Ulsepan lyophilisate for solution for injection 40mg 1pc — Made in Turkey — Free Delivery

Pharmacological properties

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

Pantoprazole is transformed into an active form in an acidic medium in parietal cells, where it inhibits the H + -K + -ATPase enzyme, that is, it blocks the final stage of the production of hydrochloric acid in the stomach. Inhibition is dose dependent and suppresses both basal and stimulated acid secretion. In most patients, symptoms resolve within 2 weeks. The use of pantoprazole, like other proton pump inhibitors (PPIs) and H2-receptor inhibitors, decreases gastric acidity and thus increases gastrin secretion in proportion to the decrease in acidity. The increase in gastrin secretion is reversible. Since pantoprazole binds the enzyme distally to the cellular receptor, it can inhibit the secretion of hydrochloric acid independently of stimulation by other substances (acetylcholine, histamine, gastrin). The effect is the same for oral and intravenous administration.

When using pantoprazole, the level of fasting gastrin increases. With short-term use, in most cases, it does not exceed the upper limit of the norm. With long-term treatment, gastrin levels double in most cases. Excessive growth, however, occurs only in rare cases. As a result, in a small number of patients with long-term treatment, there is a weak or moderate increase in the number of enterochromaffin-like (ECL-cells) in the stomach (similar to adenomatoid hyperplasia). However, according to the studies carried out to date, the formation of cells - precursors of neuroendocrine tumors (atypical hyperplasia) or neuroendocrine tumors of the stomach, which have been identified in animal experiments, have not been observed in humans.

According to the results of animal studies, it is impossible to exclude the effect of prolonged (more than 1 year) treatment with pantoprazole on the endocrine parameters of the thyroid gland.

Against the background of treatment with antisecretory agents, the level of gastrin in the blood plasma increases in response to a decrease in acid secretion. In addition, chromogranin A (CgA) levels increase due to decreased gastric acidity. Elevated CgA levels can affect the results of studies in the diagnosis of neuroendocrine tumors. Available published data suggest that PPI treatment should be discontinued 5 days to 2 weeks before CgA measurement. This allows the CgA level to return to the normal range, which may be falsely elevated after PPI treatment.

Pharmacokinetics

Suction. Pantoprazole is rapidly absorbed, and Cmax in blood plasma is reached after a single dose of 40 mg. On average, 2.5 hours after administration, Cmax in blood plasma is reached at a level of about 2–3 μg / ml; concentration remains at a constant level after repeated administration. Pharmacokinetic properties do not change after single or repeated administration. In the dose range of 10–80 mg, the pharmacokinetics of pantoprazole in blood plasma remains linear both when taken orally and when administered intravenously. It was found that the absolute bioavailability of the tablets is about 77%. Simultaneous food intake does not affect AUC or Cmax in blood plasma, and, accordingly, bioavailability. With the simultaneous intake of food, only the variability of the latent period increases.

Distribution. The binding of pantoprazole to blood plasma proteins is about 98%. The volume of distribution is about 0.15 l / kg body weight.

Biotransformation. The substance is metabolized almost exclusively in the liver. The main metabolic pathway is demethylation by CYP 2C19 followed by sulfate conjugation; other metabolic pathways include oxidation by CYP 3A4.

Excretion. The final T½ is about 1 hour and the ground clearance is 0.1 l / h / kg. There are several cases of delayed elimination. Due to the specific binding of pantoprazole to the proton pump of parietal cells, T½ does not correlate with a much longer duration of action (inhibition of acid secretion).

Most of the metabolites of pantoprazole are excreted in the urine (about 80%), the rest is excreted in the feces. The main metabolite in both blood plasma and urine is desmethylpantoprazole conjugated with sulfate. T½ of the main metabolite (about 1.5 hours) is not much higher than the T½ of pantoprazole.

Special patient groups

Slow metabolizers. Around 3% of Europeans have a functionally low activity of the CYP 2C19 enzyme; they are called slow metabolizers. In these individuals, the metabolism of pantoprazole is probably catalyzed mainly by the CYP 3A4 enzyme. After taking a single dose of 40 mg of pantoprazole, the average AUC was approximately 6 times higher in slow metabolizers than in individuals with a functionally active CYP 2C19 enzyme (fast metabolizers). Average Cmax in blood plasma increased by about 60%. These results do not affect the dosage of pantoprazole.

Impaired renal function. There are no recommendations for dose reduction when prescribing pantoprazole to patients with impaired renal function (including those on dialysis). As in healthy people, the T1 / 2 of pantoprazole is short. Only a very small amount of pantoprazole is dialyzed. Despite the fact that the main metabolite has a moderately long T1 / 2 (2-3 hours), excretion is still fast, so no cumulation occurs.

Liver dysfunction. Although in patients with liver cirrhosis (Child-Pugh classes A and B), T½ increases to 7-9 hours, and AUC increases 5-7 times, Cmax in blood plasma increases only slightly - 1.5 times compared with healthy volunteers.

Elderly patients. A slight increase in AUC and Cmax in elderly volunteers compared to younger volunteers also has no clinical significance.

Children. After a single dose of 20 or 40 mg of pantoprazole orally, AUC and Cmax in children aged 5-16 years were within the corresponding values ​​in adults. After a single intravenous administration of pantoprazole at a dose of 0.8 or 1.6 mg / kg to children aged 2–16 years, there was no significant relationship between the clearance of pantoprazole and age or body weight. AUC and volume of distribution were consistent with those obtained in studies with adults.

Indications

For adults and children over the age of 12: reflux esophagitis.

For adults:

• eradication of Helicobacter pylori (H. pylori) in patients with H. pylori-associated gastric and duodenal ulcers in combination with appropriate antibiotics;
• duodenal ulcer;
• stomach ulcer;

Zollinger-Ellison syndrome and other hypersecretory pathological conditions.

Application

Tablets:

the preparation is intended for oral administration. The tablets should be taken 1 hour before meals whole, without chewing or crushing, with water.

Adults and children over the age of 12

Reflux esophagitis treatment. The recommended dose is 40 mg (1 tablet) once a day. In some cases, the dose can be doubled to 80 mg / day (2 tablets), especially if there is no effect from the use of other preparations for the treatment of reflux esophagitis. Reflux esophagitis usually takes 4 weeks to treat. If this is not enough, a cure can be expected within the next 4 weeks.

Adults

Eradication of H. pylori in combination with two antibiotics. In adult patients with gastric and duodenal ulcers and a positive result for H. pylori, it is necessary to achieve eradication of the microorganism using combination therapy. Consideration should be given to local data on bacterial resistance and national recommendations for the use and administration of appropriate antibacterial agents. Depending on the sensitivity of microorganisms for the eradication of H. pylori in adults, the following therapeutic combinations can be prescribed:

a) 40 mg pantoprazole (1 tablet) 2 times a day

+ 1000 mg amoxicillin 2 times a day

+ 500 mg clarithromycin 2 times a day;

b) 40 mg pantoprazole (1 tablet) 2 times a day

+ 400-500 mg metronidazole (or 500 mg tinidazole) 2 times a day

+ 250-500 mg clarithromycin 2 times a day;

c) 40 mg pantoprazole (1 tablet) 2 times a day

+ 1000 mg amoxicillin 2 times a day

+ 400-500 mg of metronidazole (or 500 mg of tinidazole) 2 times a day.

When using combination therapy to eradicate H. pylori, the second pantoprazole tablet should be taken in the evening 1 hour before meals. The treatment period is 7 days and can be extended for another 7 days (the total duration of treatment is no more than 2 weeks). If further pantoprazole therapy is indicated to ensure ulcer healing, dosing recommendations for gastric and duodenal ulcers should be considered.

If combination therapy is not indicated, for example, in patients with a negative result for H. pylori, Ulsepan is prescribed for monotherapy in the following dosing regimen.

Stomach ulcer treatment. The recommended dose is 40 mg (1 tablet) per day. In some cases, the dose can be doubled to 80 mg (2 tablets per day), especially if there is no effect from the use of other preparations. Stomach ulcers usually take 4 weeks to treat. If this is not enough, a cure can be expected within the next 4 weeks.

Treatment of duodenal ulcers. The recommended dose is 40 mg (1 tablet) per day. In some cases, the dose can be doubled to 80 mg (2 tablets) per day, especially if there is no effect from the use of other preparations.

Duodenal ulcers usually take 2 weeks to treat. If this is not enough, a cure can be expected within the next 2 weeks.

Treatment for Zollinger-Ellison syndrome and other hypersecretory pathological conditions. For long-term treatment of Zollinger-Ellison syndrome and other pathological hypersecretory conditions, the initial daily dose is 80 mg (2 tablets) per day. If necessary, then the dose can be titrated, increasing or decreasing, depending on the rate of acid secretion in the stomach. If the dose exceeds 80 mg / day, it must be divided into 2 doses. A temporary increase in the dose to more than 160 mg of pantoprazole is possible, but the duration of use should be limited only by the period necessary for adequate control of acid secretion.

The duration of treatment for Zollinger-Ellison syndrome and other pathological conditions is not limited and depends on the clinical need.

Patients with impaired liver function. Patients with severely impaired liver function should not exceed the daily dose of pantoprazole 20 mg. Patients with moderate and severe hepatic impairment should not use the preparation for the eradication of H. pylori in combination therapy, since there is currently no data on the efficacy and safety of such use for this category of patients.

Patients with impaired renal function. No dose adjustment is required for patients with impaired renal function. Patients with impaired renal function should not use the preparation for the eradication of H. pylori in combination therapy, since there is currently no data on the efficacy and safety of such use for this category of patients.

Elderly patients. No dose adjustment required.

Children. The preparation is indicated for children over the age of 12 for the treatment of reflux esophagitis. The preparation is not recommended for use in children under 12 years of age, as data on the safety and efficacy of the preparation for this age group are limited.

Lyophilisate for injection solution: the preparation is used by adults as directed and under the direct supervision of a physician. IV use of the preparation is recommended only if oral administration is impossible. Available safety data relate to IV use for up to 7 days. Therefore, when clinically feasible, a transition is made from intravenous administration of pantoprazole to oral administration of pantoprazole at a dose of 40 mg.

Dosage

Treatment of reflux esophagitis, duodenal ulcer, stomach ulcer

The preparation is used in a dose of 40 mg (1 bottle) per day / day.

Treatment for Zollinger-Ellison syndrome and other hypersecretory pathological conditions

The preparation is used at the recommended initial dose of 80 mg / day. If necessary, the dose can be titrated, increasing or decreasing, depending on the rate of acid secretion in the stomach. Doses exceeding 80 mg / day must be divided into two administrations. A temporary increase in the dose of pantoprazole more than 160 mg is possible, but the duration of use should be limited only by the period necessary for adequate control of acid secretion.

If a rapid decrease in acidity is required, an initial dose of 80 mg 2 times is sufficient for most patients to achieve the desired level (10 meq / h) within 1 hour.

Liver failure. Patients with severely impaired liver function should not exceed a daily dose of 20 mg (½ bottle of the preparation).

Renal failure Patients with impaired renal function do not require dose adjustment.

Elderly patients. No dose adjustment required.

Mode of application. The powder is dissolved in 10 ml of 0.9% sodium chloride solution. The solution can be administered directly or after mixing with 100 ml of 0.9% sodium chloride solution or 5% glucose solution in plastic or glass bottles.

The prepared solution is stable for 12 hours at a temperature not exceeding 25 ° C.

However, taking into account the preservation of microbiological purity, it is recommended to use the diluted preparation immediately.

The preparation must not be prepared or mixed with solvents other than the above.

The introduction of the preparation must be performed within 2-15 minutes.

The bottle is for single use only. Before use, it is necessary to visually check the vials with the preparation (in particular, regarding discoloration, the presence of sediment).

The diluted solution should be colorless or slightly yellow.

Children. The preparation is not recommended for use in children (under the age of 18), since the data on the safety and efficacy of pantoprazole for this age group are limited. The data available to date are described in Pharmacokinetics, however dosage recommendations cannot be provided.

Contraindications

Hypersensitivity to the active substance, benzimidazole derivatives or any component of the preparation.

Side effects

The most common adverse reactions that occur with pantoprazole are diarrhea and headache (in about 1% of patients).

In terms of frequency of occurrence, side effects are classified into the following categories: very often (≥1 / 10), often (≥1 / 100 and 1/10), infrequently (≥1 / 1000 and 1/100), rarely (≥1 / 10,000 and 1/1000), very rarely (1/10 000), unknown (frequency not determined from available data).

Within each category, the frequency of adverse reactions is listed in order of decreasing severity.

All adverse reactions reported in the post-marketing period and it is impossible to determine their frequency are indicated in the category unknown.

From the side of the blood and lymphatic system: rarely - agranulocytosis; very rarely - leukopenia, thrombocytopenia, pancytopenia.

From the immune system: rarely - hypersensitivity reactions (including anaphylactic reactions, anaphylactic shock).

Metabolism and metabolic disorders: rarely - hyperlipidemia and increased lipid levels (TG, CS), changes in body weight; unknown - hyponatremia, hypomagnesemia (see SPECIAL INSTRUCTIONS), hypocalcemia1, hypokalemia.

Mental disorders: infrequently - sleep disorders; rarely - depression (including exacerbations); very rarely - disorientation (including exacerbations); unknown - hallucinations, confusion (especially in patients with a tendency to these disorders, as well as exacerbation of these symptoms if they have a history).

From the nervous system: infrequently - headache, dizziness; rarely - taste disturbances; unknown - paresthesia.

From the side of the organ of vision: rarely - visual impairment / blurred vision.

From the side of the digestive tract: often - polyps of the fundic glands (benign); infrequently - diarrhea, nausea, vomiting, bloating, constipation, dry mouth, abdominal pain and discomfort.

On the part of the hepatobiliary system: infrequently - an increase in the level of liver enzymes (transaminases, γ-glutamyl transferase); rarely - an increase in the level of bilirubin; unknown - damage to hepatocytes, jaundice, hepatocellular insufficiency.

On the part of the skin and subcutaneous tissues: infrequently - skin rash, exanthema, itching; rarely - urticaria, angioedema; unknown - Stevens-Johnson syndrome, Lyell's syndrome, erythema multiforme, photosensitivity, subacute cutaneous lupus erythematosus.

From the musculoskeletal system and connective tissue: infrequently - fractures of the hip, wrist, spine (see. SPECIAL INSTRUCTIONS); rarely - arthralgia, myalgia; unknown - muscle spasm 2.

From the kidneys and urinary system: unknown - interstitial nephritis (with the possible development of renal failure).

From the reproductive system and mammary glands: rarely - gynecomastia.

General disorders: often - thrombophlebitis at the injection site; infrequently - asthenia, fatigue, malaise; rarely - an increase in body temperature, peripheral edema.

1 Hypocalcemia simultaneously with hypomagnesemia.

2 Muscle spasm as a result of electrolyte imbalance.

special instructions

Malignant neoplasms of the stomach. a symptomatic response to pantoprazole may mask the symptoms of gastric malignancies and postpone their diagnosis. in the presence of alarming symptoms (for example, with a significant loss of body weight, recurrent vomiting, dysphagia, vomiting with blood, anemia, melena), as well as if a stomach ulcer is suspected or present, the presence of a malignant process should be excluded.

If symptoms persist with adequate treatment, additional testing is necessary.

Long-term use of the preparation. With prolonged use of the preparation, especially for more than 1 year, patients should be under regular medical supervision.

Liver dysfunction. Patients with severely impaired liver function should regularly monitor the level of liver enzymes, especially with long-term treatment. With an increase in the level of liver enzymes, therapy must be discontinued.

Application in combination therapy. When using the preparation as part of a combination therapy, it is necessary to follow the instructions for medical use of the corresponding preparations.

The presence of alarming symptoms. In the presence of alarming symptoms (for example, in the case of a significant decrease in body weight, intermittent vomiting, dysphagia, vomiting with blood, anemia, melena), as well as if a stomach ulcer is suspected or present, the presence of a malignant process should be excluded, since pantoprazole treatment can mask symptoms and delay the establishment diagnosis.

If symptoms persist with adequate treatment, additional testing is necessary.

HIV protease inhibitors. The combined use of pantoprazole with HIV protease inhibitors (such as atazanavir), the absorption of which depends on the intragastric pH, is not recommended, due to a significant decrease in their bioavailability.

Effects on the absorption of vitamin B12. In patients with Zollinger-Ellison syndrome and other hypersecretory pathological conditions requiring long-term treatment, pantoprazole, like all preparations that block the production of hydrochloric acid, can reduce the absorption of vitamin B12 (cyanocobalamin) due to the occurrence of hypo- and achlorhydria. This should be considered if patients are underweight or have risk factors for decreased absorption of vitamin B12 with prolonged treatment or the presence of appropriate clinical symptoms.

Digestive tract infections caused by bacteria. Pantoprazole, like other PPIs, can increase the number of bacteria normally found in the upper digestive tract. The use of pantoprazole may slightly increase the risk of gastrointestinal infections caused by bacteria such as Salmonella and Campylobacter or C. difficile.

Hypomagnesemia. Cases of severe hypomagnesemia have been reported in patients treated with PPIs such as pantoprazole for at least 3 months, and in most cases within 1 year. The following serious clinical manifestations of hypomagnesemia may occur and initially develop imperceptibly: fatigue, tetany, delirium, convulsions, dizziness, and ventricular arrhythmia. With hypomagnesemia, in most cases, the patient's condition improved after replacement corrective therapy with magnesium preparations and discontinuation of PPIs.

Patients who require long-term therapy or those taking PPIs concurrently with digoxin or preparations that can cause hypomagnesemia (such as diuretics) should have their magnesium levels measured before starting PPI treatment and periodically during treatment.

Bone fractures. Long-term treatment (more than 1 year) with high-dose PPIs may slightly increase the risk of fractures of the hip, wrist, and spine, mainly in the elderly or in the presence of other risk factors. Observational studies suggest that PPI use can increase the overall risk of fracture by 10–40%. Some of these may be due to other risk factors. Patients at risk of developing osteoporosis should receive treatment according to current clinical guidelines and consume adequate amounts of vitamin D and calcium.

Subacute cutaneous lupus erythematosus. PPI use has been associated with very rare cases of subacute cutaneous lupus erythematosus. If a lesion occurs, especially in areas exposed to sunlight, and this is accompanied by arthralgia, the patient should immediately see a doctor who will consider the need to discontinue the preparation. The occurrence of subacute cutaneous lupus erythematosus in patients during previous PPI therapy may increase the risk of its development with other PPIs.

Influence on the results of laboratory tests. Elevated CgA levels can affect the results of studies in the diagnosis of neuroendocrine tumors. To avoid this effect, the use of the preparation should be temporarily discontinued at least 5 days before the assessment of the CgA level. If CgA and gastrin levels have not returned to normal after initial measurement, repeat measurements should be taken 14 days after stopping PPI treatment.

Lyophilisate for injection solution: the preparation contains less than 1 mmol (23 mg) / dose of sodium, that is, practically free of sodium.

Use during pregnancy or lactation

Pregnancy. The experience of using the preparation in pregnant women is limited. In the course of studies of reproductive function in animals, reproductive toxicity was revealed. The potential risk to humans is unknown. The preparation should not be used during pregnancy, unless absolutely necessary.

Lactation. Animal tests have shown the excretion of pantoprazole in breast milk. There is evidence of the excretion of pantoprazole in human breast milk. The decision to discontinue breastfeeding or to discontinue / abstain from preparation treatment should be based on the balance between the benefits of breastfeeding for the child and the benefits of pantoprazole treatment for the woman.

The ability to influence the reaction rate when driving or operating other mechanisms. It is necessary to take into account the possible development of adverse reactions such as dizziness and visual disturbances. In such cases, you should not drive vehicles or work with mechanisms.

Interactions

Medicines, the absorption of which depends on the pH. as a result of complete and long-term inhibition of hydrochloric acid secretion, pantoprazole can affect the absorption of preparations for which the pH value of gastric juice is an important factor in their bioavailability (for example, some antifungal preparations such as ketoconazole, itraconazole, posaconazole or other preparations such as erlotinib).

HIV protease inhibitors. The combined use of pantoprazole with HIV protease inhibitors (such as atazanavir), the absorption of which depends on the intragastric pH, is not recommended, due to a significant decrease in their bioavailability. If the combined use of HIV protease inhibitors with PPIs cannot be avoided, close clinical monitoring (eg viral load) is recommended. Do not exceed the daily dose of pantoprazole 20 mg. It may be necessary to adjust the dose of HIV protease inhibitors.

Coumarin anticoagulants (phenprocoumon and warfarin). Despite the lack of interaction with simultaneous use with phenprocoumon and warfarin during clinical trials, isolated cases of changes in the international normalized ratio (INR) in the post-marketing period were recorded. Thus, in patients using indirect anticoagulants (for example, phenprocoumon and warfarin), it is recommended to monitor prothrombin time / INR after initiation, discontinuation or irregular administration of pantoprazole.

Methotrexate. It has been reported that the simultaneous use of high doses of methotrexate (eg 300 mg) and PPIs increase the level of methotrexate in the blood in some patients. Patients taking high-dose methotrexate, such as those with cancer or psoriasis, are advised to temporarily discontinue pantoprazole treatment.

Other interactions. Pantoprazole is largely metabolized in the liver through the cytochrome P450 enzyme system. The main metabolic pathway is demethylation by CYP 2C19 and other metabolic pathways, including oxidation by the CYP 3A4 enzyme. Studies with preparations that are also metabolized by these pathways, such as carbamazepine, diazepam, glibenclamide, nifedipine, and oral contraceptives containing levonorgestrel and ethinyl estradiol, have not revealed clinically significant interactions.

The results of a number of studies examining possible interactions indicate that pantoprazole does not affect the metabolism of active substances that are metabolized by CYP 1A2 (eg caffeine, theophylline), CYP 2C9 (eg piroxicam, diclofenac, naproxen), CYP 2D6 (eg metoprolol), CYP 2E1 (eg ethanol) does not affect p-glycoprotein, which is associated with digoxin absorption.

There was no interaction with concomitantly prescribed antacids.

Studies have been carried out to study the interaction of pantoprazole with certain antibiotics used simultaneously (clarithromycin, metronidazole, amoxicillin). There were no clinically significant interactions between these preparations.

Overdose

Overdose symptoms are unknown.

Doses of up to 240 mg intravenously for 2 minutes were well tolerated. Because pantoprazole binds extensively to proteins, it is not a preparation that can be easily cleared by dialysis.

In case of an overdose with the appearance of clinical signs of intoxication, symptomatic and supportive therapy is used. There are no specific therapy recommendations.

Storage conditions

At a temperature not exceeding 25 ° C in a dry, dark place.