Esomeprazol 40 TV.Pharm Treatment of stomach ulcers, gastroesophageal reflux, esophagus (3 blisters x 10 tablets)

ATC code: A02b C05.

Esomeprazol is the S-Omeprazol isomer and reduces the excretion of gastric acid with a specialized mechanism of action. The specific inhibitor of acidic pump in the walls of the stomach wall. Both types of isomers R-and S- of Omeprazol have similar pharmacological effects.

Effectus mechanism: Esomeprazol is a weak base, converted into an active form in a high acidic environment, H+/K+ATPASE inhibitors (proton pump) in the stomach wall, inactivating this enzyme system and inhibiting basic acid secretion and secretion of acid discharge when stimulated.

Pharmacological effect: After taking Esomeprazol 20mg and 40mg, the drug is effective after 1 hour. After taking the dose repeated 20mg 1 time/day, for 5 days, due to the average maximum acid after stimulation with Pentagastrin decreased by 90% when measured at 6-7 hours after taking the drug on the 5th day.

After 5 days of using Esomeprazol 20mg and 40mg, the pH in the stomach> 4 is maintained within the average time, respectively, respectively, 17 hours and 17 hours in 24 hours in patients with gastroesophageal reflux disease. The proportion of patients maintaining stomach pH> 4 at least 8 hours, 12 hours and 16 hours corresponding to Esomeprazol 20mg is 76%, 54%, 24%and 97%, 92%, 56%for Esomeprazol 40mg.

When using AUC as a parameter representing the concentration of drugs in plasma, there is a relationship between acidic inhibition 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.

H.pylori treatment for 1 week with Esomeprazol 20mg and appropriate antibiotics, killed H.pylori, the success rate of about 90% of patients.

In a random, double clinical study, a restraint, the endoscopic patient was diagnosed with gastrointestinal hemorrhage according to the classification of IA, IB, IIA or IIB (equivalent to 9%, 43%, 38%and 10%), randomly treated with Esomeprazol infusion solution (N = 375) or placebo (N = 389).

After endoscopic treatment for hemostasis, the patient is placebo or is given an intravenous 80mg of Esomeprazol for 30 minutes and continuously transferred 8mg per hour, for 72 hours. After 72 hours, all patients are continued to treat with 40mg of esomeprazol oral form for 27 days. The rate of gastrointestinal hemorrhage occurred within 3 days is 5.9% in the Esomeprazol treatment group compared to the placebo group of 10.3%.

After 30 days of treatment, the rate of gastrointestinal bleeding in the Esomeprazol treatment group is 7.7% compared to the placebo group of 13.6%.

During treatment, serum gastrin concentration increases corresponding to the reduction of gastric acid levels. CGA concentration also increases due to decrease in gastric acid, increased CGA levels can affect test screening test for endocrine nerve tumors. Reports have shown that the treatment of proton pump inhibitors should be stopped from 5 days to 2 weeks before quantifying CGA.

After a long period of treatment with gastric acid, it has recorded a slight increase in benign gastric cysts and can recover when stopped taking the drug.

Reducing stomach acid due to any cause, including using proton pump inhibitors, increasing the number of bacteria in the digestive tract. Treatment with proton pump inhibitors can lead to an increased risk of gastrointestinal infections caused by Salmonella and Campylobacter and Clostridium difficile in boarding patients.

Clinical effect: In two studies using ranitidine as a comparative substance, Esomeprazol shows better effect in healing stomach ulcers in patients using NSAIDs, including NSAID selected CDX-2.

In two studies with fake, Esomeprazol shows a better effect in preventing stomach and duodenal ulcers in patients using NSAID (age> 60 or previous ulcer), including NSAID selected CDX-2.

Children: In a study in patients with gastroesophageal reflux (

pharmacokinetics

absorption: Esomeprazol is easily decomposed in acidic environment and drinking in the form of tablets in the intestine. Invivo testing has converted into r isomers but is not significant. Esomeprazol absorbs quickly after drinking, reaching the peak concentration in plasma after 1-2 hours. Absolute bioavailability is 64% after taking Esomeprazol 40mg and increases to 89% after the dose is repeated. For Esomeprazol 20mg, absolutely can be 50% and increase to 68% after the dose is repeated.

Food slows down or reduces the absorption of ecomeprazol, but does not significantly affect the effects of ecomeprazol to the acidity in the stomach.

Distribution: The appointed distribution volume on healthy people is about 0.22 liters/kg of body weight. About 97% Esomeprazol attached to plasma proteins.

metabolism: The drug is metabolized mainly in the liver thanks to the cytochrom P450 enzyme system. The main part of the metabolism of Esomeprazol depends on the polymorphic isoenzyme CYP2C19, into hydroxy and desmethyl metabolites that are no longer active, the rest is converted through isenzyme CYP3A4 to Esomeprazol Sulphon, the main metabolic substance in plasma.

Elimination: The following parameters reflect mainly pharmacokinetics in people with strong metabolic CYP2C19 enzymes.

The total plasma clearance is about 17 liters/hour after taking a single dose and about 9 liters/hour after the dose is repeated. Selling time for plasma is about 1.3 hours. Nearly 80% of Esomeprazol is eliminated through urine in the form of inactive metabolism, the rest is eliminated through feces. Less than 1% of constant drugs are eliminated in urine.

Special subject group:

Poor metabolic group: about 2.9 ± 1.5% of patients with CYP2C19 enzyme deficiency and are called poor metabolic groups. In these patients, the metabolism of Esomeprazol is mainly thanks to the CYP3A4 enzyme. After the dose repeats 40mg of Esomeprazol, 1 time/day, the area under the average curve in the metabolic person is about 100% lower than the strong metabolic group. The average peak concentration in plasma increased by about 60%. These records do not affect the dose of Esomeprazol.

Sex: After using the only dose of Esomeprazol 40mg, the area under the average curve in women is about 30%higher than men. Do not record the difference of the area under the curve between women and men after the dose is repeated.

Hepatic failure: Esomeprazole metabolism may be impaired in patients with mild to medium liver dysfunction. Esomeprazol metabolism rate decreases in patients with severe liver dysfunction, resulting in doubling the area under the Esomeprazol curve. Therefore, do not overdose a maximum of 20mg of Esomeprazol in patients with severe liver dysfunction. Esomeprazol and the main metabolites do not tend to accumulate when used 1 time/day.

Renal failure: There is no research in patients with impaired renal function. Most eliminated drugs in the form of metabolism are no longer active, not responsible for the elimination of drugs in a constant form. Esomeprazol metabolism does not change in patients with impaired renal function.

Elderly: Esomeprazol metabolism does not change significantly in elderly patients (71-80 years old).

Adolescents aged 12-18: After using the repeated dose of Esomeprazol 20mg and Esomeprazol 40mg, the area under the AUC curve and the time to reach the maximum drug concentration in the plasma is similar to adults the dose of 20mg and 40mg.

Patients need to be treated with anti-inflammatory drugs (NSAID) continuously:

The suggested dose is:

Be cautious when using

Please see more information about the drug in the instruction sheet of the use of the drug attached.

Need to be very cautious when taking drugs for patients in the following cases:

When there is any alarm symptom (such as significant weight loss, recurrent vomiting, difficulty swallowing, vomiting of blood or black bowel movements) and when suspected or gastric ulcer, eliminate malignant diseases because Esomeprazol treatment can reduce symptoms and delay diagnostic.

Long -term treatment: More than a year, should be monitored regularly.

According to the treatment regime when necessary: ​​Contact your doctor (or medical staff) if you see the symptoms that change.

Destroy Helicobacter pylori: When indicating Esomeprazol to kill Helicobacter pylori, interactions can occur with 3 drug treatment regimens. Clarithromycin is a strong CYP3A4 inhibitor, so it is advisable to consider contraindicated and interact with Clarithromycin when using 3 drug treatment regimens in patients who are taking other drugs metabolized through CYP3A4 as Cisaprid.

Gastrointestinal infections: Proton pump inhibitors may slightly increase the risk of gastrointestinal tract infections caused by Salmonella and Campylobacter. Vitamin B12 absorption: Esomeprazol as well as all other antacids, which can reduce the absorption of vitamin B12 due to reduction or deficiency of hydrochloride acid. Treatment should be considered in mild weight patients or have risk factors for reducing vitamin B12 absorption when long -term treatment.

Lack of blood magnesia: Some cases of severe blood magnesia are reported in patients treated with proton pump inhibitors such as Esomeprazol for at least 3 months and most cases after 1 year treatment. Manifestations of serious blood magnesium such as fatigue, muscle spasticity, delirium, convulsions, dizziness, arrhythmia may occur but silently started and overlooked. Most patients, blood magnesium deficiency improved after supplementing magnesi and stopped using proton pump inhibitors.

For patients who need long -term treatment or simultaneous use of proton pump inhibitors with digoxin or drugs that cause blood magnesium (such as diuretics), should consider quantifying the blood level in the blood before starting treatment with proton pump inhibitors and periodic testing during treatment.

Risk of fractures: Using proton pump inhibitors, especially when high doses and for a long time (> 1 year), may increase the risk of hip, wrist and backbone fractures, mainly occurs in elderly patients or when there are other risk factors. Observatory studies show that proton pump inhibitors increase the risk of fractures by 10-40%. Part of this increase may be due to other risk factors. Patients at risk of osteoporosis should be supplemented with vitamin D and calcium.

Selling lupus skin lesions (SCLE): Proton pump inhibitors are less associated with cases of semi -exponent lupus skin lesions. If the damage occurs, especially in the skin exposed to the sun and if accompanied by joint pain, see a doctor or medical staff to consider stopping Esomeprazol.

Coordinate with other drugs: Should not use Esomeprazol simultaneously with Atazanavir (see the drug interaction). If it is required to combine Atazanavir with proton pump inhibitors, clinically closely monitoring when coordinating with increased dose of Atazanavir to 400mg, with Ritonavir to 100mg; Esomeprazol 20mg should not be used overdose.

Esomeprazol is a CYP2C19 inhibitor, when starting or ending treatment with Esomeprazol, the risk of drug interaction with metabolic drugs should be considered for CYP2C19. In an observed interaction between Clopidogrel and Esomeprazol (see the drug interaction). The clinical involvement of this interaction has not been determined. Should be cautious, not recommended to simultaneously use Esomeprazol and Clopidogrel.

When necessary, Esomeprazol is needed in treatment, it is advisable to consider the ability to interact with other drugs based on the oscillation of the concentration of Esomeprazol in plasma (see the drug interaction).

Interaction with tests: Increased chromographin A (CGA) level, which can affect endocrine nerve screening tests. To avoid this effect, it is recommended to stop treating with Esomeprazol at least 5 days before quantifying CGA (see the pharmacological part).

If CGA and Gastrin levels are not at normal limits after the first test, repeat the 14 -day test after stopping treatment with Proton pump inhibitors.

The effect of the drug on driving and operating machinery

Esomeprazole has little effect on driving and operating machinery. Side effects include dizziness (rare) and blurred (rare) vision (see the unwanted effect of the drug). If these reactions occur, patients should not drive or use machines.

Use drugs for women during pregnancy and lactation

Use drugs for pregnant women: Not enough clinical data in pregnant women. When using omeprazol racemic polymorphic mixture, large amounts of pregnant women use drugs that do not cause defects and toxicity on the fetus. Studies using Esomeprazol on animals do not indicate the direct or indirect harmful effect on the development of the fetal embryo. Animal research with Racemic mixture also gives similar results. Should be cautious when indicated for pregnant women.

Use medicine for nursing women: It is unknown whether esomeprazol is excreted through breast milk or not. Not enough information about the influence of Esomeprazol in newborn children/young children. Esomeprazol should not be used while breastfeeding.

Drug interaction

Interaction of drugs:

Esomeprazol's effect on the pharmacokinetics of other drugs:

Protease inhibitors: Omeprazol has been reported to interact with some protease inhibitors. It is unclear clinical importance and mechanism of action of the recorded interactions. Increasing stomach pH during treatment with omeprazol can lead to a change in the absorption of protease inhibitors. Other interactive mechanisms can occur through CYP2C19 enzyme inhibition.

For Atazanavir and Nelfinavir: Reducing serum medication concentration has been reported when used with omeprazol. Recommendations should not be used simultaneously.

Simultaneous use Omeprazol 40mg, 1 time/day with Atazanavir 300mg/ritonavir 100mg, in healthy volunteers, significantly reduces the effects of Atazanavir (reduced AUC, CMAX, Cmin remaining about 75%). Increasing Atazanavir dose to 400mg does not compensate for the effects of omeprazol on the effect of Atazanavir.

Simultaneous use Omeprazol 20mg, 1 time/day with Atazanavir 400mg/Ritonavir 100mg, in healthy volunteers, reducing about 30% of Atazanavir effects when compared to the effect of Atazanavir 300mg/Ritonavir 100mg, 1 time/day.

Use combination omeprazol 40mg, 1 time/day reduces the average value of AUC, CMAX, CMIN of Nelfinavir by 36-39% and decreases about 75-92% of the average value of AUC, CMAX, CMIN of active metabolites that have the reasonable effect of M8.

Due to the pharmacokinetic and pharmacokinetic properties of Omeprazol and Esomeprazol are similar, should not be used simultaneously Esomeprazol with Atazanavir and should not be used simultaneously Esomeprazol with nelfinavir (see the contrary section).

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

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

tacrolimus: simultaneously used with esomeprazol is reported to increase the concentration of tacrolimus in serum. Tacrolimus concentration should be closely monitored as well as kidney function (creatinine clearance).

Drugs absorb depending on the pH

Inhibiting gastric acid secretion during treatment with ecomeprazol and other proton pump inhibitors can reduce or increase the absorption of drugs with a mechanism of absorption depending on the stomach pH. The absorption of drugs such as ketoconazole, otraconazole and erlotinib may decrease and the absorption of digoxin may increase when treated with ecomeprazol.

Simultaneous treatment of omeprazol (20mg/day) with digoxin in healthy volunteers, increases the bioavailability of 10% Digoxin (up to 30% in 2 out of 10 research objects). Digoxin toxicity is rarely reported. However, be careful with older patients assigned to Esomeprazol at high doses. Should monitor regularly when treated with digoxin.

Metabolic drugs by CYP2C19 enzyme

Esomeprazol inhibits CYP2C19, the main enzyme metabolizes Esomeprazol. Therefore, when used in combination with metabolic drugs through CYP2C19 such as diazepam, citalopram, imipramin, clomipramin, phenytoin ..., plasma concentrations of these drugs may increase and need to reduce the dose, especially when prescribing Esomeprazol under the treatment mode when necessary.

Phenytoin: Concentrated with Esomeprazol 40mg, increasing the level of phenytoin in plasma 13% in epilepsy patients. Should monitor phenytoin concentration in plasma when treated with ecomeprazol is necessary or stop using esomeprazol.

Voriconazole: Omeprazol 40mg, 1 time/day, increasing 15% cmax and 45% AUC of Voriconazol.

cilostazol: Omeprazol as well as Esomeprazol, inhibit CYP2C19. Omeprazol 40mg dose for healthy volunteers in a cross -sectional study, increasing by 18% cmax and 26% AUC of Cilostazol and an increase of 29% cmax and 69% AUC a metabolic metabolites with Cilostazol activity.

Cisaprid: In healthy volunteers, simultaneously use 1 Esomeprazol 40mg tablet resulting in an increase of 32% AUC and the sale time (T1/2) lasts 31% but there is no sign of increasing the concentration of Cisaprid's absorption peak. Extending the QT interval recorded after using a solitary cisaprid dose, not extending any more when using Cisaprid in combination with Esomeprazol (see the warning and caution when taking the drug).

Warfarin: Simultaneously use 1 Esomeprazol 40mg tablet for patients with Warfarin treatment in clinical trials shows that blood clotting time is in an acceptable range. However, there are some rare cases of significant increase in Inr signs (testing tests for blood clots) clinically reported during simultaneous treatment. The patient should be monitored at the beginning and ending the treatment simultaneously Esomeprazol and Warfarin or other derivatives of Coumarin.

Clopidogrel: The results from a healthy object have shown that the pharmacokinetic/pharmacokinetic interaction between clopidogrel (attack dose of 300mg/daily maintenance dose of 75mg) and Esomeprazol 40mg (1 time/day), the result is to reduce the active metabolic effect of clopidogrel about 40% and lead to reduction in the ability to inhibit platelets about 14%.

In a healthy person study, Clopidogrel simultaneous use with a fixed dose of Esomeprazol 20mg + Aspirin 81mg, reducing about 40% of the active metabolites of clopidogrel compared to the group using mere clopidogrel. However, the maximum level of platelets inhibitors in two groups of clopidogrel medication and simultaneous use of clopidogrel (Esomeprazol + Aspirin) is the same.

Clinical manifestations of pharmacokinetic/pharmacokinetic interactions of Esomeprazol on the main cardiovascular event from clinical observation and clinical research studies are not consistent. Disecurrent use Esomeprazol and Clopidrogel.

Survey of drugs without clinical interactions:

Amoxicilin and Quinidine: Esomeprazol does not affect the pharmacokinetics of amoxicillin or quinidine.

Naproxen or Rofecoxib: Short -term research evaluating the use of Esomeprazol simultaneously with Naproxen or Rofecoxib has not identified any clinically related pharmacokinetic interactions.

The effect of other drugs on Esomeprazol pharmacokinetics:

Esomeprazol is metabolized by CYP2C19 and CYP3A4 enzymes. Concomitant use of Esomeprazol and a CYP3A4 inhibitor, Clarithromycin (500mg/2 times a day), resulting in double AUC of Esomeprazol. Simultaneous use of Esomeprazol with inhibitors inhibit both CYP2C19 and CYP3A4 enzymes may increase more than the AUC of Esomeprazol.

Voriconazole inhibits both CYP2C19 and CYP3A4 enzymes increasing the AUC of Omeprazol to 280%. Usually do not require adjusting the dose in both cases. However, the dose adjustment should be considered in patients with severe liver failure and is indicated for long -term treatment.

Enzyme CYP2C19 or CYP3A4: CYP2C19 or CYP3A4 induction drugs or both (such as rifampicin and st.john's grass) can reduce serum esomeprazol levels due to Esomeprazol metabolism.

Children: Interactive drugs are only conducted in adults.

The cavalry of the drug: due to the absence of studies on the correlation of the drug, not mixing this drug with other drugs.