Instructions for use Zolopent film-coated tablets 20 mg No. 30
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, methacrylate copolymer dispersion, 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 in most cases do not exceed the upper limit of normal. In long-term treatment, gastrin levels in most cases double. However, excessive increases occur only in isolated cases. As a result, sometimes during long-term treatment, a slight or moderate increase in specific endocrine (ECL) cells in the stomach (similar to adenomatoid hyperplasia) is observed. However, according to studies conducted so far, the formation of precursor cells of neuroendocrine tumors (atypical hyperplasia) or neuroendocrine tumors of the stomach, which were found 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. Against the background of treatment with antisecretory drugs, the level of gastrin in the blood serum increases in response to a decrease in acid secretion. In addition, decreased gastric acidity increases chromogranin A (CgA) levels. Elevated CgA levels may interfere with diagnostic tests for neuroendocrine tumors. Available published data suggest that PPI treatment should be discontinued for 5 days to 2 weeks before CgA measurements. This allows CgA levels to return to the normal range, which may be falsely elevated after PPI treatment.
Pharmacokinetics.
Absorption.
Pantoprazole is rapidly absorbed and peak plasma concentrations are achieved after a single oral dose of 20 mg. On average, peak serum concentrations (Cmax) of approximately 1–1.5 μg/ml are reached 2–2.5 hours after administration; the concentration remains constant after multiple administration. The pharmacokinetic properties do not change after single or repeated administration. In the dose range of 10 to 80 mg, the pharmacokinetics of pantoprazole in plasma 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 the area under the plasma concentration-time curve (AUC) or Cmax, 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.
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 not much longer than the half-life of pantoprazole.
Special patient groups.
Poor metabolisers. Approximately 3% of Europeans have a low functional activity 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 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 impaired renal function (including patients on dialysis). As in healthy volunteers, the elimination half-life of pantoprazole is short. Only very small amounts of pantoprazole are dialysable. Although the main metabolite has a moderately long 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, Cmax increases only slightly - 1.3-fold compared to that in healthy volunteers.
Elderly patients: The slight 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 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
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 or to any component of the drug, to benzimidazole derivatives.
Interaction with other medicinal products and other types of interactions
Medicinal products whose absorption is pH-dependent: Due to the complete and long-term inhibition of hydrochloric acid secretion, pantoprazole may affect the absorption of medicinal products for which the pH of the gastric juice is an important factor in their bioavailability (e.g. some antifungals such as ketoconazole, itraconazole, posaconazole, or other medicinal products such as erlotinib).
HIV protease inhibitors: Concomitant use of pantoprazole with HIV protease inhibitors (such as atazanavir) whose absorption is dependent on intragastric pH is not recommended due to a significant reduction in their bioavailability (see section 4.4).
In cases where concomitant use of HIV protease inhibitors with PPIs cannot be avoided, close clinical monitoring (e.g. viral load) is recommended. The daily dose of pantoprazole should not exceed 20 mg. Dose adjustment of HIV protease inhibitors may be necessary.
Coumarin anticoagulants (phenprocoumon and warfarin). Concomitant use of pantoprazole with warfarin or phenprocoumon did not affect the pharmacokinetics of warfarin, phenprocoumon or INR (international normalized ratio). However, increases in INR and prolongation of prothrombin time have been reported in patients receiving concomitant PPIs and warfarin or phenprocoumon. Increases in INR and prolongation of prothrombin time may lead to pathological bleeding and even fatal outcome. In such concomitant use, INR and prothrombin time should be monitored.
Methotrexate: Concomitant use of high doses of methotrexate (e.g. 300 mg) and PPIs 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.
Interactions of pantoprazole with other drugs that are metabolized through the same enzyme system cannot be excluded.
The results of a number of studies on possible interactions indicate that 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 is associated with the absorption of digoxin.
No interactions with concomitantly administered antacids were identified.
Studies have been conducted to study the interaction of pantoprazole with certain antibiotics (clarithromycin, metronidazole, amoxicillin) administered concomitantly. No clinically significant interactions between these drugs have been identified.
Medicinal products that inhibit or induce CYP2C19. CYP2C19 inhibitors, such as fluvoxamine, may increase the systemic exposure of pantoprazole. A dose reduction should be considered in patients receiving long-term treatment with high doses of pantoprazole and in patients with impaired liver function. Inducers of enzymes that affect CYP2C19 and CYP3A4, such as rifampicin and St. John's wort (Hypericum perforatum), may reduce plasma concentrations of PPIs that are metabolised by these enzyme systems.
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 (see section 4.2).
Concomitant use with NSAIDs. The use of Zolopent®, 20 mg tablets, for the prevention of gastric and duodenal ulcers caused by long-term use of NSAIDs should be limited to 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.
Gastric malignancies. Symptomatic response to pantoprazole may mask symptoms of gastric malignancies and delay their diagnosis. 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. If symptoms persist despite adequate treatment, further investigation is necessary.
HIV protease inhibitors: Concomitant use of pantoprazole with HIV protease inhibitors (such as atazanavir) whose absorption is dependent on intragastric pH is not recommended due to a significant reduction in their bioavailability (see section 4.5).
Vitamin B12 absorption: Pantoprazole 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 risk factors for reduced absorption of vitamin B12 during long-term treatment, or in the presence of relevant clinical symptoms.
Long-term treatment: During long-term treatment, especially for more than one year, patients should be under regular medical supervision.
Gastrointestinal infections caused by bacteria. 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.
Subacute cutaneous lupus erythematosus. The use of PPIs has been associated with very rare cases of subacute cutaneous lupus erythematosus. If lesions occur, especially in areas exposed to sunlight, and are accompanied by arthralgia, the patient should immediately consult a doctor who will consider discontinuing pantoprazole. The occurrence of subacute cutaneous lupus erythematosus in patients on previous PPI therapy may increase the risk of its development with other PPIs.
Impact on laboratory test results.
Elevated chromogranin A (CgA) levels may interfere with the results of diagnostic tests for neuroendocrine tumours. To avoid this interference, pantoprazole treatment should be temporarily discontinued for at least 5 days before CgA measurements (see section 5.2). If CgA and gastrin levels have not returned to the normal range after initial measurement, repeat measurements should be performed 14 days after discontinuation of PPI treatment.
Use during pregnancy or breastfeeding
Pregnancy: Available data on the use of pantoprazole in pregnant women (approximately 300-1000 pregnancy outcomes) indicate no embryonal or foeto-neonatal toxicity of the drug. Reproductive toxicity has been observed in animal studies. As a precautionary measure, the use of pantoprazole in pregnant women should be avoided.
Breast-feeding. Animal studies have shown excretion of pantoprazole in breast milk. There is insufficient information on the excretion of pantoprazole in human milk, but such excretion has been reported. A risk to the newborn/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from pantoprazole therapy taking into account the benefit of breast-feeding for the child and the benefit of pantoprazole therapy for the woman.
Fertility: Pantoprazole did not impair fertility in animal studies.
Ability to influence reaction speed when driving vehicles or other mechanisms
Pantoprazole has no or very minor influence on the ability to drive or use machines. It is necessary to take into account the possible development of side effects such as dizziness and visual disturbances (see section "Adverse reactions"). In such cases, you should not drive or use machines.
Method of administration and doses
Zolopent®, 20 mg, tablets should be taken 1 hour before meals whole, not chewed or crushed, with water.
Recommended dosage.
Adults and children aged 12 and over.
Symptomatic treatment of gastroesophageal reflux disease.
The recommended dose is 20 mg (1 tablet) of Zolopent® per day. Heartburn symptoms usually resolve within 2–4 weeks. If this period is not sufficient, treatment is continued for a further 4 weeks. After symptoms have resolved, recurrence of symptoms can be controlled by administering 20 mg of the drug once daily, taking 1 tablet as needed. Transition to long-term therapy should be considered if symptoms are not adequately controlled with on-demand therapy.
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 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.
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.
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 in 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. 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.
Side effects
From the blood and lymphatic system: agranulocytosis, leukopenia, thrombocytopenia, pancytopenia.
Metabolism and metabolic disorders: hyperlipidemia and increased lipid levels (triglycerides, cholesterol); weight change, hyponatremia, hypomagnesemia (see section "Special warnings and precautions for use"), hypocalcemia1, hypokalemia.
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, fundic gland polyps (benign).
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, subacute cutaneous lupus erythematosus (see section "Special warnings and precautions for use").
Musculoskeletal and connective tissue disorders: fractures of the hip, wrist or spine
(see section "Special warnings and precautions for use"), arthralgia, myalgia, muscle spasm2.
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.
1 Hypocalcemia concomitant with hypomagnesemia.
2 Muscle spasm due to electrolyte imbalance
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.
Address.
40020, Ukraine, Sumy region, Sumy city, Skryabina st., 54.
