Nexpro

Nexpro - a drug that slows down the activity of the proton pump. Used for therapy for GERD or peptic ulcer.

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

Indications Nexpro

Used with the following forms of GERD:

• reflux esophagitis, having an erosive nature;
• long-term therapy to prevent the likelihood of recurrence;
• elimination of signs of GERD.

Assigned comprehensively, together with antibacterial drugs, to destroy Helicobacter pylori:

• with an ulcer caused by the activity of Helicobacter pylori affecting the duodenum;
• preventing the development of recurrence of peptic ulcers in people with ulcers associated with H. Pylori.

Therapy for ulcers associated with prolonged use of NSAIDs. It is also used to prevent the appearance of ulcers in the gastrointestinal tract in people at risk of taking NSAIDs.

Appointed to prevent recurrence of bleeding in ulcers in the area of the gastrointestinal tract associated with the use of esomeprazole in the form of an infusion fluid.

It is used to treat gastrinomas.

[1]

Release form

The release of the therapeutic element is in tablets - 7 or 10 pieces inside the cell plate. Inside the box are 2 such records.

[2]

Pharmacodynamics

After concentration, the esomeprazole is transformed into its active form inside the excretory tubule of the lining cell, which has a high acidity environment. There, it slows down the activity of the enzyme H ⁺ K ⁺ -ATPase - an acid pump, and at the same time inhibits stimulated as well as basal secretion of acid.

During the use of anti-secretory substances, the plasma level of gastrin increases - as a reaction to the weakening of acid secretion.

The increase in the number of ECL cells, which is observed in individual patients with prolonged use of esomeprazole, may be associated with an increase in plasma values of gastrin.

There is information about an increase in the frequency of development 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 release processes.

The weakening of the secretion of gastric juice with the introduction of any medicine that slows down the action of the proton pump increases the initially normal number of bacteria inside the stomach. Therapy with the use of drugs from the above group may cause an increase in the likelihood of developing gastrointestinal infection, associated, for example, with Campylobacter or Salmonella.

[3], [4]

Pharmacokinetics

Esomeprazole is exposed to acid. Introduced tablets have an enteric coating. Conversion with the formation of the R-isomer during in vivo processes is rather insignificant.

Absorption of esomeprazole is carried out at high speed, reaching plasma values of Cmax after 1-2 hours from the moment of introduction of the drug. The indicator of bioavailability with the introduction of a 1-fold portion of 40 mg equals 64%, and with repeated administration it increases once a day to 89%. When taking 20 mg of medication, these figures are 50% and 68%, respectively.

The equilibrium distribution volume of volunteers is 0.22 l / kg. Synthesis of esomeprazole with intraplasma protein - 97%.

The consumption of food weakens and inhibits the absorption of esomeprazole, while not affecting its effectiveness against gastric acidity.

Esomeprazole is fully involved in metabolic processes, carried out with the help of hemoprotein P450 (CYP). Drug metabolism is mainly realized with the help of polymorphic 2С19, which contributes to the formation of esomeprazole desmethyl and hydroxymetabolites. The residue is metabolized with the participation of another specific isoenzyme, CYPRA4. This element helps to form the main metabolic component inside the blood plasma - esomeprazole sulfone.

The total values of intraplasma clearance are approximately 17 liters / hour with the introduction of a single portion, as well as approximately 9 liters / hour in the case of repeated use. The term half-life is about 1.3 hours with a repeated use of a serving 1-fold per day.

The pharmacokinetic characteristics of esomeprazole were studied using a 40 mg dose 2 times a day. Indicators of plasma AUC increase in case of repeated use of Nexpro. Such an increase depends on the size of the portion and causes an increase in the level of AUC proportional to the dosage during repeated administration. Such a dependence on the time period and the size of the dosage is due to the weakening of the 1st intrahepatic passage and total clearance due to the suppression of the action of the 2С19 enzyme by esomeprazole or its sulfmetabolite.

The drug is fully excreted from the plasma between the introduction of its dosages. With 1-fold use per day, the drug does not accumulate.

The main metabolic elements of the drug do not affect the secretion of gastric juice. Approximately 80% of the ingested portion of the drug is excreted in the form of metabolic components, and the remainder is excreted. Less than 1% of the unchanged substance is recorded inside the urine.

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Dosing and administration

Tablets must be swallowed whole, without crushing or chewing, while squeezing it with plain water.

Persons who have impaired swallowing function can dissolve the drug in non-carbonated liquid (0.1 l). It is forbidden to use liquids other than water, because they can destroy the enteric shell of the tablet. To dissolve, you need to shake up the liquid in the glass. The resulting mixture should be drunk within half an hour after the dissolution. After that, they pour a little more water into the glass by rinsing its walls and then drinking. Microgranules formed during dissolution cannot be crushed or chewed.

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

Use with GERD.

In the case of reflux esophagitis, which has an erosive nature: the use of 40 mg once a day for the 1st month. Individuals who have signs of illness after a specified period of time may receive an additional 1-month course of therapy.

Prolonged therapy for relapses in people with cured esophagitis: 1-time use of 20 mg of medication per day.

Treatment of signs of GERD: 1-time administration of 20 mg of drugs per day (for individuals without esophagitis). In the absence of a result after the 1st month of therapy, the patient should be examined. If the symptoms of the disease have been eliminated, the subsequent monitoring is carried out with the intake of 20 mg 1 time per day.

Combination with antibacterial substances to kill H.pylori.

For ulcers affecting the duodenum caused by Helicobacter pylori activity, as well as to prevent the recurrence 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 during the period 7 days.

Prevention and treatment of ulcers associated with prolonged administration of NSAIDs.

In case of gastric ulcers that appear as a result of treatment with NSAIDs, 20 mg Nexpro are administered once a day. Therapy lasts 1-2 months.

To prevent ulcers in the gastrointestinal tract, people in the risk category are prescribed 1 daily dose of 20 mg of drug per day.

Prevention of bleeding recurrence in ulcers in the gastrointestinal tract after using injection fluid esomeprazole.

During the 1st month, 40 mg of the substance is administered once a day. Before this course, treatment is carried out aimed at inhibition of acidity (the introduction of an infusion fluid of esomeprazole).

Therapy in case of gastrinomas.

Usually, 40 mg of the drug is prescribed 2 times a day. The portion is selected individually, and the cycle duration depends on the clinical indications. In the main part of the treatment, the disease can be controlled by applying 0.08-0.16 g of the substance per day. If you exceed the daily dosage of 80 mg, it is divided into 2 uses.

Problems with the work of the liver.

Persons with severe disorders can use no more than 20 mg of medication per day.

Use Nexpro during pregnancy

Information regarding the reception Nexpro during pregnancy is limited. Studies have not revealed a mediated or direct negative impact on the fetus. During this period, the medication is prescribed very carefully.

There is no information as to whether esomeprazole can be excreted in human milk. Drug administration during lactation has not been studied, which is why during this period it cannot be used.

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Contraindications

It is contraindicated to be prescribed for severe intolerance associated with esomeprazole, benzimidazole derivatives, or other elements of drugs. Can not be used in combination with nelfinavir or atazanavir.

Side effects Nexpro

The main side signs are:

• disorders of hematopoietic processes: thrombocyto-, leuko- or pancytopenia, as well as agranulocytosis;
• immune manifestations: symptoms of intolerance, including angioedema, fever and anaphylaxis or anaphylactic symptoms;
• metabolic disorders: hypomagnesemia or natriemia, as well as peripheral edema. In the severe stage of hypomagnesemia, hypocalcemia may develop;
• mental problems: aggression, insomnia, confusion, hallucinations, depression and agitation;
• symptoms associated with NA: paresthesia, taste disorder, headaches, drowsiness and weakness;
• visual disorders: visual impairment;
• maze disruption: dizziness;
• lesions associated with the respiratory system: bronchial spasm;
• manifestations affecting the digestive function: vomiting, pain in the abdomen and candidiasis affecting the gastrointestinal tract, constipation, and in addition nausea, dry mouth, diarrhea, flatulence, stomatitis, and microscopic colitis;
• problems associated with the hepatobiliary system: liver failure, hepatitis (accompanied by jaundice or not), an increase in liver enzymes and encephalopathy in people with hepatic abnormalities;
• lesions of the subcutaneous layer and the epidermis: rash, photosensitization, dermatitis, SJS, pruritus, erythema multiforme, urticaria, TEN and alopecia;
• musculoskeletal disorders: myalgia or arthralgia, as well as muscle weakness;
• urinary and renal impairment: tubulointerstitial nephritis;
• problems with reproductive function: gynecomastia;
• systemic signs: hyperhidrosis or weakness.

[7], [8]

Overdose

There is only limited information regarding drug poisoning. With the introduction of 0.28 g of the drug there is a weakness and signs associated with the gastrointestinal tract. A single injection of a portion of 80 mg does not cause the appearance of severe violations.

Nexpro does not have an antidote. Most of the esomeprazole is synthesized with blood protein, which is why the medicine does not respond to dialysis. Symptomatic actions are performed.

[9], [10]

Interactions with other drugs

The effects of esomeprazole in relation to the pharmacokinetics of other drugs.

Due to the decrease in gastric pH after the administration of esomeprazole, it is possible to increase or decrease the absorption of drugs whose absorption is associated with acidity indicators.

For example, there is a weakening of the absorption of drugs such as itraconazole with ketoconazole and erlotinib. But the absorption of digoxin with the introduction of aspirin or esomeprazole, on the contrary, increases. The introduction of 20 mg of omeprazole per day, as well as digoxin, in volunteers led to an increase in the bioavailability level of the latter by 10% (also in 2 out of a dozen people, the index 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 introduction of drugs in combination with substances whose metabolism proceeds using 2С19 (among them 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 level of CYP2C19 clearance for the substrate diazepam.

The use of 40 mg of medication together with phenytoin causes an increase in plasma parameters of the latter by 13% in people with epilepsy. It is necessary to monitor these indicators in the appointment or termination of the use of esomeprazole.

It is required to control the level of INR at the beginning, as well as at the end of the combined course with warfarin or other coumarin derivatives.

The combination of 40 mg of the drug with cisapride caused an increase of 32% in AUC values, and in addition, the term half-life was 31% longer; however, a significant increase in plasma indices Cmax in cisapride was not observed. A moderate increase in the QT interval was observed with a separate application of cisapride, but its subsequent prolongation did not occur when combined with esomeprazole.

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

There is evidence of an increase in blood values of methotrexate in individuals in the case of its combination with agents that slow down the action of the proton pump. If there is a need to use large amounts of methotrexate, it is necessary to consider the option of temporarily discontinuing Nexpro.

With the introduction of individual antiretroviral drugs (among those nelfinavir with atazanavir) a decrease in serum values of the latter. Because of this, the drug is not used in combination with the above medicinal substances.

The impact of other drugs on the pharmacokinetic properties of esomeprazole.

The exchange processes of esomeprazole are implemented with the participation of components 2С19, as well as CYRZA4. The administration of the drug together with clarithromycin, which slows down the action of CYPRA4 (in a dose of 0.5 g 2 times a day), doubled the level of exposure to esomeprazole.

The combination of the drug and the complex inhibitor of the elements 2C19 and CYPRA4 (for example, voriconazole) leads to an increase in more than twice the indicators of drug exposure.

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

In people with severe disorders of liver function with prolonged use of the drug, it is necessary to consider the option of changing its dosage.

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

[11]

Storage conditions

Nexpro must be kept in a closed place for small children. Temperature marks - not above the border of 25 ° C.

[12]

Shelf life

Nexpro can be applied within a 24-month term from the date of manufacture of the pharmaceutical product.

[13]

Application for children

There is no data on the use of the drug in persons under the age of 12, which is why this group is not prescribed.

[14], [15],

Analogs

Analogs of drugs are medicines Despazol, Esomealox, Ezoxium with Esomer, and also Zerzim, Esonex, Ezolong with Nexium and Esosol with Ezoks. In addition, Pemozar, Esomeprazole, Emanera and Ezer with Esomaps.

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