Structure and form of release

Structure

Active ingredient: pantoprazol;

1 gastrorezistentny tablet contains 20 mg of a pantoprazol in the form of a pantoprazol of sodium of sexivihydrat;

Excipients: mannitol (E 421), krospovidon (type A), krospovidon (type B) of sodium carbonate anhydrous, sorbite (E 420), calcium stearate, gipromelloza, povidone, titan dioxide (E 171), ferrous oxide yellow (E172), propylene glycol, methacrylate copolymer dispersion, sodium lauryl sulfate, polysorbate 80, talc, macrogoal 6000;

release Form

Tablet gastrorezistentny.

Pharmacological properties

Pharmacodynamics. pantoprazol — the substituted benzimidazole blocking secretion of hydrochloric acid in a stomach by specific influence on the proton pump of covering cells.

Pantoprazol is transformed by

to an active form in acidic environment of covering cells where it blocks H ^{enzyme +} / K ⁺ to ATFaz, namely a final stage of hydrophilic secretion of hydrochloric acid in a stomach. Oppression is dose-dependent and influences basal and stimulated secretion of gastric juice.

Treatment pantoprazoly, as well as other inhibitors of the proton pump and H _{2 inhibitors} - receptors, causes decrease in acidity of a stomach and proportional increase in discharge of gastrin. Increase in level of gastrin has reversible character. As pantoprazol contacts enzymes which are remote from cellular receptors, it influences secretion of hydrochloric acid irrespective of stimulation by other substances (acetylcholine, a histamine, gastrin). The efficiency of medicament is identical at oral administration or in in introduction.

At use of a pantoprazol the gastrin level on an empty stomach increases. At short use it in most cases does not exceed the upper bound of norm. At long-term treatment the gastrin level in most cases increases twice. Its excessive increase, however, arises only in rare instances. As a result, in a small amount of cases at long-term treatment the weak or moderate increase in quantity of enterokhromaffinnopodobny cells (ECL cells) in a stomach (adenomatoid hyperplasia) is noted. Nevertheless, it agrees carried out at the moment by researches, formation of progenitors of neuroendocrinal tumors of a stomach which are revealed in experiments on animals, at people it is noted. But at long (more than 1 year) treatment it is impossible to exclude influence of a pantoprazol on endocrine parameters of a thyroid gland.

Pharmacokinetics. Pantoprazol is quickly soaked up, the C _max in blood plasma is reached even after reception of one dose of 20 or 40 mg. On average the C _max in blood plasma of 1-1.5 mkg/ml — for a dose of 20 mg and 2–3 mkg/ml — for a dose of 40 mg is reached for 2-2.5 h after reception and remains to a constant also after repeated introduction. The volume of distribution is about 0.15 l/kg of body weight, and clearance — 0.1 l/h/kg. Meal does not affect bioavailability (AUC or C _max ), but increases instability of delay time.

T _½ is made by about 1 h. In several cases of T _½ increased. Thanks to specific linking of a pantoprazol with the proton pump of covering cells, T _½ is not accompanied by the bigger duration of action.

Pharmacokinetics does not change after single or multiple dose. In the range of doses of 10-80 mg the kinetics of a pantoprazol in blood plasma is linear as after peroral, and later in/in introductions.

Linking of a pantoprazol with proteins of blood plasma makes about 98%. Drug is almost completely metabolized in a liver. The main way of removal about 80% of metabolites of a pantoprazol — through kidneys, the rest — with a stake. The main metabolite both in blood plasma, and in urine — dismetilpantoprazol in connection with sulfate. T _½ is not much longer than the main metabolite (about 1.5 h), than a pantoprazol.

Bioavailability. After oral administration pantoprazol it is absorbed completely. The absolute bioavailability at oral administration is about 77%. Consumption of food does not influence value of an indicator of AUC, C _max in blood plasma and bioavailability; only the beginning of action changes.

Characteristic of special groups of patients. For patients with a renal failure (including being on a hemodialysis) there is no need for a dose decline. As well as at healthy people, T _½ a pantoprazola at them short. Only very small amount of a pantoprazol can be dializovano. In spite of the fact that T _½ main metabolite increases a little (2–3 h), he is quickly brought and does not kumulirutsya.

At patients with cirrhosis (the class A and B on classification of Chayld-Pyyu) T _½ increases to 7–9 h and according to it by 5–7 times max AUC, C _{values increase} pantoprazola in blood plasma raises by 1.5 times in comparison with healthy people.

Insignificant increase in AUC and C _max pantoprazola in blood plasma at volunteers of advanced age in comparison with young people is also not clinically significant.

Children. After single dose of a dose of 20 or 40 mg of a pantoprazol orally AUC and C _max at children at the age of 5–16 years were in limits of the corresponding values at adults. After single introduction of a pantoprazol in a dose of 0.8 or 1.6 mg/kg of body weight to children at the age of 2–16 years the significant communication between clearance of a pantoprazol and age or body weight is noted. AUC and volume of distribution corresponded data, received at researches on adults.

Indication

Nolpaz's

, a tablet of 20 mg

Adults and children are aged more senior than 12 years

• Symptomatic treatment of a gastroesophageal reflux disease;
• long-term treatment and prevention of a recurrence reflux esophagitis.

Adult:

• prevention of the stomach ulcer and a duodenum caused by use of NPVP for patients of risk group which have to apply NPVP a long time.

Contraindication

Hypersensitivity to a pantoprazol, derivatives of benzimidazole or any other substance which is a part of drug. pantoprazol, as well as other inhibitors of a proton pomp, it is contraindicated to apply with atazanaviry.

Use

Nolpaz's

, tablet of 20 mg

Simtomatichesky treatment of GERD. The recommended dose for adults and children is aged more senior than 12 years makes 1 tablet of the medicament Nolpaza of 20 mg/days. Symptoms, as a rule, disappear in 2–4 weeks of treatment. Treatment of the associated esophagitis, as a rule, requires 4 weeks. If this term is not enough, treatment is continued during the following 4 weeks. After disappearance of symptoms their recurrence can be controlled, applying 20 mg/days depending on need.

Long treatment and prevention of a recurrence reflux esophagitis. The recommended dose makes 1 tablet of the medicament Nolpaza of 20 mg/days. At the expected aggravation the increase in a dose to 40 mg/days is possible, use of the tablets Nolpaza of 40 mg is in that case recommended. After elimination of a recurrence the dose can be lowered to 20 mg of a pantoprazol again a day.

Prevention of stomach ulcer and the duodenum caused by reception of non-selective NPVP in patients of risk group for whom reception of NPVP a long time is necessary. The recommended dose makes 1 tablet of the medicament Nolpaza of 20 mg/days. At patients with a heavy liver failure the daily dose should not exceed 20 mg of a pantoprazol. Patients of advanced age and patients have no need for a dose decline with impaired renal function.

Duration of treatment of a syndrome of Zollinger — Ellison and other morbid conditions is not limited to

and depends on clinical need.

Patients with an abnormal liver function. Patients with heavy abnormal liver functions should not exceed a daily dose of 20 mg (1 tablet Nolpaza of 20 mg). It is not necessary to use the medicament Nolpaza for an eradikation of H. pylori in combination therapy at patients from the liver of average and heavy degree broken by function as there are no data on efficiency and safety of such use for this category of patients now.

Patients with a renal failure. For patients with impaired renal function of dose adjustment it is not required. It is not necessary to use the medicament Nolpaza for an eradikation of H. pylori in combination therapy of patients on impaired renal function as there are no data on efficiency and safety of such use for this category of patients now.

to

to Patients of advanced age does not need dose adjustment.

Special instructions

Patients with an abnormal liver function. in heavy abnormal liver functions during treatment, especially at prolonged use, regular control of the level of liver enzymes is necessary. in case of increase in level of liver enzymes the treatment needs to be stopped.

Concomitant use of an atazanavir. The concomitant use of an atazanavir with inhibitors of a proton pomp is not recommended. If the combination of an atazanavir with inhibitors of a proton pomp is inevitable, it is necessary to carry out careful clinical monitoring (for example to measure viral load) in combination with increase in a dose of an atazanavir to 400 mg using 100 mg of a ritonavir. The dose of a pantoprazol of 20 mg/days should not be exceeded.

Influence on adsorption of _{12 vitamin B} . At patients with Zollinger's syndrome — Ellisona and other hyper secretory states demanding long-term treatment, pantoprazol as well as other medicaments blocking discharge of gastric juice can reduce absorption of _{12 vitamin B} (cyanocobalamine) in connection with emergence hypo - or achlorhydrias. It should be considered at patients with the reduced body weight or presence of risk factors of decrease in digestion of _{12 vitamin B} (cyanocobalamine) especially at long-term treatment or existence of the corresponding clinical symptoms.

Long-term treatment. Lasting treatment more than 1 year the patient has to be under constant observation.

in the presence of disturbing symptoms. Before treatment it is necessary to exclude malignant diseases of a gullet or stomach as treatment pantoprazoly can mask symptoms of a malignant disease and thus interfere with establishment of the correct diagnosis.

Hypomagnesiemia. Noted cases of a heavy hypomagnesiemia at the patients receiving inhibitors of a proton pomp, such as pantoprazol, within not less than 3 months, and in most cases during 1 year. Can arise and at first imperceptibly develop the following serious clinical manifestations of a hypomagnesiemia: fatigue, tetany, delirium, spasms, dizziness and ventricular arrhythmia. In case of a hypomagnesiemia in most cases the condition of patients improved after the replacement adjusting therapy by medicaments of magnesium and the termination of intake of inhibitors of a proton pomp.

to Patients who need long therapy or to patients who accept inhibitors of a proton pomp along with digoxin or medicaments which can cause a hypomagnesiemia (for example diuretics) should determine by

magnesium level before an initiation of treatment inhibitors of a proton pomp and periodically during treatment.

Bone fractures. Long-term treatment (more than 1 year) high doses of inhibitors of a proton pomp can increase several risk of a fracture of hip, wrist and backbone, mainly at elderly people or with other risk factors. Controlled researches indicate that use of inhibitors of a proton pomp can increase the general risk of changes by 10–40%. Some of them can be caused by other risk factors. Patients with risk of developing osteoporosis have to receive treatment according to the existing clinical recommendations and use enough vitamin D and calcium.

Gastrointestinal infections caused by bacteria. Pantoprazol, as well as other inhibitors of a proton pomp, can increase quantity of bacteria which usually are present at upper parts of a GIT. Drug treatment can increase several risk of developing of the gastrointestinal infections caused by such bacteria as Salmonella and Campylobacter.

Information about excipients. The medicament Nolpaza contains sorbite. Patients with rare hereditary diseases of intolerance of fructose should not use drug.

Use during pregnancy or feeding by a breast

Experience of use of medicament during pregnancy is limited to

. In researches of reproductive function on animals the insignificant embriotoxity in doses of 5 mg/kg of body weight is noted. The potential risk for the person is unknown. Drug is used during pregnancy only in urgent cases. Data on excretion of a pantoprazol with breast milk are obtained. A breast it is necessary to make the decision on use of medicament during feeding after careful assessment advantage/risk.

Children

Experience of use of medicament for children is limited to

therefore pantoprazol, it is not recommended to apply at patients of this age category.

to Drivers

in case of side reactions, such as dizziness and disorder of vision, it is necessary to refrain from control of vehicles and work with potentially dangerous mechanisms.

Side effects

note Emergence of side reactions at about 5% of patients. the most frequent side reactions — diarrhea and a headache (about 1%).

Undesirable effects on the frequency of emergence classify

by such categories: very often (≥ 1/10), it is frequent (≥1/100 and 1/10), infrequently (≥1/1000 and 1/100), is rare (≥1/10,000 and 1/1000), is very rare (1/10,000), it is unknown (frequency is not determined by the available data).

from blood and lymphatic system: seldom — an agranulocytosis; very seldom — a leukopenia, thrombocytopenia, a pancytopenia.

from the immune system: seldom — reactions of hypersensitivity (including anaphylactic reactions, an acute anaphylaxis).

Metabolism and disbolism: seldom — a lipidemia and increase in level of lipids (TG, XC), change of body weight; it is unknown — a hyponatremia, a hypomagnesiemia (see. Special INSTRUCTIONS), hypocalcemia ¹ , hypopotassemia.

Mental disorders: infrequently — sleep disorders; seldom — a depression (including aggravations); very seldom — a disorientation (including aggravations); it is unknown — a hallucination, confusion of consciousness (especially at patients with tendency to these disorders and also aggravation of these symptoms in case of their existence in the anamnesis).

from nervous system: infrequently — a headache, dizziness; seldom — disturbances of taste; it is unknown — paresthesias.

from an organ of sight: seldom — disturbance sight/misting of sight.

from a digestive tract: infrequently — diarrhea, nausea, vomiting, an abdominal distension, a constipation, dryness in a mouth, an abdominal pain and discomfort.

from a gepatobiliarny system: infrequently — increase in level of liver enzymes (transaminases, a γ-glutamiltransferaza); seldom — increase in level of bilirubin; it is unknown — damage of hepatocytes, jaundice, hepatocellular insufficiency.

from skin and hypodermic fabrics: infrequently — skin rash, a dieback, an itching; seldom — urticaria, a Quincke's disease; it is unknown — Stephens's syndrome — Johnson, a Lyell's disease, a multiformny erythema, a photosensitization.

from a musculoskeletal system and connective tissue: infrequently — fractures of a hip, wrist, backbone (see. Special INSTRUCTIONS); seldom — an arthralgia, myalgia; it is unknown — a spasm of muscles ² .

from kidneys and an urinary system: it is unknown — interstitial nephrite (with possible development of a renal failure).

from a reproductive system and mammary glands: seldom — a gynecomastia.

General disturbances: infrequently — an asthenia, fatigue, an indisposition; seldom — fervescence, peripheral hypostases.

Overdose

is not present

Messages about overdose. in/in doses up to 240 mg were entered more than 2 min., the tolerance was good. pantoprazol extensively contacts proteins and completely it is not removed by means of dialysis.

to

in case of overdose with clinical manifestations of intoxication recommends the symptomatic and supporting treatment.

Interaction

Influence of a pantoprazol on absorption of other medicines. pantoprazol can reduce absorption of medicines which bioavailability depends on ph of gastric juice, for example some azoles, antifungal drugs, such as ketokonazol, itrakonazol, pozakonazol and other medicines, such as erlotinib.

Drugs for treatment of HIV (atazanavir). The combined reception of an atazanavir and other medicaments for treatment of HIV which adsorption depends on pH with inhibitors of a proton pomp can lead to considerable decrease in bioavailability of the last and affect their efficiency. Therefore co-administration of inhibitors of a proton pomp with atazanaviry is not recommended.

Coumarinic anticoagulants (warfarin or fenprokumon). Despite the lack of interaction at simultaneous use with fenprokumony or warfarin, at conduct of clinical trials, isolated cases of change of the international normalized relation (INR) during the post-marketing period are registered. Thus, to the patients applying anticoagulants coumarinic (for example fenprokumon or warfarin) a row, it is recommended to carry out control of a prothrombin time or MNO after the beginning, the terminations or at irregular reception of a pantoprazol.

Methotrexate. It was reported that simultaneous use of high doses of a methotrexate (for example 300 mg) and inhibitors of a proton pomp increases methotrexate level in blood at some patients. The patients accepting high doses of a methotrexate, for example the cancer patient or psoriasis are recommended to stop temporarily treatment pantoprazoly.

Research of other interactions. Pantoprazol is substantially metabolized in a liver by the system of P450 cytochrome. The main way of metabolism — demethylation by means of CYP 2C19 and other metabolic ways, including oxidation by CYP enzyme 3A4.

Research with medicines which are also metabolized by means of these ways such as carbamazepine, diazepam, glibenclamide, nifedipine, fenprokumon and the oral contraceptives containing levonorgestrel and ethinylestradiol did not reveal clinically significant interactions.

Results of researches of possible interactions specify that pantoprazol does not influence metabolism of the active agents which are metabolized by means of CYP 1A2 (such as caffeine and theophylline), CYP 2C9 (for example piroxicam, diclofenac, Naproxenum), CYP 2D6 (for example metoprolol), CYP 2E1 (for example ethanol) and does not influence the p-glycoprotein providing digoxin absorption.

by

did not reveal interaction with at the same time appointed antacids.

by

conducted special researches of interaction of a pantoprazol with certain antibiotics (klaritromitsin, metronidazole, amoxicillin), at simultaneous use of clinically significant interactions between these medicaments did not reveal.

Incompatibility. The medicament Nolpaza, injections, it is not necessary to mix with other medicines, except those which are specified in the section USE (Method of administration).

Storage conditions

Nolpaz's

, tablet, and nolpaza control: at a temperature not above 30 °C in original packing for protection against moisture.