Reflux esophagitis; duodenal ulcer; stomach ulcer; Helicobacter pylori eradication in patients with Helicobacter pylori-associated gastric and duodenal ulcers in combination with appropriate antibiotics; Zollinger-Ellison syndrome and other hypersecretory pathological conditions.
active ingredient Zolopent: pantoprazole; 1 tablet contains pantoprazole sodium sesquihydrate equivalent to pantoprazole 40 mg;
excipients Zolopent: sodium carbonate anhydrous, mannitol (E 421), crospovidone, hydroxypropyl cellulose, calcium stearate, oydragit 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.
zolopent – coated tablets, enteric.
BASIC PHYSICO-CHEMICAL PROPERTIES
Oval, biconvex, yellow film-coated tablets.
Means for the treatment of acid-related diseases. Proton pump inhibitor. ATX code А02В С02.
Pantoprazole is a substituted benzimidazole that inhibits the secretion of hydrochloric acid in the stomach by specifically blocking the proton pumps of parietal cells.
Zolopent is transformed into an active form in an acidic environment in parietal cells, where it inhibits the H + -K + -ATPase enzyme, i.e. blocks the final stage of the production of hydrochloric acid in the stomach. Inhibition is dose dependent and suppresses both basal and stimulated secretion of hydrochloric acid. The therapeutic effect of pantoprazole is achieved in most patients within 2 weeks of treatment. The use of pantoprazole, as in the case of other proton pump inhibitors and H2-receptor inhibitors, decreases gastric acidity and thus increases gastrin secretion in proportion to the decrease in acidity. The increase in gastrin secretion is reversible. Since zolopent binds the enzyme distally to the cellular receptor, it can inhibit the secretion of hydrochloric acid independently of stimulation by other substances (acetylcholine, histamine, gastrin). The effect of oral and intravenous administration of Zolopent is the same.
When using zolopent, the level of fasting gastrin increases. With short-term use of pantoprozole, gastrin levels in most cases do not exceed the upper limit of the norm. With long-term treatment, gastrin levels double in most cases. Their excessive increase, however, occurs only in isolated cases. As a consequence, in a small number of cases with long-term treatment, there is a weak or moderate increase in the number of enterochromaffin-like (ECb-cells) cells in the stomach (similar to adenomatoid hyperplasia). However, according to the studies carried out to date, the formation of precursor cells of neuroendocrine tumors (atypical hyperplasia) or neuroendocrine tumors of the stomach, identified in experiments on animals, has not been observed in humans.
Based on the results of animal studies, it is impossible to exclude the effect of prolonged (more than 1 year) treatment with pantoprazole on the endocrine parameters of the thyroid gland. Pharmacokinetics.
Suction. Zolopent is absorbed quickly, and maximum plasma concentrations are reached after a single oral dose of Zolopent 40 mg. On average, 2.5 hours after administration, the maximum serum concentration is reached at a level of about 2-3 μg / ml; the concentration remains at a constant level after repeated administration. Pharmacokinetic properties do not change after single or repeated administration. In the range of doses of Zolopent from 10 to 80 mg, the pharmacokinetics of pantoprazole in plasma remains linear both when taken orally and when administered intravenously. It has been found that the absolute bioavailability of the tablets is about 77%. Simultaneous food intake does not affect the AUC (area under the concentration-time curve) or the maximum concentration in serum, and, accordingly, and bioavailability. With the simultaneous intake of food, only the variability of the latent period increases.
The binding of zolopent to serum proteins is about 98%. The volume of distribution is about 0.15 l / kg.
Zolopent is metabolized almost exclusively in the liver. The main metabolic pathway is demethylation by CYP2C19 followed by sulfate conjugation; another metabolic pathway is oxidation by CYP3A4. The terminal half-life is about 1 hour, and the clearance is 0.1 l / h / kg. There have been several cases of delayed withdrawal of pantoprazole in patients. Due to the specific binding of pantoprazole to the proton pumps of parietal cells, the half-life does not correlate with a much longer duration of action (inhibition of acid secretion).
Most of the metabolites of pantoprazole are 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 higher than the half-life of pantoprazole. Features of use for patients / special groups of patients. About 3% of Europeans lack the active CYP2C19 enzyme; they are called slow metabolizers. In such organisms, the metabolism of pantoprazole is probably mainly catalyzed by the CYP3A4 enzyme. After taking a single dose of Zolopent 40 mg pantoprazole, the mean area bounded by the plasma concentration-time pharmacokinetic curve was approximately 6 times greater in slow metabolizers than in individuals who have an active CYP2C19 enzyme (fast metabolizers). The average peak plasma concentration has increased by about 60%. These results do not affect the dosage of zolopent.
There are no recommendations for reducing the dose of Zolopent when prescribing zolopent to patients with impaired renal function (including patients on dialysis). As in healthy people, the half-life of pantoprazole is short. Only very small amounts of zolopent are dialyzed. Despite the fact that the main metabolite has a moderately long half-life (2-3 hours), elimination is still fast, so no cumulation occurs.
Although in patients with cirrhosis of the liver (classes A and B according to Child Pugh), the half-life increases to 7-9 hours, and the AUC increases 5-7 times, the maximum serum concentration increases only slightly, 1.5 times compared with that of healthy volunteers. A slight increase in AUC and Cmax in elderly volunteers compared to younger volunteers also has no clinical significance.
After a single dose of Zolopent 20 or 40 mg of Zolopent orally, AUC and Cmax for children from 5 to 16 years old were within the corresponding values in adults. After a single intravenous administration of pantoprazole at doses of 0.8 or 1.6 mg / kg to children from 2 to 16 years old, there was no significant relationship between the clearance of pantoprazole and age or body weight. AUC and volume of distribution were consistent with data obtained from studies in adults.
Eradication of Helicobacter pylori (H. pylori) in patients with gastric and duodenal ulcers caused by this microorganism in combination with certain antibiotics.
- Duodenal ulcer.
- Stomach ulcer.
- Zollinger-Ellison syndrome and other hypersecretory conditions.
Hypersensitivity to the active substance, benzimidazole derivatives and to any component of the Zolopent preparation.
INTERACTION WITH OTHER DRUGS AND OTHER KINDS OF INTERACTIONS.
Pantoprazole may reduce the absorption of drugs whose bioavailability depends on the pH of gastric juice (for example, some antifungal drugs such as ketoconazole, itraconazole, posaconazole, or other drugs such as erlotinib)
The combined use of proton pump inhibitors with atazanavir and other drugs that are used in the treatment of HIV, the adsorption of which depends on pH, can lead to a significant decrease in the bioavailability of the latter and affect their effectiveness. Therefore, the co-administration of proton pump inhibitors with atazanavir is not recommended. Despite the lack of interaction with the simultaneous appointment with phenprocoumon and warfarin during clinical trials, isolated cases of changes in the International Normalization Index (International Normalization Index) in the post-marketing period were recorded. Thus, patients who are using coumarin anticoagulants (eg, phenprocoumon and warfarin) are advised to monitor prothrombin time / MNI after initiation, discontinuation, or irregular pantoprazole administration.
Pantoprazole is largely metabolized in the liver through the cytochrome P450 system. The main metabolic pathway is demethylation by CYP2C19 and other metabolic pathways, including oxidation by the CYP3Ä4 enzyme. Studies with drugs that are also metabolized by these pathways, such as carbamazepine, diazepam, glibenclamide, nifedipine, phenprocoumon, and oral contraceptives containing levonorgestrel and ethinyl estradiol, have not revealed clinically significant interactions. The results of a number of studies regarding possible interactions indicate that pantoprazole does not affect the metabolism of active substances that are metabolized by CYP1A2 (eg caffeine, theophylline), CYP2C9 (eg piroxicam, diclofenac, naproxen), CYP2D6 (eg metoprolol) , CYP2E1 (eg ethanol) does not affect the β-glycoprotein, which mediates digoxin absorption.
There was no interaction with concomitantly prescribed antacids.
Studies have been carried out to study the interaction of pantoprazole with certain antibiotics (clarithromycin, metronidazole, amoxicillin) simultaneously prescribed. No clinically significant interactions between these drugs have been identified.
The simultaneous use of Zolopent together with methotrexate (mainly in a large dosage) can increase and lengthen the levels of methotrexate and / or its metabolite hydromethotrexate in serum, which can cause toxicity.
FEATURES OF APPLICATION.
Patients with severely impaired liver function need to regularly monitor the level of liver enzymes, especially with long-term treatment. In case of an increase in the level of liver enzymes, treatment with Zolopent should be discontinued.
During combination therapy, the instructions for use of the respective medicinal products must be followed.
In the presence of alarming symptoms (for example, in the case of significant weight loss, intermittent vomiting, dysphagia, vomiting of blood, anemia, melena), as well as if a stomach ulcer is suspected or present, malignancy should be ruled out, since pantoprazole treatment can mask the symptoms of a malignant ulcer and delay establishing a diagnosis. If symptoms persist with further adequate treatment, further research is needed.
The combined use of atazanavir with proton pump inhibitors is not recommended (see section “Interaction with other medicinal products and other types of interactions”). If the combination of Zolopent with atazanavir is necessary, close clinical monitoring (for example, measurement of viral load) should be carried out in combination with an increase in the dose of atazanavir to 400 mg using 100 mg ritonavir. The dose of pantoprazole 20 mg per day should not be exceeded (if it is necessary to prescribe a dose of 20 mg, use pantoprazole preparations in the appropriate dosage).
In patients with Zollinger-Ellison syndrome and other hypersecretory pathological conditions that require long-term treatment, pantoprazole, like all antacids, can reduce the absorption of vitamin BJ2 (cyanocobalamin) due to the occurrence of hypo- and achlorhydria. This should be considered in the case of underweight patients or the presence of risk factors for decreased absorption of vitamin BJ2 with long-term treatment, or the presence of appropriate clinical symptoms.
With long-term treatment, especially more than 1 year, patients should be under regular medical supervision.
Zolopent, like other proton pump inhibitors, can increase the number of bacteria commonly found in the upper gastrointestinal tract. Treatment with Zolopent may slightly increase the risk of gastrointestinal infections caused by bacteria such as Salmonella and Campylobacter. Hypomagnesemia. There have been reports of severe hypomagnesemia in patients who have taken proton pump inhibitors such as pantoprozole for at least three months, and in most cases for a year. Serious manifestations of hypomagnesemia, such as fatigue, tetany, delirium, seizures, dizziness, and ventricular arrhythmias, may start unnoticed and can be missed. In most cases, patients’ condition improves after magnesium replacement therapy and discontinuation of treatment with proton pump inhibitors. Patients who are planning long-term therapy or taking proton pump inhibitors in conjunction with digoxin or drugs that can cause hypomagnesemia (for example, with diuretics) are recommended to measure magnesium levels before starting treatment with proton pump inhibitors and periodically during therapy. Bone fractures. Proton pump inhibitors, especially when used in high doses and for long-term treatment (more than 1 year), may slightly increase the risk of fractures of the hip, wrist and spine, mainly in elderly patients or in the presence of other existing risk factors. Observational studies suggest that proton pump inhibitors can increase the overall risk of fractures by 10-40%. Some of these may be due to other risk factors. Patients at risk of developing osteoporosis should receive treatment in accordance with current clinical guidelines and adequate amounts of vitamin D and calcium.
APPLICATION DURING PREGNANCY OR BREASTFEEDING.
The experience of using Zolopent for pregnant women is limited. There are data on embryotoxicity in animals at doses higher than 5 mg / kg. The potential risk to humans is unknown. Zolopent can be used during pregnancy only if absolutely necessary. There are data on the excretion of pantoprazole into breast milk. The decision to use Zolopent during breastfeeding should be made after a careful assessment of the benefits / risks.
ABILITY OF ZOLOPENT TO INFLUENCE THE RATE OF REACTIONS WHEN CONTROLLING MOTOR TRANSPORT OR OTHER MECHANISMS.
During treatment with Zolopent, some patients may experience adverse reactions, such as dizziness and visual disturbances, so you need to be careful when driving or working with complex mechanisms.
Method of administration and dosage
Zolopent, enteric-coated tablets, should be taken 1 hour before a meal, whole, not chewed or crushed, washed down with water.
Reflux esophagitis treatment.
The recommended dose of Zolopent for children aged 12 years and older is 1 tablet of Zolopent 40 mg 1 time per day. In some cases, the dose can be doubled (2 tablets of Zolopent 40 mg per day), especially if there is no effect from the use of other drugs for the treatment of reflux esophagitis.
Reflux esophagitis usually takes 4 weeks to cure. If this is not enough, a cure can be expected within the next 4 weeks.
Eradication of H. pylori in combination with two antibiotics.
In adult patients with gastric and duodenal ulcers who test positive for H. pylori, it is necessary to achieve eradication of the microorganism using combination therapy. Depending on the sensitivity of microorganisms for the eradication of Helicobacter pylori in adults, the following therapeutic combinations can be prescribed:
- 1 tablet of Zolopent 40 mg 2 times a day + 1000 mg of amoxicillin 2 times a day + 500 mg of clarithromycin 2 times a day;
- 1 tablet of Zolopent 40 mg 2 times a day + 400-500 mg of metronidazole (or 500 mg of tinidazole) 2 times a day + 500 mg of clarithromycin 2 times a day;
- 1 tablet of Zolopent 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, Zolopent should be taken in the morning and evening 1 hour before meals. The treatment period is 7 days and can be extended for another 7 days with a total treatment duration of no more than two weeks.
If combination therapy is not indicated, for example, in patients with a negative result for H. pylori, Zolopent should be prescribed for monotherapy at the following dosage.
Stomach ulcer treatment
1 tablet of Zolopent per day. In some cases, the dose can be doubled (2 tablets of Zolopent per day), especially if there is no effect from the use of other drugs.
It usually takes 4 weeks for a stomach ulcer to heal. If this is not enough, a cure can be expected within the next 4 weeks.
Treatment of duodenal ulcers
1 tablet of Zolopent per day. In some cases, the dose can be doubled (2 tablets of Zolopent per day), especially if there is no effect from the use of other drugs.
Duodenal ulcers usually take 2 weeks to heal. If this is not enough, a cure can be expected within the next 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 dose is 80 mg (2 tablets of Zolopent 40 mg each). If necessary, then the dose can be titrated, increasing or decreasing, depending on the rate of acid secretion in the stomach. If the dose of Zolopent exceeds 80 mg, it must be divided into two doses. A temporary increase in the dose over 160 mg of pantoprazole is possible, but the duration of use should be limited only by the period necessary for adequate control of acid secretion.
The duration of treatment for Zollinger-Ellison syndrome and other pathological conditions is not limited and depends on the clinical need.
Patients with severely impaired liver function should not exceed the daily dose of Zolopent 20 mg (pantoprazole preparations should be used in an appropriate dosage). Patients with moderate and severe hepatic impairment should not use Zolopent for the eradication of H. pylori in combination therapy, since there is currently no data on the efficacy and safety of such use for this category of patients.
For patients with impaired renal function, dose adjustment of Zolopent is not necessary. Patients with impaired renal function should not use Zolopent for the eradication of H. pylori in combination therapy, since there is currently no data on the efficacy and safety of such use for this category of patients.
Elderly patients do not require dose adjustment.
Zolopent is not recommended for children under 12 years of age, since the data on the safety and efficacy of pantoprazole for this age group are limited.
Symptoms of an overdose of Zolopent in humans have not been described. In case of an overdose with signs of intoxication, general detoxification measures should be taken.
On the part of the blood and lymphatic system:
agranulocytosis, leukopenia, thrombocytopenia, pancytopenia.
From the immune system:
hypersensitivity reactions (including anaphylactic reactions, anaphylactic shock).
Metabolism and metabolic disorders:
hyperlipidemia and increased lipid levels (triglycerides, cholesterol); changes in body weight, hyponatremia, hypomagnesemia.
sleep disorders, depression (and all its complications), disorientation (and all its complications), hallucinations, confusion (especially in patients with a tendency to these disorders, as well as exacerbation of these symptoms, if any). From the nervous system: headache, dizziness, taste disorders.
From the side of the organ of vision:
visual impairment / blurredness.
From the digestive tract:
diarrhea, nausea, vomiting, bloating, constipation, dry mouth, abdominal pain, discomfort.
From the hepatobiliary system:
increased levels of hepatic enzymes
(transaminases, gamma-glutamine transferase), increased bilirubin levels, damage to hepatocytes, 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 and connective tissue: arthralgia, myalgia, fractures of the hip, wrist, spine.
On the part of the kidneys and urinary system:
From the reproductive system and mammary glands:
asthenia, fatigue, malaise, fever, peripheral edema.
Store Zolopent in its original packaging at a temperature not exceeding 25 ° C. Keep Zolopent out of the reach of children.