Instructions Pantor 40 enteric-coated tablets 40 mg No. 30
Composition
active ingredient: 1 tablet contains pantoprazole sodium sesquihydrate equivalent to pantoprazole
20 mg or 40 mg;
excipients: mannitol (E 421), crospovidone, sodium carbonate anhydrous, hydroxypropylcellulose, calcium stearate, hypromellose, titanium dioxide (E 171), iron oxide yellow (E 172), propylene glycol, methacrylate copolymer dispersion, triethyl citrate, talc.
Dosage form
The film-coated tablets are enteric-coated.
Main physicochemical properties: oval biconvex tablets, coated with a yellow enteric-coated film, smooth on both sides.
Pharmacotherapeutic group
Drug for the treatment of peptic ulcers; proton pump inhibitor. ATC 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 the parietal cells. Pantoprazole is converted to its active form in the acidic environment of the parietal cells, where it inhibits the enzyme H+-K+-ATPase, i.e. blocks the final step in the production of gastric acid. The inhibition is dose-dependent and suppresses both basal and stimulated acid secretion. Most patients are relieved of symptoms within 2 weeks. The use of pantoprazole, like other proton pump inhibitors (PPIs) and H2-receptor inhibitors, reduces 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 distal to the cellular 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, gastrin levels do not exceed the upper limit of normal in most cases. In long-term treatment, gastrin levels are doubled in most cases. However, excessive increases occur only in isolated cases. As a result, a slight or moderate increase in specific endocrine (ECL) cells in the stomach (similar to adenomatoid hyperplasia) is sometimes 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, which have been identified in animal studies, has not been observed in humans.
Based on the results of animal studies, the effect of long-term (more than one year) treatment with pantoprazole on endocrine parameters of the thyroid gland cannot be completely excluded.
Pharmacokinetics
Absorption: Pantoprazole is rapidly absorbed and peak plasma concentrations are achieved after a single oral dose of 20 mg. On average, after
2-2.5 hours after administration, the maximum serum concentration is reached at a level of about
1-1.5 μg/ml; concentration remains constant after multiple administration.
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 about 77%. Concomitant food intake does not affect the AUC (area under the concentration-time curve) or the maximum serum concentration, and therefore the bioavailability. Only the variability of the latent period increases with concomitant food intake.
Distribution: The binding of pantoprazole to serum proteins is about 98%. The volume of distribution is about 0.15 l/kg.
Biotransformation. The substance 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 about 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 require a functional 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 area under the plasma concentration-time curve was approximately 6 times larger in poor metabolisers than in subjects with a functional CYP2C19 enzyme (extensive metabolisers). The mean peak plasma concentration was increased by approximately 60%. These findings do not influence the posology of pantoprazole.
Renal impairment. There are no recommendations for dose reduction when prescribing pantoprazole to patients with impaired 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 3-6 hours and the AUC increases 3-5-fold, the maximum serum concentration increases only slightly - 1.5-fold compared to that in healthy volunteers.
Elderly patients: The small increase in AUC and Cmax in elderly volunteers compared to younger volunteers 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 the patient's age or body weight. The AUC and volume of distribution were consistent with those obtained in studies in adults.
Indication
20 mg tablets:
Adults and children aged 12 and over.
– Symptomatic treatment of gastroesophageal reflux disease.
– Long-term treatment and prevention of relapses of reflux esophagitis.
Adults.
– Prevention of gastric and duodenal ulcers caused by taking non-selective non-steroidal anti-inflammatory drugs (NSAIDs) in patients at risk who must use NSAIDs for a long time.
40 mg tablets:
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 appropriate antibiotics;
– Duodenal ulcer;
– Stomach ulcer;
– Zollinger-Ellison syndrome and other hypersecretory pathological conditions.
Contraindication
Hypersensitivity to the active substance, benzimidazole derivatives or any component of the drug.
Interaction with other medicinal products and other types of interactions
Effect of pantoprazole on the absorption of other drugs. Due to complete and long-term inhibition of hydrochloric acid secretion, pantoprazole may reduce the absorption of drugs whose bioavailability depends on the pH of the gastric juice (e.g. some antifungal drugs such as ketoconazole, itraconazole, posaconazole and other drugs, including erlotinib).
Anti-HIV drugs (atazanavir). Concomitant use of PPIs with atazanavir and other anti-HIV drugs whose adsorption is pH-dependent may significantly reduce the bioavailability of the latter and affect their efficacy. Therefore, concomitant use of PPIs 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.
The results of a number of studies on possible interactions indicate that pantoprazole does not affect the metabolism of active substances metabolized by CYP1A2 (such as caffeine, theophylline), CYP2C9 (for example, piroxicam, diclofenac, naproxen), CYP2D6 (such as metoprolol), CYP2E1 (such as ethanol), and does not affect p-glycoprotein, which ensures the absorption of digoxin.
No interactions with concomitantly administered antacids were identified.
Studies on the interaction of pantoprazole with certain antibiotics (clarithromycin, metronidazole, amoxicillin) administered concomitantly have not shown any clinically significant interactions between these drugs.
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 should be discontinued.
Concomitant use with NSAIDs.
During combination therapy, the instructions for medical use of the respective medicinal products must be followed.
The use of PANTOR 20, 20 mg tablets for the prevention of gastric and duodenal ulcers caused by long-term use of NSAIDs should be limited in patients who are prone to frequent exacerbations of gastric and duodenal ulcers.
Risk assessment is based on individual risk factors, including age (> 65 years), history of gastric or duodenal ulcer, and gastrointestinal bleeding.
Alarming symptoms present. In the presence of alarming symptoms (e.g. significant weight loss, recurrent vomiting, dysphagia, haematemesis, anaemia, melena) and in the presence or suspicion of gastric ulcer, malignancy should be excluded, as treatment with pantoprazole may mask the symptoms of malignant ulcer and delay diagnosis. If symptoms persist despite continued adequate treatment, further investigation is necessary.
Concomitant use with atazanavir.
The concomitant use of atazanavir with proton pump inhibitors (PPIs) is not recommended (see section 4.5). If the combination of Pantor 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 20 mg per day should not be exceeded.
Vitamin B12 absorption: In patients with Zollinger-Ellison syndrome and other hypersecretory conditions requiring long-term treatment, pantoprazole, as with all drugs that block the secretion of hydrochloric acid, may reduce the absorption of vitamin B12 (cyanocobalamin) due to the occurrence of hypo- or 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 a long-term treatment period, 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 the drug 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 progress insidiously: fatigue, tetany, delirium, convulsions, dizziness and ventricular arrhythmias. In the case of hypomagnesemia, the condition of the patients improved in most cases after magnesium replacement therapy and discontinuation of the PPI.
Patients requiring long-term therapy or patients taking PPIs in combination with digoxin or drugs that can 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. Observational studies suggest 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
Breastfeeding. Animal studies have shown excretion of pantoprazole in breast milk. There are data on the excretion of pantoprazole in human breast milk. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with the drug should be made 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
Pantor 20 and Pantor 40, film-coated, enteric-coated tablets, should be taken 1 hour before meals whole, do not chew or crush, and washed down with water.
20 mg tablets
Recommended dosage.
Adults and children aged 12 and over.
Symptomatic treatment of gastroesophageal reflux disease.
The recommended dose is 20 mg (1 tablet) of the drug per day. Usually, heartburn symptoms disappear within 2-4 weeks. If this period is not enough, treatment is continued for another 4 weeks. After the symptoms disappear, their recurrence can be controlled by using 20 mg of the drug depending on the need.
Long-term treatment and prevention of reflux esophagitis recurrence.
For long-term treatment, the maintenance dose is 20 mg (1 tablet) of Pantor per day, with exacerbation of the disease, the dose may be increased to 40 mg per day. In this case, it is recommended to take Pantor 40 mg tablets. After the relapse is eliminated, the dose can be reduced again to 20 mg of the drug per day.
Adults.
Prevention of gastric and duodenal ulcers caused by taking non-selective non-steroidal anti-inflammatory drugs (NSAIDs) in patients at risk who must take NSAIDs for a long time.
The recommended dose is 20 mg (1 tablet) of Pantor per day.
Hepatic impairment: Patients with severe hepatic impairment should not exceed a dose of 20 mg (1 tablet) per day.
Renal impairment: Patients with renal impairment do not require dose adjustment.
Elderly patients do not require dose adjustment.
40 mg tablets
Recommended dosage.
Adults and children aged 12 and over.
Treatment of reflux esophagitis.
The recommended dose for children over 12 years of age and adults is 1 tablet (40 mg) once a day. In some cases, the dose can be doubled (2 tablets of Pantor 40 per day), especially if other drugs for the treatment of reflux esophagitis are ineffective. Reflux esophagitis usually takes 4 weeks to treat. If this is not enough, healing can be expected within another 4 weeks.
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 susceptibility, the following therapeutic combinations may be prescribed for the eradication of H. pylori in adults:
a) 1 tablet of Pantor 40 mg 2 times a day
+ 1000 mg of amoxicillin 2 times a day
+ 500 mg of clarithromycin 2 times a day;
b) 1 tablet of Pantor 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 Pantor 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 the eradication of H. pylori, the second tablet of Pantor 40 mg 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 two 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, for example, in patients with a negative result for H. pylori, Pantor 40 is used for monotherapy in the dosage indicated below.
Treatment of stomach ulcers.
1 tablet of Pantor 40 mg per day. In some cases, the dose can be doubled (2 tablets of Pantor 40 mg 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 of the ulcer can be expected within another 4 weeks.
Treatment of duodenal ulcers.
1 tablet of Pantor 40 mg per day. In some cases, the dose can be doubled (2 tablets of Pantor 40 mg per day), especially if there is no effect from the use of other drugs.
For long-term treatment of Zollinger-Ellison syndrome and other pathological hypersecretory conditions, the initial daily dose is 80 mg (2 tablets of Pantor 40 mg). 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 two 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 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 hepatic impairment. Patients with severe hepatic impairment should not exceed a daily dose of 20 mg (1 tablet of Pantor 20 mg). Pantor should not be used for the eradication of H. pylori in combination therapy in patients with moderate to severe hepatic impairment, as there is currently no data on the efficacy and safety of such use in this category of patients.
Patients with renal impairment. No dose adjustment is required for patients with renal impairment. Pantor should not be used for the eradication of H. pylori in combination therapy in patients with renal impairment, as there is currently no data on the efficacy and safety of such use in this category of patients.
Elderly patients do not require dose adjustment.
Children
The drug is indicated for 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 the safety and efficacy of the drug in this age group are limited. Do not use in children under 12 years of age.
Overdose
Symptoms of overdose are unknown.
Doses up to 240 mg given intravenously over 2 minutes have been well tolerated. Since pantoprazole is extensively protein bound, 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 approximately 5% of patients. The most common adverse reactions were diarrhea and headache (approximately 1%).
From the blood and lymphatic system: agranulocytosis, leukopenia, thrombocytopenia, pancytopenia.
Immune system disorders: hypersensitivity reactions (including anaphylactic reactions, anaphylactic shock).
Metabolic disorders:
hyperlipidemia and increased lipid levels (triglycerides, cholesterol), weight changes, hyponatremia, hypomagnesemia (see section "Special warnings and precautions for use"), hypocalcemia1, hypokalemia.
Psychiatric disorders: 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 in case of their pre-existence).
From the nervous system: headache, dizziness, taste disturbances, paresthesia.
On the part of 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, g-GT), 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.
From the musculoskeletal system:
fractures of the hip, wrist, spine (see section "Special instructions for use"), 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 25 ºС in the original packaging.
Keep out of reach of children.
Packaging
10 tablets in a blister, 1 or 3 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Torrent Pharmaceuticals Ltd.
Location of the manufacturer and its business address
Indrad Plant, Village Indrad, Taluka Kadi, Dist. Mehsana Gujarat 382721, India.
