Instructions Pantozol tablets 40 mg No. 30
Composition
active ingredient: pantoprazole;
1 tablet contains pantoprazole sodium sesquihydrate 45.1 mg equivalent to pantoprazole 40 mg;
excipients: crospovidone, calcium stearate, Opadry II 85G68918 White (polyvinyl alcohol - partially hydrolyzed, titanium dioxide (E171), talc, macrogol/PEG, soy lecithin), sodium hydroxide, Opadry Acrylose Yellow 93O92052 (methacrylate copolymer type C, talc, titanium dioxide (E171), triethyl citrate, colloidal anhydrous silicon dioxide, sodium bicarbonate, yellow iron oxide (E172), sodium lauryl sulfate), simethicone emulsion (30%), mannitol (E421), anhydrous sodium carbonate, povidone.
Dosage form
Enteric-coated tablets.
Main physicochemical properties: light yellow to yellow, round, biconvex tablets, coated with an enteric coating.
Pharmacotherapeutic group
Medications for the treatment of peptic ulcer and gastroesophageal reflux disease.
ATX code A02B C02.
Pharmacological properties
Pharmacodynamics.
Mechanism of action.
Pantoprazole is a substituted benzimidazole that inhibits gastric acid secretion by specific blockade of the proton pumps of parietal cells.
Pantoprazole is transformed into the active form in the acidic environment of the parietal cells, where it inhibits the enzyme H+-K+-ATPase, i.e. blocks the final stage of hydrochloric acid production in the stomach. Inhibition is dose-dependent and affects both basal and stimulated acid secretion. Most patients are relieved of symptoms within 2 weeks. The use of pantoprazole, as with other proton pump inhibitors and H2-receptor inhibitors, reduces acidity in the stomach and thus increases gastrin secretion in proportion to the decrease in acidity. The increase in gastrin secretion is reversible. Since pantoprazole binds the enzyme distal to the cell receptor, it can inhibit hydrochloric acid secretion regardless of stimulation by other substances (acetylcholine, histamine, gastrin). The effect is the same when the drug is administered orally and intravenously.
Pantoprazole increases fasting gastrin levels. In short-term use, they do not exceed the upper limit of normal in most cases. In long-term treatment, gastrin levels increase by a factor of two in most cases. Excessive increases occur only in isolated cases. As a result, in a small number of cases, a mild to moderate increase in specific endocrine cells in the stomach (similar to adenomatoid hyperplasia) has been observed during long-term treatment. However, according to studies conducted to date, the formation of neuroendocrine tumor precursor cells (atypical hyperplasia) or neuroendocrine tumors of the stomach has not been observed in humans.
Pharmacokinetics.
Absorption. Pantoprazole is rapidly absorbed and maximum plasma concentrations (Cmax) are reached after a single oral dose of 40 mg. On average, Cmax in serum is reached 2.5 hours after administration at a level of about 2-3 μg/ml; the concentration remains constant after multiple administration. The pharmacokinetic properties do not change after single or repeated administration. In the dose range from 10 to 80 mg, the pharmacokinetics of pantoprazole in plasma remain linear both after oral and intravenous administration.
The absolute bioavailability of the tablets has been found to be approximately 77%. Concomitant food intake does not affect the area under the concentration-time curve (AUC) or Cmax in serum, and therefore bioavailability. Only the variability of the latent period increases with concomitant food intake.
Distribution: The binding of pantoprazole to serum proteins is approximately 98%. The volume of distribution is approximately 0.15 l/kg.
Biotransformation: Pantoprazole is metabolized almost exclusively in the liver. The main metabolic pathway is demethylation by CYP2C19 followed by sulfate conjugation; other metabolic pathways include oxidation by CYP3A4.
Elimination: The terminal half-life is approximately 1 hour and the clearance is 0.1 l/h/kg. Several cases of delayed elimination have been reported. Due to the specific binding of pantoprazole to the proton pumps of the parietal cells, the half-life does not correlate with the much longer duration of action (inhibition of acid secretion).
The main part of the metabolites of pantoprazole is excreted in the urine (about 80%), the rest is excreted in the feces. The main metabolite in both serum and urine is desmethylpantoprazole, conjugated with sulfate. The half-life of the main metabolite (about 1.5 hours) is slightly longer than that of pantoprazole.
Poor metabolisers. Approximately 3% of Europeans have a functional deficiency of the CYP2C19 enzyme; they are called poor metabolisers. In these individuals, the metabolism of pantoprazole is probably mainly catalysed by the CYP3A4 enzyme. After a single dose of 40 mg pantoprazole, the mean AUC was approximately 6 times higher in poor metabolisers than in subjects with a functionally active CYP2C19 enzyme (extensive metabolisers). The mean peak plasma concentration was increased by approximately 60%. These findings do not affect the posology of pantoprazole.
Renal impairment. There are no recommendations for dose reduction when prescribing pantoprazole to patients with reduced renal function (including patients on dialysis). As in healthy subjects, the elimination half-life of pantoprazole is short. Only very small amounts of pantoprazole are dialysable. Although the main metabolite has a moderately long elimination half-life (2-3 hours), elimination is still rapid, so accumulation does not occur.
Hepatic impairment: Although in patients with cirrhosis (Child-Pugh class A and B) the half-life increases to 7-9 hours and the AUC increases 5-7-fold, the serum Cmax increases only slightly - 1.5-fold compared to that in healthy volunteers.
Elderly patients: The small increase in AUC and Cmax in elderly subjects compared to younger patients is also not clinically relevant.
Children: After a single oral dose of 20 or 40 mg pantoprazole, AUC and Cmax in children aged 5 to 16 years were within the range of the corresponding values in adults. After a single intravenous administration of pantoprazole at doses of 0.8 or 1.6 mg/kg to children aged 2 to 16 years, there was no significant relationship between the clearance of pantoprazole and age or body weight. The AUC and volume of distribution were consistent with those obtained in adult studies.
Indication
Adults and children aged 12 and over.
– Reflux esophagitis.
Adults.
– Eradication of Helicobacter pylori (H. pylori) in patients with H. pylori-associated gastric and duodenal ulcers in combination with certain antibiotics.
– Duodenal ulcer.
– Stomach ulcer.
– Zollinger-Ellison syndrome and other hypersecretory pathological conditions.
Contraindication
Hypersensitivity to pantoprazole, benzimidazole derivatives or to any component of the drug.
Interaction with other medicinal products and other types of interactions
Effect of pantoprazole on the absorption of other medicinal products: Pantoprazole may reduce the absorption of medicinal products whose bioavailability depends on the pH of the gastric juice (e.g. some antifungals such as ketoconazole, itraconazole, posaconazole, or other medicinal products such as erlotinib).
Anti-HIV drugs (atazanavir). Concomitant use of proton pump inhibitors with atazanavir and other anti-HIV drugs whose absorption depends on gastric pH may significantly reduce the bioavailability of the latter and affect their efficacy. Therefore, concomitant use of proton pump inhibitors with atazanavir is not recommended.
Coumarin anticoagulants (phenprocoumon and warfarin). Although no interaction was observed with concomitant administration of phenprocoumon and warfarin in clinical trials, isolated cases of changes in INR (International Normalized Ratio) have been reported in the post-marketing period. Therefore, in patients taking coumarin anticoagulants (e.g. phenprocoumon and warfarin), it is recommended that prothrombin time/INR be monitored after initiation, discontinuation or irregular administration of pantoprazole.
Methotrexate: Concomitant use of high doses of methotrexate (e.g. 300 mg) and proton pump inhibitors has been reported to increase blood levels of methotrexate in some patients. Patients receiving high doses of methotrexate, e.g. for cancer or psoriasis, are advised to temporarily discontinue pantoprazole treatment.
Other interactions. Pantoprazole is extensively metabolised in the liver via the cytochrome P450 enzyme system. The main route of metabolism is demethylation by CYP2C19 and other metabolic pathways, including oxidation by CYP3A4. Studies with medicinal products also metabolised by these pathways, such as carbamazepine, diazepam, glibenclamide, nifedipine, phenprocoumon and oral contraceptives containing levonorgestrel and ethinylestradiol, have not revealed any clinically significant interactions.
Pantoprazole does not affect the metabolism of active substances metabolized by CYP1A2 (e.g. caffeine, theophylline), CYP2C9 (e.g. piroxicam, diclofenac, naproxen), CYP2D6 (e.g. metoprolol), CYP2E1 (e.g. ethanol), and does not affect p-glycoprotein, which ensures the absorption of digoxin.
No interactions with concomitantly administered antacids were identified.
Pantoprazole can be used concomitantly with antibiotics (clarithromycin, metronidazole, amoxicillin). No clinically significant interactions between these drugs have been identified.
Application features
Hepatic impairment: Patients with severe hepatic impairment should have their liver enzymes monitored regularly, especially during long-term treatment. If liver enzymes increase, treatment with the drug should be discontinued.
Combination therapy. During combination therapy, the instructions for medical use of the respective medicinal products must be followed.
Alarming symptoms are present. In the presence of alarming symptoms (in the case of significant weight loss, recurrent vomiting, dysphagia, haematemesis, anemia, melena), as well as in the case of suspicion or presence of gastric ulcer, it is necessary to exclude the presence of a malignant process, since treatment with pantoprazole may mask symptoms and delay diagnosis.
If symptoms persist despite continued adequate treatment, further examination is necessary.
Concomitant use with atazanavir. Concomitant use of atazanavir with proton pump inhibitors (PPIs) is not recommended (see section 4.5). If the combination of a PPI with atazanavir is necessary, close clinical monitoring (e.g. viral load measurement) should be performed in conjunction with an increase in the dose of atazanavir to 400 mg with 100 mg ritonavir. The dose of pantoprazole should not exceed 20 mg daily.
Vitamin B12 absorption: In patients with Zollinger-Ellison syndrome and other hypersecretory pathological conditions requiring long-term treatment, pantoprazole, like all drugs that block hydrochloric acid production, may reduce the absorption of vitamin B12 (cyanocobalamin) due to the occurrence of hypo- and achlorhydria. This should be taken into account in patients with low body weight or in the presence of risk factors for reduced absorption of vitamin B12 during long-term treatment, or in the presence of relevant clinical symptoms.
Long-term treatment. With long-term treatment, especially more than 1 year, patients should be under regular medical supervision.
Gastrointestinal infections caused by bacteria. Pantoprazole, like other proton pump inhibitors, may increase the number of bacteria normally present in the upper gastrointestinal tract. Treatment with pantoprazole may slightly increase the 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 PPIs such as pantoprazole for at least three months, and in most cases for a year. The following serious clinical manifestations of hypomagnesemia may occur and may initially be insidious: fatigue, tetany, delirium, convulsions, dizziness and ventricular arrhythmias. In the case of hypomagnesemia, the majority of patients improved after magnesium replacement therapy and discontinuation of the PPI.
Patients requiring long-term therapy or patients taking PPIs concomitantly with digoxin or drugs that may cause hypomagnesemia (e.g., 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 doses of proton pump inhibitors may slightly increase the risk of hip, wrist and spine fractures, mainly in the elderly or in the presence of other risk factors. Research data indicate that the use of proton pump inhibitors may increase the overall risk of fractures by 10-40%. Some of these may be due to other risk factors. Patients at risk of osteoporosis should be treated according to current clinical guidelines and consume adequate amounts of vitamin D and calcium.
Use during pregnancy or breastfeeding
Pregnancy. Experience in pregnant women is limited. The potential risk to humans is unknown. Pantoprazole should not be used during pregnancy unless clearly necessary.
Breastfeeding. There are data on the excretion of pantoprazole in human breast milk. The decision to discontinue breast-feeding or to discontinue/abstain from therapy with the drug should be made by the doctor taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Ability to influence reaction speed when driving vehicles or other mechanisms
It is necessary to take into account the possible development of adverse reactions, such as dizziness and visual disturbances. In such cases, one should not drive or operate other mechanisms.
Method of administration and doses
Pantozol, enteric-coated tablets, should be taken whole 1 hour before meals; do not chew or crush the tablets, and drink them with water.
Recommended dosage.
Adults and children aged 12 and over.
Treatment of reflux esophagitis.
The recommended dose is 1 tablet of Pantozol per day. In some cases, the dose can be doubled (2 tablets of Pantozol 40 mg per day), especially if other drugs for the treatment of reflux esophagitis are ineffective.
Adults.
Eradication of H. pylori in combination with two antibiotics.
In adult patients with gastric and duodenal ulcers and positive for H. pylori, eradication of the organism should be achieved using combination therapy. Local data on bacterial resistance and national guidelines for the use and prescription of appropriate antibacterial agents should be taken into account. Depending on the susceptibility of microorganisms, the following therapeutic combinations may be prescribed for the eradication of H. pylori in adults:
a) 1 tablet of Pantozol 40 mg 2 times a day
+ 1000 mg of amoxicillin 2 times a day
+ 500 mg clarithromycin 2 times a day
b) 1 tablet of Pantozol 40 mg 2 times a day
+ 400-500 mg metronidazole (or 500 mg tinidazole) 2 times a day
+ 250-500 mg of clarithromycin 2 times a day;
c) 1 tablet of Pantozol 40 mg 2 times a day
+ 1000 mg of amoxicillin 2 times a day
+ 400-500 mg of metronidazole (or 500 mg of tinidazole) 2 times a day.
When using combination therapy for eradication of H. pylori, the second tablet of Pantozol should be taken in the evening 1 hour before a meal. The treatment period is 7 days and can be extended for another 7 days with a total duration of treatment of no more than 2 weeks.
If further treatment with pantoprazole is indicated to ensure ulcer healing, the dosage recommendations for gastric and duodenal ulcers should be considered. If combination therapy is not indicated, e.g. in patients with a negative result for H. pylori, Pantoprazole should be prescribed as monotherapy at the dosage indicated below.
Treatment of stomach ulcers. 1 tablet of Pantozol per day. In some cases, the dose can be doubled (2 tablets of Pantozol per day), especially if there is no effect from the use of other drugs.
It usually takes 4 weeks to heal a stomach ulcer. If this is not enough, healing can be expected within another 4 weeks.
Treatment of duodenal ulcer. 1 tablet of Pantozol per day. In some cases, the dose can be doubled (2 tablets of Pantozol per day), especially if there is no effect from the use of other drugs.
It usually takes 2 weeks for an ulcer to heal. If this is not enough, healing can be expected within another 2 weeks.
Treatment of 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 of Pantosol 40 mg each). If necessary, the dose can then be titrated up or down, depending on the acidity of the gastric juice. A dose exceeding 80 mg per day should be divided into 2 doses. A temporary increase in the dose above 160 mg of pantoprazole is possible, but the duration of use should be limited only to the period necessary for adequate acidity control.
The duration of treatment for Zollinger-Ellison syndrome and other pathological conditions is not limited and depends on clinical need.
Patients with impaired liver function. Patients with severe liver function should not exceed a daily dose of 20 mg (1 tablet of Pantozol 20 mg). Patients with moderate and severe liver function impairment should not use Pantozol for eradication of H. pylori in combination therapy, as there is currently no data on the efficacy and safety of such use.
Patients with renal impairment. No dose adjustment is required for patients with renal impairment. Patients with renal impairment should not use Pantozol for the eradication of H. pylori in combination therapy, as there is currently no data on the efficacy and safety of such use.
Elderly patients do not require dose adjustment.
Children
Pantozol is indicated in children aged 12 years and older for the treatment of reflux esophagitis. The drug is not recommended for use in children under 12 years of age, as data on safety and efficacy in this age group are limited.
Overdose
Symptoms of overdose in humans are unknown.
Doses up to 240 mg administered intravenously over 2 minutes have been well tolerated. Since pantoprazole is extensively bound to plasma proteins, it is not a drug that can be readily dialyzed.
In case of overdose with clinical signs of intoxication, symptomatic and supportive therapy is used. There are no specific therapy recommendations.
Adverse reactions
Adverse reactions were observed in about 5% of patients. The most common adverse reactions were diarrhea and headache (about 1%).
From the blood and lymphatic system: agranulocytosis, leukopenia, thrombocytopenia, pancytopenia.
Immune system disorders: hypersensitivity reactions (including anaphylactic reactions, anaphylactic shock).
Metabolic: hyperlipidemia and increased lipid levels (triglycerides, cholesterol), weight changes, hyponatremia, hypomagnesemia, hypocalcemia1, hypokalemia.
Psychiatric: sleep disorders, depression (including exacerbation), disorientation (including exacerbation), hallucinations; confusion (especially in patients with a predisposition to such disorders, as well as exacerbation of these symptoms if present).
From the organs of vision: visual impairment, blurred vision.
On the part of the digestive tract: diarrhea, nausea, vomiting, bloating, constipation, dry mouth, abdominal pain and discomfort.
On the part of the hepatobiliary system: increased levels of liver enzymes (transaminases, gamma-glutamyltransferases), increased levels of bilirubin, hepatocyte damage, jaundice, hepatocellular insufficiency.
Skin and subcutaneous tissue disorders: skin rash, exanthema, pruritus, urticaria, angioedema, Stevens-Johnson syndrome, Lyell's syndrome, erythema multiforme, photosensitivity.
Musculoskeletal system: fractures of the hip, wrist, spine (see section "Special instructions"), arthralgia, myalgia, muscle spasm2.
On the part of the urinary system: interstitial nephritis (with possible development of renal failure).
From the reproductive system: gynecomastia.
General disorders: asthenia, fatigue, malaise, fever, peripheral edema.
1. Hypocalcemia simultaneously with hypomagnesemia.
2. Muscle spasm as a result of electrolyte imbalance.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 30 ° C in the original packaging. Keep out of the reach of children.
Packaging
10 tablets in a blister. 1 or 2 or 3 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Unique Pharmaceutical Laboratories (a division of JB Chemicals & Pharmaceuticals Ltd.).
Location of the manufacturer and its business address
Plot No. 215-219, GIDC, Industrial Area, Panoli - 394 116, Dist. Braruch, India.
