Nexpro

Nexpro is a drug that slows down the activity of the proton pump. It is used to treat GERD or peptic ulcers.

The component esomeprazole acts as an S-isomer of omeprazole, which weakens the secretion of gastric juice using a specific mechanism of therapeutic effect. The drug specifically slows down the action of the proton pump inside the parietal cell. At the same time, R-, as well as S-isomers of the substance omeprazole have the same pharmacodynamic effect.

Indications Nexpro

It is used for the following forms of GERD:

• reflux esophagitis of an erosive nature;
• long-term therapy to prevent the likelihood of relapse;
• elimination of GERD symptoms.

It is prescribed in combination with antibacterial drugs to destroy Helicobacter pylori:

• in case of ulcers affecting the duodenum caused by Helicobacter pylori activity;
• prevention of recurrence of peptic ulcers in individuals with ulcers associated with H.pylori.

Treatment of ulcers associated with long-term use of NSAIDs. Also used to prevent the development of gastrointestinal ulcers in individuals at risk due to NSAID use.

It is prescribed to prevent recurrence of bleeding in ulcers in the gastrointestinal tract associated with the use of esomeprazole in the form of an infusion fluid.

It is used to treat gastrinoma.

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Release form

The therapeutic element is released in tablets - 7 or 10 pieces inside a cell plate. Inside the box - 2 such plates.

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Pharmacodynamics

After concentration, esomeprazole is transformed into its active form within the highly acidic environment of the excretory tubules of the parietal cell. There it inhibits the activity of the enzyme H ⁺ K ⁺ -ATPase, the acid pump, and thereby inhibits stimulated as well as basal acid secretion.

During the use of antisecretory substances, plasma gastrin levels increase in response to the decrease in acid secretion.

The increase in ECL cells observed in individual patients with long-term use of esomeprazole may be related to the increase in plasma gastrin values.

There is information about an increase in the incidence of granular gastric cysts in the case of prolonged administration of antisecretory agents. Such symptoms are reversible and benign and are a physiological response to prolonged inhibition of acid secretion processes.

The reduction in gastric acid secretion with any proton pump inhibitor increases the initially normal number of bacteria inside the stomach. Therapy with drugs from the above group may increase the likelihood of developing a gastrointestinal infection associated with, for example, campylobacter or salmonella.

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Pharmacokinetics

Esomeprazole is acid-active. The tablets administered orally are enteric-coated. Conversion to the R-isomer is relatively minor in vivo.

Esomeprazole is absorbed at a high rate, reaching plasma Cmax values 1-2 hours after administration of the drug. The bioavailability index when administering a single dose of 40 mg is 64%, and with repeated administration once a day it increases to 89%. When taking 20 mg of the drug, these indicators are 50% and 68%, respectively.

The equilibrium values of the distribution volume in volunteers are 0.22 l/kg. Synthesis of esomeprazole with intraplasma protein is 97%.

Food intake weakens and inhibits the absorption of esomeprazole without affecting its effectiveness in reducing gastric acidity.

Esomeprazole is fully involved in metabolic processes carried out with the help of hemoprotein P450 (CYP). The processes of drug metabolism are mainly realized with the help of polymorphic 2C19, which contributes to the formation of desmethyl and hydroxy metabolites of esomeprazole. The remainder is metabolized with the participation of another specific isoenzyme, CYP3A4. This element helps to form the main metabolic component in the blood plasma - esomeprazole sulfone.

Total plasma clearance values are approximately 17 L/hour with a single dose and approximately 9 L/hour with repeated administration. The half-life is approximately 1.3 hours with repeated administration of a single dose per day.

The pharmacokinetic properties of esomeprazole have been studied using a 40 mg dose twice daily. Plasma AUC values increase with repeated administration of Nexpro. This increase is dose-dependent and results in a dose-proportional increase in AUC with repeated administration. This time- and dose-dependency is explained by a decrease in first-pass intrahepatic clearance and total body clearance due to inhibition of the 2C19 enzyme by esomeprazole or its sulfometabolite.

The drug is completely excreted from the plasma between doses. When used once a day, the drug does not accumulate.

The main metabolic components of the drug do not affect the secretion of gastric juice. Approximately 80% of the dose taken orally is excreted as metabolic components, and the remainder is excreted in the feces. Less than 1% of the unchanged substance is recorded in the urine.

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Dosing and administration

The tablets must be swallowed whole, without crushing or chewing, and washed down with plain water.

People with impaired swallowing function can dissolve the medicine in non-carbonated liquid (0.1 l). It is forbidden to use other liquids except water, because they can destroy the enteric coating of the tablet. To dissolve, shake the liquid in a glass. The resulting mixture should be drunk within half an hour from the moment of dissolution. After this, pour a little more water into the glass, rinse its walls, and then drink. The microgranules formed during dissolution cannot be crushed or chewed.

Also, for people who have problems with swallowing, the medicine can be administered using a nasogastric tube - the tablet is also first dissolved in non-carbonated liquid (0.5 glass).

Use in GERD.

In case of reflux esophagitis of an erosive nature: use 40 mg once a day for 1 month. Persons who still have signs of the disease after this period may be prescribed an additional 1-month course of therapy.

Long-term therapy for relapses in people with cured esophagitis: 1-time use of 20 mg of the drug per day.

Treatment of GERD symptoms: 1-time administration of 20 mg of the drug per day (for people without esophagitis). If there is no result after 1 month of therapy, the patient should be examined. If the symptoms of the disease have been eliminated, subsequent monitoring is carried out with the administration of 20 mg 1-time per day.

Combination with antibacterial agents to destroy H.pylori.

For ulcers affecting the duodenum caused by the activity of Helicobacter pylori, and also to prevent relapses of peptic ulcers associated with H.pylori: 20 mg of the drug is administered with 0.5 g of clarithromycin and 1000 mg of amoxicillin 2 times a day for 7 days.

Prevention and treatment of ulcers associated with long-term administration of NSAIDs.

For gastric ulcers that have developed as a result of treatment with NSAIDs, 20 mg of Nexpro is used once a day. Therapy lasts 1-2 months.

To prevent ulcers in the gastrointestinal tract in individuals at risk, 20 mg of the drug is prescribed once a day.

Prevention of recurrent bleeding in gastrointestinal ulcers after use of esomeprazole injection liquid.

During the first month, 40 mg of the substance is administered once a day. Before this course, treatment is carried out aimed at suppressing acidity (administration of esomeprazole infusion fluid).

Therapy in case of gastrinoma.

Usually, 40 mg of the drug is prescribed twice a day. The dose is selected individually, and the duration of the cycle depends on clinical indications. In most patients, the disease can be controlled by using 0.08-0.16 g of the substance per day. If the daily dosage of 80 mg is exceeded, it is divided into 2 uses.

Problems with liver function.

People with severe disorders can take no more than 20 mg of the drug per day.

Use Nexpro during pregnancy

Information on taking Nexpro during pregnancy is limited. Studies have not revealed any indirect or direct negative effects on the fetus. The medication should be prescribed with extreme caution during this period.

There is no information on whether esomeprazole can be excreted in breast milk. Taking the drug during lactation has not been studied, which is why it cannot be used during this period.

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Contraindications

Contraindicated in cases of severe intolerance associated with esomeprazole, benzimidazole derivatives or other components of the drug. Cannot be used in combination with nelfinavir or atazanavir.

Side effects Nexpro

Main side effects:

• disorders of hematopoiesis: thrombocytopenia, leukopenia, or pancytopenia, as well as agranulocytosis;
• immune manifestations: symptoms of intolerance, including Quincke's edema, fever and anaphylaxis or anaphylactic symptoms;
• metabolic disorders: hypomagnesemia or -natremia, as well as peripheral edema. In severe hypomagnesemia, hypocalcemia may develop;
• mental health problems: aggression, insomnia, confusion, hallucinations, depression and agitation;
• symptoms associated with NS: paresthesia, taste disturbance, headaches, drowsiness and weakness;
• visual disturbances: blurred vision;
• labyrinth disorders: dizziness;
• lesions associated with the respiratory system: bronchial spasm;
• manifestations affecting the digestive function: vomiting, pain in the abdominal area and candidiasis affecting the gastrointestinal tract, constipation, and in addition nausea, xerostomia, diarrhea, flatulence, stomatitis, and also microscopic colitis;
• problems associated with the hepatobiliary system: liver failure, hepatitis (with or without jaundice), increased liver enzyme levels and encephalopathy in individuals with liver pathologies;
• subcutaneous and epidermal lesions: rashes, photosensitivity, dermatitis, SJS, itching, erythema multiforme, urticaria, TEN and alopecia;
• musculoskeletal disorders: myalgia or arthralgia, as well as muscle weakness;
• urinary and renal dysfunction: tubulointerstitial nephritis;
• problems with reproductive function: gynecomastia;
• systemic signs: hyperhidrosis or weakness.

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Overdose

There is limited information regarding drug poisoning. When 0.28 g of the drug is administered, weakness and gastrointestinal symptoms are observed. A single administration of 80 mg does not cause severe disorders.

Nexpro has no antidote. Most of the esomeprazole is synthesized with blood protein, which is why the drug is not dialyzable. Symptomatic actions are performed.

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Interactions with other drugs

Effect of esomeprazole on the pharmacokinetics of other drugs.

Due to the decrease in gastric pH after administration of esomeprazole, the absorption of drugs whose absorption is related to acidity may be enhanced or weakened.

For example, the absorption of such medications as itraconazole with ketoconazole and erlotinib is weakened. But the absorption of digoxin with the introduction of aspirin or esomeprazole, on the contrary, is enhanced. The introduction of 20 mg of omeprazole per day, as well as digoxin, led to an increase in the bioavailability of the latter by 10% in volunteers (also in 2 out of ten people the indicator increased by 30%).

Esomeprazole slows down the action of the enzyme 2C19, which is the main participant in its metabolic processes. Because of this, the administration of the drug in combination with substances whose metabolism occurs with the help of 2C19 (including phenytoin with diazepam, imipramine and citalopram with clomipramine) can increase their plasma index, which requires a reduction in their dosage. This factor must be taken into account when using esomeprazole.

The combination of esomeprazole (30 mg) with diazepam causes a 45% decrease in the CYP2C19 clearance rate of the diazepam substrate.

The use of 40 mg of the drug together with phenytoin causes an increase in plasma levels of the latter by 13% in people with epilepsy. These values should be monitored when prescribing or stopping the use of esomeprazole.

It is necessary to monitor the INR level at the beginning and also at the end of a combined course with warfarin or other coumarin derivatives.

Combination of 40 mg of the drug with cisapride caused a 32% increase in AUC values, and also prolonged the half-life by 31%; however, no significant increase in plasma Cmax values was observed for cisapride. A moderate increase in QT interval was observed with cisapride alone, but its subsequent prolongation did not occur with combination with esomeprazole.

Combination with the drug leads to an increase in serum tacrolimus levels.

There are reports of increased blood levels of methotrexate in some individuals when combined with proton pump inhibitors. If large doses of methotrexate are required, temporary discontinuation of Nexpro should be considered.

When introducing certain antiretroviral drugs (including nelfinavir and atazanavir), a decrease in serum values of the latter is observed. Because of this, the drug is not used in combination with the above-mentioned medicinal substances.

Effects of other medicinal products on the pharmacokinetic properties of esomeprazole.

The processes of esomeprazole metabolism are realized with the participation of components 2C19, as well as CYP3A4. The introduction of the drug together with clarithromycin, which slows down the action of CYP3A4 (in a portion of 0.5 g 2 times per day), caused a doubling of the level of exposure to esomeprazole.

The combination of the drug and a complex inhibitor of CYP3A4 and CYP2C19 elements (for example, voriconazole) leads to a more than twofold increase in drug exposure rates.

In addition, voriconazole causes a 280% increase in the AUCτ values of the drug.

In people with severe liver dysfunction, when taking the drug for a long time, it is necessary to consider changing its dosage.

Medicines that induce the activity of CYP2C19 and CYP3A4 or both enzymes (including St. John's wort and rifampicin) can reduce serum levels of esomeprazole by increasing the rate of its metabolic processes.

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Storage conditions

Nexpro should be stored in a place closed to small children. Temperature marks - not higher than 25°C.

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Shelf life

Nexpro can be used within 24 months from the date of manufacture of the pharmaceutical product.

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Application for children

There is no data regarding the use of the drug in individuals under 12 years of age, which is why it is not prescribed to this group.

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Analogues

Analogues of the drug are the following medications: Despazol, Esomealox, Ezoxium with Esomer, and also Zercim, Ezonexa, Ezolong with Nexium and Esozol with Ezox. In addition, Pemozar, Esomeprazole, Emanera and Ezera with Ezomaps.

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