Esomeprazole Magnesium

FDA Drug Information • Also known as: Acid Reducer, Esomeprazole, Esomeprazole Magnesium, Esomeprazole Magnesium Delayed Release,...

Brand Names: Acid Reducer, Esomeprazole, Esomeprazole Magnesium, Esomeprazole Magnesium Delayed Release, Esomeprazole Magnesium Dr, Esomeprazole Magnesium For Delayed-Release Oral Suspension, Nexium, Nexium 24Hr, Nexium 24Hr Clearminis, Topcare Esomeprazole Magnesium, Up And Up Esomeprazole Magnesium
Dosage Form: CAPSULE
Product Type: DRUG FOR FURTHER PROCESSING

Description

11 DESCRIPTION The active ingredient in esomeprazole magnesium delayed-release capsules USP for oral administration is bis(5-methoxy-2-[(S)-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1 H -benzimidazole-1-yl) magnesium dihydrate, 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 2 H 2 O with molecular weight of 749.15 as a dihydrate and 713.12 on an anhydrous basis. The structural formula is: The magnesium salt is a white to slightly colored powder. It contains 2 moles of water of solvation and is practically insoluble 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. Esomeprazole magnesium is supplied in delayed-release capsules. Each esomeprazole magnesium delayed-release capsule contains 20 mg of esomeprazole (equivalent to 21.75 mg esomeprazole magnesium dihydrate USP) or 40 mg of esomeprazole (equivalent to 43.5 mg esomeprazole magnesium dihydrate USP) in the form of enteric-coated granules with the following inactive ingredients: colloidal silicon dioxide, hydroxypropyl cellulose, hypromellose, magnesium carbonate, magnesium oxide, methacrylic acid and ethyl acrylate copolymer dispersion, mono and di glycerides, polysorbate 80, sugar spheres (which contains liquid glucose, starch (maize) and sucrose), talc, titanium dioxide, and triethyl citrate. In addition, the empty hard gelatin capsule shells contain gelatin and sodium lauryl sulfate. The capsule shells are imprinted with edible ink containing butyl alcohol, dehydrated alcohol, isopropyl alcohol, propylene glycol, shellac, strong ammonia solution and yellow iron oxide. Meets USP Dissolution Test 2. Chemical Structure

What Is Esomeprazole Magnesium Used For?

1 INDICATIONS AND USAGE Esomeprazole magnesium delayed-release capsules are a proton pump inhibitor (PPI). Esomeprazole magnesium delayed-release capsules 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 ) 1.1 Healing of Erosive Esophagitis (EE) Adults Esomeprazole magnesium delayed-release capsules 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 esomeprazole magnesium delayed-release capsules may be considered. Pediatric Patients 12 Years to 17 Years of Age Esomeprazole magnesium delayed-release capsules 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. 1.2 Maintenance of Healing of EE Esomeprazole magnesium delayed-release capsules 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 Esomeprazole magnesium delayed-release capsules 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 Esomeprazole magnesium delayed-release capsules 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. 1.4 Risk Reduction of Nonsteroidal Anti-Inflammatory Drugs (NSAID)-Associated Gastric Ulcer Esomeprazole magnesium delayed-release capsules 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 Esomeprazole magnesium delayed-release capsules...

Dosage and Administration

2 DOSAGE AND ADMINISTRATION 1 A maximum dosage of 20 mg once daily is recommended for patients with severe liver impairment (Child-Pugh Class C). 2 Controlled studies do not extend beyond 6 months. 3 Refer to the amoxicillin and clarithromycin prescribing information for dosage adjustments in elderly and renally-impaired patients. 4 A starting dosage of 20 mg twice daily is recommended for patients with severe liver impairment (Child-Pugh Class C). Population Recommended Adult ( 2.1 ) and Pediatric Dosage ( 2.2 ) Healing of EE (12 years and older) Adults 20 mg or 40 mg 1 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 1 once daily for 4 to 8 weeks 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 for 4 weeks some patients may require an additional 4 weeks 12 years to 17 years 20 mg once daily for 4 weeks Risk Reduction of NSAID-Associated Gastric Ulcer Adults 20 mg or 40 mg 1 once daily for up to 6 months 2 H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence Adults Esomeprazole magnesium delayed-release capsules 40 mg 1 once daily for 10 days Amoxicillin 1000 mg twice daily for 10 days 3 Clarithromycin 500 mg twice daily for 10 days 3 Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome Adults Starting dosage is 40 mg twice daily 4 (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 ) Opened capsules can be administered through a nasogastric tube. ( 2.3 ) 2.1 Recommended Dosage in Adults by Indication Table 1 shows the recommended adult dosage of esomeprazole magnesium delayed-release capsules by indication. The duration of esomeprazole magnesium delayed-release capsules treatment should be based on available safety and efficacy data specific to the defined indication and dosing frequency and individual patient medical needs. Esomeprazole magnesium delayed-release capsules should only be initiated and continued if the benefits outweigh the risks of treatment. Table 1: Recommended Dosage of Esomeprazole Magnesium Delayed-Release Capsules in Adults by Indication 1. 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) ]. 2. 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) ] . 3. Refer to the amoxicillin and clarithromycin prescribing information for dosage adjustments in elderly and renally-impaired patients. 4. A starting dosage of 20 mg twice daily is recommended...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS 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. To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 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 esomeprazole magnesium 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 esomeprazole magnesium delayed-release capsules 20 mg once daily, 2,434 patients on esomeprazole magnesium delayed-release capsules 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 esomeprazole magnesium delayed-release capsules 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,...

Drug Interactions

7 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 esomeprazole magnesium delayed-release capsules are contraindicated [see Contraindications (4) ] . Atazanavir: See prescribing information for atazanavir for dosing information. Nelfinavir: Avoid concomitant use with esomeprazole magnesium delayed-release capsules. 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 esomeprazole magnesium delayed-release capsules 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...

Contraindications

4 CONTRAINDICATIONS Esomeprazole magnesium delayed-release capsules are 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 esomeprazole magnesium delayed-release capsules 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 esomeprazole magnesium delayed-release capsules, 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 esomeprazole magnesium delayed-release capsules. ( 4 )

Pregnancy and Breastfeeding

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...

Overdosage

10 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.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Esomeprazole Magnesium Delayed-Release Capsules USP, 20 mg are white/white size ‘4’ hard gelatin capsules filled with white to off white spherical to oval pellets and imprinted with “I81” on body with gold tek ink. Esomeprazole Magnesium Delayed-Release Capsules USP, 40 mg are white/white size ‘2’ hard gelatin capsules filled with white to off white spherical to oval pellets and imprinted with "I82" on body with gold tek ink. They are supplied as follows: Blistercards of 30 NDC 0615-8396-39 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Keep esomeprazole magnesium delayed-release capsules container tightly closed. Dispense in a tight container if the esomeprazole magnesium delayed-release capsules product package is subdivided.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.