Esomeprazole Stada 20mg Treatment of gastroesophageal reflux, esophagus (2 blisters x 10 tablets)

Esomeprazole is the S isomorphic form of Omeprazole is similar to Omeprazole in the treatment of gastric ulcer - duodenum and gastroesophageal reflux disease.

Esomeprazole is connected to H+/K* - ATPase cells into stomach, inhibiting this enzyme system, preventing the final step of acidic excretion into the stomach heart. Therefore, Esomeprazole has the effect of inhibiting the basic acid secretion and even when stimulated by any agent.

Dynamic pharmacokinetics

absorption

Esomeprazole is quickly absorbed after oral, the peak concentration in plasma is achieved after 1-2 hours.

Esomeprazole's bioavailability increases with the dose and when reminded, reaching about 68% when taking the dose of 20 mg and 89% when taking the dose of 40 mg.

Esomeprazole slow and reducing foods.

Distribution

Esomeprazole binds to plasma proteins about 97%.

transformation

The drug is metabolized mainly in the liver thanks to the isenzy CYP2C19, the cytochrome p450 enzyme system, into hydroxy and desmethyl metabolites that are no longer active.

Elimination

The waste time in plasma is about 1-1.5 hours. Most 80% of oral doses are eliminated in the form of metabolites in urine, the rest is eliminated through feces.

Special patient groups

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 Esomeprazole is catalyzed mainly by CYP3A4. After repeating the dose of Esomeprazole 40 mg, 1 time/day, the area under the curve shows concentration over time (AUC) on average in people with less than 100% lower metabolic people than people with enzymes CYP2019 (strong metabolic group). The average peak concentration in plasma increased by about 60%.

These records do not affect the dose of Esomeprazole.

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

After taking the single dose of Esomeprazole 40 mg, 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 Esomeprazole.

Patients with impaired organs

Esomeprazole metabolism may be reduced in patients with mild to medium liver dysfunction. The metabolic rate decreases in patients with severe liver dysfunction, resulting in double the AUC of Esormeprazole. Therefore, do not overdose up to 20 mg in patients with severe liver dysfunction. Esomeprazole or main metabolites do not tend to accumulate when used 1 time/day.

No studies have been conducted in patients with renal function impairment. Because the kidney is responsible for the excretion of the metabolites of Esomeprazole but is not responsible for the elimination of drugs in a constant form, it is impossible for the metabolism of unchecked Esomeprazole in patients with impaired kidney function.

Children

Juin 12 - 18 years old: After using the dose of 20 mg and 40 mg Esomeprazole, the total concentration, AUC and the time to reach the maximum concentration in plasma (TMAX) in children 12 - 18 years old similar to adults for both doses of Esomeprazole.

Be cautious when using

when there is any alert symptom (such as significant weight loss, recurrent vomiting, difficulty swallowing, vomiting blood or black stool) and when suspected or stomach ulcers should eliminate malignant because Esomeprazole can reduce symptoms and delay diagnostic.

Long -term treatment

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

Treatment according to the regime when necessary

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

eradication of 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 contraindicating and interacting with clarithromycin when using 3 drugs for patients who are taking other drugs metabolized through CYP3A4 as Cisaprid.

gastrointestinal infections

Treatment with proton pump inhibitors (PPI) may increase the risk of gastrointestinal infections caused by Salmonella and Campylobacter.

Absorb vitamin B12

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

Magnesi blood

There have been reports on severe reduction of blood magnesia in patients treated with PPI for at least 3 months, and in most cases is for 1 year. The severe manifestation of blood magnesia reduced blood like fatigue, stiffness, delirium, convulsions, dizziness and ventricular arrhythmia may occur but silently start. In most patients, blood magnesium reduction is improved after using magnesium instead and stop using PPI.

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

Risk of fractures

PPIs, especially when used in high doses for a long time (> 1 year), may increase the risk of hip fractures, wrist bones and spine, especially in elderly patients or when the presence of other known risk factors. Observing studies found that PPIs could increase the overall risk of fractures by about 10 - 40%. Part of this increase may be due to other risk factors. Patients at risk of osteoporosis need to be cared for under the current clinical instructions and should be used enough vitamin D and calcium.

Lupus erythematosus on skin (SCLE)

PPIs are very frequent in case of SCLE. If the lesions occur, especially in the skin of the sun, and if it comes with joint pain, patients should promptly look for medical support and the doctor should consider stopping Esomeprazole. Sale after treatment with the previous PPI may increase the risk of SCLE with another PPI.

coordinated with other drugs

It is not recommended to simultaneously use Esomeprazole with Atazanavir. If the combination of Atazanavir with PPI is inevitable, clinically closely monitoring when increasing the dose of Atazanavir to 400 mg, combined with 100 mg of Ritonavir; Do not use more than 20 mg Esomeprazole.

Esomeprazole is CYP2019 inhibitor. When starting or ending treatment with Esomeprazole, the risk of interacting with metabolic drugs should be considered through CYP2019. Observed the interaction between clopidogrel and Esomeprazole.

Clinically correlation of this interaction is unknown. In order to be cautious, not encouraged to simultaneously use Esomeprazole and Clopidogrel.

When prescribing Esomeprazole according to the treatment regime when necessary, it is advisable to consider interaction with other drugs because the concentration of Esomeprazole in plasma may change.

excipients

This drug contains Sugar Pellets (Sucrose and Maize Starch). Patients with rare genetic problems such as fructose intolerance, malventia - Galactose or lack of sucrose - Isomaltase should not use this drug.

This drug contains 1,4651 mg sodium in each tablet. Note when used in patients with sodium control diet.

interact with tests

Increased chromographin A (CGA) level may interfere with the hormonal nerve tumor. In order to avoid this intervention, it is necessary to temporarily stop treatment with Esomeprazole at least 5 days before the quantification of CGA.

Use drugs for women during pregnancy and lactation

Pregnant women:

There is no adequate study when using Esomeprazole in pregnant people.

Only use Esomeprazole when really necessary during pregnancy.

breastfeeding women:

It is not known whether Esomeprazole is excreted through breast milk or not. However, the concentration of omeprazole has been measured in breast milk after taking 20 mg of omeprazole.

Esomeprazole has the potential to cause serious 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.

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

Patients with dizziness or hallucinations while using Esomeprazole should not drive or operate machinery.

Drug interaction

Esomeprazole'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 mechanism of impact of the recorded interactions. Increasing stomach pH during treatment with omeprazole can lead to a change in the absorption of protease inhibitors. Another possible interactive mechanism is through the inhibition of CYP2019 enzyme.

For Atazanavir and Nelfinavir, the serum levels are reduced when used simultaneously with omeprazole, so it is not recommended to simultaneously use these drugs.

In healthy volunteers, simultaneous use of omeprazole (40 mg, once a day) with Atazanavir 300 mg/ ritonavir 100 mg significantly reduces the level of Atazanavir contact (reducing AUC, CMAX and CMIN by about 75%). Increasing Atazanavir dose to 400 mg is not enough to compensate for the effects of omeprazole on the level of Atazanavir.

In healthy volunteers, simultaneous use of omeprazole (20 mg, once a day) with Atazanavir 400 mg/ritonavir 100 mg decreased by 30% of Atazanavir contact when compared to the Atazanavir contact level recorded in the case of using Atazanavir 300 mg/ritonavir 100 mg, 1 time/day without using Omeprazole 20 mg, each 1 time.

Use in combination with omeprazole (40 mg, once a day) reduces the average value of NELFINAVIR's cmin and cmin by 36 - 39% and decreases about 75 - 92% of the average AUC, CMAX and CMIN values ​​of metabolites with pharmacological activity M8.

Due to the impact of the same force and pharmacokinetic properties of Omeprazole and Esomeprazole, it is not recommended to use Esomeprazole simultaneously with Atazanavir and contraindicated using Esomeprazole simultaneously with NEMFINAVIR.

For sequinavir (simultaneously used with ritonavir), increasing serum concentration (80 - 100%) when concurrent use Omeprazole (40 mg, once a day). Treatment with Omeprazole 20 mg, once a day does not affect the contact level of Darunavir (when used simultaneously with Ritonavir) and Amprenavir (when used simultaneously with Ritonavir).

Treatment with Esomeprazole 20 mg, once a day does not affect the contact level of Amprenavir (used or not used simultaneously with Ritonavir). Treatment with omeprazole 40 mg, once a day does not affect the contact level of Lopinavir (simultaneously used with Ritonavir).

methotrexate

When used simultaneously with PPIs, methotrexate concentration is reported increased in some patients. When using high doses of methotrexate, it is advisable to consider the suspension of Esomeprazole.

tacrolimus

There have been simultaneous reports with Esomeprazole increasing the serum levels of Tacrolimus. Need to increase monitoring tacrolimus concentration as well as renal function (creatinine clearance) and adjust the dose of tacrolimus if necessary.

Absorbed drug depends on pH

The reduction of stomach acid when treated with Esomeprazole and other PPIs may increase or decrease the absorption of other drugs with a mechanism of absorption dependent on the stomach pH. Like other drugs that reduce other stomach acid, the absorption of drugs such as ketoconazole, otraconazole and erlotinib may decrease and the absorption of digoxin may increase during treatment with ecomeprazole.

Simultaneous use of omeprazole (20 mg/day) and digoxin in healthy objects that increase the bioavailability of digoxin about 10% (up to 30% in 2 out of 10 research objects). There are rare reports on Digoxin toxicity. However, caution should be used when using high doses of Esomeprazole in elderly patients. Need to strengthen monitoring with digoxin.

Metabolic drugs through CYP2C19

Esomeprazole inhibits CYP2C19, the main enzyme metabolizes Esomeprazole. Therefore, when Esomeprazole is used with metabolic drugs with CYP2C19 such as diazepam, citalopram, imipramin, clomipramin, phenytoin ... the concentration of these drugs in plasma can increase and need to decrease the dose. This should be paid special attention when prescribing Esomeprazole according to the treatment mode when necessary.

diazepam

Concentrated with Esomeprazole 30 mg reduces 45% of the clearance of diazepam (a substrate of CYP2C19).

phenytoin

When used simultaneously with Esomeprazole 40 mg increases 13% of the bottom concentration of phenytoin in plasma in epilepsy patients. Should monitor phenytoin concentration in plasma when starting or stopping treatment with Esomeprazole.

voriconazole

omeprazole (40 mg, once a day) increases 15% cmax and 41% AUC of Voriconazole (a substrate of CYP2C19).

cilostazol

Omeprazole, as well as Esomeprazole, acts as CYP2019 inhibitors. In a cross study, Omeprazole used at a dose of 40 mg on healthy objects increased CMAX and AUC of Cilostazol, both 18% and 26% and CMAX and AUC of a metabolic substance with its activity are 29% and 69%.

cisaprid

In healthy volunteers, when used with 40 mg of Esomeprazole, AUC increased to 32% and the time of selling Cisaprid excreted by 31% but the Cisaprid peak concentration in plasma increased significantly. The period of QTC is slightly lasting after using Cisaprid
separately, not longer when used simultaneously Cisaprid with Esomeprazole.

warfarin

When using 40 mg of Esomeprazole in the same time, people who are being treated with warfarin in a clinical trial have shown that blood clotting time is in an acceptable range. However, after a period of circulation of drugs, there were a very rare number of cases of significant Inr clinical increase when treated simultaneously harming the above drugs.

Should monitor patients when starting and terminating at the same time Esomeprazole with Warfarin or other Coumarin derivatives.

clopidogrel

Results of studies on healthy subjects have shown that the pharmacokinetic/pharmaceutical interaction between clopidogrel (dose of 800 mg/daily maintenance dose 75 mg) and esomeprazole (40 mg daily oral) leads to reduced exposure to the active metabolites of clopidogrel an average of 40% and reduces the maximum supply inhibitors (caused by ADP).

In a healthy study, when using Clopidogrel with a combination of Esomeprazole fixed dose combination, 20 mg + acetylsalicylic acid (ASA) 81 mg, the exposure to the active metabolitus of Clopidogrel decreased by nearly 40% compared to the use of clopidogrel. However, the level of maximum inhibition of platelets (caused by ADP) on these objects is the same in the purely clopidogrel group and Clopidogrel in combination with (Esomeprazole+ ASA).

The inconsistent data on clinical manifestations of Omeprazole's pharmaceutical/pharmaceutical interactions on the main cardiovascular events have been reported from clinical observation and research studies. To be cautious, not recommended to simultaneously use with clopidogrel.

The drug has studied without clinical interactions

amoxicillin and quinidine

Esomeprazole has been shown to have no significant clinical impact on pharmacokinetics of amoxicillin, quinidine.

Naproxen or Rofecoxib

Short -term studies evaluate the use of Esomeprazole simultaneously with Naproxen or Rofecoxib has not identified any clinical pharmacokinetics.

The effect of other drugs on Esomeprazole

CYP2C19 and/or CYP3A4 inhibitors

Esomeprazole is metabolized by CYP2019 and CYP3A4. When used simultaneously Esomeprazole with a CYP3A4 inhibitor such as Clarithromycin (500 mg, 2 times/day) double the AUC of Esomeprazole. Simultaneous use with a inhibitor both CYP2019 and CYP3A4 may increase more than twice the exposure to Esomeprazole.

CYP2C19 and CYP3A4 Voriconazole inhibitors increase the AUC of Omeprazole to 280%. No need to adjust the dose of Esomeprazole regularly in these cases. Dosage adjustment in patients with severe liver failure or long -term treatment.

CYP2019 and/or CYP3A4 induction drugs

CYP2C19 and/or CYP3A4 (such as Rifampicin and St John's Wort) can cause Esomeprazole concentration due to metabolism of Esomeprazole.