Pantoprazole-LF tablets enteric-soluble 20mg No. 10×3

Name:
Pantoprazole-LF. Release form: Enteric-coated tablets.
Description:
Round tablets, yellowish-beige color, biconvex, film-coated. Composition Each tablet contains: Active substance: pantoprazole (as pantoprazole sodium sesquihydrate) – 20 mg or 40 mg; Excipients: anhydrous sodium carbonate, calcium stearate, crospovidone, povidone (K-17), mannitol. Shell composition: Aquarius Preferred® yellow (hypromellose, copovidone plasdon, polydextrose, polyethylene glycol, caprylic/capric acid triglyceride, titanium dioxide E-171, iron oxide yellow E-172); Acrylic-IZ® colorless (copolymer of methacrylic acid and ethyl acrylate, talc, macrogol/PEG, anhydrous colloidal silicon dioxide, sodium bicarbonate, sodium lauryl sulfate), simethicone. Pharmacotherapeutic groupAntiulcer drugs and drugs used in gastroesophageal reflux disease. proton pump inhibitors. ATX code: A02BC02. Pharmacological action Mechanism of action Pantoprazole is a substituted benzimidazole that inhibits the secretion of hydrochloric acid in the stomach by specifically blocking the parietal cell proton pump. Pantoprazole is converted to its active form in the acidic environment of parietal cells, where it inhibits the enzyme H +, K + -ATPase, that is, the final stage in the production of hydrochloric acid in the stomach. The inhibition is dose dependent and affects both basal and stimulated acid secretion. Pantoprazole reduces acidity in the stomach, and thus increases gastrin levels in proportion to the decrease in acidity. The increase in gastrin is reversible. Since pantoprazole interacts with an enzyme distal to the receptor, it can inhibit the secretion of hydrochloric acid, regardless of stimulation by other substances (acetylcholine, histamine, gastrin). The same effect is observed when the active substance is administered orally or intravenously. Fasting gastrin values increase with pantoprazole. With short-term use in most cases, they do not exceed the upper limit of normal. During long-term treatment, gastrin levels double in most cases. Excessive increase, however, occurs only in isolated cases. As a result, mild to moderate increases in specific endocrine cells (ECL) (simple to adenomatoid hyperplasia) have been observed in the stomach in a small number of long-term treatments. However, according to studies conducted to date, the formation of carcinoid progenitors (atypical hyperplasia) or gastric carcinoids, as found in animal experiments, has not been observed in humans. When treated with drugs that suppress secretion, the level of serum gastrin increases in response to a decrease in the secretion of hydrochloric acid. With a decrease in the acidity of gastric juice, the level of chromogranin A (CgA) increases. Elevated levels of CgA may distort the results of studies to detect neuroendocrine tumors. Available published data suggest that the use of proton pump inhibitors should be discontinued between 5 days and 2 weeks before CgA levels are measured. This allows the CgA level to return to the range of normal values that can be falsely elevated after treatment with proton pump inhibitors. Clinical efficacy In a retrospective analysis of 17 studies in 5960 patients with gastroesophageal reflux disease (GERD) who received pantoprazole 20 mg as monotherapy, symptoms associated with acid reflux, such as heartburn and acid regurgitation, were assessed according to a standardized procedure. Selected studies were required to have at least one acid reflux symptom reporting point at 2 weeks. The diagnosis of GERD in these studies was based on endoscopic assessment, with the exception of one study in which patients were enrolled on the basis of symptoms only. In these studies, the percentage of patients who experienced complete resolution of heartburn after 7 days ranged from 54.0% to 80.6% in the pantoprazole group. After 14 and 28 days, the complete disappearance of heartburn was observed in 62.9-88.6% and 68.1-92.3% of patients, respectively. For the complete disappearance of sour belching, results similar to those for heartburn have been obtained. After 7 days, the percentage of patients in whom sour eructation completely disappeared ranged from 61.5% to 84.4%, after 14 days – from 67.7% to 90.4%, and after 28 days – from 75.2% up to 94.5%, respectively. Pantoprazole consistently performed better than placebo and H2 receptor antagonists, at least as well as other proton pump inhibitors. The disappearance of acid reflux symptoms was largely independent of the initial stage of GERD. Pharmacokinetics Absorption Pantoprazole is rapidly absorbed and the maximum plasma concentration (Cmax) when administered orally is reached after the first dose of 40 mg. On average, Cmax, equal to 2.0-3.0 µg/ml, is achieved after 2.5 hours. This indicator remains constant after repeated use of the drug. Pharmacokinetics after a single or repeated administration does not differ. In the dose range of 10 to 80 mg, the plasma kinetics of pantoprazole are virtually linear both after oral and intravenous administration. The absolute bioavailability of pantoprazole tablets is about 77%. Their simultaneous use with food does not affect the AUC and Cmax and thus the bioavailability. When co-administered with food, only latency variability was increased. Distribution The binding of pantoprazole to plasma proteins is 98%. The volume of distribution is 0.15 l/kg. Metabolism. Metabolized almost exclusively in the liver. Withdrawal The terminal half-life is about 1 hour and the clearance is 0.1 l / h / kg. Several cases of delayed elimination have been described. Due to the specific binding of pantoprazole to the proton pump of the parietal cell, the half-life does not correlate with a significantly longer period of action (suppression of acid secretion). The main route of excretion is through the kidneys (about 80%) in the form of pantoprazole metabolites, the rest is excreted in the feces. The main metabolite in plasma and urine is desmethylpantoprazole conjugated with sulfate. The half-life of the main metabolite (about 1.5 hours) significantly exceeds that of pantoprazole. Characteristics in Special Patient Populations Approximately 3% of the European population does not have a functional CYP2C19 enzyme and is designated as poor metabolizers. In these individuals, the metabolism of pantoprazole is probably catalyzed by CYP3A4. After a single dose of 40 mg pantoprazole, the mean AUC was approximately 6 times greater in poor metabolizers than in individuals with a functional CYP2C19 enzyme (strong metabolizers). Average Cmax increased by about 60%. These data do not affect dosing regimens for pantoprazole. Patients with impaired renal function When using pantoprazole in patients with impaired renal function (including patients on hemodialysis, which removes only a small amount of pantoprazole), dose reduction is not required. As in healthy patients, the half-life of pantoprazole is short. Although the half-life of the main metabolite is slightly longer (2-3 hours), excretion remains rapid and no cumulation occurs. Patients with impaired liver function After taking pantoprazole in patients with hepatic insufficiency (Child-Pugh classes A, B and C), the half-life increased to 3-7 hours, and AUC values increased 3-6 times, while Cmax increased only slightly (1.3 times) compared with healthy subjects. Children After a single oral administration of 20 or 40 mg of pantoprazole to children from 5 to 16 years of age, AUC and Cmax were in the range of corresponding values in adults. Following a single intravenous dose of 0.8 or 1.6 mg/kg pantoprazole in children 2 to 16 years of age, there was no significant association between pantoprazole clearance and age or weight. AUC and volume of distribution were consistent with those obtained in adults. Elderly patients The slight increase in AUC and Cmax in elderly volunteers compared to younger subjects was not clinically significant. Indications for use The drug Pantoprazole-LF 20 mg is used for the short-term treatment of reflux symptoms (eg heartburn, sour belching) in adults. The drug Pantoprazole-LF 40 mg is used for the following indications: Adults and children 12 years and older: – reflux esophagitis. Adults: – eradication of Helicobacter pylori as part of combination therapy with antibacterial agents; – gastric or duodenal ulcer; – Zollinger-Ellison syndrome and other pathological conditions associated with increased gastric secretion. Contraindications – hypersensitivity to the active substance, benzimidazole derivatives or any component of the drug; The combined use of pantoprazole with HIV protease inhibitors, such as atazanavir, nelfinavir, the absorption of which depends on the acidity of intragastric pH, is not recommended due to a significant decrease in their bioavailability. Dosage and administration Tablets should be swallowed whole, they should not be chewed or broken. Take 1 hour before meals with plenty of water. Short-term treatment of reflux symptoms The recommended adult dose is 20 mg Pantase-LF (1 tablet) per day. It may be necessary to take the drug for 2-3 days to relieve symptoms. After the symptoms have disappeared, the ongoing treatment may be discontinued. Treatment should not exceed 4 weeks without medical advice. If no improvement in symptoms is obtained within 2 weeks of continuous treatment, the patient should be informed of the need to consult a physician. Reflux esophagitis The recommended dose for adults and children 12 years of age and older is 40 mg of Pantaza-LF (1 tablet) per day. In some cases, the dose may be doubled (increased to 2 tablets per day), especially when there was no response to other therapy. A 4-week treatment period is usually required. If it is not sufficient, the therapeutic effect is usually achieved within the next 4 weeks. Eradication of Helicobacter pylori as part of combination therapy with antibacterial agents In Helicobacter pylori-positive adult patients with gastric and duodenal ulcers, eradication of the microorganism should be achieved using combination therapy. Reference should be made to official local guidelines (eg national guidelines) on bacterial resistance and the appropriate prescribing and use of antibacterial agents. Depending on the spectrum of resistance, the following combinations may be recommended: a) one tablet (40 mg) of Pantaza-LF twice a day + 1000 mg of amoxicillin twice a day + 500 mg of clarithromycin twice a day. b) one tablet (40 mg) of Pantaza-LF twice a day + 400-500 mg of metronidazole (or 500 mg of tinidazole) twice a day + 250-500 mg of clarithromycin twice a day. c) one tablet (40 mg) of Pantaza-LF twice a day + 1000 mg of amoxicillin twice a day + 400-500 mg of metronidazole (or 500 mg of tinidazole) twice a day. When carrying out eradication therapy, the second tablet of the drug Pantaza-LF should be taken 1 hour before the evening meal. Combination therapy is usually carried out for 7 days and can be continued for another 7 days for a total duration of 14 days. Further therapy with pantoprazole is then indicated to ensure healing of the ulcers, using doses recommended for duodenal and gastric ulcers. If combination therapy is not indicated (Helicobacter pylori is a negative patient), the following dose regimens for Pantaza-LF monotherapy should be followed: Treatment of gastric ulcer 1 tablet (40 mg) of Pantaza-LF drug per day. In some cases, the dose may be doubled (increased to 2 tablets per day), especially when there was no response to other therapy. A 4-week treatment period is usually required. If it is not sufficient, healing is usually achieved within the next 4 weeks. Treatment of duodenal ulcer 1 tablet (40 mg) of Pantaza-LF per day. In some cases, the dose may be doubled (increased to 2 tablets per day), especially when there was no response to other therapy. Healing of a duodenal ulcer usually occurs within 2 weeks. If this period is not sufficient, healing is achieved in almost all cases within the next 4 weeks. Zollinger-Ellison syndrome and other pathological conditions associated with increased gastric secretion For long-term treatment of Zollinger-Ellison syndrome and other pathological hypersecretory conditions, start with a daily dose of 80 mg (2 tablets of Pantase-LF 40 mg). The dose should then be titrated up or down based on measurements of gastric acid secretion. Daily doses exceeding 80 mg should be divided into 2 doses. A temporary increase in dosage above 160 mg is possible, but it should not be longer than required for adequate control of secretion. The duration of treatment for Zollinger-Ellison syndrome and other pathological hypersecretory conditions is not limited and should be consistent with clinical need. Special groups of patients Patients with impaired liver function In patients with severe hepatic insufficiency, the daily dose of pantoprazole 20 mg should not be exceeded. The drug should not be used as part of combination therapy for the eradication of Helicobacter pylori in patients with moderate or severe liver dysfunction, since there are currently no data on the efficacy and safety of pantoprazole as part of combination therapy in such patients. Patients with impaired renal function In patients with impaired renal function, dose adjustment is not required. The drug should not be used as part of combination therapy for the eradication of Helicobacter pylori in patients with impaired renal function, since there are currently no data on the efficacy and safety of pantoprazole as part of combination therapy in such patients. Children under 12 years of age: Not recommended due to limited safety and efficacy data in this age group. Elderly patients: Dose adjustment is not required. Side effects Approximately 5% of cases may experience adverse reactions. The most common adverse reactions are diarrhea and headache. Both of these reactions occur in approximately 1% of patients. Adverse reactions are evaluated according to the frequency of their occurrence. When using pantoprazole, undesirable effects were registered with the following frequency: very often – 1/10 or more; often – from 1/100 to 1/10; infrequently – from 1/1000 to 1/100; rarely – from 1/10,000 to 1/1000; very rare – less than 1/10000, frequency unknown – cannot be determined from the available data. Within each frequency category, adverse reactions are listed in descending order of severity. Blood and lymphatic system disorders: rarely – agranulocytosis; very rarely – thrombocytopenia, leukopenia, pancytopenia. Immune system disorders: rarely – hypersensitivity (including anaphylactic reactions and anaphylactic shock). Metabolic and nutritional disorders: rarely – hyperlipidemia and increased lipid levels (triglycerides, cholesterol); changes in body weight; frequency unknown – hyponatremia, hypomagnesemia, hypocalcemia1, hypokalemia. Mental disorders: infrequently – sleep disorders; rarely – depression (and worsening); very rarely – disorientation (and deterioration); frequency unknown – hallucinations, confusion (especially in predisposed patients, as well as aggravation of pre-existing symptoms). Nervous system disorders: infrequently – headache, dizziness; rarely – taste disturbances. On the part of the organ of vision: rarely – visual disturbances / blurred vision. Gastrointestinal disorders: often – stomach polyps (benign); infrequently – diarrhea, nausea / vomiting, flatulence and bloating, constipation, dry mouth, pain and discomfort in the abdomen. Liver and biliary tract disorders: infrequently – increased levels of liver enzymes (transaminases, γGTP); rarely, an increase in the level of bilirubin; frequency unknown – damage to hepatocytes, jaundice, hepatocellular insufficiency. Skin and subcutaneous tissue disorders: infrequently – rash / exanthema / rash, itching; rarely – urticaria, angioedema; frequency unknown – Stevens-Johnson syndrome, Lyell’s syndrome, erythema multiforme, photosensitivity, subacute cutaneous lupus erythematosus. Musculoskeletal and connective tissue disorders: infrequently – fracture of the hip, wrist, spine; rarely – arthralgia, myalgia; frequency unknown – muscle spasm2. Renal and urinary tract disorders: frequency unknown – interstitial nephritis (with possible progression to renal failure). Violations of the genital organs and mammary gland: rarely – gynecomastia. General disorders: infrequently – asthenia, fatigue and malaise; rarely – fever, peripheral edema. 1Hypocalcemia associated with hypomagnesemia. 2 Muscle spasm as a result of electrolyte imbalance. Overdose So far, no overdose effects have been noted as a result of the use of pantoprazole. Doses up to 240 mg were administered intravenously over 2 minutes and were well tolerated. However, in case of overdose and only in the presence of clinical manifestations, symptomatic and supportive treatment is carried out. Since pantoprazole has a high protein affinity, it is difficult to hemodialyze. Precautions Hepatic insufficiency In patients with severe hepatic insufficiency during treatment with pantoprazole, regular monitoring of liver enzymes should be carried out, especially with prolonged use of the drug. In the event of an increase in their level, treatment should be discontinued. Combination therapy When conducting combination therapy, the instructions for medical use of the respective medicinal products should be taken into account. Gastric malignancy If any warning sign is present (eg, significant involuntary weight loss, repeated vomiting, dysphagia, hematemesis, anemia, melena) and if a gastric ulcer is present or suspected, malignancy should be ruled out because treatment with pantoprazole may relieve symptoms and delay diagnosis. Additional testing should be considered if symptoms persist despite adequate therapy. Co-administration with HIV protease inhibitors Co-administration of pantoprazole with HIV protease inhibitors, the absorption of which depends on the pH of the stomach, such as atazanavir, is not recommended due to a significant decrease in their bioavailability. Effect on vitamin B12 absorption In patients with Zollinger-Ellison syndrome and other pathological hypersecretory conditions requiring long-term therapy, pantoprazole, like all antisecretory agents, may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be considered in patients with reduced stores of this vitamin or in the presence of risk factors for reducing its absorption during long-term therapy or in the presence of relevant clinical symptoms. Long-term treatment During long-term therapy, especially when it exceeds a period of one year, patients should be monitored regularly. Gastrointestinal infections of a bacterial nature Treatment with pantoprazole may lead to a slightly increased risk of gastrointestinal infections caused by bacteria such as Salmonella and Campylobacter or C. difficile. Hypomagnesemia Severe hypomagnesemia has been reported in patients treated with proton pump inhibitors for at least three months (in most cases within a year). Serious manifestations of hypomagnesaemia such as fatigue, tetany, delirium, convulsions, dizziness, and ventricular arrhythmias may occur, but they may begin insidiously and may go unnoticed. In the majority of patients, hypomagnesemia was cured by the administration of magnesium against the background of discontinuation of proton pump inhibitors. For patients who are expected to be on long-term treatment or who are taking proton pump inhibitors with digoxin or drugs that can cause hypomagnesaemia (eg, diuretics), healthcare professionals should consider measuring blood magnesium levels prior to initiating treatment and periodically during treatment. Bone fractures Proton pump inhibitors, especially when used at high doses and for a long time (greater than one year), may moderately increase the risk of hip, wrist and spine fractures, mainly in the elderly or in the presence of other recognized risk factors. Observational studies indicate that proton pump inhibitors may increase the overall risk of fractures by 10-40%. Some of this increase may be due to other risk factors. Patients at risk of osteoporosis should receive medical care in accordance with current clinical guidelines and consume adequate amounts of vitamin D and calcium. Subacute cutaneous lupus erythematosus (SCLE) The use of proton pump inhibitors has been associated with very rare cases of SCLE. In the event of the appearance of pathological changes, especially in areas of the skin exposed to the sun, and in the event of arthralgia, the patient should immediately seek medical help, and the medical professional should evaluate the advisability of discontinuing the drug. SCLE after prior treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors. Laboratory Confounding Elevated CgA levels can confound test results for neuroendocrine tumors. To avoid interference, treatment with Pantaza-LF should be discontinued at least 5 days before the CgA level is determined. If the levels of CgA and gastrin have not returned to the normal range after the initial determination, the measurement should be repeated 14 days after cessation of therapy with proton pump inhibitors. Pregnancy and breastfeeding Pregnancy A small amount of data on the use of pantoprazole in pregnant women (300-1000 cases) indicates the absence of toxicity that causes malformations or toxicity to the fetus / newborn associated with the drug Pantaza-LF. Animal studies have demonstrated reproductive toxicity. As a precautionary measure, it is advisable to avoid the use of Pantaza-LF during pregnancy. Lactation Animal studies have shown that pantoprazole passes into breast milk. It has been reported that it passes into human breast milk. A risk to the infant cannot be ruled out. Therefore, the decision to continue / stop breastfeeding or continue / stop therapy with pantoprazole should be made taking into account the benefits of breastfeeding for the child and the benefits of therapy with the drug Pantaza-LF for the woman. Fertility Animal studies have not shown evidence of impaired fertility after the use of pantoprazole. Influence on the ability to drive vehicles and work with mechanisms Pantoprazole has no or negligible effect on the ability to drive a vehicle or work with mechanisms. Adverse reactions such as dizziness or visual disturbances may occur. If they occur, patients should not drive or operate machinery. Interactions with other medicinal products Drugs with gastric pH-dependent absorption Due to the pronounced and prolonged suppression of gastric secretion, pantoprazole may interfere with the absorption of drugs whose bioavailability depends on gastric pH, for example, some azole antifungals such as ketoconazole, itraconazole, posaconazole , as well as other drugs such as erlotinib. HIV Protease Inhibitors Co-administration of pantoprazole with HIV protease inhibitors whose absorption is dependent on acidic intragastric pH, such as atazanavir, may result in a significant reduction in their bioavailability. If it is not possible to avoid the combination of HIV protease inhibitors with a proton pump inhibitor, careful monitoring (eg, viral load monitoring) is recommended. The dose of pantoprazole 20 mg per day should not be exceeded. Dose adjustment of HIV protease inhibitors may be required. Coumarin anticoagulants (phenprocoumon or warfarin) Co-administration of pantoprazole with warfarin or phenprocoumon did not affect the pharmacokinetics of warfarin, phenprocoumon or international normalized ratio (INR). However, an increase in INR and prothrombin time has been reported in patients receiving other proton pump inhibitors and warfarin or phenprocoumon at the same time. An increase in INR and prothrombin time can lead to bleeding and even death. Patients receiving pantoprazole and warfarin or phenprocoumon may need to be monitored for increases in INR and prothrombin time. Methotrexate It has been reported that the combined use of a high dose of methotrexate (eg, 300 mg) and proton pump inhibitors increases the levels of methotrexate in some patients. Thus, in the setting of high doses of methotrexate, such as cancer and psoriasis, temporary withdrawal of pantoprazole may be considered. Other Interaction Studies Pantoprazole is extensively metabolized in the liver via the cytochrome P450 enzyme system. The main metabolic pathway is demethylation by CYP2C19, other metabolic pathways include oxidation by CYP3A4. Interaction studies with drugs metabolized by these pathways, such as carbamazepine, diazepam, glibenclamide, nifedipine, an oral contraceptive containing levonorgestrel and ethinyl estradiol, did not reveal clinically significant interactions. An interaction of pantoprazole with other drugs or compounds that are metabolized by the same enzyme system cannot be ruled out. The results of a number of interaction studies indicate that pantoprazole does not affect the metabolism of active substances metabolized by CYP1A2 (such as caffeine, theophylline), CYP2C9 (such as piroxicam, diclofenac, naproxen), CYP2D6 (such as metoprolol), CYP2E1 (such as ethanol) and does not change p-glycoprotein-dependent absorption of digoxin. There are no interactions with co-administered antacids. Interaction studies have also been conducted with antibiotics co-administered with pantoprazole (clarithromycin, metronidazole, amoxicillin). No clinically significant interactions were found. Medicinal products that inhibit or induce CYP2C19 CYP2C19 inhibitors such as fluvoxamine may increase the systemic exposure to pantoprazole. A dose reduction may be required in patients who receive high doses of pantoprazole for a long time, or in those who have hepatic insufficiency. Enzyme inducers that affect CYP2C19 and CYP3A4, such as rifampicin and St. John’s wort (Hypericum perforatum), may reduce plasma concentrations of proton pump inhibitors metabolized by these enzyme systems. Storage conditions In a place protected from moisture and light at a temperature not exceeding 25 ° C. Keep out of the reach of children. Shelf life 2 years. Do not use after the expiry date stated on the package. Packing: 10 tablets in a blister pack made of polymer film and aluminum foil. Three blister packs together with instructions for medical use in a pack of cardboard. Buy Pantoprazole-LF tablets p / o enteric 20 mg No. 10×3 about enteric 20mg №10×3