Jiracek 40mg Davipharm medicine for stomach - duodenal ulcer (4 blisters x 7 tablets)

Esomeprazol is used for children to treat gastroesophageal reflux disease - esophagus and scratched esophagitis.

Pharmacology

Pharmacological group: Aggress inhibitors of gastric acids belonging to the proton pump inhibitor group.

ATC code: A02BC05.

Esomeprazol is the S isomers of omeprazol, used similarly to Omeprazol in the treatment of gastric ulcer - duodenum and gastroesophageal reflux disease and Zollinger -Elison syndrome.

Esomeprazol is a weak base, attached to H+/K+-Aatpase (also known as proton pump) in the cell wall of the stomach, inactivating this enzyme system, preventing the final step of the excretion of hydrochloric acid in the stomach. Therefore, Esomeprazol has the effect of inhibiting the stomach secretion of basic acid and even when stimulated by any agent. The drug works strongly, prolonged.

Proton pump inhibitors have an inhibitory but not except for Helicobacter pylori, so it must be coordinated with antibiotics (such as amoxicillin, tetracycline and clarithromycin) to effectively eradicate this bacteria.

pharmacokinetics

absorption: Esomeprazol is an unstable substance in an acidic environment and is taken orally in the form of a tablet in the intestine. In Vivo, Esomeprazol is transferred to negligible r-Isomer isomer. Esomeprazol absorbs quickly after oral, promoting within 1 hour, reaching the highest concentration in plasma after 1-2 hours. Esomeprazol's bioavailability increases according to the dose and when reminded: reaching about 50% after using the only 20 mg dose, increasing to 68% when the dose is repeated daily, 64% when using a single dose of 40 mg and up to 89% after daily dose. Food slows down and reduces the absorption of Esomeprazol, but does not change the effect of the effect of the drug on the concentration of acid in the stomach. The area under the curve (AUC) after taking a single dose Esomeprazol 40 mg at meals compared to the hunger decreased from 43% to 53%. Therefore, Esomeprazol should take at least 1 hour before meals.

distribution:

About 97% Esomeprazol attaches to plasma proteins. The volume of distribution when the concentration of drugs is stable in healthy volunteers is 0.22 l/kg body weight.

metabolism:

The main metabolic drug in the liver thanks to the cytochrom P450 enzyme system, isenzyme CYP2C19 into hydroxy and desmethyl metabolites is no longer active, the rest is converted through isoenzyme CYP3A4 into esomeprazol sulfon. When used repeated, initially metabolized through the liver and the clearance of the drug reduced, possibly due to the inhibited ISOENZYM CYP2C19. However, there is no phenomenon of accumulation of drugs when used once a day.

excretion:

The total removal of the drug in plasma is about 17 l/hour after taking the only dose and about 9 l/hour after taking the dose repeated. Selling time for plasma is about 1.3 hours. Esomeprazol is completely eliminated from the plasma between the doses and does not cause accumulation when taking the dose repeated once a day. The main metabolites of Esomeprazol does not affect stomach acid secretion. About 80% of oral doses are eliminated in the form of non -active metabolites in the urine, the rest is eliminated in the feces. Under 1% of the drug is eliminated in the urine.

linear/linearly: Esomeprazol's

pharmacokinetics has been studied at a dose of up to 40 mg twice a day. The area below the concentration curve over time (AUC) increases when using the repeated dose esomeprazol. This increase depends on the dose and leads to an increase in AUC at a larger rate than the dose increase after the dose is repeated. This time and dosage dependence is due to the first metabolism of the liver and the whole body, possibly due to the effect of inhibiting CYP2C19 of esomeprazol and/or its sulphon metabolism.

pharmacokinetics on special subjects:

Poor metabolic people:

In some people because of the lack of CYP2C19 due to genetics (15-20% of Asians), they should slow down the metabolism of Esomeprazol. In these people, Esomeprazol's metabolism is mainly catalyzed by CYP3A4 enzyme. In a stable state, the AUC value in people deficient in CYP2C19 enzyme increases about 2 times compared to people with enough enzymes.

Sex:

After taking the single dose of Esomeprazol 40 mg, AUC in women is about 30%higher than men. There is no difference between gender when using daily dose.

Hepatic failure:

Esomeprazol metabolism in people with medium and mild liver dysfunction may decrease. The metabolic rate decreases in patients with severe liver dysfunction that doubles the AUC of Esomeprazol. Therefore, do not use more than 20 mg of esomeprazol for patients with severe disorders. Esomeprazol and its main metabolites do not cause accumulation when used 1 time/day.

kidney failure:

There have been no studies conducted in patients with impaired renal function. Because the kidney plays the role of eliminating the metabolites of Esomeprazol but does not eliminate the original active ingredient, the metabolism of Esomeprazol may not change in patients with impaired renal function.

Elderly:

Esomeprazol metabolism has not changed significantly on the subject of the elderly (71-80 years old).

Children:

Adolescents 12-18 years old: After repeating Esomeprazol dose of 20 mg and 40 mg, AUC and TMAX in objects 12 - 18 years old similar to adults in both doses.

Very rare, ADR

Instructions for handling ADR:

Must stop the drug when there is a severe ADR manifestation. Notify physicians of unwanted effects when using the drug.

Be cautious when used

Before taking proton pump inhibitors, it is necessary to eliminate the possibility of stomach cancer because the drug can cover symptoms, slow down the diagnosis of cancer.

Be cautious when used in people with liver disease, pregnant or nursing.

Prolonged treatment patients (especially over 1 year): Should be monitored regularly.

using ecomeprazol can cause gastric atrophy or an increased risk of infection (such as pneumonia in the community).

Patients treated as required: should be instructed to contact the doctor if there is a change in the properties of symptoms.

Helicobacter pylori:

It is necessary to consider the possibility of interacting with other drugs when taking Esomeprazol in the Helicobacter pylori kills. Clarithromycin is a powerful CYP3A4 inhibitor, so it should be noted for the contraindications and interactions of Clarithromycin when using Clarithromycin in the 3 -drug regimen for patients who are using concurrently metabolic drugs through CYP3A4 as Cisaprid.

Gastrointestinal infections:

Treatment with proton pump inhibitors may increase the risk of gastrointestinal infections such as Samonella and Campylobacter.

may increase the risk of diarrhea due to Clostridium difficile when using proton pump inhibitors.

Absorb vitamin B12:

As other antacids, Esomeprazol can reduce the absorption of vitamin B12 (cyanocobalamin) due to the effect of reducing or deficiency of gastric acid. It is necessary to consider when taking the drug for patients with a reduced reserve of vitamin B12 or have risk factors that reduce the absorption of vitamin B12 when treated for a long time.

Hypotension (with or asymptomatic) rarely encountered in patients using prolonged proton pump inhibitors (at least 3 months or in most cases that last for more than 1 year).

There have been cases of severe magnesi in patients treated with proton pump inhibitors such as Esomeprazol for at least 3 months and in most cases that last for more than 1 year. The serious manifestation of the blood magnesi such as fatigue, spasticity, delirium, convulsions, dizziness and ventricular arrhythmia may occur, but these symptoms may not be clear and overlooked. In patients most affected, the condition of lowering blood magnesium can be improved after stopping the drug and replacing Magnesi.

For patients who are likely to be treated with prolonged proton pump inhibitors or use in combination with digoxin or other drugs that can cause other blood magnesium (such as diuretics), treatment doctors should conduct testing and evaluation of blood blood levels before starting treatment and periodically during treatment with proton pump inhibitors, including Esomeprazole.

Risk of fractures:

When using proton pump inhibitors, especially when taking high and prolonged doses (≥ 1 year), it may increase the risk of pelvic fractures, wrist or spine due to osteoporosis, mainly occurs in the elderly or people with risk factors available. The mechanism of this phenomenon has not been explained, but it may be due to reducing unanimidated calcium absorption due to gastric pH hypoglycemia. The lowest dosage recommendation works in the shortest possible time, suitable for clinical status. Patients at risk of osteoporosis should use enough calcium and vitamin D, assess bone condition and manage as instructed.

Lupus erythematosus in the skin (SCLE):

Proton pump inhibitors are related to frequency of non -frequency SCLE. If the damage occurs, especially the skin in direct sun exposure to the sun, with joint pain, it is recommended that patients see a doctor and consider stopping the drug for the patient. The patient had a history of SCLE after taking a proton pump inhibitor that could increase the risk of SCLE with other proton pump inhibitors.

Use other drugs:

It is not recommended to simultaneously use Esomeprazol and Atazanavir. If required, it must be closely monitored, increasing the atzanavir dose to 400 mg in combination with 100 mg of ritonavir, should not use Esomeprazol more than 20 mg.

Esomeprazol is CYP2C19 inhibitor. When starting or ending treatment with esomeprazol, it is necessary to consider the interactions that may occur with metabolic drugs through CYP2C19. There have been drug interaction reports between clopidogrel and esomeprazol. The clinical relevance of this interaction is uncertain. Be careful with this interaction, not recommended to simultaneously use Esomeprazol and Clopidogrel.

Subclinical tests:

Increased chromographin A (CGA) can hinder the diagnosis of endocrine nerve tumors. To avoid this effect, stop Esomeprazol at least 5 days before CGA test.

Be cautious for excipients Magnesi Hydroxid

The drug contains magnesium magnesi laxative, which can lead to diarrhea.

Hypergathed blood (causing hypotension, mental impairment, coma), especially cautious when used for people with kidney failure.

to be out of reach of children.

The effect of the drug on driving and operating machinery

Esomeprazol slightly affects the ability to drive and operate machinery. Unwanted effects such as: headache, dizziness (rare), drowsiness, reduction of vision (rare) ... Be careful when participating in dangerous activities that need alertness such as working on high, operating machinery or driving train.

Use drugs for women during pregnancy and lactation

Pregnancy

There is no adequate study when using Esomeprazol in pregnant people. On animals, white rats oral Esomeprazol dose of 280 mg/kg/day (57 times the dose on humans calculated by the body surface area) and the oral rabbit dose of 86 mg/kg/day (35 times the dose on humans calculated by the surface area of ​​the body) does not see evidence of reproductive or toxic fetus due to Esomeprazol. However, only use Esomeprazol during pregnancy when really necessary.

Breastfeeding period

It is not known whether esomeprazole will excrete in milk or not. However, omeprazol is distributed into breast milk.

Esomeprazol is likely to cause unwanted effects in breastfed babies, so it is necessary to decide to stop breastfeeding or stop the drug, depending on the importance of the medication for the mother.

fertility

Animal research with racemic mixture of omeprazol oral oral use is not visible on fertility.

Drug interaction

Esomeprazol's effect on pharmacokinetics of other drugs:

Protease inhibitors

There has been an interactive report between omeprazol and some protease inhibitors. Clinical importance and mechanism behind these interactions are unknown. Gastric pH increases during omeprazol treatment may change the absorption of protease inhibitors. Other mechanisms that can be explained to the above interaction are through CYP2C19 inhibition. There have been reports to reduce serum levels of Aticanavir and Nelfinavir when used simultaneously with omeprazol, so it can reduce antiviral effects. It is not recommended to simultaneously use these drugs. Because Omeprazol and Esomeprazol are similar in terms of pharmacokinetics and pharmacokinetics, it is not recommended to simultaneously use Esomeprazol and Atazanavir and Conv Lend to simultaneously use Esomeprazol and Nelfinavir.

Omeprazol (40 mg/day) increases the serum concentration of saqinavir (ritonavir combination) 80 - 100%. Omeprazol 20 mg/day does not affect the bioavailability of Darunavir (Ritonavir) or Amprenavir (Ritonavir). Esomeprazol 20 mg/day does not affect the bioavailability of Amprenavir (whether or not ritonavir). Omeprazol 40 mg/day does not affect the bioavailability of Lopinavir (Ritonavir combination).

methotrexate:

Increased methotrexate levels in some patients when using proton pump inhibitors simultaneously. Consider the discontinuation of Esomeprazol when indicating high doses of methotrexate for patients.

tacrolimus:

Increased serum concentration of tacrolimus when using Esomeprazol simultaneously. Tacrolimus concentration should be closely monitored as well as monitoring the patient's kidney function (CLCR), adjusting the tacrolimus dose if necessary.

Absorbed drug depends on pH:

Inhibiting gastric acid secretion when treated with ecomeprazol or other proton pump inhibitors may increase or reduce the absorption of drugs that depend on the pH of the stomach. Increasing gastric pH reduces some drugs such as ketoconazole, otraconazole and erlotinib and increases the absorption of drugs like digoxin. The toxicity of digoxin is rarely reported, however, careful when taking high doses of Esomeprazol for the elderly. Closely monitor the treatment process with digoxin.

The drug is metabolized by CYP2C19:

Esomeprazol inhibits CYP2C19, the main metabolic enzyme of Esomeprazol. Therefore, when using Esomeprazol simultaneously with metabolic drugs by CYP2C19 such as Diazepam, Citalopram, Imipramin, Clomipramin, Phenitoin will increase the concentration of the above drugs in plasma, which may need to reduce the dose.

diazepam: simultaneously use Esomeprazol and Diazepam to reduce diazepam metabolism and increase diazepam concentration in plasma.

Phenytoin: simultaneously use 40 mg of Esomeprazol to increase the level of phenytoin in plasma of epilepsy patients. Recommendation for monitoring phenytoin concentrations in plasma when starting or stopping treatment with Esomeprazol.

Voriconazole: Omeprazol (40 mg/day) increases CMAX and AUC of Voriconazole, respectively 15% and 11% respectively.

Cilostazol: Concomitance Esomeprazol with cilostazol increases the level of Cilostazol and its active metabolites, considering reducing the dose of cilostazol.

Cisaprid: In healthy volunteers, simultaneously used with Esomeprazol 40 mg increases AUC and prolongs the sale time but does not significantly increase the peak concentration in the plasma of Cisaprid. There has been a report that extends the mild QT period after using only Cisaprid and does not last longer when using Cisaprid with Esomeprazol.

Warfarin: Inrang and prothrombin time when using warfarin simultaneously with proton pump inhibitors, can cause abnormal bleeding and death. Follow the INR and the prothrombin time at the beginning and at the end of Esomeprazol treatment simultaneously with Warfarin or other Coumarin derivatives.

Clopidogrel: Use the same proton pump inhibitors reduces the plasma concentration of the metabolites that have the activity of clopidogrel that reduces platelet resistance.

Use Esomeprazol with CYP2C19 and CYP3A4 induction drugs such as rifampin reduces Esomeprazol levels, avoiding simultaneous use.

Research on drugs without clinical interactions:

amoxicillin and quinidine:

There is no influence of ecomeprazol on amoxicillin pharmacokinetics, clinical quinidine.

Naproxen or Rofecoxib:

In short -term studies, simultaneously used Esomeprazol with Naproxen or Rofecoxib, there is no clinical pharmacokinetic interaction.

Effect of other drugs to be kinetic to Esomeprazol:

CYP2C19 and/or CYP3A4 inhibitors:

Esomeprazol metabolized by CYP2C19 and CYP3A4. Concomitant use of Esomeprazol and a CYP3A4 inhibitor such as Clarythromycin (500 mg x 2 times/day) double the AUC of Esomeprazol. Simultaneous use of ecomeprazol and clarithromycin increases the concentration of ecomeprazol and 14-hydroxyclarithromycin in the blood.

Simultaneous use of Esomeprazol and an inhibitor both CYP2C19 and CYP3A4 may increase more than the AUC of Esomeprazol. Voriconazole inhibits CYP2C19 and CYP3A4, increasing the AUC of Esomeprazol about 280%, considering in patients with high doses of Esomeprazol (240 mg/day) like Zollinger-Elison syndrome treatment.

In these cases, the adjustment of the dose may not be necessary. However, considering adjusting the dose when taking the drug for patients with severe hepatic failure or being indicated for prolonged treatment.

CYP2C19 and/or CYP3A4 induction drugs:

CYP2C19 or CYP3A4 induction drugs or both (such as Rifamicin and St John's Wort) can reduce serum ecomeprazol levels due to increased Esomeprazol metabolism.

Sucralfate: Inhibition of absorption and reducing the bioavailability of proton pump inhibitors. Use proton pump inhibitors at least 30 minutes before using sucralfat.

Pharmacological interaction:

may increase the risk of hypoglycemia when taking ecomeprazol and drugs that also causes hypotension such as thiazid diuretics, strap diuretic. Check blood magnesium levels before taking proton pump inhibitors and periodically.

Digoxin: Lowering blood magnesia due to prolonged use of proton pump inhibitors that cause heart muscle to increase sensitivity to digoxin, which can increase the risk of toxicity to Digoxin's heart. In patients who are using digoxin, check the magnesium concentration before starting to use proton pump inhibitors and periodically later.

Children:

Esomeprazol interactive studies have only been done on adults.