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Effect of esomeprazole on the pharmacokinetics of other drugs.
Reduction of the secretion of hydrochloric acid in the stomach during the treatment with esomeprazole and other proton pump inhibitors may reduce or increase the absorption of drugs whose absorption depends on the acidity of the medium. Like trenbolone acetate kits other drugs that reduce gastric acidity, esomeprazole treatment may reduce the absorption of ketoconazole, itraconazole and erlotinib and enhance absorption of drugs such as digoxin. Co-administration of omeprazole 20 mg once daily digoxin and digoxin increases bioavailability by 10% (bioavailability of digoxin was increased by up to 30% in two out of ten patients).
It was shown that the omeprazole is reacted with some antiretroviral drugs. The mechanisms and clinical implications of these interactions are not always known.
Increasing the pH of the therapy with omeprazole may interfere with the absorption of antiretroviral drugs. It is also possible to isoenzyme CYP2C19 interaction level. In a joint application of omeprazole and certain antiretroviral drugs, such as atazanavir and nelfinavir, against the backdrop of omeprazole therapy, there is a decrease in their serum concentrations. Therefore, their simultaneous use is not recommended. The combined use of omeprazole (40 mg once daily) with atazanavir 300 mg / ritonavir 100 mg to healthy volunteers resulted in a significant decrease in the bioavailability of atazanavir (area under the curve “concentration – time”, the maximum (C max ) and minimal (C min ) concentration decreased by about 75%). Increasing the dose of atazanavir to 400 mg of an offset impact the bioavailability of omeprazole atazanavir.
With simultaneous use of omeprazole saquinavir and saquinavir increase was observed in serum, when used with some other antiretroviral drugs, their concentration was not changed. Given the similar pharmacokinetic and pharmacodynamic properties trenbolone acetate kits of omeprazole and esomeprazole, concomitant use of esomeprazole with antiretroviral drugs, such as atazanavir and nelfinavir is not recommended.
Esomeprazole inhibits CYP2C19 main isoenzyme involved in its metabolism. Accordingly, the combined use of esomeprazole with other drugs, in which metabolism is involved isoenzyme CYP2C19, such as diazepam, citalopram, imipramine, clomipramine, phenytoin, et al., May lead to increased concentrations of these drugs in the plasma, which in turn may require dose reduction. This cooperation is especially important to remember when using Nexium in the “if necessary”. When co-administered 30 mg of esomeprazole and diazepam which is a substrate for the isoenzyme CYP2C19, diazepam marked reduction in clearance of 45%.
The use of esomeprazole 40 mg resulted in increased residual concentration of phenytoin in patients with epilepsy is 13%. In this regard, it is recommended to control the concentration of phenytoin in plasma at the start of treatment with esomeprazole and its cancellation.

The joint use of warfarin with 40 mg esomeprazole does not change coagulation time in patients receiving long-term warfarin. However, several reported cases of clinically significant increase MHO index (international normalized ratio) in the combined use of warfarin and esomeprazole. It is recommended to monitor the MHO at the beginning and at the end of the joint use of esomeprazole and warfarin or other coumarin derivatives.

Clinical significance of this interaction is not clear. In a prospective study of patients treated with placebo or omeprazole 20 mg / day. simultaneously with clopidogrel and acetylsalicylic acid (ASA), and in the analysis of clinical outcomes of large-scale, randomized studies have not shown an increased risk of cardiovascular events in the combined use of clopidogrel and proton pump inhibitors, including esomeprazole.
A number of observational studies are inconsistent and do not give a clear answer the presence or absence of an increased risk of thromboembolic cardiovascular events against the background of the joint use of clopidogrel and proton pump inhibitors.
When using clopidogrel in conjunction with the fixed combination of 20 mg esomeprazole and 81 mg ASA exposure of the active metabolite of clopidogrel was decreased by almost 40% compared with monotherapy with clopidogrel, with maximal levels of inhibition of ADP-induced platelet aggregation were trenbolone acetate kits identical, which is probably due to the simultaneous reception of the ACK at a low dose.
omeprazole 40 mg resulted in an increase in C max and AUC (area under “concentration-time” curve) cilostazol 18% and 26%, respectively; for one of the active metabolites cilostazol increase was 29% and 69% respectively.
The joint reception of cisapride with 40 mg of esomeprazole increases the cisapride pharmacokinetic parameters in healthy volunteers: AUC – 32% and the half-life is 31%, but the maximum concentration of cisapride plasma while not significantly changed. A slight lengthening the interval QT, which was observed during monotherapy cisapride, adding Nexium has not increased (see. Section “Special Instructions”).
With the simultaneous use of esomeprazole and tacrolimus have seen an increase tacrolimus concentration in blood serum.
Some patients have noted an increase of methotrexate concentration in the background joint use with proton pump inhibitors. When using high doses of methotrexate should be considered a temporary cancellation of Esomeprazole.
Nexium do not cause clinically significant changes in the pharmacokinetics of amoxicillin and quinidine.
Studies evaluating the short-term joint use of esomeprazole and naproxen or rofecoxib did not reveal any clinically significant pharmacokinetic interaction.

In the presence of any alarm symptoms (eg, such as a large spontaneous weight loss, repeated vomiting, dysphagia, vomiting with blood or melena), and in the presence of gastric ulcers (or suspected stomach ulcer) should exclude the presence of cancer, as treatment Nexium can cause smoothing of symptoms and delay diagnosis.
in rare cases, patients long time taking omeprazole, histological examination of biopsy samples of gastric mucosa body shell detected atrophic gastritis.
The patients taking the drug for a long period (especially over one year), should be under regular medical supervision. Patients taking Nexium “on demand”, should be instructed to contact their physician if symptoms change in character. Taking into account the fluctuations in the plasma concentration of esomeprazole in the appointment of therapy “as necessary”, should take into account the interaction of the drug with other drugs (see. Section “Interaction with other medicinal products and other forms of drug interactions”). In the appointment of Nexium for Helicobacter pylori eradication should be considered the possibility of drug interactions for all components of triple therapy. Clarithromycin is a potent inhibitor of CYP3A4, so the appointment of eradication therapy in patients receiving other drugs metabolized by the CYP3A4 (eg cisapride), it is necessary to take into account possible contraindications and interactions of clarithromycin with these drugs.
Nexium Tablets contain sucrose, so they are contraindicated in patients with hereditary trenbolone acetate kits fructose intolerance, glucose-galactose malabsorption or sucrase-izomaltaznoy failure.
According to the research mentioned pharmacokinetic / farmakodinamiches-some interaction between clopidogrel (loading dose of 300 mg and a maintenance dose of 75 mg / day.) and esomeprazole (40 mg / day. inside) which leads to lower exposure to the active metabolite of clopidogrel in average and reducing 40% maximal inhibition of ADP-induced platelet aggregation in average 14%. Therefore, you should avoid the simultaneous use of esomeprazole and clopidogrel (see. Section “Interaction with other medicinal products and other forms of drug interactions”).
Some observational studies suggest that treatment with proton pump inhibitors may slightly increase the risk of osteoporosis-related fractures, but in other such studies increased risk was observed.
In a randomized, double-blind, controlled clinical trials of omeprazole and esomeprazole, including two outdoor study long-term treatment (over 12 years), was not confirmed by Us fractures by osteoporosis background with the use of proton pump inhibitors.
Although a causal communication applications omeprazole / esomeprazole with fractures to osteoporosis has not been established, patients with a risk of osteoporosis or fractures on his background should be under the relevant clinical observation.

Effects on ability to drive and use other mechanisms

Due to the fact that during therapy with Nexium may experience dizziness, blurred vision and drowsiness, caution should be exercised when driving and other mechanisms.

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