Instructions for use Zolopent enteric-coated tablets 20 mg blister No. 14
Composition
active ingredient: pantoprazole;
1 tablet contains pantoprazole sodium sesquihydrate equivalent to pantoprazole 20 mg;
excipients: sodium carbonate anhydrous, mannitol (E 421), crospovidone, hydroxypropylcellulose, calcium stearate, hydragit L30D55, triethyl citrate, sodium lauryl sulfate, titanium dioxide (E 171), iron oxide yellow (E 172), talc, Opadry 03F58750 white*.
* Opadry 03F58750 white: hypromellose, titanium dioxide (E 171), polyethylene glycol, talc.
Dosage form
The film-coated tablets are enteric-coated.
Main physicochemical properties: oval biconvex tablets, coated with a yellow shell.
Pharmacotherapeutic group
Drugs for the treatment of acid-dependent diseases. Proton pump inhibitor.
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 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 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, gastrin levels do not exceed the upper limit of normal in most cases. In long-term treatment, gastrin levels double 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, there is currently no data on the formation of neuroendocrine tumor precursor cells (atypical hyperplasia) or neuroendocrine tumors of the stomach in humans. Based on published data, an 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 reached after a single oral dose of 20 mg. On average, peak serum concentrations of approximately 1–1.5 μg/ml are reached 2–2.5 hours after administration; concentrations remain constant after multiple administration. The pharmacokinetic properties are not altered after single or repeated administration. In the dose range of 10 to 80 mg, the plasma pharmacokinetics of pantoprazole remain linear after both oral and intravenous administration. The absolute bioavailability of the tablets has been shown to be approximately 77%. Concomitant food intake does not affect AUC (area under the plasma concentration-time curve) or peak serum concentrations, and therefore bioavailability. Concomitant food intake only increases the variability of the latent period.
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 correspond to 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 likely to be 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 slight increase in AUC and Cmax in elderly patients compared to younger patients is not clinically significant.
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.
Indication
Adults and children aged 12 and over.
Symptomatic treatment of gastroesophageal reflux disease.
Long-term treatment and prevention of reflux esophagitis recurrence.
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.
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 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 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 there is insufficient data on the interaction of pantoprazole with phenprocoumon and warfarin, it is recommended that patients taking coumarin anticoagulants monitor prothrombin time/INR (international normalized ratio) after starting, stopping or irregularly taking 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. There are no data on clinically significant interactions between pantoprazole and medicinal products also metabolised by these pathways (carbamazepine, diazepam, glibenclamide, nifedipine, phenprocoumon, oral contraceptives containing levonorgestrel and ethinylestradiol). Pantoprazole is known not to affect the metabolism of active substances metabolised by CYP1A2 (such as caffeine, theophylline), CYP2C9 (e.g. piroxicam, diclofenac, naproxen), CYP2D6 (such as metoprolol), CYP2E1 (such as ethanol). Pantoprazole also does not affect p-glycoprotein, which ensures the absorption of digoxin.
No interactions with concomitantly administered antacids were identified.
There are no data on clinically significant interactions between pantoprazole and certain concomitantly administered antibiotics (clarithromycin, metronidazole, amoxicillin).
Application features
Liver function disorders: Patients with severe liver function disorders should have their liver enzymes monitored regularly. 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.
Long-term use of Zolopent®, 20 mg tablets for the prevention of gastric and duodenal ulcers caused by taking 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. Proton pump inhibitors are not recommended for concomitant use with atazanavir (see section 4.5). If the combination of Zolopent® 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 per day.
Vitamin B12 absorption: In patients with 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 a long-term treatment period, especially more than a year, patients should be under constant 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, in most cases the patient's condition improved 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. It is known that the use of proton pump inhibitors may increase the overall risk of fractures by 10-40%. 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 with pantoprazole in pregnant women is limited. There is evidence of embryotoxicity with pantoprazole. The potential risk to humans is unknown. The drug should not be used during pregnancy unless clearly necessary.
Breastfeeding. Pantoprazole is excreted in human milk. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Zolopent® therapy taking into account the benefit of breast-feeding for the child and the benefit of Zolopent® 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
Zolopent® 20 mg should be taken 1 hour before meals whole, without chewing or crushing, with water.
Recommended dosage.
Adults and children aged 12 and over.
Symptomatic treatment of gastroesophageal reflux disease.
Long-term treatment and prevention of reflux esophagitis recurrence.
For long-term treatment, the maintenance dose is 20 mg (1 tablet) of Zolopent® 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 Zolopent® 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 Zolopent® per day.
Patients with hepatic impairment: Patients with severe hepatic impairment should not exceed a dose of 20 mg (1 tablet) per day.
Patients with renal impairment: Patients with renal impairment do not require dose adjustment.
Elderly patients do not require dose adjustment.
Children
The drug is not recommended for use in children under 12 years of age, as data on the safety and efficacy of the drug for this age group are limited.
Overdose
Symptoms of overdose are unknown.
Doses up to 240 mg administered intravenously over 2 minutes have been well tolerated. Pantoprazole is extensively protein bound and is not completely dialysable.
In case of overdose with clinical signs of intoxication, symptomatic and supportive therapy is used. There are no specific therapy recommendations.
Adverse reactions
From the blood and lymphatic system: agranulocytosis, leukopenia, thrombocytopenia, pancytopenia.
Immune system disorders: hypersensitivity reactions (including anaphylactic reactions, anaphylactic shock).
Metabolism and metabolic disorders: hyperlipidemia and increased lipid levels (triglycerides, cholesterol); weight changes, hyponatremia, hypomagnesemia.
Psychiatric: sleep disorders, depression (including exacerbation), disorientation (including exacerbation), hallucinations, confusion (especially in patients with a predisposition to these 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.
Musculoskeletal and connective tissue disorders: fracture of the hip, wrist or spine, arthralgia, myalgia, muscle spasm.
On the part of the kidneys and urinary system: interstitial nephritis (with possible development of renal failure).
Reproductive system and breast disorders: gynecomastia.
General disorders: asthenia, fatigue, malaise, fever, peripheral edema.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25°C.
Keep out of reach of children.
Packaging
14 tablets in a blister. 1 blister in a cardboard box.
Vacation category
According to the recipe.
Producer
"KUSUM FARM" LLC.
Location of the manufacturer and its business address
Ukraine, 40020, Sumy, Skryabina St., 54.
