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Indications/Uses
Treatment of Gastroesophageal Reflux Disease (GERD): Healing of Erosive Esophagitis: Esomeprazole is indicated for the short-term treatment (4 to 8 weeks) in the healing and symptomatic resolution of diagnostically confirmed erosive esophagitis. For those patients who have not healed after 4 to 8 weeks of treatment, an additional 4 to 8 week course of esomeprazole may be considered.
In infants 1 month to less than 1 year, esomeprazole is indicated for short-term treatment (up to 6 weeks) of erosive esophagitis due to acid-mediated GERD.
Maintenance of Healing Erosive Esophagitis: Esomeprazole is indicated to maintain symptom resolution and healing of erosive esophagitis. Controlled studies do not extend beyond 6 months.
Symptomatic Gastroesophageal Reflux Disease: Esomeprazole is indicated for short-term treatment (4 to 8 weeks) of heartburn and other symptoms associated with GERD in adults and children 1 year or older.
Risk Reduction of NSAID-Associated Gastric Ulcer: Esomeprazole is indicated for the reduction in the occurrence of gastric ulcers associated with continuous NSAID therapy in patients at risk for developing gastric ulcers. Patients are considered to be at risk due to their age (≥ 60) and/or documented history of gastric ulcers. Controlled studies do not extend beyond 6 months.
H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence: Triple Therapy (esomeprazole plus amoxicillin and clarithromycin): esomeprazole, in combination with amoxicillin and clarithromycin, is indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or history of within the past 5 years) to eradicate H. pylori. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence (see Dosage & Administration). 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.
Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome: Esomeprazole is indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison Syndrome
In infants 1 month to less than 1 year, esomeprazole is indicated for short-term treatment (up to 6 weeks) of erosive esophagitis due to acid-mediated GERD.
Maintenance of Healing Erosive Esophagitis: Esomeprazole is indicated to maintain symptom resolution and healing of erosive esophagitis. Controlled studies do not extend beyond 6 months.
Symptomatic Gastroesophageal Reflux Disease: Esomeprazole is indicated for short-term treatment (4 to 8 weeks) of heartburn and other symptoms associated with GERD in adults and children 1 year or older.
Risk Reduction of NSAID-Associated Gastric Ulcer: Esomeprazole is indicated for the reduction in the occurrence of gastric ulcers associated with continuous NSAID therapy in patients at risk for developing gastric ulcers. Patients are considered to be at risk due to their age (≥ 60) and/or documented history of gastric ulcers. Controlled studies do not extend beyond 6 months.
H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence: Triple Therapy (esomeprazole plus amoxicillin and clarithromycin): esomeprazole, in combination with amoxicillin and clarithromycin, is indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or history of within the past 5 years) to eradicate H. pylori. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence (see Dosage & Administration). 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.
Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome: Esomeprazole is indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison Syndrome
Dosage/Direction for Use
Esomeprazole is supplied as delayed-release capsules for oral administration or in packets for preparation of delayed-release oral suspensions. The recommended dosages are outlined in Table 1 (see Table 1). Esomeprazole should be taken at least one hour before meals.
Please refer to amoxicillin and clarithromycin prescribing information for Contraindications, Warnings, and dosing in elderly and renally-impaired patients.
The duration of proton pump inhibitor administration should be based on available safety and efficacy data specific to the defined indication and dosing frequency, as described in the prescribing information, and individual patient medical needs. Proton pump inhibitor dose of 20 kg of esomeprazole should not be exceeded.
Directions for use specific to the route and available methods of administration for these dosage forms are presented in Table 2. (See Table 2.)
The duration of proton pump inhibitor administration should be based on available safety and efficacy data specific to the defined indication and dosing frequency, as described in the prescribing information, and individual patient medical needs. Proton pump inhibitor dose of 20 kg of esomeprazole should not be exceeded.
Directions for use specific to the route and available methods of administration for these dosage forms are presented in Table 2. (See Table 2.)
Esomeprazole Delayed-Release Tablet: Esomeprazole Delayed-Release tablet should be swallowed whole.
Alternatively, for patients who have difficulty swallowing capsules, one tablespoon of applesauce can be added to an empty bowl and the esomeprazole Delayed-Release tablet can be opened, and the granules inside the capsule carefully emptied onto the applesauce. The granules should be mixed with the applesauce and then swallowed immediately: do not store for future use. The applesauce used should not be hot and should be soften enough to be swallowed without chewing. The granules should not be chewed or crushed. If the granules/applesauce mixture is not used in its entirety, the remaining mixture should be discarded immediately.
For patients who have a nasogastric tube in place, esomeprazole Delayed-Release Tablets can be opened and the intact granules emptied into a 60 mL catheter tipped syringe and mixed with 50 mL water.
Alternatively, for patients who have difficulty swallowing capsules, one tablespoon of applesauce can be added to an empty bowl and the esomeprazole Delayed-Release tablet can be opened, and the granules inside the capsule carefully emptied onto the applesauce. The granules should be mixed with the applesauce and then swallowed immediately: do not store for future use. The applesauce used should not be hot and should be soften enough to be swallowed without chewing. The granules should not be chewed or crushed. If the granules/applesauce mixture is not used in its entirety, the remaining mixture should be discarded immediately.
For patients who have a nasogastric tube in place, esomeprazole Delayed-Release Tablets can be opened and the intact granules emptied into a 60 mL catheter tipped syringe and mixed with 50 mL water.
Overdosage
A single oral dose of esomeprazole at 510 mg/kg (about 103 times the human dose on a body surface area basis), was lethal to rats. The major signs of acute toxicity were reduced motor activity, changes in respiratory frequency, tremor, ataxia, and intermittent clonic convulsions.
The symptoms described in connection with deliberate ESOMEPRAZOLE overdose (limited experience of doses in excess of 240 mg/day) are transient. Single doses of 80 mg of esomeprazole were uneventful. 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 in normal clinical experience (see omeprazole package insert - Adverse Reactions). No specific antidote for esomeprazole is known. Since esomeprazole is extensively protein bound, it is not expected to be removed in dialysis. In the event of overdosage, treatment should be symptomatic and supportive.
As with the management of any overdose, the possibility of multiple drug ingestion should be considered.
The symptoms described in connection with deliberate ESOMEPRAZOLE overdose (limited experience of doses in excess of 240 mg/day) are transient. Single doses of 80 mg of esomeprazole were uneventful. 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 in normal clinical experience (see omeprazole package insert - Adverse Reactions). No specific antidote for esomeprazole is known. Since esomeprazole is extensively protein bound, it is not expected to be removed in dialysis. In the event of overdosage, treatment should be symptomatic and supportive.
As with the management of any overdose, the possibility of multiple drug ingestion should be considered.
Administration
Should be taken on an empty stomach: Take at least 1 hr before meals. Swallow whole. For patients w/ swallowing difficulties, open tab & empty granules in 1 tbsp applesauce. Swallow mixt immediately, do not chew/crush granules. For patients w/ nasogastric tube, open tab & empty granules in 60 mL catheter tipped syringe & mix w/ 50 mL of water.
Special Precautions
Atrophic Gastritis: Atrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated tong-term with omeprazole, of which esomeprazole is an enantiomer.
Clostridium difficile associated diarrhea: Published observational studies suggest that PPI therapy like ESOMEPRAZOLE 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].
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 ESOMEPRAZOLE, refer to WARNINGS and PRECAUTIONS sections of those package inserts.
Interaction with Clopidogrel: Avoid concomitant use of ESOMEPRAZOLE with clopidogrel. Clopidogrel is a prodrug. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. The metabolism of clopidogrel to its active metabolite can be impaired by with use of concomitant medications, such as esomeprazole, that inhibit CYP2C19 activity. Concomitant use of clopidogrel with 40 mg esomeprazole, reduces the pharmacological activity of clopidogrel. When using ESOMEPRAZOLE consider alternative anti-platelet therapy [see Interactions].
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, defines 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 & Administration and Adverse Reactions].
Hypomagnesemia: Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypermagnesemia required magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically. [See Adverse Reactions.]
Concomitant use of ESOMEPRAZOLE with St. John's Wort or Rifampin: Drugs which induce CYP2C19 or CYP3A4 (such as St. John's Wort or Rifampin) can substantially decrease esomeprazole concentrations [see Interactions]. Avoid concomitant use of ESOMEPRAZOLE with St. John's Wort, or Rifampin.
Interactions with Diagnostic Investigations for Neuroendocrine Tumors: Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations.
Use in Children: The safety and effectiveness of ESOMEPRAZOLE have been established in pediatric patients 1 to 17 years of age for short-term treatment (up to eight weeks) of GERD. The safety and effectiveness of ESOMEPRAZOLE have been established in pediatric patients 1 month to less than 1 year for short-term treatment (up to 6 weeks) of erosive esophagitis due to acid-mediated GERD. However, the safety and effectiveness of ESOMEPRAZOLE have not been established in patients less than 1 month of age.
1 to 17 years of age: Use of ESOMEPRAZOLE in pediatric and adolescent patients 1 to 17 years of age for short-term treatment (up to eight weeks) of GERD is supported by extrapolation of results from adequate and well-controlled studies for adults and safety and pharmacokinetic studies performed in pediatric and adolescent patients [see Dosage & Administration and Adverse Reactions]. The safety and effectiveness of ESOMEPRAZOLE for other pediatric uses have not been established.
Erosive esophagitis due to acid-mediated GERD in infants 1 month to less than one year of age: Use of ESOMEPRAZOLE in pediatric patients 1 month to less than 1 year of age for treatment (up to 6 weeks) of erosive esophagitis due to acid-mediated GERD is supported by extrapolation of results from adequate and well-controlled studies for adults and safety, pharmacokinetic, and pharmacodynamic studies performed in pediatric patients [see Dosage & Administration and Adverse Reactions].
Symptomatic GERD in infants 1 month less than one year of age: There was no statistically significant difference between ESOMEPRAZOLE and placebo in the rate of discontinuation due to symptom worsening in a multicenter, randomized, double-blind, controlled, treatment-withdrawal study of 98 patients ages 1 to 11 months, inclusive. 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 erosive esophagitis on endoscopy at baseline. All patients received ESOMEPRAZOLE 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 ESOMEPRAZOLE 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.
The following pharmacokinetic and pharmacodynamic information was obtained in pediatric patients with GERD aged birth to less than one year of age. In infants (1 to 11 months old, inclusive) given ESOMEPRAZOLE 1 mg/kg once daily, the percent time with intragastric pH > 4 increased from 29% at baseline to 69% on Day 7, which is similar to the pharmacodynamic effect in adults. Apparent clearance (CL/F) increases with age in pediatric patients from birth to 2 years of age.
Neonates 0 to 1 month age: Following administration of oral ESOMEPRAZOLE in neonates the geometric mean (range) for the apparent clearance (CL/F) was 0.55 L/h/kg (0.25-1.6 L/h/kg).
The safety and effectiveness of ESOMEPRAZOLE in neonates have not been established.
Use in Elderly: Of the total number of patients who received ESOMEPRAZOLE in clinical trials, 1459 were 65 to 74 years of age and 354 patients were 75 years of age.
No overall differences in safety and efficacy were observed between the elderly and younger individuals, and other reported clinical experience has not identified difference in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Clostridium difficile associated diarrhea: Published observational studies suggest that PPI therapy like ESOMEPRAZOLE 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].
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 ESOMEPRAZOLE, refer to WARNINGS and PRECAUTIONS sections of those package inserts.
Interaction with Clopidogrel: Avoid concomitant use of ESOMEPRAZOLE with clopidogrel. Clopidogrel is a prodrug. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. The metabolism of clopidogrel to its active metabolite can be impaired by with use of concomitant medications, such as esomeprazole, that inhibit CYP2C19 activity. Concomitant use of clopidogrel with 40 mg esomeprazole, reduces the pharmacological activity of clopidogrel. When using ESOMEPRAZOLE consider alternative anti-platelet therapy [see Interactions].
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, defines 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 & Administration and Adverse Reactions].
Hypomagnesemia: Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypermagnesemia required magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically. [See Adverse Reactions.]
Concomitant use of ESOMEPRAZOLE with St. John's Wort or Rifampin: Drugs which induce CYP2C19 or CYP3A4 (such as St. John's Wort or Rifampin) can substantially decrease esomeprazole concentrations [see Interactions]. Avoid concomitant use of ESOMEPRAZOLE with St. John's Wort, or Rifampin.
Interactions with Diagnostic Investigations for Neuroendocrine Tumors: Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations.
Use in Children: The safety and effectiveness of ESOMEPRAZOLE have been established in pediatric patients 1 to 17 years of age for short-term treatment (up to eight weeks) of GERD. The safety and effectiveness of ESOMEPRAZOLE have been established in pediatric patients 1 month to less than 1 year for short-term treatment (up to 6 weeks) of erosive esophagitis due to acid-mediated GERD. However, the safety and effectiveness of ESOMEPRAZOLE have not been established in patients less than 1 month of age.
1 to 17 years of age: Use of ESOMEPRAZOLE in pediatric and adolescent patients 1 to 17 years of age for short-term treatment (up to eight weeks) of GERD is supported by extrapolation of results from adequate and well-controlled studies for adults and safety and pharmacokinetic studies performed in pediatric and adolescent patients [see Dosage & Administration and Adverse Reactions]. The safety and effectiveness of ESOMEPRAZOLE for other pediatric uses have not been established.
Erosive esophagitis due to acid-mediated GERD in infants 1 month to less than one year of age: Use of ESOMEPRAZOLE in pediatric patients 1 month to less than 1 year of age for treatment (up to 6 weeks) of erosive esophagitis due to acid-mediated GERD is supported by extrapolation of results from adequate and well-controlled studies for adults and safety, pharmacokinetic, and pharmacodynamic studies performed in pediatric patients [see Dosage & Administration and Adverse Reactions].
Symptomatic GERD in infants 1 month less than one year of age: There was no statistically significant difference between ESOMEPRAZOLE and placebo in the rate of discontinuation due to symptom worsening in a multicenter, randomized, double-blind, controlled, treatment-withdrawal study of 98 patients ages 1 to 11 months, inclusive. 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 erosive esophagitis on endoscopy at baseline. All patients received ESOMEPRAZOLE 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 ESOMEPRAZOLE 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.
The following pharmacokinetic and pharmacodynamic information was obtained in pediatric patients with GERD aged birth to less than one year of age. In infants (1 to 11 months old, inclusive) given ESOMEPRAZOLE 1 mg/kg once daily, the percent time with intragastric pH > 4 increased from 29% at baseline to 69% on Day 7, which is similar to the pharmacodynamic effect in adults. Apparent clearance (CL/F) increases with age in pediatric patients from birth to 2 years of age.
Neonates 0 to 1 month age: Following administration of oral ESOMEPRAZOLE in neonates the geometric mean (range) for the apparent clearance (CL/F) was 0.55 L/h/kg (0.25-1.6 L/h/kg).
The safety and effectiveness of ESOMEPRAZOLE in neonates have not been established.
Use in Elderly: Of the total number of patients who received ESOMEPRAZOLE in clinical trials, 1459 were 65 to 74 years of age and 354 patients were 75 years of age.
No overall differences in safety and efficacy were observed between the elderly and younger individuals, and other reported clinical experience has not identified difference in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Use In Pregnancy & Lactation
Pregnancy: Pregnancy Category B.
Reproductive studies in rats and rabbits with ESOMEPRAZOLE (esomeprazole) and multiple cohort studies in pregnant women with omeprazole use during the first trimester do not show an increased risk of congenital anomalies or adverse pregnancy outcomes. There are, however, no adequate and well controlled studies of ESOMEPRAZOLE use in pregnancy. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Esomeprazole is the s-isomer of omeprazole. In four population-based cohort studies that included 1226 women exposed during the first trimester of pregnancy to omeprazole there was no increased risk of congenital anomalies.
Reproductive studies with esomeprazole have been performed in rats at doses up to 57 times the human dose and in rabbits at doses up to 35 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus.
Reproductive studies conducted with omeprazole on rats at oral doses up to 56 times the human dose and in rabbits at doses up to 56 times the human dose did not show any evidence of teratogenicity. In pregnant rabbits omeprazole at doses about 5.5 to 56 times the human dose produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy loss. In rats treated with omeprazole at doses about 5.6 to 56 times the human dose, dose-related embryo/fetal toxicity and postnatal development toxicity occurred in offspring.
Nursing Mothers: Omeprazole concentrations have been measured in breast milk of one woman taking omeprazole 20 mg per day. However, the excretion of omeprazole in milk has not been studied. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for tumorigenicity shown for ESOMEPRAZOLE in rat carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue the drug taking into account the importance of the drug to the mother.
Reproductive studies in rats and rabbits with ESOMEPRAZOLE (esomeprazole) and multiple cohort studies in pregnant women with omeprazole use during the first trimester do not show an increased risk of congenital anomalies or adverse pregnancy outcomes. There are, however, no adequate and well controlled studies of ESOMEPRAZOLE use in pregnancy. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Esomeprazole is the s-isomer of omeprazole. In four population-based cohort studies that included 1226 women exposed during the first trimester of pregnancy to omeprazole there was no increased risk of congenital anomalies.
Reproductive studies with esomeprazole have been performed in rats at doses up to 57 times the human dose and in rabbits at doses up to 35 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus.
Reproductive studies conducted with omeprazole on rats at oral doses up to 56 times the human dose and in rabbits at doses up to 56 times the human dose did not show any evidence of teratogenicity. In pregnant rabbits omeprazole at doses about 5.5 to 56 times the human dose produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy loss. In rats treated with omeprazole at doses about 5.6 to 56 times the human dose, dose-related embryo/fetal toxicity and postnatal development toxicity occurred in offspring.
Nursing Mothers: Omeprazole concentrations have been measured in breast milk of one woman taking omeprazole 20 mg per day. However, the excretion of omeprazole in milk has not been studied. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for tumorigenicity shown for ESOMEPRAZOLE in rat carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue the drug taking into account the importance of the drug to the mother.
Adverse Reactions
Postmarketing Experience: The following adverse reactions have been identified during post-approval use of ESOMEPRAZOLE. Because these reactions are reported voluntary from a population of uncertain size. It is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reports are listed as follows by body system.
Blood And Lymphatic: agranulocytosis pancytopenia.
Eye: Blurred vision.
Gastrointestinal: pancreatitis; stomatitis; microscopic colitis.
Hepatobiliary: hepatic failure, hepatitis with or without jaundice.
Immune System: anaphylactic reaction/shock.
Infections and Infestations: GI candidiasis; Clostridium difficile associated diarrhea.
Metabolism and nutritional disorders: hypomagnesemia.
Musculoskeletal and Connective Tissue: muscular weakness, myalgia, bone fracture.
Nervous System: hepatic encephalopathy, taste disturbance.
Psychiatric: aggression agitation, depression hallucination.
Renal and Urinary: interstitial nephritis.
Reproductive System and Breast: gynecomastia.
Respiratory, Thoracic, and Mediastinal: bronchospasm.
Skin and Subcutaneous Tissue: alopecia, erythema multiforme, hyperhidrosis, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal).
Seek medical attention immediately at the first sign of any adverse drug reaction.
Blood And Lymphatic: agranulocytosis pancytopenia.
Eye: Blurred vision.
Gastrointestinal: pancreatitis; stomatitis; microscopic colitis.
Hepatobiliary: hepatic failure, hepatitis with or without jaundice.
Immune System: anaphylactic reaction/shock.
Infections and Infestations: GI candidiasis; Clostridium difficile associated diarrhea.
Metabolism and nutritional disorders: hypomagnesemia.
Musculoskeletal and Connective Tissue: muscular weakness, myalgia, bone fracture.
Nervous System: hepatic encephalopathy, taste disturbance.
Psychiatric: aggression agitation, depression hallucination.
Renal and Urinary: interstitial nephritis.
Reproductive System and Breast: gynecomastia.
Respiratory, Thoracic, and Mediastinal: bronchospasm.
Skin and Subcutaneous Tissue: alopecia, erythema multiforme, hyperhidrosis, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal).
Seek medical attention immediately at the first sign of any adverse drug reaction.
Drug Interactions
Interference with Antiretroviral Therapy: Concomitant use of atazanavir and nelfinavir with proton pump inhibitors is not recommended. Co-administration of atazanavir with proton pump inhibitors is expected to substantially decrease atazanavir plasma concentrations and may result in a loss of therapeutic effect and the development of drug resistance. Co-administration of saquinavir with proton pump inhibitors is expected to increase saquinavir concentrations, which may increase toxicity and require dose reduction.
Omeprazole of which esomeprazole is an enantiomer, has been reported to interact with some antiretroviral drugs. The clinical importance and the mechanisms behind these interactions are not always known. Increased gastric pH during omeprazole treatment may change the absorption of the antiretroviral drug. Other possible interaction mechanisms are via CYP 2C19.
Reduced concentrations of atazanavir and nelfinavir: For some antiretroviral drugs, such as atazanavir and nelfinavir decreased serum levels have been reported when given together with omeprazole.
Increased concentrations of saquinavir: For other antiretroviral drugs, such as saquinavir elevated serum levels have been reported. There are also some antiretroviral drugs of which unchanged serum level have been reported when given with omeprazole.
Drugs for Which Gastric pH Can Affect Bioavailability: Esomeprazole inhibits gastric acid secretion. Therefore, esomeprazole may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability. Like with other drugs that decrease the intragastric acidity, the absorption of drugs such as ketoconazole, atazanavir, iron salts, and erlotinib can decrease, while the absorption of drugs such as digoxin can increase during treatment with esomeprazole.
Effects on Hepatic Metabolism/Cytochrome P-450 Pathways: Esomeprazole is extensively metabolized in the liver by CYP 2C19 and CYP 3A4. Drug interaction studies have shown that esomeprazole does not have any clinically significant interactions with phenytoin, warfarin, quinidine, clarithromycin or amoxicillin. However, post-marketing reports of changes in prothrombin measures have been received among patients on concomitant warfarin and esomeprazole therapy. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time.
Esomeprazole may potentially interfere with CYP 2C19, the major esomeprazole metabolizing enzyme. Coadministration of esomeprazole 30 mg and diazepam, A CYP 2C19 substrate, resulted in a 45% decrease in clearance of diazepam.
Clopidogrel: Clopidogrel is metabolized to its active metabolite in part by CYP2C19. Concomitant use of esomeprazole 40 mg results in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction of platelet inhibition. Avoid concomitant administration of ESOMEPRAZOLE with clopidogrel. When using ESOMEPRAZOLE, consider use of alternative anti-platelet therapy.
Co-administration of cilostazol with esomeprazole is expected to increase concentrations of cilostazol and it's previously mentioned active metabolite. Therefore a dose reduction of cilostazol from 100 mg twice daily to 50 mg twice daily should be considered.
Interactions with Investigations of Neuroendocrine Tumors: Drug-induced decrease in gastric acidity results in enterochromaffin-like cell hyperplasia and increased Chromogranin A levels which may interfere with investigations for neuroendocrine tumors [see Precautions].
Tacrolimus: Concomitant administration of esomeprazole and tacrolimus may increase the serum levels of tacrolimus.
Combination Therapy with Clarithromycin: Co-administration of esomeprazole, clarithromycin, and amoxicillin has resulted in increases in the plasma levels of esomeprazole and 14-hydroxyclarithromycin.
Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions due to drug interactions [see Precautions in prescribing information for clarithromycin]. Because of these drug interactions, clarithromycin is contraindicated for co-administration with certain drugs [see Contraindications in prescribing information for clarithromycin].
Methotrexate: Case reports, published population pharmacokinetic studies, and retrospective analysis suggest that concomitant administration of PPIs and methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate. However, no formal drug interaction studies of methotrexate with PPIs have been conducted [see Precautions].
Omeprazole of which esomeprazole is an enantiomer, has been reported to interact with some antiretroviral drugs. The clinical importance and the mechanisms behind these interactions are not always known. Increased gastric pH during omeprazole treatment may change the absorption of the antiretroviral drug. Other possible interaction mechanisms are via CYP 2C19.
Reduced concentrations of atazanavir and nelfinavir: For some antiretroviral drugs, such as atazanavir and nelfinavir decreased serum levels have been reported when given together with omeprazole.
Increased concentrations of saquinavir: For other antiretroviral drugs, such as saquinavir elevated serum levels have been reported. There are also some antiretroviral drugs of which unchanged serum level have been reported when given with omeprazole.
Drugs for Which Gastric pH Can Affect Bioavailability: Esomeprazole inhibits gastric acid secretion. Therefore, esomeprazole may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability. Like with other drugs that decrease the intragastric acidity, the absorption of drugs such as ketoconazole, atazanavir, iron salts, and erlotinib can decrease, while the absorption of drugs such as digoxin can increase during treatment with esomeprazole.
Effects on Hepatic Metabolism/Cytochrome P-450 Pathways: Esomeprazole is extensively metabolized in the liver by CYP 2C19 and CYP 3A4. Drug interaction studies have shown that esomeprazole does not have any clinically significant interactions with phenytoin, warfarin, quinidine, clarithromycin or amoxicillin. However, post-marketing reports of changes in prothrombin measures have been received among patients on concomitant warfarin and esomeprazole therapy. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time.
Esomeprazole may potentially interfere with CYP 2C19, the major esomeprazole metabolizing enzyme. Coadministration of esomeprazole 30 mg and diazepam, A CYP 2C19 substrate, resulted in a 45% decrease in clearance of diazepam.
Clopidogrel: Clopidogrel is metabolized to its active metabolite in part by CYP2C19. Concomitant use of esomeprazole 40 mg results in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction of platelet inhibition. Avoid concomitant administration of ESOMEPRAZOLE with clopidogrel. When using ESOMEPRAZOLE, consider use of alternative anti-platelet therapy.
Co-administration of cilostazol with esomeprazole is expected to increase concentrations of cilostazol and it's previously mentioned active metabolite. Therefore a dose reduction of cilostazol from 100 mg twice daily to 50 mg twice daily should be considered.
Interactions with Investigations of Neuroendocrine Tumors: Drug-induced decrease in gastric acidity results in enterochromaffin-like cell hyperplasia and increased Chromogranin A levels which may interfere with investigations for neuroendocrine tumors [see Precautions].
Tacrolimus: Concomitant administration of esomeprazole and tacrolimus may increase the serum levels of tacrolimus.
Combination Therapy with Clarithromycin: Co-administration of esomeprazole, clarithromycin, and amoxicillin has resulted in increases in the plasma levels of esomeprazole and 14-hydroxyclarithromycin.
Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions due to drug interactions [see Precautions in prescribing information for clarithromycin]. Because of these drug interactions, clarithromycin is contraindicated for co-administration with certain drugs [see Contraindications in prescribing information for clarithromycin].
Methotrexate: Case reports, published population pharmacokinetic studies, and retrospective analysis suggest that concomitant administration of PPIs and methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate. However, no formal drug interaction studies of methotrexate with PPIs have been conducted [see Precautions].
Storage
Store at temperatures not exceeding 30°C.
Shelf Life: 24 months.
Shelf Life: 24 months.
Action
Pharmacology: Pharmacokinetics: Esomeprazole is rapidly absorbed after oral doses, with peak plasma levels occurring about 1 to 2 hours. It is acid labile and an enteric coated formulation has been developed. Bioavailability of Esomeprazole increases with both dose and repeated administration to about 60 and 89% for doses for 20 mg and 40 mg respectively. Food delays and decreases the absorption of esomeprazole, but this does not significantly change its effect on intragastric acidity. Esomeprazole is about 97% bound to plasma proteins. It is extensively metabolized in the liver by the cytochrome P450 isoenzyme CYP2C19 to hydroxyl and desmethyl metabolites, which have no effect on gastric acid secretion. The remainder is metabolized by the cytochrome P450 isoenzyme CYP3A4 to esomeprazole sulfone. With repeated dosage, there is a decrease in first pass metabolism and systemic clearance, probably caused by an inhibition of the CYP2C19 isoenzyme. However there is no accumulation during once daily use. The plasma elimination half-life is about 1.3 hours. Almost 80% of an oral dose is eliminated as metabolites in the urine, the remainder of the feces.
Metabolism: As for Esomeprazole the cytochrome isoenzyme CYP2C19 is involved in the metabolism of esomeprazole, and individuals who are deficient in this enzyme are poor metabolisers of esomeprazole. However, there is some suggestion that the metabolism of esomeprazole is less dependent on this genotype, as there may be a metabolic shift towards the CYP3A4 mediated pathway.
Metabolism: As for Esomeprazole the cytochrome isoenzyme CYP2C19 is involved in the metabolism of esomeprazole, and individuals who are deficient in this enzyme are poor metabolisers of esomeprazole. However, there is some suggestion that the metabolism of esomeprazole is less dependent on this genotype, as there may be a metabolic shift towards the CYP3A4 mediated pathway.
MedsGo Class
Antacids, Antireflux Agents & Antiulcerants
Features
Brand
Esoget
Full Details
Dosage Strength
40mg
Drug Ingredients
- Esomeprazole
Drug Packaging
Delayed-Release Tablet 1's
Generic Name
Esomeprazole Magnesium
Dosage Form
Delayed-Release Tablet
Registration Number
DRP-6336
Drug Classification
Prescription Drug (RX)