Esomeprazole Sodium

What is Esomeprazole Sodium?

11 DESCRIPTION The active ingredient in esomeprazole sodium for injection is ( S )-5-methoxy-2[[(4-methoxy-3,5- dimethyl-2-pyridinyl)-methyl]sulfinyl]-1 H -benzimidazole sodium, a PPI. Esomeprazole is the S-isomer of omeprazole, which is a mixture of the S- and R- isomers. Its empirical formula is C 17 H 18 N 3 O 3 SNa with molecular weight of 367.4 g/mol (sodium salt) and 345.4 g/mol (parent compound). Esomeprazole sodium is very soluble in water and freely soluble in ethanol (95%). The structural formula is: Esomeprazole sodium for injection is supplied as a sterile, lyophilized, white to off-white, porous cake or powder in a 5 mL single-dose vial, intended for intravenous administration after reconstitution with 0.9% Sodium Chloride Injection, USP; Lactated Ringer’s Injection, USP or 5% Dextrose Injection, USP. Esomeprazole sodium for injection contains 40 mg esomeprazole (equivalent to 42.5 mg esomeprazole sodium), edetate disodium 1.5 mg and sodium hydroxide q.s. for pH adjustment. The pH of reconstituted solution of esomeprazole sodium for injection depends on the reconstitution volume and is in the pH range of 9 to 11. The stability of esomeprazole sodium in aqueous solution

Uses of Esomeprazole Sodium

Established uses

1 INDICATIONS AND USAGE Esomeprazole sodium for injection is a proton pump inhibitor (PPI) indicated for the: Short-term treatment of Gastroesophageal Reflux Disease (GERD) with erosive esophagitis (EE) in adults and pediatric patients 1 month to 17 years of age, as an alternative to oral therapy when oral esomeprazole is not possible or appropriate.
(1.1) Risk reduction of rebleeding of gastric or duodenal ulcers following therapeutic endoscopy for acute bleeding gastric or duodenal ulcers in adults.
(1.2) 1.1 Treatment of Gastroesophageal Reflux Disease (GERD) with Erosive Esophagitis (EE) Esomeprazole sodium for injection is indicated for the short-term treatment of GERD with EE in adults and pediatric patients 1 month to 17 years, inclusively as an alternative to oral therapy when oral esomeprazole is not possible or appropriate.
1.2 Risk Reduction of Rebleeding of Gastric or Duodenal Ulcers following Therapeutic Endoscopy in Adults Esomeprazole sodium for injection is indicated for risk reduction of rebleeding of gastric or duodenal ulcers following therapeutic endoscopy for acute bleeding gastric or duodenal ulcers in adults.

How Esomeprazole Sodium works

In more detail: 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 to take Esomeprazole Sodium

2 DOSAGE AND ADMINISTRATION GERD with Erosive Esophagitis (2.1) : The recommended adult dosage is either 20 mg or 40 mg once daily by intravenous injection (no less than 3 minutes) or intravenous infusion (10 minutes to 30 minutes) for up to 10 days. The recommended pediatric dosage is based upon age and weight. See full prescribing information. Risk Reduction of Rebleeding of Gastric and Duodenal Ulcers (2.2) : The recommended adult dosage is 80 mg administered as an intravenous infusion over 30 minutes, followed by a continuous infusion of 8 mg/hour for a total treatment duration of 72 hours. Dosage Adjustment for Hepatic Impairment (2.3) : See full prescribing information for dosage adjustment by severity of impairment and by indication. Preparation and Administration (2.4 , 2.5) : See full prescribing information for preparation and administration instructions by indication. 2.1 Dosage for GERD with EE Adult Patients The recommended adult dosage is either 20 mg or 40 mg esomeprazole sodium for injection given once daily by intravenous injection (over at least 3 minutes) or intravenous infusion (10 minutes to 30 minutes) for up to 10 days [see Dosage and Administration (2.4) ].

Dosage

Follow the dose prescribed by your doctor or pharmacist. The ranges below are general information, not a personal prescription.

Adults: 2 DOSAGE AND ADMINISTRATION GERD with Erosive Esophagitis (2.1) : The recommended adult dosage is either 20 mg or 40 mg once daily by intravenous injection (no less than 3 minutes) or intravenous infusion (10 minutes to 30 minutes) for up to 10 days. The recommended pediatric dosage is based upon age and weight. See full prescribing information. Risk Reduction of Rebleeding of Gastric and Duodenal Ulcers (2.2) : The recommended adult dosage is 80 mg administered as an intravenous infusion over 30 minutes, followed by a continuous infusion of 8 mg/hour for a total treatment duration of 72 hours. Dosage Adjustment for Hepatic Impairment (2.3) : See full prescribing information for dosage adjustment by severity of impairment and by indication. Preparation and Administration (2.4 , 2.5) : See full prescribing information for preparation and administration instructions by indication. 2.1 Dosage for GERD with EE Adult Patients The recommended adult dosage is either 20 mg or 40 mg esomeprazole sodium for injection given once daily by intravenous injection (over at least 3 minutes) or intravenous infusion (10 minutes to 30 minutes) for up to 10 days [see Dosage and Administration (2.4) ].

Side effects of Esomeprazole Sodium

Common

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) ] Hypomagnesemia and Mineral Metabolism [see Warnings and Precautions (5.8) ] Fundic Gland Polyps [see Warnings and Precautions (5.12) ] Most common adverse reactions (≥1%) are: headache, flatulence, nausea, abdominal pain, injection site reaction, diarrhea, dry mouth, dizziness/vertigo, constipation and pruritus.
(6.1) To report SUSPECTED ADVERSE REACTIONS, contact Slate Run Pharmaceuticals, LLC at 1-888-341-9214 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

Warnings and who should not take it

Who should NOT take Esomeprazole Sodium?

4 CONTRAINDICATIONS Esomeprazole sodium for injection 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) ] .
Proton pump inhibitors (PPIs), including esomeprazole sodium for injection, are contraindicated in patients receiving rilpivirine-containing products [see Drug Interactions (7) ] .
Patients with known hypersensitivity to any component of the formulation or to substituted benzimidazoles.
(4) Patients receiving rilpivirine-containing products.
(4 , 7)

Overdose

10 OVERDOSAGE The symptoms described in connection with deliberate esomeprazole overdose (limited experience of doses in excess of 240 mg/day) are transient. Reports of overdosage with omeprazole in humans may also be relevant. Doses ranged up to 2,400 mg (120 times the usual recommended clinical dose). Manifestations were variable, but included 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 oral 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.

Safety at a glance

PregnancyCaution

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. 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

Children and elderly

Children

8.4 Pediatric Use The safety and effectiveness of esomeprazole sodium for injection have been established in pediatric patients 1 month to 17 years of age for the short-term treatment of GERD with EE, as an alternative to oral therapy when oral esomeprazole is not possible or appropriate. Use of esomeprazole sodium for injection in this age group is based on extrapolation of adult efficacy to children and the selection of dose based on exposure-matching of pediatrics to adults supported by the following evidence: a) results observed from a pharmacokinetic (PK) study on esomeprazole sodium for injection in pediatric patients, b) predictions from a population PK model comparing I.V. PK data between adult and pediatric patients, and c) relationship between exposure and pharmacodynamic results obtained from adult I.V. and pediatric oral data and d) PK results from adequate and well-controlled studies that supported the approval of esomeprazole sodium for injection in adults [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , Clinical Studies (14.1) ] . The safety and effectiveness of esomeprazole sodium for injection have not been established in patients less than 1 month of

Elderly

8.5 Geriatric Use In a clinical trial of patients with bleeding gastric or duodenal ulcers, 52% of 375 patients randomized to esomeprazole sodium for injection were 65 years of age and over. No overall differences in safety and efficacy were observed between the elderly and younger individuals, and other reported clinical experience with esomeprazole sodium for injection and oral esomeprazole has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Interactions

Medicine and medicine

7 DRUG INTERACTIONS Tables 5 and 6 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 5: 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) ].

Frequently asked questions

What is Esomeprazole Sodium used for?

1 INDICATIONS AND USAGE Esomeprazole sodium for injection is a proton pump inhibitor (PPI) indicated for the: Short-term treatment of Gastroesophageal Reflux Disease (GERD) with erosive esophagitis (EE) in adults and pediatric patients 1 month to 17 years of age, as an alternative to oral therapy when oral esomeprazole is not possible or appropriate., (1.1) Risk reduction of rebleeding of gastric or duodenal ulcers following therapeutic endoscopy for acute bleeding gastric or duodenal ulcers in adults., (1.2) 1.1 Treatment of Gastroesophageal Reflux Disease (GERD) with Erosive Esophagitis (EE) Esomeprazole sodium for injection is indicated for the short-term treatment of GERD with EE in adults and pediatric patients 1 month to 17 years, inclusively as an alternative to oral therapy when oral esomeprazole is not possible or appropriate., 1.2 Risk Reduction of Rebleeding of Gastric or Duodenal Ulcers following Therapeutic Endoscopy in Adults Esomeprazole sodium for injection is indicated for risk reduction of rebleeding of gastric or duodenal ulcers following therapeutic endoscopy for acute bleeding gastric or duodenal ulcers in adults..

How should I take Esomeprazole Sodium?

2 DOSAGE AND ADMINISTRATION GERD with Erosive Esophagitis (2.1) : The recommended adult dosage is either 20 mg or 40 mg once daily by intravenous injection (no less than 3 minutes) or intravenous infusion (10 minutes to 30 minutes) for up to 10 days. The recommended pediatric dosage is based upon age and weight. See full prescribing information. Risk Reduction of Rebleeding of Gastric and Duodenal Ulcers (2.2) : The recommended adult dosage is 80 mg administered as an intravenous infusion over 30 minutes, followed by a continuous infusion of 8 mg/hour for a total treatment duration of 72 hours. Dosage Adjustment for Hepatic Impairment (2.3) : See full prescribing information for dosage adjustment by severity of impairment and by indication. Preparation and Administration (2.4 , 2.5) : See full prescribing information for preparation and administration instructions by indication. 2.1 Dosage for GERD with EE Adult Patients The recommended adult dosage is either 20 mg or 40 mg esomeprazole sodium for injection given once daily by intravenous injection (over at least 3 minutes) or intravenous infusion (10 minutes to 30 minutes) for up to 10 days [see Dosage and Administration (2.4) ].

What are the common side effects?

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) ] Hypomagnesemia and Mineral Metabolism [see Warnings and Precautions (5.8) ] Fundic Gland Polyps [see Warnings and Precautions (5.12) ] Most common adverse reactions (≥1%) are: headache, flatulence, nausea, abdominal pain, injection site reaction, diarrhea, dry mouth, dizziness/vertigo, constipation and pruritus., (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Slate Run Pharmaceuticals, LLC at 1-888-341-9214 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.

Who should not take Esomeprazole Sodium?

4 CONTRAINDICATIONS Esomeprazole sodium for injection 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) ] .; Proton pump inhibitors (PPIs), including esomeprazole sodium for injection, are contraindicated in patients receiving rilpivirine-containing products [see Drug Interactions (7) ] .; Patients with known hypersensitivity to any component of the formulation or to substituted benzimidazoles.; (4) Patients receiving rilpivirine-containing products.; (4 , 7).

Can I take Esomeprazole Sodium during 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. 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

Can children take Esomeprazole Sodium?

8.4 Pediatric Use The safety and effectiveness of esomeprazole sodium for injection have been established in pediatric patients 1 month to 17 years of age for the short-term treatment of GERD with EE, as an alternative to oral therapy when oral esomeprazole is not possible or appropriate. Use of esomeprazole sodium for injection in this age group is based on extrapolation of adult efficacy to children and the selection of dose based on exposure-matching of pediatrics to adults supported by the following evidence: a) results observed from a pharmacokinetic (PK) study on esomeprazole sodium for injection in pediatric patients, b) predictions from a population PK model comparing I.V. PK data between adult and pediatric patients, and c) relationship between exposure and pharmacodynamic results obtained from adult I.V. and pediatric oral data and d) PK results from adequate and well-controlled studies that supported the approval of esomeprazole sodium for injection in adults [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , Clinical Studies (14.1) ] . The safety and effectiveness of esomeprazole sodium for injection have not been established in patients less than 1 month of

Does Esomeprazole Sodium interact with other medicines?

7 DRUG INTERACTIONS Tables 5 and 6 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 5: 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) ]..