Pantoprazol-Acrihin enteric-Soluble tablets 20mg, 30pcs

Composition

1 tablet contains: Active ingredient: pantoprazole sodium sesquihydrate-22.57 mg mg (based on pantoprazole-20 mg); excipients: sodium carbonate anhydrous, mannitol, crospovidone, povidone (type K 90), calcium stearate; protective shell:  ready mix “OPADRAY” colorless [hypromellose-2910, triacetin, talc]; enteric coating:  ready mix “ACRYL-IZ” yellow [methacrylic acid and ethyl acrylate copolymer [1: 1], talc, titanium dioxide, iron oxide yellow, colloidal anhydrous silicon dioxide, sodium bicarbonate, sodium lauryl sulfate], triethyl citrate.

Pharmacological action

Pharmacotherapeutic group: gastric glands secretion reducing agent proton pump inhibitor ATX code: A 02 BC 02.

Pharmacological properties

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 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).

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 Pantoprazole-Akrikhin, a decrease in gastric juice secretion by 24% occurs in 2.5-3.5 hours and by 26% in 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 proton pump inhibitors, Pantoprazole-Acriquine has a higher chemical stability at neutral pH, and a lower potential for interaction with the liver’s cytochrome P450-dependent oxidase system. Therefore, there was no clinically significant interaction between Pantoprazole-Akrikhine and many other drugs.

Pharmacokinetics

Pantoprazole is rapidly absorbed after oral use. The maximum concentration in blood plasma (Cmax) with oral use is reached after the first dose of 40 mg. On average, approximately 2-2.5 hours after use, the maximum serum concentration is reached, about 1.0-1.5 mcg / ml and Cmax, and remains constant after repeated use of this 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%. Joint food intake does not affect the area under the concentration-time curve (AUC), the maximum serum concentration and, accordingly, 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 CYP2C19 followed by sulfate conjugation. Other metabolic pathways include oxidation by CYP3A4.

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

The main route of elimination is through 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 half-life of the main metabolite is about 1.5 hours, which is not much longer than the half-life of pantoprazole.

In individuals with low functional activity of the CYP2C19 isoenzyme (so-called 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).

The average values of maximum plasma concentrations are increased by about 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 elimination half-life of pantoprazole is short. Only a very small portion of the drug is dialyzed. Despite the moderately long half-life of the main metabolite (2-3 hours), its elimination occurs quite quickly, and therefore accumulation does not occur.

In patients with cirrhosis of the liver (classes A and B according to the Child-Pugh classification), the half-life increases to 3-6 hours, the AUC values increase 3-5 times, and the maximum serum concentration increases slightly, only 1.5 times in comparison with that in healthy volunteers.

A small increase in AUC and Cmax in older adults compared to the corresponding values in younger individuals is not clinically significant.

Indications

• 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

Use during pregnancy due to the lack of data on the use of pantoprazole in pregnant women, as a precautionary measure, it is necessary to exclude the use of Pantoprazole-Akrikhin during pregnancy. Breast-feeding Due to insufficient information on the use of Pantoprazole-Acriquine 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 Pantoprazole-Akrikhin. Fertility There are no data on the effect of Pantoprazole-Acriquine 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;
• age up to 18 years;
• pregnancy, lactation.

Side effects

When taking the drug Pantoprazole-Akrikhin in accordance with the indications and in the recommended doses, adverse reactions occur extremely rarely. The most common adverse reactions are diarrhea and headache, which occur in approximately 1% of patients. Data on adverse reactions, depending on the frequency of their occurrence, are given below: Very common ≥1/10 Common ≥1/100 and <1/10 Uncommon ≥ 1/1000 and <1/100 Rare ≥ 1/10000 and <1/1000 Very rare Circulatory and lymphatic system disorders: Rare: Agranulocytosis. Very rare:  Thrombocytopenia, leukopenia, pancytopenia. Nervous system disorders: Infrequent:  Headache, dizziness. Rarely:  Taste disorders. Visual disturbances: Rare:  Visual impairment (blurring). Gastrointestinal disorders: Common:  Polyps of the fundal glands of the stomach (benign). Infrequently:  Diarrhea, nausea/vomiting, bloating and flatulence, constipation, dry mouth, abdominal discomfort and pain. Renal and urinary tract disorders: Frequency unknown:  Interstitial nephritis (with possible progression to renal failure). Skin and subcutaneous tissue disorders: Infrequent:  Exanthema/rash, pruritus, dermatitis. Rarely:  Urticaria, angioedema. Frequency unknown:  Malignant exudative erythema (Stevens-Johnson syndrome), exudative erythema multiforme, toxic epidermal necrolysis, photosensitivity, subacute cutaneous lupus erythematosus.Metabolic disorders: Rare: Hyperlipidemia and elevated lipid concentrations (triglycerides, cholesterol), changes in body weight. Frequency unknown: Hyponatremia, hypomagnesemia, hypocalcemia 1, hypokalemia. Musculoskeletal and connective tissue disorders: Infrequent: Fracture of the femur, wrist, or spine. Rarely: Arthralgia, myalgia. Frequency unknown: muscle spasm 2. Common disorders: Infrequently: Weakness, fatigue, and malaise. Rarely: Increased body temperature, peripheral edema. Immune system disorders: Rare: Hypersensitivity (including anaphylactic reactions and anaphylactic shock). Liver and biliary tract disorders: Infrequently: Increased activity of liver enzymes (transaminases, gamma-glutamintransferases). Rarely: Increased bilirubin levels. Frequency unknown: Hepatocellular damage, jaundice, hepatic cell failure. Genital and breast disorders: Rare: Gynecomastia. Mental disorders: Infrequent: 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 exist before the start of therapy. 1 Hypocalcemia in combination with hypomagnesemia 2 Muscle spasm as a result of electrolyte imbalance

Interaction

Concomitant use of other proton pump inhibitors or H2-histamine receptor blockers is not recommended without medical advice.

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

The combined use of pantoprazole and HIV protease inhibitors, the absorption of which depends on the acidity (pH) of gastric juice, such as atazanavir, nelfinavir, significantly reduces their bioavailability.

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

• in patients with cardiovascular diseases receiving cardiac glycosides (digoxin), blockers of slow calcium channels (nifedipine), beta-blockers (metoprolol);
• in patients with diseases of the gastrointestinal tract taking antacids, antibiotics (amoxicillin, clarithromycin);
• in patients receiving oral contraceptives containing levonorgestrel and ethinyl estradiol;
• in patients receiving nonsteroidal anti-inflammatory drugs (diclofenac, Naproxen, piroxicam);
• in patients with diseases of the endocrine system, the receiving glibenclamide, levothyroxine;
• patients with anxiety and sleep disorders, receiving diazepam;
• in patients with epilepsy taking carbamazepine and phenytoin;
• patients receiving indirect anticoagulants, such as warfarin and phenprocoumon, under the control of prothrombin time and 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 proton pump inhibitors 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 timely detection of an increase in 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 proton pump inhibitors. Therefore, when using high doses of methotrexate, for example in cancer or psoriasis, it may be necessary to consider temporarily discontinuing 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 CYP2C19 and CYPJA4 isoenzymes, such as rifampicin and Hypericum perforatum, can reduce plasma concentrations of proton pump inhibitors that are 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, atazanovir), due to a significant decrease in their bioavailability.

If the combined use of HIV protease inhibitors and proton pump inhibitors is still necessary, careful clinical monitoring (for example, viral load determination) is recommended. 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

Pantoprazole-Akrikhin is taken orally, before meals, without chewing or grinding, with a sufficient amount of liquid.

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

Eradication of Helicobacter pylori.

The following combinations are recommended:

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 Pantoprazole-Akrikhin tablets of 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 pantoprazole 20 mg). In this regard, the use of pantoprazole at a dosage of 40 mg in this group of patients is not recommended. Liver enzymes should be monitored regularly during treatment with pantoprazole, especially with prolonged use of the drug. If the level of liver enzymes increases, 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 Pantoprazole-Akrikhin 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

To date, no overdose events have been observed as a result of the use of pantoprazole preparations. Doses up to 240 mg were administered intravenously for 2 minutes and were well tolerated. In case of overdose, in the presence of clinical manifestations of intoxication, symptomatic and supportive therapy is performed. Pantoprazole is not eliminated by hemodialysis.

Special instructions

Before starting treatment with Pantoprazole-Akrikhin, the possibility of malignancy should be excluded, since the drug can mask the 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.

Patients should not expect immediate relief of symptoms of malaise.Relief of symptoms is possible after approximately one day of taking pantoprazole, but it should also be taken into account that it may take approximately 7 days to completely eliminate heartburn.

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

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, atazanovir), 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 study 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 moderately increase the risk of fractures of the femur, wrist and spine, mainly in the elderly 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 (PKKV) is very rare when treated with proton pump inhibitors. If skin lesions occur, especially in areas exposed to sunlight, or if there is concomitant arthralgia, the patient should immediately seek medical attention, and the doctor should evaluate whether to stop treatment with Pantoprazole-Akrikhin. The occurrence of PCV after previous treatment with a proton pump inhibitor 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 Pantoprazole-Akrikhin 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/mechanisms.

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

Storage conditions

At a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf

life is 2 years. Do not use after the expiration date.

Active ingredient

Pantoprazole

Conditions of release from pharmacies

By prescription

Dosage form

Tablets