC products (7)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0186-4010 | Esomeprazole Magnesium Trihydrate 10 mg/1 Granule, Delayed Release | AstraZeneca Pharmaceuticals LP | NDA |
| 0186-4020 | Esomeprazole Magnesium Trihydrate 20 mg/1 Granule, Delayed Release | AstraZeneca Pharmaceuticals LP | NDA |
| 0186-4025 | Esomeprazole Magnesium Trihydrate 2.5 mg/1 Granule, Delayed Release | AstraZeneca Pharmaceuticals LP | NDA |
| 0186-4040 | Esomeprazole Magnesium Trihydrate 40 mg/1 Granule, Delayed Release | AstraZeneca Pharmaceuticals LP | NDA |
| 0186-4050 | Esomeprazole Magnesium Trihydrate 5 mg/1 Granule, Delayed Release | AstraZeneca Pharmaceuticals LP | NDA |
| 0186-5020 | Esomeprazole Magnesium Trihydrate 20 mg/1 Capsule, Delayed Release | AstraZeneca Pharmaceuticals LP | NDA |
| 0186-5040 | Esomeprazole Magnesium Trihydrate 40 mg/1 Capsule, Delayed Release | AstraZeneca Pharmaceuticals LP | NDA |
Nexium recalls
- D-1410-2012 Jul 18, 2012 · Class III · Terminated
Adulterated Presence of Foreign Tablets/Capsules: Some bottles may contain a small number of Nexium 20 mg capsules intended for the Japanese market in addtion to Nexium 40 mg capsules.
Frequently asked questions
What is Nexium used for?
1 INDICATIONS AND USAGE NEXIUM is a proton pump inhibitor (PPI). NEXIUM delayed-release capsules and NEXIUM for delayed-release oral suspension are indicated for the: • Short-term treatment in the healing of erosive esophagitis (EE) in adults and pediatric patients 12 years to 17 years of age. ( 1.1 ) • Maintenance of healing of EE in adults. ( 1.2 ) • Short-term treatment of heartburn and other…
What are the side effects of Nexium?
The following serious adverse reactions are described below and elsewhere in labeling: • Acute Tubulointerstitial Nephritis [see Warnings and Precautions (5.2) ] • Clostridium difficile-Associated Diarrhea [see Warnings and Precautions (5.3) ] • Bone Fracture [see Warnings and Precautions (5.4) ] • Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.5) ] • Cutaneous and Systemic… See the full label for the complete list.
Who makes Nexium?
Nexium is listed by 1 labeler in the FDA NDC directory, including AstraZeneca Pharmaceuticals LP.
Has Nexium been recalled?
The FDA enforcement database lists 1 recall for Nexium, most recently D-1410-2012 (class iii): Adulterated Presence of Foreign Tablets/Capsules: Some bottles may contain a small number of Nexium 20 mg capsules intended for the Japanese market in addtion…