Nolpaza, pills 20mg, 28pcs

Composition

for 1 tablet 20 mg / 40 mg

Core:

Active ingredient:

Pantoprazole sodium sesquihydrate 22.55 mg / 45.10 mg, equivalent to Pantoprazole 20.00 mg/40.00 mg

Excipients: mannitol, crospovidone, sodium carbonate, sorbitol, calcium stearate

Film shell:

Hypromellose, povidone K-25, titanium dioxide (E 171), dye iron oxide yellow (E 172), propylene glycol, methacrylic acid and ethylacrylate copolymer (1: 1),30% variance 1, talc, macrogol-6000

1 Polymer dispersion contains 0.7% sodium lauryl sulfate and 2.3% of Polysorbate-80 as emulsifiers.

Pharmacological action

of gastric glands Secretion Lowering agent-Proton Pump Inhibitor

Clinical Pharmacology

Pharmacodynamics

Proton pump inhibitor (H+/K+-ATPase). Blocks the final stage of hydrochloric acid secretion, regardless of the nature of the irritant.

Pantoprazole is a substituted benzimidazole that suppresses the secretion of hydrochloric acid in the stomach by specifically blocking the proton pumps of parietal cells.

Pantoprazole is transformed into its active form in an acidic environment in parietal cells, where it suppresses the activity of the H+/K+-ATPase enzyme, i. e. blocks the final stage of formation of hydrochloric acid in the stomach. The suppression of activity is dose-dependent, and as a result, both basal and stimulated acid secretion decreases. When treated with pantoprazole, as with other proton pump inhibitors (PPI) and_H2-receptor blockers, the acidity in the stomach decreases and, thereby, the level of gastrin increases in proportion to the decrease in acidity. The increase in gastrin levels is reversible. Since pantoprazole binds the enzyme distally to the cell receptor, it can inhibit the secretion of hydrochloric acid independently of stimulation with other substances (acetylcholine, histamine, gastrin).

The effect of oral and intravenous use of the drug is the same.

Also, the content of chromogranin A (CgA) in the blood serum increases due to a decrease in the secretion of hydrochloric acid. Elevated levels of CgA can distort the results of diagnostic tests to detect neuroendocrine tumors.

Antisecretory activity

After the first oral use of 20 mg of Nolpaza®, a 24% decrease in gastric juice secretion occurs after 2.5-3.5 hours and by 26% after 24.5-25.5 hours. After oral use of pantoprazole once a day for 7 days, its antisecretory activity, measured 2.5-3.5 hours after use, increases to 56%, and after 24.5-25.5 hours – to 50%. In Helicobacter pylori-associated duodenal ulcer, a decrease in gastric secretion increases the sensitivity of microorganisms to antibiotics. It does not affect the motility of the gastrointestinal tract. Secretory activity normalizes in 3-4 days after the end of treatment.

Compared to other IPNs, Nolpaza® has a higher chemical stability at neutral pH, and a lower potential for interaction with the liver oxidase system, which depends on the cytochrome P450 system. Therefore, there was no clinically significant interaction between Nolpaza and many other drugs.

Pharmacokinetics

Pantoprazole is rapidly absorbed after oral use. The maximum concentration (C_max) in plasma when administered orally achieved after the first dose of 20 mg or 40 mg. C_max of about 1.0 to 1.5 µg/ml is achieved on average after approximately 2.0 to 2.5 hours after taking a dose of 20 mg and about 2.0 to 3.0 µg/ml after 2.5 h after oral dose of 40 mg C_mAh remains constant after repeated use of the drug.

The pharmacokinetics of pantoprazole after single and multiple use are the same. In the dose range of 10-80 mg, the plasma pharmacokinetics of pantoprazole remain linear with both oral and intravenous use.

The absolute bioavailability of pantoprazole tablets is about 77%. Co-use of food does not affect the area under the concentration-time curve (AUC), on serum cmax and, accordingly, on bioavailability. When taken together with food, the time of onset of action of the drug may vary. The binding of pantoprazole to plasma proteins is 98%. The volume of distribution is 0.15 l / kg.

It is mainly metabolized in the liver. The main metabolic pathway is demethylation by the CYP2C19 isoenzyme followed by sulfate conjugation. Other metabolic pathways include oxidation by the CYP3A4 isoenzyme.

The final half-life (T_1/2) is approximately 1 h, and the clearance is about 0.1 l / h / kg. Due to the specific binding of pantoprazole to the proton pumps of parietal cells, T_1/2 does not correlate with a much longer duration of action (inhibition of acid secretion).

The main route of excretion is by the kidneys (about 80%) in the form of pantoprazole metabolites, the rest is excreted in the faeces. The main metabolite in blood plasma and urine is desmethylpantoprazole conjugating with sulfate. The T_1/2 of the main metabolite is about 1.5 hours, which is not much higher than the T_1/2 of pantoprazole.

In individuals with low functional activity of the CYP2C19 isoenzyme (slow metabolizers), pantoprazole metabolism is probably mainly carried out by the CYP3A4 isoenzyme. After a single dose of pantoprazole 40 mg, the average area under the concentration-time curve was approximately 6 times larger in slow metabolizers than in individuals with the functionally active CYP2C19 isoenzyme (fast metabolizers). Mean plasma cmax values are increased by approximately 60%. These features do not affect the dosage of pantoprazole.

When using pantoprazole in patients with limited renal function (including patients on hemodialysis), no dose reduction is required. As in healthy volunteers, the T_1/2 of pantoprazole is short. Only a very small portion of the drug is dialyzed. Despite a moderately long T_1/2 of the main metabolite (2-3 h), its elimination occurs quite quickly, and therefore accumulation does not occur.

In patients with liver cirrhosis (classes A and b according to the classification of child-Pugh) time, T_1/2 increases up to 3-6 h, AUC values increase 3-5 times, With_mAh in serum increases slightly, only 1.3 times in comparison with that of healthy volunteers in the application of pantoprazole dosage 20 mg, respectively, with the use of pantoprazole in a dosage of 40 mg time T_1/2 increased to 7-9 hours, AUC values increased by 5-7 times, C_max in the serum increased 1.5 times compared to that in healthy volunteers.

A small increase in AUC and _{cmax in}elderly patients compared with the corresponding indicators in younger individuals is not clinically significant.

Indications

Gastroesophageal reflux disease (GERD), including erosive and ulcerative reflux esophagitis and GERD-related symptoms: heartburn, acid regurgitation, pain when swallowing.

Peptic ulcer of the stomach and duodenum (in the acute phase), erosive gastritis (including those associated with taking nonsteroidal anti-inflammatory drugs (NSAIDs)).

Zollinger-Ellison syndrome.

Eradication of Helicobacter pylori in combination with antibacterial agents.

Use during pregnancy and lactation

Pregnancy

As a precautionary measure, it is necessary to exclude the use of Nolpaza during pregnancy.

Breast-feeding period

Due to insufficient information on the use of Nolpaza® in women during breastfeeding, the potential risk for newborns and children who are breastfed cannot be excluded. In this regard, it is necessary to make a decision on stopping breastfeeding or on canceling / suspending treatment with Nolpaza®.

Fertility

There are no data available on the effects of Nolpaza on human fertility. Preclinical studies have shown no effect on male or female fertility.

Contraindications

• Hypersensitivity to any of the components of the drug, as well as to substituted benzimidazoles.
• Dyspepsia of neurotic origin.
• Concomitant use of HIV protease inhibitors, such as atazanavir, nelfinavir, and drugs whose absorption depends on the acidity (pH) of gastric juice.
• Children under 18 years of age.
• Pregnancy, breast-feeding period.
• Patients with congenital fructose intolerance are not recommended to take Nolpaza®, as it contains sorbitol.

Side effects

Approximately 5% of patients can expect to develop adverse drug reactions (NLR). The most common NLRs are diarrhea and headache, which develop in approximately 1% of patients.

NLRs reported with pantoprazole are listed below, classified according to the frequency of occurrence as follows: :

• very often (3 1/10)
• often (3 1/100 and < 1/10)
• infrequently (3 1/1000 and
• rarely (3 1/10 000 and
• very rare (
• the frequency is unknown (it is impossible to estimate based on the available data).

For adverse reactions identified during post-marketing use of the drug, it is not possible to apply any category of frequency of occurrence, and therefore they are indicated as “frequency unknown”.

Within each frequency group, adverse reactions are presented in decreasing order of severity.

Disorders of the blood and lymphatic system:

rare: agranulocytosis;

very rare: thrombocytopenia, leukopenia, pancytopenia.

Immune system disorders:

rarely: hypersensitivity (including anaphylactic reactions, including anaphylactic shock).

Metabolic and nutritional disorders:

rare: hyperlipidemia and increased concentration of lipids (triglycerides, cholesterol) in blood plasma, changes in body weight;

frequency unknown: hyponatremia, hypomagnesemia, hypocalcemia in combination with hypomagnesemia, hypokalemia.

Mental disorders:

infrequently: sleep disorders;

rarely: depression (including exacerbations of existing disorders);

very rarely: disorientation (including exacerbations of existing disorders);

frequency unknown: hallucinations, confusion (especially in predisposed patients, as well as possible exacerbation of symptoms if they are present before using the drug).

Nervous system disorders:

infrequently: headache, dizziness;

rarely: dysgeusia (taste disorder);

frequency unknown: paresthesia.

Visual disturbances:

rare: visual impairment/blurred vision.

Disorders of the gastrointestinal tract:

common: glandular polyps of the stomach floor (benign);

uncommon: diarrhea, nausea/vomiting, bloating and flatulence, constipation, dry oral mucosa, abdominal pain and discomfort;

frequency unknown: microscopic colitis.

Liver and biliary tract disorders:

infrequently: increased activity of “liver” enzymes (transaminases, gamma-glutamyltransferases) in blood plasma;

rarely: increased concentration of bilirubin in blood plasma;

frequency unknown: hepatocellular damage, jaundice, hepatocellular insufficiency.

Skin and subcutaneous tissue disorders:

Infrequently: skin rash/exanthema / rash, pruritus;

rarely: urticaria, angioedema;

frequency unknown: malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), exudative erythema multiforme, photosensitivity, subacute cutaneous lupus erythematosus (PKKV).

Musculoskeletal and connective tissue disorders:

infrequently: fracture of the femoral neck, wrist or spine;

rarely: arthralgia, myalgia;

frequency unknown: muscle spasm due to electrolyte imbalance.

Kidney and urinary tract disorders:

frequency unknown: interstitial nephritis (with possible progression to renal failure).

Genital and breast disorders:

rare: gynecomastia.

General disorders and disorders at the injection site:

infrequently: asthenia, excessive fatigue and malaise;

rarely: fever, peripheral edema.

Interaction

Concomitant use of other proton pump inhibitors or_H2-histamine receptor blockers is not recommended without medical advice.

Concomitant use of Nolpaza may reduce the absorption of drugs whose bioavailability depends on the pH of the gastric environment (for example, ketoconazole, itraconazole, posaconazole and other drugs such as erlotinib).

During drug interaction studies, no clinically significant interactions were identified with pantoprazole in the following cases::

• patients with cardiovascular diseases receiving cardiac glycosides (digoxin), blockers of slow calcium channels (nifedipine), beta-blockers (metoprolol);
• patients with diseases of the gastrointestinal tract taking antacids, antibiotics (amoxicillin, clarithromycin);
• patients receiving oral contraceptives containing levonorgestrel and ethinyl estradiol;
• patients receiving nonsteroidal anti-inflammatory drugs (diclofenac, naproxen, piroxicam);
• patients with diseases of the endocrine system, the receiving glibenclamide, levothyroxine;
• patients with anxiety and sleep disorders receiving diazepam;
• patients with epilepsy taking carbamazepine and phenytoin;
• patients receiving indirect anticoagulants, such as warfarin and phenprocoumon, under the control of the prothrombin time and international normalized ratio (INR) at the beginning and at the end of treatment and during irregular intake of pantoprazole. At the same time, it should be noted that there are known cases of increased INR and prothrombin time in patients who received IPN together with warfarin or fenprocumone. Increased INR and prothrombin time can lead to life-threatening abnormal bleeding. In this regard, such patients should be monitored for increased INR and prothrombin time.

There was also no clinically significant drug interaction with caffeine, ethanol, and theophylline.

There are reports of increased blood levels of methotrexate in some patients when it is co-administered in high doses (for example,300 mg) with IPN. Therefore, when using high doses of methotrexate, for example, in cancer or psoriasis, it may be necessary to consider temporary discontinuation of pantoprazole.

Inhibitors of CYP2C19 activity, such as fluvoxamine, may increase the systemic exposure of pantoprazole. Reducing the dose may be necessary for patients receiving long-term treatment with high doses of pantoprazole or patients with hepatic insufficiency.

Inducers of the activity of CYP2C19 and CYP3A4 isoenzymes, such as rifampicin andHypericum perforatum, can reduce the plasma concentration of IPN metabolized by these enzyme systems.

HIV protease inhibitors

Pantoprazole is not recommended to be used together with HIV protease inhibitors, the absorption of which depends on the pH of the stomach environment (for example, atazanavir), due to a significant decrease in their bioavailability.

If the combined use of HIV protease inhibitors and IPN is still necessary, it is recommended to conduct careful clinical monitoring (for example, determining the viral load). The dose of pantoprazole should not exceed 20 mg per day. You may also need to adjust the dosage of the HIV protease inhibitor.

How to take, course of use and dosage

Nolpaza® is taken orally, before meals, without chewing or grinding, with a sufficient amount of liquid.

GERD, including erosive and ulcerative reflux esophagitis and GERD-related symptoms:heartburn, acid regurgitation, pain when swallowing:

light grade: the recommended dose is 1 tablet of Nolpaza® (20 mg) per day;

moderate to severe: the recommended dose is 1-2 tablets of Nolpaza 40 mg per day (40-80 mg / day). Relief of symptoms usually occurs within 2-4 weeks. The course of therapy is 4-8 weeks. For prevention, as well as as a long-term maintenance therapy, take 20 mg/day (1 tablet of Nolpaza® 20 mg), if necessary, the dose is increased to 40-80 mg/day. It is possible to take the drug “on demand” if symptoms occur.

Peptic ulcer of the stomach and duodenum, erosive gastritis (including those associated with taking nonsteroidal anti-inflammatory drugs)

40-80 mg per day.

The course of treatment is 2 weeks in case of exacerbation of duodenal ulcer, if this time is not enough, then healing can usually be achieved during the next 2 weeks of therapy. The course of treatment is 4-8 weeks in case of exacerbation of gastric ulcer and erosive gastritis.

Anti-relapse treatment of peptic ulcer of the stomach and duodenum-20 mg/day.

Eradication of Helicobacter pylori

The following combinations are recommended:

Nolpaza ® 40 mg 2 times a day + amoxicillin 1000 mg 2 times a day + clarithromycin 500 mg 2 times a day.

Nolpaza ® 40 mg 2 times a day + metronidazole 500 mg 2 times a day + clarithromycin 500 mg 2 times a day.

Nolpaza ® 40 mg 2 times a day + amoxicillin 1000 mg 2 times a day + metronidazole 500 mg 2 times a day.

The course of treatment is 7-14 days.

Zollinger-Ellison syndrome

For long-term treatment of Zollinger-Ellison syndrome and other pathological hypersecretory conditions, treatment should begin with a daily dose of 80 mg (2 tablets of Nolpaza® 40 mg). Then, if necessary, the dose can be increased or reduced, depending on the acidity of gastric juice. Doses above 80 mg per day should be divided and administered twice daily. It is possible to temporarily increase the dose of pantoprazole above 160 mg, but it should not last longer than it is necessary to achieve acidity control. The duration of treatment for Zollinger-Ellison syndrome and other pathological hypersecretory conditions is not limited, and the duration of therapy can be determined depending on the clinical need.

In patients with severe hepatic impairment, the daily dose of pantoprazole should not exceed 20 mg per day (1 tablet of Nolpaza® 20 mg). In this regard, the use of pantoprazole at a dosage of 40 mg in this group of patients is not recommended. The activity of “liver” enzymes should be regularly monitored during treatment with pantoprazole, especially with prolonged use of the drug. In case of increased activity of “liver” enzymes, treatment should be discontinued.

No dose adjustment is required in elderly patients and patients with renal insufficiency.

Due to the lack of data on the use of Nolpaza® in combination antimicrobial therapy against Helicobacter pylori in patients with impaired renal function, as well as in patients with moderate to severe hepatic insufficiency, the drug should not be used.

Overdose

There were no cases of overdose resulting from the use of Nolpaza®.

Doses of pantoprazole up to 240 mg were administered intravenously for 2 minutes and were well tolerated.

In case of overdose and only when clinical manifestations occur, symptomatic and supportive therapy is performed. Pantoprazole is not eliminated by hemodialysis.

Description

Oval, slightly biconvex tablets, covered with a film-coated light yellowish-brown color.

View on the fracture: a rough mass from white to light yellowish-brown with a film shell of light yellowish-brown color.

Special instructions

Liver failure, risk factors for cyanocobalamin (vitamin_B12) deficiency (especially on the background of hypo – and achlorhydria).

Contraindicated in persons under 18 years of age.

In patients with severe hepatic impairment, the daily dose of pantoprazole should not exceed 20 mg per day (1 tablet of Nolpaza® 20 mg). In this regard, the use of pantoprazole at a dosage of 40 mg in this group of patients is not recommended. The activity of “liver” enzymes should be regularly monitored during treatment with pantoprazole, especially with prolonged use of the drug. In case of increased activity of “liver” enzymes, treatment should be discontinued.

No dose adjustment is required in elderly patients and patients with renal insufficiency.

Due to the lack of data on the use of Nolpaza® in combination antimicrobial therapy against Helicobacter pylori in patients with impaired renal function, as well as in patients with moderate to severe hepatic insufficiency, the drug should not be used.

Before starting treatment with Nolpaza®, the possibility of malignancy should be excluded, since the drug can mask symptoms and delay the correct diagnosis.

Patients should consult their doctor if they are going to have an endoscopy or urea breath test.

Patients should consult their doctor if the following cases occur::

• unintentional weight loss, anemia, gastrointestinal bleeding, difficulty swallowing, persistent vomiting or vomiting of blood. In these cases, taking the drug may partially alleviate symptoms and delay proper diagnosis;
• previous gastrointestinal surgery or stomach ulcers;
• continuous symptomatic treatment of dyspepsia and heartburn for 4 weeks or more;
• liver diseases, including jaundice and liver failure;
• and other serious diseases that worsen overall health.

Patients over the age of 55 who have new or recently changed symptoms should consult a doctor.

When taking medications that reduce the acidity of gastric juice, the risk of gastrointestinal infections caused by bacteria of the genus Salmonella spp., Campylobacter spp. slightly increases. or C. difficile.

In patients with Zollinger-Ellison syndrome and other pathological hypersecretory conditions that require long-term treatment, pantoprazole, like other drugs that block gastric juice secretion, may reduce the absorption of vitamin_B12 (cyanocobalamin) due to hypo-and achlorhydria. This should be taken into account in the treatment of patients with reduced reserves of this vitamin in the body, or in the long-term treatment of patients with risk factors for developing vitamin_{B12 deficiency}, as well as in the observation of appropriate clinical symptoms.

Long-term therapy, especially with a duration of more than 1 year, requires regular monitoring of patients.

Pantoprazole is not recommended to be used together with HIV protease inhibitors, the absorption of which depends on the pH of the stomach environment (for example, atazanavir), due to a significant decrease in their bioavailability.

Severe hypomagnesaemia has been reported in patients treated with IPN for at least 3 months, and in most cases within a year. Serious manifestations of hypomagnesemia may occur, such as fatigue, tetany, delirium, seizures, dizziness, and ventricular arrhythmia, but hypomagnesemia may develop unnoticed and not be recognized in a timely manner. In most patients with hypomagnesemia, it decreases after magnesium replacement therapy and discontinuation of IPN. In patients who are scheduled for long-term treatment, or in patients receiving IPN together with digoxin or other drugs that can cause hypomagnesemia (for example, diuretics), it is necessary to determine the serum magnesium content before starting IPN treatment and periodically during treatment.

Proton pump inhibitors, especially when used at high doses and for a long time (>1 year), may slightly increase the risk of fractures of the femur, wrist and spine, mainly in elderly patients or in the presence of other generally recognized risk factors. Observational studies indicate that proton pump inhibitors may increase the overall risk of fractures by 10-40%. Some of these fractures may be due to the presence of other risk factors. Patients at risk of osteoporosis should receive treatment in accordance with current clinical guidelines and adequate amounts of vitamin D and calcium.

Subacute cutaneous lupus erythematosus is very rare in the treatment of IPN. If skin lesions occur, especially in areas that have been exposed to sunlight, or if there is concomitant arthralgia, the patient should immediately seek medical attention, and the health care professional should evaluate whether treatment with Nolpaza should be discontinued. The occurrence of PCV after previous IPN treatment may increase the risk of developing PCV when treated with other proton pump inhibitors.

When conducting laboratory tests, it should be taken into account that an increased content of CgA in the blood serum can distort the results of diagnostic studies to detect neuroendocrine tumors. In this regard, the use of Nolpaza® should be discontinued at least 5 days before the CgA content study. If CgA and gastrin levels do not return to normal values after the first determination, the study should be repeated 14 days after discontinuation of the proton pump inhibitor.

Influence on the ability to drive vehicles and mechanisms

You should refrain from driving vehicles and other mechanisms that require increased attention, because of the likelihood of dizziness and visual impairment.

You should refrain from driving vehicles and other mechanisms that require increased attention, because of the likelihood of dizziness and visual impairment.

Form of production

Enteric-soluble film-coated tablets,20 mg,40 mg.

Storage conditions

At a temperature not exceeding 25 ° C, in the original packaging.

Keep out of reach of children.

Shelf

life is 5 years.

Do not use the drug after the expiration date.

Active ingredient

Pantoprazole

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Gastritis, Gastric and Duodenal ulcers, GI infections caused by Helicobacter Pylori, Heartburn