Esole

Treatment Of Gastroesophageal Reflux Disease (GERD)

Healing Of Erosive Esophagitis

Esole 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 Esole may be considered.

In infants 1 month to less than 1 year, Esole is indicated for short-term treatment (up to 6 weeks) of erosive esophagitis due to acid-mediated GERD.

Maintenance Of Healing Of Erosive Esophagitis

Esole is indicated to maintain symptom resolution and healing of erosive esophagitis. Controlled studies do not extend beyond 6 months.

Symptomatic Gastroesophageal Reflux Disease

Esole 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

Esole 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 (Esole plus amoxicillin and clarithromycin): Esole, 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-Ellis On Syndrome

Esole is indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison Syndrome.

Esole strontium is used to treat conditions where there is too much acid in the stomach. It is used to treat duodenal and gastric ulcers, erosive esophagitis, gastroesophageal reflux disease (GERD), and the Zollinger-Ellison syndrome. Esole is also used with antibiotics (eg, amoxicillin, clarithromycin) to treat ulcers that are caused by the H. pylori bacteria. Esole strontium is also used to prevent stomach ulcers and stomach irritation in patients taking pain and arthritis drugs called NSAIDs, such as aspirin or ibuprofen, for long periods of time.

Esole strontium is a proton pump inhibitor (PPI). It works by decreasing the amount of acid that is produced by the stomach.

Esole strontium is available only with your doctor’s prescription.

Usual Adult Dose for Gastroesophageal Reflux Disease:

Esole Magnesium:

-20 mg orally once a day for 4 weeks

Esole Strontium:

-24.65 mg orally once a day for 4 to 8 weeks.

Comment:

-If symptoms do not resolve after 4 weeks, an additional 4 weeks may be considered.

GERD with Erosive Esophagitis:

Esole Sodium:

-20 mg or 40 mg IV injection once a day, over no less than 3 minutes; or IV infusion once a day, over no less than 10 to 30 minutes

Comment: Safety and efficacy of Esole sodium IV for Injection for more than 10 days have not been demonstrated.

Uses: Short term treatment of heartburn and symptomatic gastroesophageal reflux disease; short term treatment of GERD with erosive esophagitis, inclusively as an alternative to oral therapy, if unable to use oral route

Usual Adult Dose for Erosive Esophagitis:

Healing:

-Esole Magnesium: 20 to 40 mg orally once a day for 4 to 8 weeks

-Esole Strontium: 24.65 to 49.3 mg orally once a day for 4 to 8 weeks

-An additional 4 to 8 week course of therapy may be considered in patients not healed after initial treatment.

Maintenance of healing:

-Esole Magnesium: 20 mg orally once a day

-Esole Strontium: 24.65 mg orally once a daily

Comments:

-Esole Sodium injection may be used as an alternative to oral therapy, if unable to use oral route.

-Maintenance of healing: Controlled studies did not extend beyond six months.

Uses: Short-term treatment in the healing and symptomatic resolution of diagnostically confirmed erosive esophagitis; to maintain symptom resolution and healing of erosive esophagitis

Usual Adult Dose for Helicobacter pylori Infection:

Esole Magnesium:

Triple therapy:

-40 mg orally once a day for 10 days, along with amoxicillin 1000 mg and clarithromycin 500 mg orally twice a day for 10 days

Esole Strontium:

Triple therapy:

-49.3 mg orally once a day for 10 days, along with amoxicillin 1000 mg and clarithromycin 500 mg orally twice a day for 10 days

Comments:

-Susceptibility testing should be done in patients who fail therapy.

-If resistance to clarithromycin is demonstrated or susceptibility testing is not possible, alternative antimicrobial therapy should be instituted.

-Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence.

Use: Triple therapy (Esole plus amoxicillin and clarithromycin): Treatment of H. pylori infection and duodenal ulcer disease (active or history of within the past 5 years) to eradicate H. pylori

Usual Adult Dose for NSAID-Induced Gastric Ulcer:

Esole Magnesium:

-20 mg to 40 mg orally once daily for up to 6 months

Esole Strontium:

-24.65 mg to 49.3 mg orally once a day for up to 6 months

Comment:

-Patients older than 60 years and/or with history of gastric ulcers are considered to be at risk for developing gastric ulcers.

-Controlled studies do not extend beyond 6 months

Use: Reduction in the occurrence of gastric ulcers associated with continuous NSAID therapy in patients at risk for developing gastric ulcers.

Usual Adult Dose for Zollinger-Ellison Syndrome:

Esole Magnesium:

-40 mg orally twice a day

Esole Strontium:

-49.3 mg orally twice a day

Comment: Doses up to 240 mg daily have been used.

Use: Long term treatment of pathological hypersecretory conditions, including Zollinger-Ellison Syndrome

Usual Adult Dose for Pathological Hypersecretory Conditions:

Esole Magnesium:

-40 mg orally twice a day

Esole Strontium:

-49.3 mg orally twice a day

Comment: Doses up to 240 mg daily have been used.

Use: Long term treatment of pathological hypersecretory conditions, including Zollinger-Ellison Syndrome

Usual Adult Dose for Duodenal Ulcer Prophylaxis:

Esole Sodium:

-Initial dose: 80 mg IV infusion over 30 minutes

-Maintenance dose: 8 mg/hr IV continuous infusion for a total of 72 hours (includes initial 30 minute dose plus 71.5 hours of continuous infusion)

Comments:

-Intravenous therapy is aimed solely at the acute initial management of bleeding gastric or duodenal ulcers and does not constitute full treatment.

-Intravenous therapy should be followed by oral acid-suppressive therapy.

Use: Risk reduction of rebleeding of gastric or duodenal ulcers following therapeutic endoscopy

Usual Adult Dose for Gastric Ulcer Prophylaxis:

Esole Sodium:

-Initial dose: 80 mg IV infusion over 30 minutes

-Maintenance dose: 8 mg/hr IV continuous infusion for a total of 72 hours (includes initial 30 minute dose plus 71.5 hours of continuous infusion)

Comments:

-Intravenous therapy is aimed solely at the acute initial management of bleeding gastric or duodenal ulcers and does not constitute full treatment.

-Intravenous therapy should be followed by oral acid-suppressive therapy.

Use: Risk reduction of rebleeding of gastric or duodenal ulcers following therapeutic endoscopy

Usual Pediatric Dose for Gastroesophageal Reflux Disease:

Esole Magnesium:

Less than 1 year:

-Data not available

1 to 11 years:

-10 mg once a day for up to 8 weeks

-Comment: Doses over 1 mg/kg/day have not been studied.

12 to 17 years:

-20 mg once a day for 4 weeks

Esole Sodium:

GERD with Erosive Esophagitis:

Less than 1 month:

-Not recommended.

1 month to less than 1 year:

-0.5 mg/kg IV infused over 10 to 30 minutes

1 to 17 years:

-Less than 55 kg: 10 mg IV infused over 10 to 30 minutes

-55 kg or more: 20 mg IV infused over 10 to 30 minutes

Esole Strontium: Not recommended.

Uses: Short term treatment of symptomatic GERD; short term treatment of GERD with erosive esophagitis, inclusively as an alternative to oral therapy, if unable to use oral route

Usual Pediatric Dose for Erosive Esophagitis:

Esole Magnesium:

Healing:

Less than 1 year:

-Data not available

1 to 11 years:

-Less than 20 kg: 10 mg once a day for 8 weeks

-20 kg or more: 10 mg or 20 mg once a day for 8 weeks

12 to 17 years:

-20 or 40 mg once a day for 4 to 8 weeks

Comment: Doses over 1 mg/kg/day have not been studied.

Erosive Esophagitis due to acid-mediated GERD:

Less than 1 month:

-Data not available

1 month to less than 1 year old:

-3 kg to 5 kg: 2.5 mg once a day

-Greater than 5 kg to 7.5 kg: 5 mg once a day

-Greater than 7.5 kg to 12 kg: 10 mg once a day

Duration of therapy: For up to 6 weeks

Comment: Doses over 1.33 mg/kg/day have not been studied.

1 year and older:

-Data not available

Uses: Short-term treatment in the healing and symptomatic resolution of diagnostically confirmed erosive esophagitis; short term treatment of erosive esophagitis due to acid-mediated GERD in infants

See also:
What is the most important information I should know about Esole?

Esole is rapidly absorbed after oral doses, with peak plasma levels occurring after about 1-2 hrs. It is acid labile and an enteric-coated formulation has been developed. Bioavailability of Esole increases with both dose and repeated administration to about 68% and 89% for doses of 20 mg and 40 mg, respectively. Food delays and decreases the absorption of Esole, but this does not significantly change its effect of intragastric acidity. Esole is about 97% bound to plasma proteins. It is extensively metabolized in the liver by the cytochrome P450 (CYP450) isoenzyme CYP2C19 to hydroxy and desmethyl metabolites, which have no effect on gastric acid section. The remainder is metabolized by the CYP450 isoenzyme CYP3A4 to Esole 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 (t_½) is about 1.3 hrs. Almost 80% of an oral dose is eliminated as metabolites in the urine, the remainder in the feces.

Use Esole suspension as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Esole suspension comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Esole suspension refilled.
• Take Esole suspension by mouth on an empty stomach at least 1 hour before a meal.
• You will need to mix Esole suspension in a small amount of water before taking your dose. You should use an oral syringe to measure the amount of water needed to mix your dose. Ask your pharmacist for an oral syringe. The recommended amount of water for the mixing of each dose is as follows:
  • If your dose of Esole suspension is 2.5 or 5 mg, add 1 teaspoon (5 mL) of water to a container.
  • If your dose of Esole suspension is 10, 20, or 40 mg, add 1 tablespoon (15 mL) of water to a container
• Tear open the medicine packet and add the contents of the packet to the container. Stir well. Allow the mixture to thicken for 2 to 3 minutes. Stir again. Drink the mixture within 30 minutes. If it is not used within 30 minutes, throw away this dose and mix a new dose. If any medicine remains in the glass after drinking, add more water. Stir and then drink right away.
• If the patient is taking Esole suspension through a nasogastric (NG) tube or gastric tube, follow the instructions for use in the extra patient leaflet.
• If your doctor has instructed you to use more than 1 packet for your dose, follow the mixing instructions provided by your doctor or pharmacist.
• You may take antacids while you are using Esole suspension if you are directed to do so by your doctor.
• Continue to take Esole suspension even if you feel well. Do not miss any doses.
• If you miss a dose of Esole suspension, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Esole suspension.

Use: Labeled Indications

Oral:

Esole magnesium and Esole strontium:

Gastroesophageal reflux disease (Rx only):

Healing of erosive esophagitis: Short-term (4 to 8 weeks) treatment of erosive esophagitis

Maintenance of healing of erosive esophagitis: Maintaining symptom resolution and healing of erosive esophagitis

Symptomatic gastroesophageal reflux disease: Short-term (4 to 8 weeks) treatment of symptomatic gastroesophageal reflux disease (GERD)

Helicobacter pylori eradication (Rx only): As part of a multidrug regimen for Helicobacter pylori eradication in patients with duodenal ulcer disease (active or history of within the past 5 years)

Risk reduction of nonsteroidal anti-inflammatory drug-associated gastric ulcer (Rx only): Prevention of gastric ulcers associated with continuous NSAID therapy in patients at risk (age ≥60 years and/or history of gastric ulcer)

Pathological hypersecretory conditions, including Zollinger-Ellison syndrome (Rx only): Treatment (long-term) of pathological hypersecretory conditions including Zollinger-Ellison syndrome

Esole magnesium:

Heartburn (OTC labeling): Treatment of frequent heartburn (≥2 days per week).

IV: Esole sodium:

Gastroesophageal reflux disease (Rx only): Short-term (≤10 days) treatment of gastroesophageal reflux disease (GERD) with erosive esophagitis in pediatric patients 1 month to 17 years of age and adults when oral therapy is not possible or appropriate

Risk reduction of ulcer rebleeding postprocedure (Rx only): Decrease the risk of rebleeding postendoscopy for acute bleeding gastric or duodenal ulcers in adults

Off Label Uses

Barrett esophagus

Data from a meta-analysis of observational studies evaluating acid suppressive therapy and the risk of esophageal adenocarcinoma or high-grade dysplasia in patients with Barrett esophagus showed that proton pump inhibitors were associated with a reduction in the risk of esophageal adenocarcinoma and high-grade dysplasia associated with Barrett esophagus; a longer duration of PPI use was associated with a greater protective effect.

See also:
What other drugs will affect Esole?

Esole is extensively metabolized in the liver by CYP2C19 and CYP3A4.

In vitro and in vivo studies have shown that Esole is not likely to inhibit CYPs 1A2, 2A6, 2C9, 206, 2E1 and 3A4. No clinically relevant interactions with drugs metabolized by these CYP enzymes would be expected. Drug interaction studies have shown that Esole does not have any clinically significant interactions with phenytoin, warfarin, quinidine, clarithromycin or amoxicillin. Post-marketing reports of changes in prothrombin measures have been received among patients on concomitant warfarin and Esole 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.

Esole may potentially interfere with CYP2C19, the major Esole metabolizing enzyme. Coadministration of Esole 30 mg and diazepam, a CYP2C19 substrate, resulted in a 45% decrease in clearance of diazepam. Increased plasma levels of diazepam were observed 12 hours after dosing and onwards. However, at that time, the plasma levels of diazepam were below the therapeutic interval, and thus this interaction is unlikely to be of clinical relevance.

Concomitant administration of Esole and a combined inhibitor of CYP2C19 and CYP3A4, such as voriconazole, may result in more than doubling of the Esole exposure. Dose adjustment of Esole is not normally required for the recommended doses. However, in patients who may require higher doses, dose adjustment may be considered.

Esole acts as an inhibitor of CYP2C19. Esole given in doses of 40 mg daily for one week to 20 healthy subjects in cross-over study, increased C_max and AUC of cilostazol by 18% and 26% respectively. C_max and AUC of one of its active metabolites, 3,4-dihydro-cilostazol, which has 4-7 times the activity of cilostazol, were increased by 29% and 69% respectively. Co-administration of cilostazol with Esole is expected to increase concentrations of cilostazol and its above mentioned active metabolite. Therefore a dose reduction of cilostazol from 100 mg b.i.d. to 50 mg b.i.d. should be considered.

Co-administration of' oral contraceptives, diazepam, phenytoin, or quinidine did not seen to change the pharmacokinetic profile of Esole.

Antiretroviral Agents: 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 thereby reduce its therapeutic effect.

Esole 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 Esole treatment may change the absorption of the antiretroviral drug. Other possible interaction mechanisms are via CYP2C19. 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, bid) and Esole (40 mg qd). AUC was decreased by 36% and 92%, C_max by 37% and 89% and C_min by 39% and 75% respectively for nelfinavir and M8. Following multiple doses of atazanavir (400 mg, qd) and Esole (40 mg, qd, 2 hr before atazanavir), AUC was decreased by 94%, C_max by 96%, and C_min by 95%. Concomitant administration with Esole and drugs such as atazanavir and nelfinavir is therefore not recommended. For other antiretroviral drugs, such as saquinavir, elevated serum levels have been reported with an increases in AUC by 82%, in C_max by 75% and in C_min by 106% following multiple dosing of saquinavir/ritonavir (1000/100 mg) bid for 15 days with Esole 40 mg qd coadministered days 11 to 15. Therefore, clinical and laboratory monitoring for saquinavir toxicity is recommended during concurrent use with Esole.

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 Esole.

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

Esole inhibits gastric acid secretion. Therefore, Esole may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (eg, ketoconazole, iron salts and digoxin).

See also:
What are the possible side effects of Esole?

Clinical Trials Experience with

Intravenous Esole

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 intravenous Esole is based on results from clinical trials conducted in four different populations including patients having symptomatic GERD with or without a history of erosive esophagitis (n=199), patients with erosive esophagitis (n=160), healthy subjects (n=204) and patients with bleeding gastric or duodenal ulcers (n=375).

Symptomatic GERD and Erosive Esophagitis Trials

The data described below reflect exposure to Esole I.V. for Injection in 359 patients. Esole I.V. for Injection was studied only in actively-controlled trials. The population was 18 to 77 years of age; 45% Male, 52% Caucasian, 17% Black, 3% Asian, 28% Other, and had either erosive reflux esophagitis (44%) or GERD (56%). Most patients received doses of either 20 or 40 mg either as an infusion or an injection. Adverse reactions occurring in ≥1% of patients treated with intravenous Esole (n=359) in clinical trials are listed below:

Intravenous treatment with Esole 20 and 40 mg-administered as an injection or as an infusion was found to have a safety profile similar to that of oral administration of Esole.

Pediatric

A randomized, open-label, multi-national study to evaluate the pharmacokinetics of repeated intravenous doses of once daily Esole in pediatric patients 1 month to 17 years old, inclusive was performed. The safety results are consistent with the known safety profile of Esole and no unexpected safety signals were identified [seeClinical Pharmacology (12.3)].

Risk Reduction of Rebleeding of Gastric or Duodenal Ulcers in Adults

The data described below reflect exposure to Esole I.V. for Injection in 375 patients. Esole I.V. for Injection was studied in a placebo-controlled trial. Patients were randomized to receive Esole I.V. for Injection (n=375) or placebo (n=389). The population was 18 to 98 years old; 68% Male, 87% Caucasian, 1% Black, 7% Asian, 4% other, who presented with endoscopically confirmed gastric or duodenal ulcer bleeding. Following endoscopic hemostasis, patients received either 80 mg Esole as an intravenous infusion over 30 minutes followed by a continuous infusion of 8 mg per hour or placebo for a total treatment duration of 72 hours. After the initial 72-hour period, all patients received oral proton pump inhibitor (PPI) for 27 days.

With the exception of injection site reactions described above, intravenous treatment with Esole administered as an injection or as an infusion was found to have a safety profile similar to that of oral administration of Esole.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Esole. 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.

Postmarketing Reports - There have been spontaneous reports of adverse events with postmarketing use of Esole. These reports occurred rarely and are listed below by body system:

Blood And Lymphatic System Disorders: agranulocytosis, pancytopenia; Eye Disorders: blurred vision; Gastrointestinal Disorders: pancreatitis; stomatitis; microscopic colitis; Hepatobiliary Disorders: hepatic failure, hepatitis with or without jaundice; Immune System Disorders: anaphylactic reaction/shock; Infections and Infestations: GI candidiasis; Metabolism and nutritional disorders: hypomagnesemia with or without hypocalcemia and/or hypokalemia; Musculoskeletal And Connective Tissue Disorders: muscular weakness, myalgia, bone fracture; Nervous System Disorders: hepatic encephalopathy, taste disturbance; Psychiatric Disorders: aggression, agitation, depression, hallucination; Renal and Urinary Disorders: interstitial nephritis; Reproductive System and Breast Disorders: gynecomastia; Respiratory, Thoracic and Mediastinal Disorders: bronchospasm; Skin and Subcutaneous Tissue Disorders: alopecia, erythema multiforme, hyperhidrosis, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN, some fatal).

Other adverse events not observed with Esole, but occurring with omeprazole can be found in the omeprazole package insert, ADVERSE REACTIONS section.

Each tablet contains 20 mg or 40 mg Esole (as magnesium trihydrate).

Each tablet contains esomeprazole as enteric-coated pellets (MUPS).

Esole MUPS is a proton pump inhibitor. The active ingredient in Esole MUPS is Esole magnesium trihydrate, a substituted benzimidazole. Esole is the S-isomer of omeprazole. It is optically stable in vivo, with negligible conversion to the R-isomer. The chemical name is di-(S)-5-methoxy-2-[[4-methoxy-3,5-dimethyl-2-pyridinyl)methyl] sulfinyl] -1H- benzimidazole magnesium salt trihydrate.

Its molecular formula is C₃₄H₃₆N₆O₆S₂Mg·3H₂O and has a molecular weight of 767.2 (trihydrate).

Excipients/Inactive Ingredients: Glycerol monostearate 40-55, hyprolose, hypromellose, iron oxide (E 172) (Tablet 20 mg, reddish-brown CI 77491, yellow, CI 77492) (Tablet 40 mg, reddish-brown CI 77491), magnesium stearate, methacrylic acid ethyl acrylate copolymer (1:1) dispersion 30 percent, cellulose microcrystalline, synthetic paraffin, macrogols, polysorbate 80, crospovidone, sodium stearyl fumarate, sugar spheres (sucrose and maize starch), talc, titanium dioxide (E 171), triethyl citrate.

Esole 20 mg: Sucrose 28 mg.

Esole 40 mg: Sucrose 30 mg.