Esomeprazole

(es oh me' pray zol)

PCaution when used during lactation / LCaution when used during lactation : Caution - pregnancy &  lactation (breast feeding)

Molecule Info

| See TERMINOLOGY & ABBREVIATIONS |
Indication(s)

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 of 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.

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 & Administration

Esomeprazole may be 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. Esomeprazole should be taken at least one hour before meals.

Table 1: Recommended Dosage Schedule of Esomeprazole

INDICATION DOSE FREQUENCY
Gastroesophageal Reflux Disease (GERD)
  Healing of Erosive Esophagitis 20 mg or 40 mg Once Daily for 4 to 8 Weeks*
  Maintenance of Healing of Erosive Esophagitis 20 mg Once Daily**
  Symptomatic Gastroesophageal Reflux Disease 20 mg Once Daily for 4 Weeks***
Pediatric GERD
12 to 17 Year Olds
Healing of Erosive Esophagitis 20 mg or 40 mg Once Daily for 4 to 8 Weeks
Symptomatic GERD 20 mg Once Daily for 4 Weeks
1 to 11 Year Olds+ Short-term Treatment of Symptomatic GERD 10 mg Once Daily for up to 8 Weeks
Healing of Erosive Esophagitis    
  weight < 20 kg 10 mg Once Daily for 8 Weeks
  weight ≥ 20 kg 10 mg or 20 mg Once Daily for 8 Weeks
1 month to < 1 year old ‡‡
Erosive esophagitis due to acid-mediated GERD
weight 3 kg to 5 kg 2.5 mg Once Daily for up to 6 Weeks
weight > 5 kg to 7.5 kg 5 mg Once Daily for up to 6 Weeks
weight > 7.5 kg to 12 kg 10 mg Once Daily for up to 6 Weeks
Risk Reduction of NSAID-Associated Gastric Ulcer 20 mg or 40 mg Once Daily for up to 6 months**
H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence Triple Therapy:
Esomeprazole 40 mg Once Daily for 10 Days
Amoxicillin 1000 mg Twice Daily for 10 Days
Clarithromycin 500 mg Twice Daily for 10 Days
Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome 40 mg† ‡Twice Daily
*The majority of 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 considered.
**Controlled studies did not extend beyond six months.
***If symptoms do not resolve completely after 4 weeks, an additional 4 weeks of treatment may be considered.
+Doses over 1 mg/kg/day have not been studied.
†The dosage of Esomeprazole in patients with pathological hypersecretory conditions varies with the individual patient. Dosage regimens should be adjusted to individual patient needs.
‡Doses up to 240 mg daily have been administered.
‡‡Doses over 1.33 mg/kg/day have not been studied.

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 treatment should only be initiated and continued if the benefits outweigh the risks of treatment. Please refer to amoxicillin and clarithromycin prescribing information for Contraindications, Warnings, and dosing in elderly and renally-impaired patients.

Special Populations

Hepatic Insufficiency

In patients with mild to moderate liver impairment (Child Pugh Classes A and B), no dosage adjustment is necessary. For patients with severe liver impairment (Child Pugh Class C), a dose of 20 mg of Esomeprazole should not be exceeded.

Directions for use specific to the route and available methods of administration for each of these dosage forms are presented in Table 2.

Table 2: Administration Options

DOSAGE FORM ROUTE OPTIONS
Delayed-Release Capsules Oral Capsule can be swallowed whole. -or- Capsule can be opened and mixed with applesauce.
Delayed-Release Capsules Nasogastric Tube Capsule can be opened and the intact granules emptied into a syringe and delivered through the nasogastric tube.
For Delayed-Release Oral Suspension Oral For the 2.5 mg and 5 mg strengths, mix the contents of packet with 5 mL of water, leave 2 to 3 minutes to thicken, stir and drink within 30 minutes. 
For the 10 mg, 20 mg and 40 mg strengths, mix contents of packet with 15 mL of water, and follow the instructions above.
For Delayed-Release Oral Suspension Nasogastric or Gastric Tube For the 2.5 mg and 5 mg strengths, add 5 mL of water to a syringe and then add contents of packet. Shake the syringe; leave 2 to 3 minutes to thicken. Shake the syringe and inject through the nasogastric or gastric tube within 30 minutes. 
For the 10 mg, 20 mg and 40 mg strengths, add 15 mL of water, and follow the instructions above.

 

Esomeprazole Delayed-Release Capsule

Esomeprazole Delayed-Release Capsules 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 Capsule 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 soft 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 Capsules can be opened and the intact granules emptied into a 60 mL catheter tipped syringe and mixed with 50 mL of water. It is important to only use a catheter tipped syringe when administering Esomeprazole through a nasogastric tube. Replace the plunger and shake the syringe vigorously for 15 seconds. Hold the syringe with the tip up and check for granules remaining in the tip. Attach the syringe to a nasogastric tube and deliver the contents of the syringe through the nasogastric tube into the stomach. After administering the granules, the nasogastric tube should be flushed with additional water. Do not administer the granules if they have dissolved or disintegrated.

The mixture must be used immediately after preparation.

Esomeprazole For Delayed-Release Oral Suspension

Esomeprazole For Delayed-Release Oral Suspension should be administered as follows:

  • Empty the contents of a 2.5 mg or 5 mg packet into a container containing 5 mL of water. For the 10 mg, 20 mg, and 40 mg strengths, the contents of a packet should be emptied into a container containing 15 mL of water.
  • Stir.
  • Leave 2 to 3 minutes to thicken.
  • Stir and drink within 30 minutes.
  • If any medicine remains after drinking, add more water, stir, and drink immediately.
  • In cases where there is a need to use two packets, they may be mixed in a similar way by adding twice the required amount of water or follow the mixing instructions provided by your pharmacist or doctor.

For patients who have a nasogastric or gastric tube in place, Esomeprazole For Delayed-Release Oral Suspension can be administered as follows:

  • Add 5 mL of water to a catheter tipped syringe and then add the contents of a 2.5 mg or 5 mg Esomeprazole packet. For the 10 mg, 20 mg, and 40 mg strengths, the volume of water in the syringe should be 15 mL. It is important to only use a catheter tipped syringe when administering Esomeprazole through a nasogastric tube or gastric tube.
  • Immediately shake the syringe and leave 2 to 3 minutes to thicken.
  • Shake the syringe and inject through the nasogastric or gastric tube, French size 6 or larger, into the stomach within 30 minutes.
  • Refill the syringe with an equal amount of water (5 mL or 15 mL).
  • Shake and flush any remaining contents from the nasogastric or gastric tube into the stomach.

 

Contraindication(s)
Hypersensitivity.
Precaution(s)

Concurrent Gastric Malignancy

Symptomatic response to therapy with Esomeprazole does not preclude the presence of gastric malignancy.

Atrophic Gastritis

Atrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated long-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.

Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.

Clostridium diffficile 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.

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 use with 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.

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.

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 hypomagnesemia 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.

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 DRUG 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 for neuroendocrine tumors. Providers should temporarily stop esomeprazole treatment before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary.

Concomitant use of Esomeprazole with Methotrexate

Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration a temporary withdrawal of the PPI may be considered in some patients.

Adverse Drug Reaction(s)

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 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 6-12 months. In general, Esomeprazole was well tolerated in both short and long-term clinical trials.

The safety in the treatment of healing of erosive esophagitis was assessed in four randomized comparative clinical trials, which included 1,240 patients on Esomeprazole 20 mg, 2,434 patients on Esomeprazole 40 mg, and 3,008 patients on omeprazole 20 mg daily. The most frequently occurring adverse reactions ( ≥ 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 or omeprazole.

Additional adverse reactions that were reported as possibly or probably related to Esomeprazole with an incidence < 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.

Pediatrics

The safety of Esomeprazole was evaluated in 316 pediatric and adolescent patients aged 1 to 17 years in four clinical trials for the treatment of symptomatic GERD. In 109 pediatric patients aged 1 to 11 years, the most frequently reported (at least 1%) treatment-related adverse reactions in these patients were diarrhea (2.8%), headache (1.9%) and somnolence (1.9%). In 149 pediatric patients aged 12 to 17 years the most frequently reported (at least 2%) treatment-related adverse reactions in these patients were headache (8.1%), abdominal pain (2.7%), diarrhea (2%), and nausea (2%).

The safety of Esomeprazole was evaluated in 167 pediatric patients from birth to < 1 year of age in three clinical trials. In a study that included 26 pediatric patients aged birth to 1 month there were no treatment related adverse reactions. In a study that included 43 pediatric patients age 1 to 11 months, inclusive the most frequently reported (at least 5%) adverse reactions, irrespective of causality, were irritability and vomiting. In a study that included 98 pediatric patients, age 1 to 11 months, inclusive exposed to esomeprazole for up to 6 weeks (including 39 patients randomized to the withdrawal phase), there were 4 treatment-related adverse reactions: abdominal pain (1%), regurgitation (1%), tachypnea (1%), and increased ALT (1%).

No new safety concerns were identified in pediatric patients.

Combination Treatment with Amoxicillin and Clarithromycin

In clinical trials using combination therapy with Esomeprazole plus amoxicillin and clarithromycin, no additional adverse reactions specific to these drug combinations were observed. Adverse reactions that occurred were limited to those observed when using Esomeprazole, amoxicillin, or clarithromycin alone.

The most frequently reported drug-related adverse reactions for patients who received triple therapy for 10 days were diarrhea (9.2%), taste perversion (6.6%), and abdominal pain (3.7%). No treatment-emergent adverse reactions were observed at higher rates with triple therapy than were observed with Esomeprazole alone.

For more information on adverse reactions with amoxicillin or clarithromycin, refer to their package inserts, Adverse Reactions sections.

In clinical trials using combination therapy with Esomeprazole plus amoxicillin and clarithromycin, no additional increased laboratory abnormalities particular to these drug combinations were observed.

For more information on clinical trial responses please see 'Brand Manufacturer's Detailed Prescribing Information'.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Esomeprazole. Because these reactions are reported voluntarily 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 below 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 candidiasisClostridium 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 cases reported).

Drug Interaction(s) & Lab interferene:

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. Following multiple doses of nelfinavir (1250 mg, twice daily) and omeprazole (40 mg daily), AUC was decreased by 36% and 92%, Cmax by 37% and 89% and Cmin by 39% and 75% respectively for nelfinavir and M8. Following multiple doses of atazanavir (400 mg, daily) and omeprazole (40 mg, daily, 2 hr before atazanavir), AUC was decreased by 94%, Cmax by 96%, and Cmin by 95%. Concomitant administration with omeprazole and drugs such as atazanavir and nelfinavir is therefore not recommended.

Increased concentrations of saquinavir

For other antiretroviral drugs, such as saquinavir, elevated serum levels have been reported, with an increase in AUC by 82%, in Cmax by 75%, and in Cmin by 106%, following multiple dosing of saquinavir/ritonavir (1000/100 mg) twice daily for 15 days with omeprazole 40 mg daily co-administered days 11 to 15. Therefore, clinical and laboratory monitoring for saquinavir toxicity is recommended during concurrent use with Esomeprazole. Dose reduction of saquinavir should be considered from the safety perspective for individual patients.

There are also some antiretroviral drugs of which unchanged serum levels 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. Concomitant treatment with omeprazole (20 mg daily) and digoxin in healthy subjects increased the bioavailability of digoxin by 10% (30% in two subjects). Esomeprazole is an enantiomer of omeprazole. Coadministration of digoxin with esomeprazole is expected to increase the systemic exposure of digoxin. Therefore, patients may need to be monitored when digoxin is taken concomitantly with esomeprazole.

Effects on Hepatic Metabolism/Cytochrome P-450 Pathways

Esomeprazole is extensively metabolized in the liver by CYP 2C19 and CYP 3A4.

 and in vivo studies have shown that esomeprazole is not likely to inhibit CYPs 1A2, 2A6, 2C9, 2D6, 2E1, and 3A4. No clinically relevant interactions with drugs metabolized by these CYP enzymes would be expected. 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 in platelet inhibition. Avoid concomitant administration of Esomeprazole with clopidogrel. When using Esomeprazole, consider use of alternative anti-platelet therapy [see Pharmacokinetics].

Omeprazole acts as an inhibitor of CYP 2C19. Omeprazole, given in doses of 40 mg daily for one week to 20 healthy subjects in cross-over study, increased Cmax and AUC of cilostazol by 18% and 26% respectively. Cmax and AUC of one of its active metabolites, 3,4-dihydrocilostazol, which has 4-7 times the activity of cilostazol, were increased by 29% and 69% respectively. Co-administration of cilostazol with esomeprazole is expected to increase concentrations of cilostazol and its above mentioned active metabolite. Therefore a dose reduction of cilostazol from 100 mg twice daily to 50 mg twice daily should be considered.

Concomitant administration of esomeprazole and a combined inhibitor of CYP 2C19 and CYP 3A4, such as voriconazole, may result in more than doubling of the esomeprazole exposure. Dose adjustment of esomeprazole is not normally required. However, in patients with Zollinger-Ellison's Syndrome, who may require higher doses up to 240 mg/day, dose adjustment may be considered.

Drugs known to induce CYP2C19 or CYP3A4 or both (such as rifampin) may lead to decreased esomeprazole serum levels. Omeprazole, of which esomeprazole is an enantiomer, has been reported to interact with St. John's wort an inducer of CYP3A4. In a cross-over study in 12 healthy male subjects, St John's wort (300 mg three times daily for 14 days) significantly decreased the systemic exposure of omeprazole in CYP2C19 poor metabolisers (Cmax and AUC decreased by 37.5% and 37.9%, respectively) and extensive metabolisers (Cmax and AUC decreased by 49.6 % and 43.9%, respectively). Avoid concomitant use of St. John's Wort or rifampin with Esomeprazole.

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.

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. Because of these drug interactions, clarithromycin is contraindicated for co-administration with certain drugs.

Methotrexate

Case reports, published population pharmacokinetic studies, and retrospective analyses 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.

Absorption delayed with food.

Lab interferene: Increased creatinine, uric acid, bilirubin, alkaline phosphatase, ALT, AST. Altered thyroid function tests.

Pregnancy Category (FDA) and use in Specific Population

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, doserelated embryo/fetal toxicity and postnatal developmental 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 esomeprazole 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.

Pediatric Use

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. 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.

Symptomatic GERD in infants 1 month to 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 1mg/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 of 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.

Geriatric Use

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 differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Pharmacology

Mechanism of Action

Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. The S- and R-isomers of omeprazole are protonated and converted in the acidic compartment of the parietal cell forming the active inhibitor, the achiral sulphenamide. By acting specifically on the proton pump, esomeprazole blocks the final step in acid production, thus reducing gastric acidity. This effect is dose-related up to a daily dose of 20 to 40 mg and leads to inhibition of gastric acid secretion.

Pharmacodynamics

Antisecretory Activity

The effect of Esomeprazole on intragastric pH was determined in patients with symptomatic gastroesophageal reflux disease in two separate studies. In the first study of 36 patients, Esomeprazole 40 mg and 20 mg capsules were administered over 5 days. 

In a second study, the effect on intragastric pH of Esomeprazole 40 mg administered once daily over a five day period was similar to the first study, (% time with pH > 4 was 68% or 16.3 hours).

Serum Gastrin Effects

The effect of Esomeprazole on serum gastrin concentrations was evaluated in approximately 2,700 patients in clinical trials up to 8 weeks and in over 1,300 patients for up to 6 to 12 months. The mean fasting gastrin level increased in a dose-related manner. This increase reached a plateau within two to three months of therapy and returned to baseline levels within four weeks after discontinuation of therapy.

Increased gastrin causes enterochromaffin-like cell hyperplasia and increased serum Chromogranin A (CgA) levels. The increased CgA levels may cause false positive results in diagnostic investigations for neuroendocrine tumors.

Enterochromaffin-like (ECL) Cell Effects

In 24-month carcinogenicity studies of omeprazole in rats, a dose-related significant occurrence of gastric ECL cell carcinoid tumors and ECL cell hyperplasia was observed in both male and female animals [see Nonclinical Toxicology]. Carcinoid tumors have also been observed in rats subjected to fundectomy or long-term treatment with other proton pump inhibitors or high doses of H2-receptor antagonists.

Human gastric biopsy specimens have been obtained from more than 3,000 patients treated with omeprazole in long-term clinical trials. The incidence of ECL cell hyperplasia in these studies increased with time; however, no case of ECL cell carcinoids, dysplasia, or neoplasia has been found in these patients.

In over 1,000 patients treated with Esomeprazole (10, 20 or 40 mg/day) up to 6 to 12 months, the prevalence of ECL cell hyperplasia increased with time and dose. No patient developed ECL cell carcinoids, dysplasia, or neoplasia in the gastric mucosa.

Endocrine Effects

Esomeprazole had no effect on thyroid function when given in oral doses of 20 or 40 mg for 4 weeks. Other effects of Esomeprazole on the endocrine system were assessed using omeprazole studies. Omeprazole given in oral doses of 30 or 40 mg for 2 to 4 weeks had no effect on carbohydrate  , circulating levels ofparathyroid hormone, cortisol, estradiol, testosterone, prolactin,cholecystokinin, or secretin.

Pharmacokinetics

Absorption

Esomeprazole Delayed-Release Capsules and Esomeprazole For Delayed-Release Oral Suspension contain a bioequivalent enteric-coated granule formulation of esomeprazole magnesium. Bioequivalency is based on a single dose (40 mg) study in 94 healthy male and female volunteers under fasting condition. After oral administration peak plasma levels (Cmax) occur at approximately 1.5 hours (Tmax). The Cmax increases proportionally when the dose is increased, and there is a three-fold increase in the area under the plasma concentration-time curve (AUC) from 20 to 40 mg. At repeated once-daily dosing with 40 mg, the systemic bioavailability is approximately 90% compared to 64% after a single dose of 40 mg. The mean exposure (AUC) to esomeprazole increases from 4.32 μmol*hr/L on Day 1 to 11.2 μmol*hr/L on Day 5 after 40 mg once daily dosing.

The AUC after administration of a single 40 mg dose of Esomeprazole is decreased by 43% to 53% after food intake compared to fasting conditions. Esomeprazole should be taken at least one hour before meals.

The pharmacokinetic profile of Esomeprazole was determined in 36 patients with symptomatic gastroesophageal reflux disease following repeated once daily administration of 20 mg and 40 mg capsules of Esomeprazole over a period of five days.  

Distribution

Esomeprazole is 97% bound to plasma proteins. Plasma protein binding is constant over the concentration range of 2 to 20 μmol/L. The apparent volume of distribution at steady state in healthy volunteers is approximately 16 L.

Metabolism

Esomeprazole is extensively metabolized in the liver by the cytochrome P450 (CYP) enzyme system. The metabolites of esomeprazole lack antisecretory activity. The major part of esomeprazole's metabolism is dependent upon the CYP 2C19 isoenzyme, which forms the hydroxy and desmethyl metabolites. The remaining amount is dependent on CYP 3A4 which forms the sulphone metabolite. CYP 2C19 isoenzyme exhibits polymorphism in the metabolism of esomeprazole, since some 3% of Caucasians and 15 to 20% of Asians lack CYP 2C19 and are termed Poor Metabolizers. At steady state, the ratio of AUC in Poor Metabolizers to AUC in the rest of the population (Extensive Metabolizers) is approximately 2.

Following administration of equimolar doses, the S- and R-isomers are metabolized differently by the liver, resulting in higher plasma levels of the S- than of the R-isomer.

Excretion

The plasma elimination half-life of esomeprazole is approximately 1 to 1.5 hours. Less than 1% of parent drug is excreted in the urine. Approximately 80% of an oral dose of esomeprazole is excreted as inactive metabolites in the urine, and the remainder is found as inactive metabolites in the feces.

Pharmacokinetics: Combination Therapy with Antimicrobials

Esomeprazole magnesium 40 mg once daily was given in combination with clarithromycin 500 mg twice daily and amoxicillin 1000 mg twice daily for 7 days to 17 healthy male and female subjects. The mean steady state AUC and Cmax of esomeprazole increased by 70% and 18%, respectively during triple combination therapy compared to treatment with esomeprazole alone. The observed increase in esomeprazole exposure during coadministration with clarithromycin and amoxicillin is not expected to produce significant safety concerns.

The pharmacokinetic parameters for clarithromycin and amoxicillin were similar during triple combination therapy and administration of each drug alone. However, the mean AUC and Cmax for 14-hydroxyclarithromycin increased by 19% and 22%, respectively, during triple combination therapy compared to treatment with clarithromycin alone. This increase in exposure to 14-hydroxyclarithromycin is not considered to be clinically significant.

Concomitant Use with Clopidogrel

Results from a crossover study in healthy subjects have shown a pharmacokinetic interaction between clopidogrel (300 mg loading dose/75 mg daily maintenance dose) and esomeprazole (40 mg p.o. once daily) when co-administered for 30 days. Exposure to the active metabolite of clopidogrel was reduced by 35% to 40% over this time period. Pharmacodynamic parameters were also measured and demonstrated that the change in inhibition of platelet aggregation was related to the change in the exposure to clopidogrel active metabolite.

Special Populations

Geriatric

The AUC and Cmax values were slightly higher (25% and 18%, respectively) in the elderly as compared to younger subjects at steady state. Dosage adjustment based on age is not necessary.

Pediatric (1 to 11 month of age)

The pharmacokinetic parameters following repeated dose administration of 1.0 mg/kg esomeprazole in 1 to 11 month old infants also studied.

Subsequent pharmacokinetic simulation analyses showed that a dosage regimen of 2.5 mg once-daily for pediatric patients with body weight 3-5 kg, 5.0 mg once-daily for > 5 to 7.5 kg and 10 mg once-daily for > 7.5 to 12 kg would achieve comparable steady-state plasma exposures (AUC) to that observed after 10 mg in 1 to 11 year olds, and 20 mg in 12 to 18 year-olds as well as adults.

1 to 11 Years of Age

The pharmacokinetics of esomeprazole were studied in pediatric patients with GERD aged 1 to 11 years. Following once daily dosing for 5 days, the total exposure (AUC) for the 10 mg dose in patients aged 6 to 11 years was similar to that seen with the 20 mg dose in adults and adolescents aged 12 to 17 years. The total exposure for the 10 mg dose in patients aged 1 to 5 years was approximately 30% higher than the 10 mg dose in patients aged 6 to 11 years. The total exposure for the 20 mg dose in patients aged 6 to 11 years was higher than that observed with the 20 mg dose in 12 to 17 year-olds and adults, but lower than that observed with the 40 mg dose in 12 to 17 year-olds and adults.

12 to 17 Years of Age

The pharmacokinetics of Esomeprazole were studied in 28 adolescent patients with GERD aged 12 to 17 years inclusive, in a single center study. Patients were randomized to receive Esomeprazole 20 mg or 40 mg once daily for 8 days. Mean Cmax and AUC values of esomeprazole were not affected by body weight or age; and more than dose-proportional increases in mean Cmax and AUC values were observed between the two dose groups in the study. Overall, Esomeprazole pharmacokinetics in adolescent patients aged 12 to 17 years were similar to those observed in adult patients with symptomatic GERD. 

Gender

The AUC and Cmax values were slightly higher (13%) in females than in males at steady state. Dosage adjustment based on gender is not necessary.

Hepatic Insufficiency

The steady state pharmacokinetics of esomeprazole obtained after administration of 40 mg once daily to 4 patients each with mild (Child Pugh A), moderate (Child Pugh Class B), and severe (Child Pugh Class C) liver insufficiency were compared to those obtained in 36 male and female GERD patients with normal liver function. In patients with mild and moderate hepatic insufficiency, the AUCs were within the range that could be expected in patients with normal liver function. In patients with severe hepatic insufficiency the AUCs were 2 to 3 times higher than in the patients with normal liver function. No dosage adjustment is recommended for patients with mild to moderate hepatic insufficiency (Child Pugh Classes A and B). However, in patients with severe hepatic insufficiency (Child Pugh Class C) a dose of 20 mg once daily should not be exceeded.

Renal Insufficiency

The pharmacokinetics of Esomeprazole in patients with renal impairment are not expected to be altered relative to healthy volunteers as less than 1% of esomeprazole is excreted unchanged in urine.

Other pharmacokinetic observations

Coadministration of oral contraceptives, diazepam, phenytoin, or quinidine did not seem to change the pharmacokinetic profile of esomeprazole.

Studies evaluating concomitant administration of esomeprazole and either naproxen (nonselective NSAID) or rofecoxib (COX-2 selective NSAID) did not identify any clinically relevant changes in the pharmacokinetic profiles of esomeprazole or these NSAIDs.

Microbiology

Esomeprazole, amoxicillin, and clarithromycin triple therapy has been shown to be active against most strains of Helicobacter pylori (H. pyloriin vitro and in clinical infections.

Helicobacter pylori: Susceptibility testing of H. pylori isolates was performed for amoxicillin and clarithromycin using agar dilution methodology, and minimum inhibitory concentrations (MICs) were determined.

Pretreatment Resistance: Clarithromycin pretreatment resistance rate (MIC ≥ 1 mcg/mL) to H. pylori was 15% (66/445) at baseline in all treatment groups combined. A total of > 99% (394/395) of patients had H. pyloriisolates that were considered to be susceptible (MIC < 0.25 mcg/mL) to amoxicillin at baseline. One patient had a baseline H. pylori isolate with an amoxicillin MIC = 0.5 mcg/mL.

Patients not eradicated of H. pylori following Esomeprazole/amoxicillin/clarithromycin triple therapy will likely have clarithromycin resistant H. pylori isolates. Therefore, clarithromycin susceptibility testing should be done, when possible. Patients with clarithromycin resistant H. pylori should not be re-treated with a clarithromycin-containing regimen.

Amoxicillin Susceptibility Test Results and Clinical/Bacteriological Outcomes

In the Esomeprazole/amoxicillin/clarithromycin clinical trials, 83% (176/212) of the patients in the Esomeprazole/amoxicillin/clarithromycin treatment group who had pretreatment amoxicillin susceptible MICs ( < 0.25 mcg/mL) were eradicated of H. pylori, and 17% (36/212) were not eradicated of H. pylori. Of the 36 patients who were not eradicated of H. pylori on triple therapy, 16 had no post-treatment susceptibility test results and 20 had post-treatment H. pylori isolates with amoxicillin susceptible MICs. Fifteen of the patients who were not eradicated of H. pylori on triple therapy also had post-treatment H. pylori isolates with clarithromycin resistant MICs. There were no patients with H. pylori isolates who developed treatment emergent resistance to amoxicillin.

Susceptibility Test for Helicobacter pyloriFor susceptibility testing information about Helicobacter pylori, see Microbiology section in prescribing information for clarithromycin and amoxicillin.

Effects on Gastrointestinal Microbial Ecology: Decreased gastric acidity due to any means, including proton pump inhibitors, increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with proton pump inhibitors may lead to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter and possibly Clostridium difficile in hospitalized patients.

Animal Toxicology and/or Pharmacology

Reproductive Toxicology Studies

Reproductive studies have been performed in rats at oral doses up to 280 mg/kg/day (about 57 times the human dose on a body surface area basis) and in rabbits at oral doses up to 86 mg/kg/day (about 35 times the human dose on a body surface area basis) and have revealed no evidence of impaired fertility or harm to the fetus due to esomeprazole.

Reproductive studies conducted with omeprazole in rats at oral doses up to 138 mg/kg/day (about 56 times the human dose on a body surface area basis) and in rabbits at doses up to 69 mg/kg/day (about 56 times the human dose on a body surface area basis) 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 5.5 to 56 times the human dose on a body surface area basis) 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 5.6 to 56 times the human dose on a body surface area basis).

Clinical Studies

Healing of Erosive Esophagitis

The healing rates of Esomeprazole 40 mg, Esomeprazole 20 mg, and omeprazole 20 mg (the approved dose for this indication) were evaluated in patients with endoscopically diagnosed erosive esophagitis in four multicenter, double-blind, randomized studies.  

In these same studies of patients with erosive esophagitis, sustained heartburn resolution and time to sustained heartburn resolution were evaluated and are shown in the Table 10:

There are no comparisons of 40 mg of Esomeprazole with 40 mg of omeprazole in clinical trials assessing either healing or symptomatic relief of erosive esophagitis.In these four studies, the range of median days to the start of sustained resolution (defined as 7 consecutive days with no heartburn) was 5 days for Esomeprazole 40 mg, 7 to 8 days for Esomeprazole 20 mg and 7 to 9 days for omeprazole 20 mg.

Long-Term Maintenance of Healing of Erosive Esophagitis

Two multicenter, randomized, double-blind placebo-controlled 4-arm trials were conducted in patients with endoscopically confirmed, healed erosive esophagitis to evaluate Esomeprazole 40 mg (n=174), 20 mg (n=180), 10 mg (n=168) or placebo (n=171) once daily over six months of treatment.

No additional clinical benefit was seen with Esomeprazole 40 mg over Esomeprazole 20 mg.

Patients remained in remission significantly longer and the number of recurrences of erosive esophagitis was significantly less in patients treated with Esomeprazole compared to placebo.

In both studies, the proportion of patients on Esomeprazole who remained in remission and were free of heartburn and other GERD symptoms was well differentiated from placebo.

In a third multicenter open label study of 808 patients treated for 12 months with Esomeprazole 40 mg, the percentage of patients that maintained healing of erosive esophagitis was 93.7% for six months and 89.4% for one year.

Symptomatic Gastroesophageal Reflux Disease (GERD)

Two multicenter, randomized, double-blind, placebo-controlled studies were conducted in a total of 717 patients comparing four weeks of treatment with Esomeprazole 20 mg or 40 mg once daily versus placebo for resolution of GERD symptoms. Patients had ≥ 6-month history of heartburn episodes, no erosive esophagitis by endoscopy, and heartburn on at least four of the seven days immediately preceding randomization.

The percentage of patients that were symptom-free of heartburn was significantly higher in the Esomeprazole groups compared to placebo at all follow-up visits (Weeks 1, 2, and 4).

No additional clinical benefit was seen with Esomeprazole 40 mg over Esomeprazole 20 mg. 

In three European symptomatic GERD trials, Esomeprazole 20 mg and 40 mg and omeprazole 20 mg were evaluated. No significant treatment related differences were seen.

Pediatric Gastroesophageal Reflux Disease (GERD)

1 to 11 Years of Age

In a multicenter, parallel-group study, 109 pediatric patients with a history of endoscopicallyproven GERD (1 to 11 years of age; 53 female; 89 Caucasian, 19 Black, 1 Other) were treated with Esomeprazole once daily for up to 8 weeks to evaluate safety and tolerability. Dosing by patient weight was as follows:

weight < 20 kg: once daily treatment with Esomeprazole 5 mg or 10 mg

weight ≥ 20 kg: once daily treatment with Esomeprazole 10 mg or 20 mg

Patients were endoscopically characterized as to the presence or absence of erosive esophagitis.

Of the 109 patients, 53 had erosive esophagitis at baseline (51 had mild, 1 moderate, and 1 severe esophagitis). Although most of the patients who had a follow up endoscopy at the end of 8 weeks of treatment healed, spontaneous healing cannot be ruled out because these patients had low grade erosive esophagitis prior to treatment, and the trial did not include a concomitant control.

12 to 17 Years of Age

In a multicenter, randomized, double-blind, parallel-group study, 149 adolescent patients (12 to 17 years of age; 89 female; 124 Caucasian, 15 Black, 10 Other) with clinically diagnosed GERD were treated with either Esomeprazole 20 mg or Esomeprazole 40 mg once daily for up to 8 weeks to evaluate safety and tolerability. Patients were not endoscopically characterized as to the presence or absence of erosive esophagitis.

Risk Reduction of NSAID-Associated Gastric Ulcer

Two multicenter, double-blind, placebo-controlled studies were conducted in patients at risk of developing gastric and/or duodenal ulcers associated with continuous use of non-selective and COX-2 selective NSAIDs. A total of 1429 patients were randomized across the 2 studies. Patients ranged in age from 19 to 89 (median age 66.0 years) with 70.7% female, 29.3% male, 82.9% Caucasian, 5.5% Black, 3.7% Asian, and 8.0% Others. At baseline, the patients in these studies were endoscopically confirmed not to have ulcers but were determined to be at risk for ulcer occurrence due to their age ( > 60 years) and/or history of a documented gastric or duodenal ulcer within the past 5 years. Patients receiving NSAIDs and treated with Esomeprazole 20 mg or 40 mg once-a-day experienced significant reduction in gastric ulceroccurrences relative to placebo treatment at 26 weeks. See Table 11. No additional benefit was seen with Esomeprazole 40 mg over Esomeprazole 20 mg. These studies did not demonstrate significant reduction in the development of NSAID-associated duodenal ulcer due to the low incidence. 

Helicobacter pylori (H. pylori) Eradication in Patients with Duodenal Ulcer Disease

Triple Therapy (Esomeprazole/amoxicillin/clarithromycin): Two multicenter, randomized, double-blind studies were conducted using a 10 day treatment regimen. The first study (191) compared Esomeprazole 40 mg once daily in combination with amoxicillin 1000 mg twice daily and clarithromycin 500 mg twice daily to Esomeprazole 40 mg once daily plus clarithromycin 500 mg twice daily. The second study (193) compared Esomeprazole 40 mg once daily in combination with amoxicillin 1000 mg twice daily and clarithromycin 500 mg twice daily to Esomeprazole 40 mg once daily. H. pylori eradication rates, defined as at least two negative tests and no positive tests from CLOtest®, histologyand/or culture, at 4 weeks post-therapy were significantly higher in the Esomeprazole plus amoxicillin and clarithromycin group than in the Esomeprazole plus clarithromycin or Esomeprazole alone group.

Hypersecretory Conditions Including Zollinger-Ellison Syndrome

In a multicenter, open-label dose-escalation study of 21 patients (15 males and 6 females, 18 Caucasian and 3 Black, mean age of 55.5 years) with pathological hypersecretory conditions, such as Zollinger-Ellison Syndrome, Esomeprazole significantly inhibited gastric acid secretion. Initial dose was 40 mg twice daily in 19/21 patients and 80 mg twice daily in 2/21 patients. Total daily doses ranging from 80 mg to 240 mg for 12 months maintained gastric acid output below the target levels of 10 mEq/h in patients without prior gastric acid-reducing surgery and below 5 mEq/hr in patients with prior gastric acid-reducing surgery. At the Month 12 final visit, 18/20 (90%) patients had Basal Acid Output (BAO) under satisfactory control (median BAO = 0.17 mmol/hr). Of the 18 patients evaluated with a starting dose of 40 mg twice daily, 13 (72%) had their BAO controlled with the original dosing regimen at the final visit.

ATC Classification
A02BC05 - esomeprazole; Belongs to the class of proton pump inhibitors. Used in the treatment of peptic ulcer and gastro-oesophageal reflux disease (GERD). 
Storage
Intravenous: Powder for inj: Store at 25°C (77°F). Protect from light. Reconstituted solution for inj should be stored at room temperature up to 30°C and administered within 12 hr after preparation. Reconstituted solution for infusion should be stored at room temperature up to 30°C and administered within 12 hr (if normal saline or lactated Ringer's inj is used as the diluent) or 6 hr (if dextrose 5% inj is used as the diluent). Oral: Store at 25°C.

Brands/Products Info



Total Products : 70                                                                      
Brand Name Manufacturer/Marketer Composition Dosage Form Pack Size & Price
ALENIA Delta Pharma Limited Esomeprazole INN 20mg Capsule 20mg x 64's: 320.00 MRP
ALTON General Pharmaceuticals Ltd Esomeprazole INN 20mg & 40mg Tablet (enteric coated) 20mg x 30's, 40mg x 30's: 120.00 & 210.00 MRP
ASECTOR Novo Healthcare and Pharma Ltd. Esomeprazole INN 20mg & 40mg Capsule (enteric coated) 20mg x 30's, 40mg x 28's: 165.00 & 224.00 MRP
CURACID Rangs Pharmaceuticals Ltd. Esomeprazole INN 20mg & 40mg Tablet (enteric coated) 20mg x 28's, 40mg x 20's: 140.00 & 140.00 MRP
EMA-20 Globe Pharmaceuticals Ltd Esomeprazole INN 20mg Tablet (enteric coated) 30's: 120.00 MRP
EMEP Aristopharma Ltd. Esomeprazole INN 20mg Tablet (enteric coated) 60's: 300.00 MRP
EMEP Capsule Aristopharma Ltd. Esomeprazole INN 20mg & 40mg Capsule 20mg x 60's, 40mg x 40's: 300.00 & 320.00 MRP
EMEP IV Aristopharma Ltd. Esomeprazole Sodium INN equivalent to Esomeprazole 40mg Injection 40mg vial: 90.00 MRP
EMO-20 Pharmadesh Laboratories Limited Esomeprazole INN 20mg Tablet (enteric coated) 30's: 135.00 MRP
EPA Zenith Pharmaceuticals Ltd. Esomeprazole INN 20mg Tablet (enteric coated) 50's: 200.00 MRP
ERAZOLE-20 Kemiko Pharmaceuticals Ltd Esomeprazole INN 20mg Tablet (enteric coated) 30's: 120.00 MRP
ESMAX 20 Concord Pharmaceuticals Ltd. Esomeprazole INN 20mg Capsule 30's: 150.00 MRP
ESMOTAC Gaco Pharmaceutical Ltd. Esomeprazole INN 20mg & 40mg Tablet (enteric coated) 20mg x 30's, 40mg x 20's: 120.00 & 140.00 MRP
ESO-20 Asiatic Laboratories Ltd. Esomeprazole INN 20mg Tablet (enteric coated) 30's: 150.00 MRP
ESOFAST S.N. Pharmaceuticals Ltd. Esomeprazole INN 20mg Tablet (enteric coated) 30's: 136.50 MRP
ESOGAP Euro Pharma Ltd. Esomeprazole INN 20mg & 40mg Tablet (enteric coated) 20mg x 30's, 40mg x 30's: 120.00 & 210.00 MRP
ESOLOK IBN SINA Pharmaceutical Industry Ltd. Esomeprazole INN 20mg & 40mg Tablet (enteric coated) 20mg x 30's, 40mg x 30's: 120.00 & 210.00 MRP
ESOLOK Capsule IBN SINA Pharmaceutical Industry Ltd. Esomeprazole INN 20mg & 40mg Capsule 20mg x 100's, 40mg x 48's: 650.00 & 384.00 MRP
ESOMENTA R A K Pharmaceuticals Pvt. Ltd. Esomeprazole INN 20mg Capsule 30's: 150.00 MRP
ESOMEP ACI Ltd. Esomeprazole INN 20mg & 40mg Tablet (enteric coated) 20mg x 50's, 40mg x 30's: 201.00 & 210.90 MRP
ESOMILOC Kumudini Pharma Ltd Esomeprazole INN 20mg Tablet (enteric coated) 50's: 700.00 MRP
Esonix 20 Incepta Pharmaceuticals Limited Esomeprazole Magnesium Trihydrate BP equivalent to Esomeprazole 20mg Tablet (Delayed Release) 10x5's:MRP 250 Tk
Esonix 40 Incepta Pharmaceuticals Limited Esomeprazole Magnesium Trihydrate BP equivalent to Esomeprazole 40mg Tablet (Delayed Release) 10x3's:MRP 240 Tk
Esonix Injection Incepta Pharmaceuticals Limited Esomeprazole Sodium INN equivalent to Esomeprazole 40 mg Injection 1x1's :MRP 70 Tk
ESOPIN 20 Hallmark Pharmaceuticals Ltd Esomeprazole INN 20mg Tablet 30's & 50's: 120.60 & 201.00 MRP
ESOPRA-20 Alco Pharma Ltd Esomeprazole INN 20mg Tablet (enteric coated) 20mg x 30's: 120.00 MRP
ESOPREX Beacon Pharmaceuticals Limited Esomeprazole INN 20mg & 40mg Capsule 20mg x 40's, 40mg x 30's: 200.00 & 240.00 MRP
ESOPROL Ziska Pharmaceuticals Ltd. Esomeprazole INN 20mg & 40mg Capsule 20mg x 28's, 40mg x 28's: 112.00 & 168.00 MRP
ESORAL Eskayef Bangladesh Ltd Esomeprazole INN 20mg & 40mg Tablet (enteric coated) 20mg x50's & 40mg x20's & 30's MRP: 200.00, 140.00 & 210.01
ESORAL Capsule Eskayef Bangladesh Ltd Esomeprazole INN 20mg Capsule 20mg x50's & 40mg x30's MRP: 250.00 & 240.00
ESORAL IV Eskayef Bangladesh Ltd Esomeprazole Sodium INN equivalent to Esomeprazole 40mg Injection Injection 40mg MRP: 70.00
ESOTAC Navana Pharmaceuticals Limited Esomeprazole INN 20mg & 40mg Tablet (enteric coated) 20mg x 60's, 20mg x 100's, 40mg x 30's: 241.20, 402.00 & 210.90 MRP
ESOTID Opsonin Pharma Limited Esomeprazole INN 20mg & 40mg Tablet (enteric coated) 20mg x 50's, 40mg x 50's: 250.00 & 350.00 MRP
ESOTID Capsule Opsonin Pharma Limited Esomeprazole INN 20mg & 40mg Capsule 20mg x 90's, 40mg x 30's: 540.00 & 270.00 MRP
ESOTID Injection Opsonin Pharma Limited Esomeprazole Sodium INN equivalent to Esomeprazole 40mg Injection 40mg vial: 70.00 MRP
ESPRAM Mystic Pharmaceuticals Limited Esomeprazole INN 20mg Tablet (enteric coated) 30's: 120.00 MRP
ESPRAZO Pacific Pharmaceuticals Ltd. Esomeprazole INN 20mg Capsule 30's: 150.00 MRP
ESRU-20 Doctors Chemical Works Ltd Esomeprazole INN 20mg Tablet 50's: 200.00 MRP
EXIUM Radiant Pharmaceuticals Ltd. Esomeprazole INN 20mg & 40mg Capsule 20mg x 60's, 40mg x 24's: 405.00 & 198.00 MRP
EXMART-20 Syntho Laboratories Ltd. Esomeprazole INN 20mg Tablet (enteric coated) 30's: 90.00 MRP
EXOME Chemist Laboratories Ltd. Esomeprazole INN 20mg Tablet 50's: 200.00 MRP
EZOOM Everest Pharmaceuticals Ltd. Esomeprazole INN 20mg Tablet 50's: 200.00 MRP
KSOCON Biopharma Laboratories Ltd Esomeprazole INN 20mg & 40mg Tablet (enteric coated) 20mg x 60's, 40mg x 40's: 241.20 & 281.20 MRP
MAXIMA The Acme Laboratories Ltd. Esomeprazole INN 20mg & 40mg Capsule 20mg x 40's, 40mg x 20's: 200.40 & 160.80 MRP
MAXIMA Injection The Acme Laboratories Ltd. Esomeprazole Sodium INN equivalent to Esomeprazole 40mg Injection 40mg vial: 70.26 MRP
MAXPRO Renata Limited Esomeprazole INN 20mg & 40mg Tablet (enteric coated) 20mg x 100's, 40mg x 30's: 500.00 & 240.00 MRP
MAXPRO Capsule Renata Limited Esomeprazole INN 20mg & 40mg Capsule 20mg x 42's, 40mg x 30's: 294.00 & 300.00 MRP
MAXPRO Injection Renata Limited Esomeprazole Sodium INN equivalent to Esomeprazole 40mg Injection 40mg vial: 90.00 MRP
NEPTOR Sandoz/Novartis Esomeprazole INN 20mg & 40mg Capsule (enteric coated ) 20mg x 60s: MRP 480.00; 40mg x 30s: MRP 360.00
NEXCAP DR Unimed & Unihealth Manufacturers Ltd. Esomeprazole INN 20mg & 40mg Capsule 28's each: 140.00 & 224.00 MRP
NEXE Apex Pharmaceuticals Ltd. Esomeprazole INN 20mg & 40mg Tablet (enteric coated) 30's each: 120.00 & 210.00 MRP
NEXUM 20 Square Pharmaceuticals Ltd. Esomeprazole 20mg Capsule 6x10's: 421.20 MRP
NEXUM 20 TAB Square Pharmaceuticals Ltd. Esomeprazole 20mg Tablet 5x10's: 251.50 MRP
NEXUM 40 Square Pharmaceuticals Ltd. Esomeprazole 40mg Capsule 3x10's: 300.90 MRP
NEXUM 40 IV Square Pharmaceuticals Ltd. Esomeprazole 40mg/vial IV Injection 1x1's: 90.27 MRP
NEXUM 40 TAB Square Pharmaceuticals Ltd. Esomeprazole 40mg Tablet 3x10's: 242.10 MRP
OPTON 20 Beximco Pharmaceuticals Ltd Esomeprazole Magnesium USP equivalent to Esomeprazole 20mg Tablet 30 & 60's: 150.00 & 300.00 MRP
OPTON 40 Beximco Pharmaceuticals Ltd Esomeprazole Magnesium USP eq. to Esomeprazole 40mg Tablet 30's: 240.00 MRP
OPTON 40 IV Beximco Pharmaceuticals Ltd Esomeprazole Sodium INN eq. to Esomeprazole 40mg Injection IV INJECTION 1's: 100.00 MRP
PROGUT Popular Pharmaceuticals Ltd. Esomeprazole INN 20mg & 40mg Tablet (enteric coated) 20mg x 100's, 40mg x 32's: 500.00 & 256.96 MRP
PROGUT IV Popular Pharmaceuticals Ltd. Esomeprazole Sodium INN equivalent to Esomeprazole 40mg Injection 40mg vial: 70.26 MRP
PRONEX Drug International Ltd Esomeprazole INN 20mg & 40mg Tablet (enteric coated) 20mg x 50's, 40mg x 50's: 250.00 & 400.00 MRP
SERGEL 20mg Healthcare Pharmacuticals Ltd. Esomeprazole Magnesium USP equivalent to Esomeprazole 20mg Capsule 90's MRP 630 Tk
SERGEL 40mg Healthcare Pharmacuticals Ltd. Esomeprazole Magnesium USP equivalent to Esomeprazole 40mg Capsule 30's MRP 270 Tk
SERGEL Injection Healthcare Pharmacuticals Ltd. Esomeprazole Sodium INN equivalent to Esomeprazole 40 mg Injection 40mg: 100.00 MRP
SERGEL TABLET 20 MG Healthcare Pharmacuticals Ltd. Esomeprazole Magnesium USP equivalent to Esomeprazole 20mg Tablet 30's MRP 210 Tk
SERGEL TABLET 40 MG Healthcare Pharmacuticals Ltd. Esomeprazole Magnesium USP equivalent to Esomeprazole 40mg Tablet 30's MRP 270 Tk
SOMAZOLE Ad-din pharmaceuticals Ltd. Esomeprazole INN 20mg Capsule 100's 400.00 MRP
SOMPRAZ Sun Pharmaceutical (Bangladesh) Ltd. Esomeprazole INN 20mg & 40mg Tablet (enteric coated) 50's each: 250.00 & 400.00 MRP
SOMPRAZOL Sharif Pharmaceuticals Ltd. Esomeprazole INN 20mg & 40mg Tablet (enteric coated) 20mg x 40's, 40mg x 20's: 200.00 & 160.00 MRP

General MedInfo

 

Why do I need this medicine?

Esomeprazole is a gastric medicine.

It is used to treat conditions caused by excessive acidity in your stomach, such as stomach ulcers and reflux disease (reflux is also known as "heartburn", in which food or acid from your stomach backs up into your mouth, leaving a sour or bitter taste).

Esomeprazole treats these conditions by reducing the amount of acid your stomach makes.

Esomeprazole may also be used together with other medicines to treat a specific type of gastric problem called Helicobacter pylori or H. pylori gastritis.

How do I take this medicine?

Take Esomeprazole exactly as directed by your doctor. Do not take more or less than instructed by your doctor.

You may need to take Esomeprazole for some time before the full benefits can be felt. Continue to take it even when you feel better and do not stop taking it unless advised by your doctor to do so.

The Esomeprazole tablet may be taken with or without food. If you have trouble swallowing, it may also be dispersed in half a glass of non-carbonated ("non-fizzy") water. Do not use other types of liquids to disperse the tablet. Stir gently until the tablet dissolves into little pellets. Drink the liquid with the pellets immediately or within 30 minutes. Rinse the glass with half a glass of water and drink this to ensure that no medicine is left behind in the glass. Do not chew or crush the tablet or the pellets.

What should I do if I have forgotten to take this medicine?

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and return to your normal dosing schedule.

DO NOT double a dose under any circumstances.

Remember to take your medicine regularly. Esomeprazole must be taken exactly as directed for it to be effective. If you often forget to take your medicine, let your doctor and pharmacist know.

When should I not use this medicine?

Inform your doctor if you have ever had an allergic reaction to other gastric medicines such as omeprazole, lansoprazole, pantoprazole or rabeprazole.

What should I take note of while taking this medicine?

Inform your doctor if you are pregnant or breastfeeding.

Do not breastfeed while you are being treated with Esomeprazole.

Alert your doctor if you have liver disease.

Let your doctor know if your gastric problem seems to be getting worse. Do not take Esomeprazole for a long period of time unless instructed by your doctor.

What side effects could I experience?

Esomeprazole may cause dizziness. If you feel dizzy, do not drive or take part in any activity in which you need to be alert.

Other side effects with Esomeprazole may include headache, diarrhoea, nausea and wind in the stomach. These should get better or go away as your body adjusts to the medicine.

Let your doctor know if these side effects bother you or if they do not go away.

Can I take this with other medicines?

Inform your doctor if you are taking any other medicines, especially those listed here:

- warfarin (a blood-thinning medicine)
- ketoconazole, itraconazole, voriconazole or similar antifungal medicines
- diazepam (used as a mood medicine or sleeping pill)
- other medicines such as atazanavir and iron pills.

Alert your doctor if you are taking a blood-thinning medicine called clopidogrel.

Do not take antacids together with Esomeprazole. If you must take antacids, take them at least 1 hour before or 2 hours after you have taken Esomeprazole. Antacids can reduce the effectiveness of Esomeprazole when taken together.

Always inform your doctor and pharmacist if you are taking any other medicines, including herbal tonics, supplements and medicines that you buy without a prescription.

What special dietary instructions should I follow?

It may be helpful to discuss your diet with your doctor or dietitian. A change in diet may help improve your symptoms. For example, spicy food tends to worsen reflux and should be avoided. Likewise, carbonated ("fizzy") drinks such as soft drinks should also be avoided.

You should also try to avoid lying down soon after eating as this will worsen the reflux symptoms.

Avoid alcohol.

How should I store this medicine?

Store in a cool, dry place away from the reach of children. Medicines must be used within the expiry date mentioned.

 

This information is provided for reference only and not a replacement for and should only be used in conjunction with full consultation with a registered medical practitioner. It may not contain all the available information you require and cannot substitute professional medical care, nor does it take into account all individual circumstances. Although great effort has been made to ensure content accuracy, mph-bd shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise.

| See FDA approved Prescribing Information from Brand Manufacturer |    Manufacturer's 


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