Nexium, 40 mg 28 pcs.

Indications

Patients taking long-term NSAIDs

NSAIDs in patients at risk

Zollinger-Ellison syndrome or other conditions characterized by abnormal hypersecretion of gastric glands, including idiopathic hypersecretion.

Active ingredient

Composition

How to take, the dosage

Ingestion. The tablet should be swallowed whole with liquids. The tablets should not be chewed or crushed.

For patients with difficulty swallowing, the tablets may be dissolved in half a glass of still water (do not use other liquids as the protective coating on the microgranules may dissolve), stirring until the microgranules have dissolved, then the suspension of microgranules should be drunk immediately or within 30 minutes, then the glass should be refilled with half the water, stirred and drunk. Microgranules should not be chewed or crushed.

For patients who cannot swallow, the tablets should be dissolved in non-carbonated water and administered through a nasogastric tube. It is important that the syringe and tube chosen are suitable for this procedure. For instructions on preparation and administration of the drug through the nasogastric tube, see section “Administration of the drug through the nasogastric tube”.

Treatment of erosive reflux esophagitis: 40 mg once daily for 4 weeks. An additional 4-week course of treatment is recommended if esophagitis does not heal after the first course, or if symptoms persist.

Long-term maintenance treatment after healing of erosive reflux esophagitis to prevent recurrence: 20 mg once daily.

Symptomatic treatment for gastroesophageal reflux disease: 20 mg once daily in patients without esophagitis. If after 4 weeks of treatment the symptoms do not disappear, further examination of the patient should be carried out. After elimination of symptoms, it is possible to switch to the mode of taking the drug “as needed”, i.e. to take Nexium 20 mg once a day when symptoms recur. For patients taking NSAIDs who are at risk of developing gastric or duodenal ulcer, treatment on an “as needed” regimen is not recommended.

Adults

.Peptic ulcer disease of the stomach and duodenum

.As part of combination therapy for eradication of Helicobacter pylori

Interaction

Effects of esomeprazole on the pharmacokinetics of other drugs

The decrease in gastric hydrochloric acid secretion during treatment with esomeprazole and other proton pump inhibitors may result in decreased or increased absorption of drugs whose absorption depends on the acidity of the environment. Like other drugs that reduce gastric acidity, treatment with esomeprazole may lead to decreased absorption of ketoconazole, itraconazole and erlotinib, and increased absorption of drugs such as digoxin. Co-administration of omeprazole at a dose of 20 mg once daily and digoxin increased digoxin bioavailability by 10% (digoxin bioavailability was increased by up to 30% in two out of ten patients). Omeprazole has been shown to interact with some antiretroviral drugs. The mechanisms and clinical significance of these interactions are not always known. An increase in pH during therapy with omeprazole may affect the absorption of antiretroviral drugs. There may also be an interaction at the level of CYP2C19 isoenzyme. When coadministration of omeprazole and some antiretroviral drugs such as atazanavir and nelfinavir during therapy with omeprazole, a decrease in their serum concentrations is noted. Therefore, their concomitant use is not recommended. The co-administration of omeprazole (40 mg once daily) with atazanavir 300 mg/ritonavir 100 mg in healthy volunteers led to a significant decrease of atazanavir bioavailability (area under the “concentration-time curve”, maximum (Cmax) and minimum (Cmin) concentrations decreased by approximately 75%). Increasing the atazanavir dose to 400 mg did not compensate for the effect of omeprazole on atazanavir bioavailability.

Concomitant use of omeprazole and saquinavir resulted in increased serum concentrations of saquinavir; when used with some other antiretrovirals their concentrations were unchanged. Given the similar pharmacokinetic and pharmacodynamic properties of omeprazole and esomeprazole, co-administration of esomeprazole with antiretrovirals such as atazanavir and nelfinavir is not recommended.

Esomeprazole inhibits CYP2C19, the main isoenzyme involved in its metabolism. Accordingly, co-administration of esomeprazole with other drugs whose metabolism involves the CYP2C19 isoenzyme, such as diazepam, citalopram, imipramine, clomipramine, phenytoin, etc., may lead to increased plasma concentrations of these drugs, which in turn may require dose reduction. This interaction is particularly important to keep in mind when using Nexium on an “as needed” regimen. Co-administration of esomeprazole 30 mg and diazepam, which is a substrate of CYP2C19 isoenzyme, decreases diazepam clearance by 45%.

The use of esomeprazole at a dose of 40 mg resulted in a 13% increase in residual phenytoin concentrations in patients with epilepsy. Therefore, it is recommended to monitor plasma concentrations of phenytoin at the beginning of treatment with esomeprazole and at its withdrawal.

The use of omeprazole in dose of 40 mg once daily increased area under curve “concentration – time” and Cmax of voriconazole (substrate of CYP2C19 isoenzyme) by 15% and 41%, respectively.

The co-administration of warfarin with 40 mg of esomeprazole does not alter the coagulation time in patients taking long-term warfarin. However, several cases of clinically significant increases in INR (international normalized ratio) have been reported when warfarin and esomeprazole are coadministered. It is recommended to monitor INR at the beginning and at the end of coadministration of esomeprazole and warfarin or other coumarin derivatives.

In studies, a pharmacokinetic/pharmacodynamic interaction between clopidogrel (loading dose 300 mg and maintenance dose

75 mg/day) and esomeprazole (40 mg/day. orally), which results in an average 40% decrease in exposure to the active metabolite clopidogrel and an average 14% decrease in maximal inhibition of ADP-induced platelet aggregation.

The clinical significance of this interaction is unclear. In a prospective study in patients receiving placebo or omeprazole at a dose of 20 mg/day concomitantly with clopidogrel and acetylsalicylic acid (ASA) therapy and in an analysis of clinical outcomes of large randomized trials, no increased risk of cardiovascular complications was shown when clopidogrel and proton pump inhibitors including esomeprazole were used together.

The results of several observational studies are inconsistent and do not provide a definitive answer about the presence or absence of an increased risk of thromboembolic cardiovascular complications with clopidogrel and proton pump inhibitors.

When clopidogrel was coadministered with a fixed combination of 20 mg of esomeprazole and 81 mg of ASA, exposure to the active metabolite clopidogrel was reduced by nearly 40% compared with clopidogrel monotherapy, while maximum levels of inhibition of ADP-induced platelet aggregation were similar, which is likely due to the simultaneous administration of low-dose ASA.

The use of omeprazole at a dose of 40 mg resulted in an 18% and 26% increase in Cmax and AUC (area under the concentration-time curve) of cilostazol, respectively; for one of the active metabolites of cilostazol, the increases were 29% and 69%, respectively. Concomitant administration of cisapride with 40 mg of esomeprazole leads to increased values of pharmacokinetic parameters of cisapride in healthy volunteers: AUC – by 32% and elimination half-life – by 31%, but maximum cisapride plasma concentration is not significantly changed. Slight prolongation of the QT interval, which was observed with cisapride monotherapy, was not increased when Nexium was added (see section “Special Precautions”).

Concomitant use of esomeprazole and tacrolimus resulted in increased serum concentrations of tacrolimus.

In some patients, increased concentrations of methotrexate have been noted when coadministered with proton pump inhibitors. If high doses of methotrexate are used, temporary withdrawal of esomeprazole should be considered.

The drug Nexium does not cause clinically significant changes in the pharmacokinetics of amoxicillin and quinidine.

Studies evaluating short-term co-administration of esomeprazole and naproxen or rofecoxib have shown no clinically significant pharmacokinetic interaction.

Influence of drugs on the pharmacokinetics of esomeprazole

The CYP2C19 and CYP3A4 isoenzymes are involved in metabolism of esomeprazole. Co-administration of esomeprazole with clarithromycin (500 mg 2 times per day), which inhibits the CYP3A4 isoenzyme, leads to a 2-fold increase in the AUC of esomeprazole. Concomitant use of esomeprazole and a combined CYP3A4 and CYP2C19 isoenzyme inhibitor such as voriconazole may lead to more than a 2-fold increase in the AUC of esomeprazole. No dose adjustment of esomeprazole is usually required in such cases. A dose adjustment of esomeprazole may be required in patients with severe hepatic impairment and long-term use.

Drugs inducing CYP2C19 and CYP3A4 isoenzymes, such as rifampicin and preparations of St. John’s wort, when used in combination with esomeprazole may lead to decreased plasma concentration of esomeprazole due to accelerated metabolism of esomeprazole.

Special Instructions

Synopsis

Contraindications

Side effects

Overdose

Pregnancy use

Similarities