Composition:
1 enteric-coated tablet film-coated, 20 mg contains: active ingredient: pantoprazole sodium sesquihydrate 22.57 mg, in terms of pa pantoprazole 20.00 mg; excipients: calcium stearate 1.20 mg, colloidal silicon dioxide 1.00 mg, crospovidone 20.00 mg, heavy magnesium hydroxycarbonate 7.53 mg, macrogol (polyethylene glycol) 1.20 mg,
mannitol 63.00 mg, povidone K-30 3.50 mg; film coating composition: Opadry clear 2,400 mg, including: [hypromellose (hydroxypropyl methylcellulose) 1,920 mg, macrogol (polyethylene glycol) 0,480 mg];
Acrylic-Is green 8.600 mg, including: [iron oxide yellow 0.060 mg, diamond blue dye 0.026 mg, indigo carmine dye 0.069 mg, colloidal silicon dioxide 0.086 mg, methacrylic acid and ethyl acrylate copolymer [1: 1] 5.676 mg, sodium bicarbonate 0.086 mg, sodium lauryl sulfate 0.043 mg, talc 1.419 mg, titanium dioxide 1.135 mg]; triethyl citrate 1.00 mg.
Pharmacodynamics:
Proton pump inhibitor (H + / K + -ATPase). It blocks the final stage of hydrochloric acid secretion, reducing basal and stimulated secretion, regardless of the nature of the stimulus. Pantoprazole is a substituted benzimidazole that inhibits the secretion of hydrochloric acid in the stomach through specific blockade of proton pumps of parietal cells. Pantoprazole transforms into its active form under acidic conditions in parietal cells, where it inhibits the activity of the enzyme H + / K + -ATPase, i.e. blocks the final stage of the formation of hydrochloric acid in the stomach.
The suppression of activity is dose-dependent and, as a result, both basal and stimulated acid secretion are reduced. During treatment with pantoprazole, as with other proton pump inhibitors and blockers of PG receptors, acidity in the stomach decreases, and thereby the level of gastrin increases in proportion to the decrease in acidity.
Increased gastrin levels are reversible. Since pantoprazole binds the enzyme distally by pubescence to the cellular receptor, it can inhibit the secretion of hydrochloric acid regardless of stimulation with other substances (acetylcholine, histamine, gastrin). The content of chromogranin A (CgA) in the blood serum also increases due to a decrease in the secretion of hydrochloric acid.
Elevated CgA levels may distort diagnostic tests to detect neuroendocrine tumors. Antisecretory asset) yuan. After the first oral administration of 20 mg of Pantoprazole Canon, a 24% reduction in gastric acid secretion occurs after 2.5-3.5 hours and 26% after 24.5-25.5 hours. After oral administration of pantoprazole once a day for 7 days, its antisecretory activity, measured 2.5-3.5 hours after administration, increases to 56%, and after 24.5-25.5 hours - up to 50%. With duodenal ulcer associated with Helicobacter pylori, a decrease in gastric secretion increases the sensitivity of microorganisms to antibiotics. Does not affect gastrointestinal motility. Secretory activity is normalized 3-4 days after the end of the dose. Compared to other proton pump inhibitors, pantoprazole has greater chemical stability at neutral pH and lower potential for interaction with the liver oxidase system, which depends on cytochrome P450. Therefore, no clinically significant interaction was observed between pantoprazole and many other drugs.
Pharmacokinetics:
Pantoprazole is rapidly absorbed after oral administration. The maximum concentration in blood plasma (Cmax) for oral administration is achieved after the first dose of 20 mg. On average, approximately 2-2.5 hours after ingestion, the maximum serum graft co-concept is reached, about 1.0-1.5 μg / ml, and Cmax remains constant after repeated use of this drug. The pharmacokinetics of pantoprazole after a single and multiple use is the same.
In the dose range of 10-80 mg, the pharmacokinetics of pantoprazole in the blood plasma remains linear with both oral and intravenous administration. The absolute bioavailability of pantoprazole tablets is about 77%. Joint eating does not affect the area under the concentration-time curve (AUC), the maximum concentration in serum and, accordingly, the bioavailability.
When taken together with food, the time of onset of the drug may vary. The binding of pantoprazole to plasma proteins is 98%. The volume of distribution is 0.15 l / kg. Metabolized mainly in the liver. The main metabolic pathway is demethylation using CYP2C19 followed by sulfate conjugation.
Other metabolic pathways include oxidation with 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 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 excretion is through the kidneys (about 80%) in the form of pantoprazole metabolites, the rest is excreted in the feces. The main metabolite in blood plasma and urine is desmethyl pantoprazole conjugated to sulfate. The half-life of the main metabolite is about 1.5 hours, which slightly exceeds the half-life of pantoprazole.
When pantoprazole is used in patients with limited renal function (including patients undergoing hemodialysis), dose reduction is not required. As with healthy volunteers, the half-life of pantoprazole is short. Only a very small fraction of the drug is dialyzed. Despite the moderately long half-life of the main metabolite (2-3 hours), its excretion occurs rather quickly, and therefore, accumulation does not occur. In patients with cirrhosis of the liver (Child-Pyo classes A and B), the half-life period increases to 3-6 hours, AUC values increase 3-5 times, the maximum concentration in serum increases slightly, only 1.5 times in comparison with that in healthy volunteers with pantoprazole in a dosage of 20 mg. A slight increase in AUC and Cmax in older people compared to those in younger people is not clinically significant.
Side effects:
When taking Pantoprazole Canon, in accordance with the indications and in the recommended doses, undesirable reactions occur extremely rarely. The most common adverse reactions are diarrhea and headache - observed in approximately 1% of patients.
The following are data on adverse reactions depending on the frequency of their occurrence: Very often - ≥1 / 10 appointments (> 10%) Often - ≥1 / 100 to <1/10 appointments (> 1% and <10%) Infrequently - from ≥1 / 1000 to <1/100 appointments (> 0.1% and <1%) Rarely from ≥1 / 10000 to <1/1000 appointments (> 0.01% and <0.1%) Very rarely : <1/10000 appointments (<0.01%) Frequency unknown - cannot be estimated based on available data. Disorders from the circulatory and lymphatic systems Rarely: agranulocytosis;
Very rarely: thrombocytopenia, leukopenia, pancytopenia. Disorders from the nervous system Infrequently: headache, dizziness;
Rarely: taste disturbances.
Visual impairment
Rarely: visual impairment (fogging). Violations of the gastrointestinal tract Often: polyps of the fundic glands of the stomach (benign);
Uncommon: diarrhea, nausea / vomiting, bloating and flatulence, constipation, dry mouth, discomfort and abdominal pain. Disorders from the kidneys and urinary tract Frequency unknown: interstitial nephritis.
Disorders from the skin and subcutaneous tissues Infrequently: exanthema / rash, skin itching, dermatitis; Rarely: urticaria, angioedema;
Frequency unknown: malignant exudative erythema (Stevens-Johnson syndrome), exudative erythema multiforme, toxic epidermal necrolysis, photosensitivity, subacute cutaneous lupus erythematosus. Violations of the musculoskeletal and connective tissue Infrequently: fracture of the wrist, thigh and spine; Rarely: arthralgia, myalgia.
Metabolic disorders Rarely: hyperlipidemia and an increased concentration of lipids (triglycerides, cholesterol), changes in body weight; Frequency unknown: hyponatremia, hypomagnesemia. General disorders Infrequently: weakness, fatigue and malaise;
Rarely: fever, peripheral edema. Immune system disorders Rarely: hypersensitivity (including anaphylactic reactions and anaphylactic shock). Disorders from the liver and the same urinary tract Infrequently: increased activity of liver enzymes (transaminases, ƴ-glutamine transferase);
Rarely: increased bilirubin levels; Frequency unknown: hepatocellular lesions, jaundice, hepatocellular failure. Disorders from the genitals and the mammary gland Rarely: gynecomastia. Mental disorders Infrequently: sleep disturbances; Rarely: depression (including exacerbation of existing disorders);
Very rarely: disorientation (including exacerbation of existing disorders); The frequency is unknown: hallucinations, confusion (especially in patients predisposed to this), as well as a possible exacerbation of symptoms if they exist before starting therapy.
Special conditions:
Before starting treatment with Pantoprazole Canon, the possibility of a malignant neoplasm should be excluded, since the drug can mask the symptoms and delay the correct diagnosis. Patients should consult a doctor if they have to undergo an endoscopy or urea breath test.
Patients should consult a doctor if there are the following cases: - Unintentional weight loss, anemia, gastrointestinal bleeding, swallowing disorder, persistent vomiting or vomiting of blood. In these cases, taking the drug can partially alleviate the symptoms and delay the correct diagnosis; - previous surgery on the gastrointestinal tract or stomach ulcer; - continuous symptomatic treatment of dyspepsia and heartburn for 4 weeks or more; - liver diseases, including jaundice and liver failure; - other serious diseases that worsen the general state of health.
Patients over 55 years of age with 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, it must also be taken into account that it may take approximately 7 days to completely eliminate heartburn.
When taking drugs that reduce the acidity of gastric juice, the risk of gastrointestinal infections, which are caused by bacteria of the genus Salmonella spp., Campylobacter spp., Is slightly increased. or C. difficile.
In the treatment with proton pump inhibitors, the development of subacute cutaneous lupus erythematosus (PKKV) is very rarely observed. If skin lesions occur, especially in areas exposed to sunlight, as well as in the presence of concomitant arthralgia, the patient should immediately seek medical help, and the doctor should assess the need to stop treatment with Pantoprazole Canon.
The occurrence of PKKV after previous treatment with a proton pump inhibitor may increase the risk of developing PKKV when treated with other proton pump inhibitors. When conducting laboratory studies, it must be borne in mind 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 the drug
Pantoprazole Canon should be discontinued at least 5 days prior to the study of the content of CgA. If the content of CgA and gastrin has not returned to normal values after the first determination, then the study should be repeated 14 days after stopping the use of the proton pump inhibitor. The drug is intended for short-term use (up to 4 weeks).
With prolonged use of the drug, additional risks may arise, and you must consult a doctor to prescribe the drug, followed by regular medical supervision. The following additional risks are considered significant with prolonged use of the drug.
Effect on Vitamin B12 Absorption Pantoprazole, like all proton pump inhibitors, can reduce the absorption of vitamin B12 (cyanocobalamin) as a result of hypo- or achlorhydria.
This should be taken into account in patients with reduced reserves in the body or risk factors for a decrease in the absorption of vitamin B12 with prolonged therapy or in the presence of appropriate clinical symptoms. Effect on bone fractures
Proton pump inhibitors, especially in large doses and with prolonged therapy (> 1 year), may slightly increase the risk of hip, wrist and spine fracture, mainly in the elderly or in the presence of other known risk factors.
Observations have shown that proton pump inhibitors can increase the overall risk of fractures by 10–40%. This increase may be partly due to other risk factors. Patients at risk of developing osteoporosis should receive treatment in accordance with current clinical guidelines, and they should have adequate intake of vitamin D and calcium.
Hypomagnesemia In patients taking proton pump inhibitors (TINs), including pantoprazole, severe hypomagnesemia was observed for at least three months and in most cases during the year.
In this case, serious manifestations of hypomagnesemia, such as fatigue, tetany, delirium, cramps, dizziness and ventricular arrhythmia, may develop, they can begin unnoticed and be missed.
In most patients with similar disorders, hypomagnesemia was corrected after magnesium replacement therapy and discontinuation of PPI.
In patients who are to receive long-term treatment, or in patients taking PPI together with digoxin or other drugs that can cause hypomagnesemia (for example, diuretics), a study of the serum magnesium content should be performed before starting treatment with PPI and periodically monitored during treatment . Fertility
There are no data on the effects of pantoprazole on human fertility. Preclinical studies have shown no effect on male or female fertility. 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.
Indications:
Treatment of symptoms of mild gastroesophageal reflux disease (such as heartburn, sour belching) in adults.
Contraindications:
- Hypersensitivity to any of the components of the drug, as well as to substituted benzimidazoles;
- dyspepsia of neurotic origin;
- taking HIV protease inhibitors such as atazanavir and nelfinavir, the absorption of which depends on the acidity (pH) of the gastric juice;
- age up to 18 years;
- Pregnancy, the period of breastfeeding.
Use during pregnancy and during breastfeeding
Use during pregnancy Due to the lack of data on the use of pantoprazole in pregnant women as a precaution, it is necessary to exclude the use of the drug during pregnancy.
Breastfeeding Pantoprazole and its metabolites have been found in breast milk. The effect of pantoprazole on newborn / infants is unknown. Pantoprazole should not be used during breastfeeding. If it is necessary to use the drug during lactation, breastfeeding should be discontinued.
Drug Interactions:
The simultaneous use of other proton pump inhibitors or H2-histamine receptor blockers is not recommended without consulting a doctor.
The use of Pantoprazole Canon can reduce the absorption of drugs whose bioavailability depends on the pH of the stomach (for example, ketoconazole, itraconazole, posaconazole and other medicines, 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 studies on the drug interaction, no clinically significant interactions were detected with pantoprazole in the following cases: - in patients with diseases of the cardiovascular system taking cardiac glycosides (digoxin), slow calcium channel blockers (nifedipine), β-adrenergic blockers (metonrolol );
- in patients with diseases of the gastrointestinal tract taking antacids, antibiotics (amoxicillin, clarithromycin);
- in patients taking oral contraceptives containing levonorgestrel and ethinyl estradiol;
- in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) (diclofenac, nanroxen, piroxicam);
- in patients with diseases of the endocrine system taking glibenclamide, levothyroxine;
- in patients with anxiety and sleep disorders taking diazepam;
- in patients with epilepsy taking carbamazepine and phenytoin;
- in patients taking indirect anticoagulants, such as warfarin and fenprocoumone, under the control of prothrombin time and international normalized ratio (INR) at the beginning and at the end of treatment, as well as during irregular use of pantoprazole.
At the same time, it should be noted that there are known cases of an increase in INR and prothrombin time in patients receiving proton pump inhibitors together with warfarin or fenprocumene.
An increase in INR and prothrombin time can lead to life-threatening bleeding. In this regard, such patients should be monitored in order to timely detect an increase in MPO and prothrombin time. The absence of clinically significant drug interactions with caffeine, ethanol, theophylline was also noted.
There are reports of increased levels of methotrexate in the blood of some patients when used together in high doses (for example, 300 mg) with proton pump inhibitors. Therefore, when using high doses of methotrexate, for example, for cancer or psoriasis, it may be necessary to consider the temporary withdrawal of pantoprazole.
Dosage:
The drug Pantoprazole Canon is taken orally, before meals, without chewing or grinding, with a sufficient amount of liquid, 20 mg per day.
To achieve positive dynamics in eliminating symptoms, you may need to take the drug for 2-3 days, however, to completely eliminate the symptoms, you may need to use the drug for 7 days. If the condition worsens during the first 3 days of treatment, a doctor's consultation is recommended.
Taking the drug should be stopped immediately after the disappearance of symptoms. Taking the drug without consulting a doctor should not exceed 4 weeks. If within 2 weeks of continuous administration of the drug there is no positive dynamics, it is necessary to consult a doctor. Pantoprazole Canon should not be taken for prophylaxis. No dose adjustment is required in elderly patients and patients with renal or hepatic insufficiency.
Overdose:
To date, the effects of overdose as a result of pantoprazole have not been noted. 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 excreted by hemodialysis.
