Gaspemin 40mg ACME treatment of gastroesophageal reflux disease, gastrointestinal ulcer (3 blisters x 10 tablets)

Preventive treatment for hemorrhage recurrence in patients with stomach ulcers - duodenal ulcer after taking intravenously Esomeprazole.

teenagers 12 - 18 years old

Gastroesophageal reflux disease (Gord):

Pharmacokinus

Pharmacological group: Proton pump inhibitors (PPI).

ATC code: a02bc05.

Mechanism of action

Esomeprazole is a weak basic. In high acidic environments secreted by stomach wall cells, Esomeprazole transforms into active form, inhibits H+ K+ enzyme inhibitors - ATPASE - Acid pumps. Esomeprazole's activity is inhibited both as usual and when there is an acid -increasing stimulus factor.

affects gastric acid secretion

After taking a dose of 20 mg or 40 mg Esomeprazole, the effect of the drug begins within 1 hour. After repeating the dose of Esomeprazole 20 mg/time/day for 5 days, the amount of acid peak after stimulating Pentagastrin decreases about 90 % when measured at 6-7 hours after drinking the fifth dose.

After five days of taking the dose of Esomeprazole 20 mg/day/time or 40 mg/day/day, the stomach pH is maintained at over 4 in the range of 13-17 hours, and 24 hours in patients with Gord symptoms. The proportion of patients after oral repeated dose of 20 mg/day/time with stomach pH maintained over 4 for at least 8, 12, 16 hours are 76%, 54%and 24%respectively. The ratio corresponds to the dose of 40 mg/time/day is 97%, 92%and 56%.

Acid inhibitor treatment effect

With a dose of 40 mg Esomeprazole/time/day, the healing rate of ulcers in esophageal reflux after 4 weeks of treatment is 78% of patients and after 8 weeks of treatment is 93% of patients.

Esomeprazole dose of 20 mg/day/time in combination with appropriate antibiotics for a week, about 90% of patients remove Helicobacter pylori.

Other effects related to acid secretion

While treating with PPIS, the serum gastrin level increases in corresponding to the reduction of acid secretion. Chromogranin A (CGA) also increases due to decrease in stomach acid levels.

Increased increased number of ECl cells (Enthochromaffin - likes) may be related to the increase in serum gastrin levels in patients with long -term treatment with ecomeprazole.

Long -term treatment with ppi drugs has recorded cases of gastric gland cysts. However, these tumors are benign and can disappear by themselves.

Using Esomeprazole reduces stomach acid, leading to an increase in the number of normal stomach bacteria still appear in the digestive tract, slightly increasing the risk of gastrointestinal infections caused by Salmonella, Campylobacter, maybe clostridium difficile.

A comparative study with Rantidine shows that Esomeprazole has a better effect in healing stomach ulcers in patients using NSAIDs, including selective and non-selective COX-2 inhibitors.

Two comparative studies with placebo showed that the better effect of Esomeprazole in the prevention of stomach -duodenal ulcer in patients using NSAIDs (over 60 years old and a history of stomach - duodenal ulcer), including selective COX -2 inhibitors.

In a study conducted in Gord (1 - 17 years old) patients with long -term PPI treatment, 61% of children appear to increase ECL cells without clinical significance and no growth to atrophy or carcinoid tumor.

Dynamic pharmacokinetics

Absorb

Esomeprazole is used orally and is not durable in the acidic environment, so it is prepared in the form of tablets in the intestine. In the body, Esomeprazole converts negligible to R - isomer. Esomeprazole absorbs quickly through oral, peaked plasma concentrations after about 1-2 hours of drinking. Absolute bioavailability after taking the only 40 mg dose is 64% and increases to 89% after using many doses. For Esomeprazole 20mg of values, respectively, respectively, respectively, 68%. The food slows down and reduces the absorption of Esomeprazole, but does not significantly affect the effectiveness of Esomeprazole for stomach acid levels.

distribution

The distribution of healthy people is about 0.22 l/kg of body weight. Esomeprazole binds to plasma proteins about 97%.

transformation

Esomeprazole is completely transformed by the Cytochrome P450 (CYP) system mainly through CYP2C19 transformed into hydroxyl and desmethyl derivatives of Esomeprazole, the rest through CYP3A4 transformed into sulphone Esomeprazole - main metabolites in plasma.

Elimination

Plasma clearance is about 17 l/h after the single dose and about 9 l/h after repeated use. The sale time is about 1.3 hours after repeating the dose. Esomeprazole is completely removed from the body between doses and does not accumulate in the body.

The main metabolites of Esomeprazole do not work on gastric acid secretion. Nearly 80% of oral doses of Esomeprazole are excreted the metabolites through the urine, the rest in the feces. Only less than 1% of Esomeprazole has not metabolized excreted through urine.

Special subjects

Weak metabolism

about 2.9 ± 1.5% of the population has a weak enzyme CYP2C19 and is called a weak metabolic group. In these people, Esomeprazole metabolizes mainly through CYP3A4. After the daily dose is 40 mg, compared to those who have metabolized through the strong CYP2C19, the area under the curve shows the drug concentration in plasma (ACMAX) of Esomeprazole in these patients twice as high as those who have metabolized through CYP2C19 strong, the peak concentration in plasma increases by about 60%. However, no need to adjust the dose of Esomeprazole with these patients.

kidney failure

There is no study on the change of pharmacokinetics parameters of Esomeprazole in patients with renal failure. Because almost only metabolites of Esomeprazole are eliminated through the kidneys, the pharmacokinetics of the drug change negligible in patients with renal impairment.

Hepatic failure

In people with liver function, the bioavailability of the drug tank and the clearance of drugs decreases, but there is no accumulation of drugs and metabolites of the drug in the body. Metabolic reduction in patients with severe liver dysfunction leads to double ACMAX of Esomeprazole. Therefore, for patients with severe liver dysfunction, the dose must not exceed 20 mg.

Elderly

The pharmacokinetics of the drug changes without clinical significance in the elderly.

Youth from 12 - 18 years old

After repeating the dose of Esomeprazole 20 mg/day/time or 40 mg/day/day, the total area under the curve (AUC) and the time to reach the maximum concentration (TMAX) in teenagers 12 - 18 years old similar to adults with the corresponding dose.

The initial dose is recommended as 40 mg of esomeprazole/time x 2 times/day. The dosage can then be adjusted depending on the patient's pathology. Based on the existing clinical data, most patients may be controlled when using the dosage between 80 - 160 mg Esomeprazole daily. With a dose of over 80 mg/day, the dose should be divided 2 times/day.

teenagers over 12 years old

Treatment of duodenal ulcer caused by Helicobacter pylori:

Be cautious when using

need to be very careful when taking the drug for patients in the following cases:

Before using Esomeprazole, it is necessary to eliminate malignant stomach or malignant gastroenteritis, because it may temporarily overshadow the symptoms of malignant ulcer disease, thus slow diagnosis.

There is no recommendation to use PPI with Atazanavir. If this combination is inevitable, clinical monitoring (e.g., virus load) combines an increase in Atazanavir dose to 400 mg. With 100 mg of ritonavir, the dose of Esomeprazole recommends 20 mg/day.

Bacterial gastrointestinal infections: Like all proton pump inhibitors (PPI), Esomeprazole may increase the number of gastrointestinal bacteria. Treatment with Esomeprazole can lead to a slight increase in the risk of bacterial gastrointestinal infections such as Salmonella and Campylobacter or C. Difficile.

Like other gastric acid secretions, Esomprazole can reduce the absorption of vitamin B12 due to Hypo or Achlorhydria. Therefore, it is necessary to be cautious when treating Esomeprazole for a long time in patients with reduced absorption or with risk factors for reducing vitamin B12 absorption.

Hemiaphas' decrease in blood magnesium: Blood magnesium has been reported in patients treated with PPI drugs such as Esomeprazole for at least three months, and in many cases in a year. The serious manifestation of reduced magnesium blood is fatigue, delusion, convulsions, dizziness and ventricular arrhythmia may occur but silent symptoms and may be ignored. These symptoms may end when adding magnesium and stop using PPI.

Select lupus erythematosus (SCLE): Proton pump inhibitors can lead to SCLE. If the lesions occur, especially in the area of ​​sunlight exposure, and if it comes with joint pain, patients should be treated promptly and should consider stopping esomeprazole. Patients who appear SCLE when using Esomeprazole may also experience SCLE when using other PPIs.

fracture: PPI, especially if taken in high doses and is over a long period of time (1 year), may increase the risk of hip, wrist and spine fractures, mainly in the elderly or people with other risk factors. Observing research shows that PPIS may increase the risk of fractures by 10-40%. Some of these increase may be due to other risk factors. Patients at risk of osteoporosis should be taken care of under the current clinical instructions and need to be fully supplemented with vitamin D and calcium.

It is not recommended to simultaneously use Esomeprazole and Clopidogrel. Because Esomeprazole inhibits CYP2C19 is the metabolic catalyst enzyme of clopidogrel that reduces the effect of clopidogrel.

The drug contains lactose. Patients with rare genetic problems are galactose intolerance, deficiency of lactase lactase or malposure - galactose should not take this drug.

The effect of the drug on the ability to drive and operate machinery

The drug has little impact on the ability to drive and operate machinery. Some unwanted effects such as dizziness (rare), blurred (rare) vision may occur. If these unwanted effects occur, patients should not drive and operate machinery.

Use drugs for women during pregnancy and lactation

used for pregnant women

For Esomeprazole, there is no enough clinical data on pregnant women. According to epidemiological research on a large amount of pregnant cases using omeprazole mixed, non -toxic and deformity for the fetus. However, it is still necessary to be cautious when using drugs for pregnant women. Follow the indications from the doctor. The drug should only be used when the benefits are out of risks.

used for breastfeeding women

It is not known whether Esomeprazole will excrete in human milk or not. Therefore, it is necessary to consider stopping breastfeeding or stopping the medicine, depending on the benefits of Esomeprazole with the mother.

Drug interaction

Esomeprazole effect on pharmacokinetics of other drugs

According to studies, the concentration of protease inhibitors in plasma decreases when used simultaneously with omeprazole. Simultaneous use of omeprazole dose of 40 mg/day/day reduces 40% of Nelfinavir in plasma, down 75-90% of Nelfinavir's active metabolites. Use omeprazole 40 mg/day/day and Atazanavir 300 mg/ritonavir 100 mg on healthy people leads to 75% reduction of AUC of Atazanavir. Increasing the dose of Atazanavir to 400 mg also does not compensate for the amount of Atazanavir decline. Due to the pharmacokinetics and pharmacodynamics of Esomeprazole and Omeprazole similarly, it is not recommended to simultaneously use Esomeprazole and Atazanavir, contraindicated use Esomeprazole and Nelfinavir.

Esomeprazole treatment increases gastric acid leading to an increase or decrease in the absorption of drugs that the absorption mechanism is affected by stomach acid. For example, the absorption of ketoconazole and iTraconazole may decrease during treatment with Esomeprazole.

Esomeprazole inhibits CYP2C19, the main enzyme metabolizes Esomeprazole. Therefore, when Esomeprazole is used with metabolic drugs through CYP2C19 such as Diazepam, Citalopram, Imipramine, Clomipramine, Phenytoin ..., the concentration of these drugs in plasma can increase and decrease the dose. Concomitant use with Esomeprazole 30 mg oral form reduces 45% of Diazepam clearance - a metabolite through CYP2C19. When simultaneously used with Esomeprazole 40 mg orally and phenytoin increases 13% of the bottom plasma level (trough plasma level) of phenytoin in plasma in epilepsy patients. Should monitor phenytoin concentration in plasma when starting or stopping treatment with Esomeprazole. When using 40 mg of Esomeprazole oral in people who are being treated with warfarin in a clinical trial, it proves that the time of blood clotting is in an acceptable range. However, after bringing the oral drug to the market, there were some very rare cases of significant Inr clinical increase when treated simultaneously on the two drugs. The patient should be monitored from the beginning to the end of the treatment at the same time. In healthy volunteers, when used with 40 mg Esomeprazole oral and Cisapride, Cisapride's AUC increased to 32% and the sale time (T1/2) Cisapride lasted by 31% but the cisapride peak concentration increased negligible. Esomeprazole Sodium has been shown to be not a significant clinical effect on amoxicillin or quinidine pharmacokinetics.

The effect of other drugs on Esomeprazole's pharmacokinetics

Esomeprazole is metabolized by CYP2C19 and CYP3A4. When using Esomeprazole Sodium oral with a CYP3A4 inhibitor, Clarithromycin (500 mg, 2 times/day) doubled the area under the curve (AUC) of Esomeprazole. No need to adjust the dose of Esomeprazole.

Interactive mechanism

Methotrexate: simultaneously using high doses of methotrexate (300 mg) and proton pump inhibitors increase methotrexate levels in some patients. Therefore, patients using high doses of methotrexate (such as cancer and psoriasis) can temporarily stop using Esomeprazole.

Mutual medicine

Due to the absence of studies on the correlation of the drug, not mixing this drug with other drugs.