Glesoz 20 Glenmark treatment for gastroesophageal reflux disease (1 blister x 10 tablets)

Esomeprazole tablets are indicated in adolescents 12 years of age or older for:

Gastroesophageal reflux disease (GERD)

Pharmacology

Pharmaceutical Group: Drugs for acid -related disorders, Proton pump inhibitors

ATC code: A02BC05

Esomeprazol is the S-Omeprazol isomer and reduces the secretion of stomach acid with a specialized mechanism of action. The drug is a specific inhibitor of acid pump in the wall of the wall. Both types of isomers and Omeprazol screens have similar pharmacological effects.

Mechanism of impact

Esomeprazol is a weak, concentrated and transformed basic into a highly acidic environment in the sub-control tube of the cell's secretion, where H+K+--Aatpase inhibitors (acid pump) and inhibit both basic fluid and stimulating fluid.

Pharmacological effect

After taking the oral dose of Esomeprazol 20mg and 40mg, the drug on the beginning is within 1 hour. After repeating the dose of Esomeprazol 20mg, 1 time/day for 5 days, the maximum maximum acid secretion after stimulation with Pentagastrin decreases 90% when measured at 6-7 hours after taking the drug on the 5th day.

After 5 days of taking the oral dosage of Esomeprazol 20mg and 40mg, the pH of the stomach> 4 has been maintained within the average period of 13 and 17 hours, within 24 hours in patients with symptomatic gastroesophageal reflux. The proportion of patients maintaining pH in the stomach> 4 minimum for 8, 12 and 16 hours respectively, equivalent 76%, 54% and 24% for Esomeprazol 20mg and 97%, 92% and 56% for Esomeprazol 40 mg.

When using AUC as a parameter representing the concentration of drugs in plasma, people have proven to have the relationship between acid secretion and drug concentration and contact time.

When using Esomeprazol 40mg, about 78% of patients with esophagitis due to reflux are healed after 4 weeks and about 93% are healed after 8 weeks.

Esomeprazol 20mg treatment, 2 times/day and appropriate antibiotics for 1 week have eradicated Helicobacter Pylori successfully in about 90% of patients. After treatment for 1 week, no additional anti -acid anti -acid medications to heal ulcers and reduce symptoms in patients with uncomplicated duodenal ulcer.

During the treatment with anti -acid antimicrobial drugs, serum galastin concentration responds to a decrease in gastric acid. CGA concentration also increases due to reduced gastric acid. The increase in CGA levels can interfere with the detection of hormonal tumors. Medical reports indicate that it is advisable to stop treating with proton pump inhibitors at least 5 days before quantifying CGA. If CGA and Gastrin concentrations do not return to normal after 5 days, should conduct quantitative after 14 days after stopping using Esomeprazol.

Increasing the number of ECL cells is probably due to increased serum gastrin levels that have been recorded in both children and adults when treated for long -term with Esomeprazol. This is considered not clinical significance.

After a long period of treatment with anti -acid discharge drugs, the frequency of gastric gland follicles appeared slightly. These changes are due to the inhibition of gastric acid excretion, which is benign and recovered.

Reducing stomach acid for any cause, including using proton pump inhibitors, increasing the number of permanent bacteria in the digestive tract. Proton pump inhibitors may slightly increase the risk of gastrointestinal tract infections caused by Salmonella and Campylobacter, and possibly Clostridium difficile on boarding patients.

Clinical effectiveness

In two studies using ranitidin as a comparative drug, Esomeprazol proves to be better effective to heal stomach ulcers in patients taking NSAIDs, including NSAID drugs selected on COX-2.

In two controlled studies with placebo, Esomeprazol shows a better effect in preventing stomach and duodenal ulcers in patients taking NSAID drugs (aged> 60 and/or having previous ulcers), including NSAID drugs selected on COX-2.

Pediatric subjects

In a study on children with gastroesophageal reflux disease (

Pharmacokinetics

absorption

Esomeprazol is easily destroyed in acidic environments and is taken in the form of grain soluble in the intestine. In animals (in vivo), the transition to isomer R is negligible. Esomeprazol is quickly absorbed with peak concentration in plasma reaching about 1-2 hours after drinking. Absolute bioavailability is 64% after taking a single dose of 40mg and increased to 89% after the dose is repeated once a day. For the dose of Esomeprazol 20mg, these values ​​correspond to 50% and 68%.

Food slows down and reduces the absorption of Esomeprazol, although this does not significantly affect the effects of Esomeprazol on gastric acid secretion.

Distribution

Expected distribution integral in a healthy state is about 0.22 l/kg of body weight. Esomeprazol binds 97% to plasma protein.

Metabolism

Esomeprazol is completely metabolized through the Cytochrom P450 (CYP) system. The main part of the Esomeprazol metabolism depends on the morphological CYP2C19 enzyme, forming the metabolites of hydroxy and desmethyl of esomeprazol. The rest of the metabolic process depends on another specific same, CYP3A4, forming Esomeprazol Sulfon, the main metabolite in plasma.

Elimination

The following parameters mainly reflect pharmacokinetics in individuals with CYP2C19 function yeast, a group of strong metabolic people.

The total plasma clearance is about 17 l/hour after the single dose and about 9 l/hour after the dose is repeated. Selling time for plasma is about 1.3 hours after the dose is repeated once a day. Esomeprazol completely eliminated from plasma between doses without a tendency to accumulate when used 1 time/day.

The main metabolites of Esomeprazol does not affect stomach acid secretion. About 80% of Esomeprazol oral dose is excreted in the urine in the form of metabolites, the rest through feces. Less than 1% of constant drugs found in urine.

Linear/non -linear level

pharmacokinetics has been studied at a dose of up to 40mg, 2 times/day. The area under the curve shows the plasma concentration over time (AUC) increases after repeated use of esomeprazol. This increase depends on the dose and the AUC increase ratio is more than the dose increase rate after the dose is repeated. This time and dosage dependence is due to a decrease in the first stage of the liver and a reduction in systemic clearance is probably due to the inhibition of Esomeprazol's CYP2C19 enzyme and/or sulfon metabolites.

Special patient groups

Poor metabolic people

about 2.9 ± 1.5% of patients do not have CYP2C19 function enzyme and are called poor metabolic people. In these individuals, the metabolism of Esomeprazol is catalyzed mainly by CYP3A4. After the repeated dose of Esomeprazol 40mg, 1 time/day, the average AUC in the metabolic person is about 100% lower than that of patients with CYP2C19 function yeast (strong metabolic group). The average peak concentration in plasma increased by about 60%. These records do not affect the dose of Esomeprazol.

Gender

After taking the single dose of Esomeprazol 40mg, the average AUC in women is about 30%higher than that of men. There is no difference in AUC between gender after the dose is repeated once a day. These records do not affect the dose of Esomeprazol.

Hepatic failure

Esomeprazol's metabolism may be impaired in patients with mild to moderate liver dysfunction. The metabolic rate decreases in patients with severe liver dysfunction, leading to doubling the concentration and contact time of Esomeprazol. Therefore, do not overdose up to 20mg in patients with severe liver dysfunction. Esomeprazol or main metabolites do not tend to accumulate when used 1 time/day.

kidney failure

No studies have been conducted in patients with renal function. Because the kidney is responsible for the excretion of the metabolites of Esomeprazol but not responsible for the elimination of drugs in a constant form, it is considered that the metabolism of esomeprazol is unchanged in patients with impaired kidney function.

Elderly

Esomeprazol's metabolism has not changed significantly in elderly patients (71-80 years old)

Children

Teenage children 12 - 18 years old:

After using the repeated dose of 20mg and 40mg Esomeprazol, the total concentration and contact time (AUC) and the maximum concentration time in plasma (TMAX) in children are 12-18 years similar to adults for both doses of esomeprazol.

Caution when using

when there is any alert symptom (such as significant weight loss, recurrent vomiting, difficulty swallowing, vomiting of blood or black defecation) and when suspected or gastric ulcer should eliminate malignant diseases because Esomeprazole treatment can reduce symptoms and delay diagnosis.

Long -term treatment

Patients with long -term treatment (especially those who have been treated for more than 1 year) should be monitored regularly.

Treatment when necessary

Patients treated according to the regime when necessary should contact the doctor if there are symptoms that change in characteristics.

Eliminate Helicobacter pylori

When prescribing Esomeprazole to eliminate Helicobacter pylori, drug interactions should be considered in the 3 -drug treatment regimen. Clarithromycin is a strong CYP3A4 inhibitor and therefore should consider contraindicated and interact with Clarithromycin when using a 3 -drug regimen for patients who are taking other drugs metabolized through CYP3A4 as Cisaprid.

Gastrointestinal tract infections

Proton pump inhibitors may increase the risk of gastrointestinal tract infections caused by Salmonella and Campylobacter.

Vitamin B12 absorption

Esomeprazol, as well as other antacids, can reduce the absorption of vitamin B12 (cyanocobalamin) due to a reduction or deficiency of gastric juice. This should be considered in patients with reduced vitamin B12 reserves or have risk factors for reducing vitamin B12 absorption when long -term treatment.

Magnesium reduction

There have been reports on severe blood magnesium reduction in patients treated with proton pump inhibitors (PPI) such as Esomeprazol for at least 3 months, and in most cases is for 1 year. The severe manifestation of blood magnesium decreased such as fatigue, spasticity, delirium, convulsions, dizziness and ventricular arrhyths may occur but silently started and not concerned. In the majority of patients, blood magnesium reduction is improved after using magnesium therapy instead and stop using PPI.

For patients who need prolonged treatment or patients with simultaneous use of ppi and digoxin or other drugs that can cause blood magnesium (such as diuretics), health workers should consider quantifying blood magnesium levels before starting PPI treatment and periodic monitoring during treatment.

Risk of fracture

Proton pump inhibitors, especially when high doses and long -term (> 1 year), may increase the risk of hip, wrist and spine fractures, especially in elderly patients or when there is a presence of other risk factors.

Lupus Red Red Red Reds (SCLE)

Proton pump inhibitors are very little related to the skin -red lesions in the skin. If these lesions occur, especially in skin areas exposed to sunlight, and if there is joint pain, patients should soon find medical support and medical staff should consider stopping the use of the drug. Skin -acute luPus lesions after treatment with previous Proton pump inhibitors may increase the risk of semi -acute erythema lupus lesions for other proton pump inhibitors.

Coordinate with other drugs

It is not recommended to simultaneously use Esomeprazol with Atazanavir. If Atazanavir combination with proton pump inhibitors is inevitable, clinically closely monitored when increasing the dose of Atazanavir to 400mg combined with 100mg of ritonavir; Do not use more than 20mg of esomeprazol.

Esomeprazol is CYP2C19 inhibitor. When starting or ending treatment with Esomeprazol, the risk of drug interaction with metabolic drugs should be considered through CYP2C19. There has been an interaction between clopidogrel and omeprazol. It is unclear clinical related relationship of this interaction. As a cautious measure, it is not recommended to simultaneously use Esomeprazol and Clopidogrel.

When prescribing Esomeprazole according to the treatment regime when necessary, it is advisable to consider the interaction associated with other drugs due to the change in the plasma Esomeprazol level.

Interaction with tests

Increased chromgranin A (CGA) concentration may interfere with the detection of endocrine nerve tumors. In order to avoid this intervention, it is recommended to stop treating with Esomeprazol at least 5 days before quantifying CGA. If the CGA and Gastrin concentrations do not return to normal after the initial quantitative, should conduct quantitative after 14 days after using Esomeprazol.

lactose

The drug contains lactose. Patients with rare genetic problems such as galactose intolerance, lapp-lactose deficiency or Glucose-Galactose are under absorbent.

The effect of the drug on driving and operating machinery

Esomeprazol has a small impact on driving and operating machinery. Side effects such as dizziness (rarely) and blurred vision have been reported. If the patient has these adultery effects, you should not drive and operate the machine.

Use drugs for women during pregnancy and lactation

Pregnant women:

There is no enough clinical data on the use of Esomeprazole tablets in pregnant women. When using omeprazol racemic contract mixture, a large number of pregnant women use drugs from epidemiological studies shows that the drug does not cause defects or toxicity on the fetus. Esomeprazol studies on animals do not show that the drug has a direct or indirect harmful effect on the development of embryo/fetus. Animal studies with Racemic mixture do not show that there is a direct or indirect effect on pregnancy, birth or postpartum development. Should be cautious when prescribing pregnant women.

A moderate amount of data on pregnant women (between 300-1000 pregnancy results) indicates that the drug is not likely to cause defects or fetal/infant toxicity.

Animal studies do not show that the drug has a direct or indirect harmful effect on reproductive toxicity.

breastfeeding women:

It is not known whether esomeprazol is secreted through breast milk or not. There are no studies on breastfeeding women. Therefore, Esomeprazole should not be used during breastfeeding.

reproductive ability:

Animal studies for omeprazol racemic mixture, oral use, does not show the drug that has a fertility.

Drug interaction

Esomeprazol's effect on pharmacokinetics of other drugs

Protease inhibitors

There has been reported that Omeprazole interacts with some protease inhibitors. It is unclear clinical importance and the mechanism of impact of the recorded interactions. Increasing stomach pH during treatment with omeprazole can lead to changes in the absorption of protease inhibitors. Another possible interactive mechanism occurs through CYP 2C19.

For Atazanavir and Nelfinavir, the serum concentration has been recorded when used with omeprazol, so it is not recommended to simultaneously use these drugs.

In healthy volunteers, simultaneous use of omeprazol (40 mg, 1 time/day) and Atazanavir 300 mg/ritonavir 100 mg significantly reduces the concentration and time of Atazanavir (reduced AUC, CMAX and CMIN by about 75%). Increasing the dose of Atazanavir to 400 mg has not compensated for the effects of omeprazol on concentration and time of Atazanavir contact. Use combined omeprazol (20 mg, 1 time/day) with Atazanavir 400 mg/ritonavir 100 mg in healthy volunteers reduces about 30% of the concentration and time of Atazanavir contact when compared to the concentration and time of contact in case of using Atazanavir 300 mg/ritonavir 100 mg, 1 time/day, without using Omeprazol 20 mg, 1 time/1 mg, 1 time/1 mg, 1 time/1 mg, 1 time/1 mg, 1 time Used in combination with omeprazol (40 mg, 1 time/day) reduces the average value of AUC, CMAX and CMIN of Nelfinavir by 36-39% and decreases about 75-92% of the average AUC, CMAX and CMIN values ​​of active metabolites with pharmacological effects M8. Due to the effects of pharmaceutical force and similar pharmacokinetic properties of omeprazol and esomeprazol, it is not recommended to use Esomeprazol simultaneously with Atazanavir (see the warning section) and contraindicated use of Esomeprazol simultaneously with NELFINAVIR (see the contraindication section).

For Saquinavir (simultaneously used with ritonavir), increasing serum medication (80-100%) when used simultaneously with omeprazol (40 mg, 1 time/day). Treatment with omeprazol 20 mg, 1 time/day, does not affect the contact of Darunavir (when used simultaneously with Ritonavir) and Amprenavir (when used simultaneously with Ritonavir). Treatment with Esomeprazol 20 mg, 1 time/day, does not affect the contact of Amprenavir (used or not used simultaneously with Ritonavir). Treatment with omeprazol 40 mg, 1 time/day, does not affect the contact of Lopinavir (simultaneously used with Ritonavir).

Methotrexate: When used simultaneously with PPIs, methotrexate concentration is reported to increase in some patients. When using high doses of methotrexate, it is recommended to temporarily pause Esomeprazol.

tacrolimus: Concomitant use with Esomeprazol has been reported to increase the serum concentration of Tacrolimus. Increasing monitoring of the concentration of tacrolimus as well as renal function (creatinine clearance) should be performed, and adjust the dose of tacrolimus if necessary.

The drug has a pH absorption: The reduction of stomach acid when treated with ecomeprazol and other ppi may increase or decrease the absorption of absorption drugs dependent on gastric pH. Like other medications that reduce other gastric pH, the absorption of drugs such as ketoconazole, otraconazole and erlotinib may decrease and the absorption of Digoxin may increase during treatment with ecomeprazol. Simultaneous use of omeprazol (20 mg/day) and digoxin in healthy objects that increase the bioavailability of digoxin about 10% (up to 30% in 2 out of 10 researchers). There are rare reports on Digoxin toxicity. However, it is necessary to be cautious when using high doses of Esomeprazol in the elderly. Need to increase monitoring treatment with digoxin.

Metabolic drugs through CYP2C19: Esomeprazol inhibits CYP2C19, main enzyme metabolism Esomeprazol. Therefore, when Esomeprazol is used with metabolic drugs through CYP2C19 such as Diazepam, Citalopram, Imipramin, Clomipramin, Phenytoin ..., the concentration of these drugs in plasma can increase and need to decrease the dose.

Diazepam: Concentrated with Esomeprazol 30 mg oral form reduces 45% of Diazepam clearance (a substrate of CYP2C19).

Phenytoin: When used simultaneously with Esomeprazol 40 mg oral and phenytoin, it increases the bottom plasma level level of phenytoin in plasma in epilepsy patients. Should monitor phenytoin concentration in plasma when starting or stopping treatment with Esomeprazol.

Voriconazole: Omeprazol (40 mg, 1 time/day) increases 15% cmax and 41% AUCT of Voriconazole (a substrate of CYP2C19)

cilostazol: Omeprazol as well as Esomeprazol acts like CYP2C19 inhibitors. In a cross study, Omeprazol used at a dose of 40 mg on healthy objects increased by 18% CMAX and 26% AUC of Cilostazol and increased by 29% CMAX and 69% AUC of one of one of the active metabolites.

Cisaprid: In healthy volunteers, when used with 40 mg of esomeprazol oral and cisaprid form, the area under the curve shows the cisaprid concentration in plasma over time (AUC) increases to 32% and the sale time (T1/2) Cisaprid lasts an additional 31% but the Cisaprid peak concentration in plasma increases negatively. The QTC range is slightly extended after using a separate Cisaprid, not longer lasting when used simultaneously Cisaprid with Esomeprazol.

Warfarin: When using 40 mg of Esomeprazol oral form in a human being treated with warfarin in a clinical trial, it shows that blood clotting time is in an acceptable range. However, after bringing the drug to the market, there were a very rare number of cases of significant Inr clinical increase when treated simultaneously the above two drugs. The patient should be monitored at the beginning and when the treatment is terminated simultaneously Esomeprazol during treatment with Warfarin or other derivatives of Coumarin.

clopidogrel

Results from studies on healthy volunteers have shown that the pharmacokinetic interaction - the force between clopidogrel (the dose of 300 mg/maintenance dose of 75 mg) and esomeprazol (40 mg/day orally) leads to an average of 40% reduction of the concentration and contact time of the active metabolites of clopidogrel and the average reduction of 14% of the maximum inhibition of platelet collection (causing by ADP).

In a study on healthy objects, when using Clopidogrel simultaneously with a combination of fixed dose of Esomeprazol 20mg +Asa 81mg compared to the solitary clopidogrel, the concentration and contact time of the active metabolites of clopidogrels drop by nearly 40%. However, the maximum level of platelets inhibitors (caused by ADP) on these objects is the same in the single clopidogrel and the group uses Clopidogrel and Esomeprazol + ASA.

The inconsistent data on clinical manifestations of pharmacokinetic/ pharmaceutical interactions of Esomeprazol on the main cardiovascular events have been reported from both clinical observation and research research. For careful purpose, simultaneous use with clopidogrel is not recommended.

Medications without clinical interaction

Amoxicillin or quinidine: Esomeprazol has been shown to not significantly affect clinical effects on pharmacokinetics of amoxicillin or quinidine.

Naproxen or Rofecoxid: Studies performed when using simultaneously Esomeprazol and Naproxen or Rofecoxid do not identify any clinical pharmacokinetic interactions.

The effect of other drugs on Esomeprazol pharmacokinetics

CYP2C19 and/or CYP3A4 inhibitors

Esomeprazol is metabolized by CYP2C19 and CYP3A4. When concurrent use Esomeprazol oral form with a CYP3A4 inhibitor, Clarithromycin (500 mg, 2 times/day) doubled the area under the curve (AUC) of Esomeprazol. Concomitant use of Esomeprazol along with inhibitors both CYP2C19 and CYP3A4 may increase the concentration and exposure time of Esomeprazol. CYP2C19 and CYP3A4 Voriconazole inhibitors increase the AUCT of Omeprazol to 280%. No need to adjust the dose of Esomeprazol regularly in these cases. However, the adjustment of the dose should be considered in patients with severe liver failure or long -term indications.

CYP2C19 and/or CYP3A4 induction drugs: CYP2C19 or CYP3A4 induction drugs or both (such as rifampicin and st. John’s grass) can cause decreased serum ecomeprazol due to increased Esomeprazol metabolism.

Pediatric patients: Medicine interaction studies are only done in adults.