Ulcernil
Ulcernil: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Drug interactions
- 14. Analogs
- 15. Terms and conditions of storage
- 16. Terms of dispensing from pharmacies
- 17. Reviews
- 18. Price in pharmacies
Latin name: Ulcernil
ATX code: A02BC04
Active ingredient: Rabeprazole (Rabeprazole)
Manufacturer: San Pharmaceutical Industries, Ltd. (Sun Pharmaceutical Industries, Ltd.) (India)
Description and photo update: 2020-11-03
Prices in pharmacies: from 344 rubles.
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Ulcernil is a proton pump inhibitor (PPI) that effectively reduces the secretory function of the gastric glands.
Release form and composition
Dosage form - enteric tablets, film-coated: yellow, biconvex, round, smooth on one side; dosage 10 mg - printed “R” on the other side; dosage 20 mg - "RA" (7 pcs. in blisters; in a cardboard box 2 or 4 blisters and instructions for the use of Ulcernil).
Composition of 1 tablet:
- active substance: rabeprazole sodium - 10 or 20 mg;
- auxiliary components (intragranular layer): hyprolosis, low-substituted hyprolosis, heavy magnesium oxide, mannitol;
- auxiliary components (extragranular layer): magnesium stearate, mannitol, low-substituted hyprolose;
- core shell: hyprolose, light magnesium oxide, ethyl cellulose;
- enteric coating: titanium dioxide, talc, diacetylated monoglyceride, hypromellose phthalate, iron oxide dye (yellow);
- red ink: Opacode Sl-1666 Red [SDA 3A alcohol 27CFR, titanium dioxide, propylene glycol, n-butyl alcohol, dye red charming AC, glazed shellac (20% esterified) in ethanol].
Pharmacological properties
Pharmacodynamics
Rabeprazole sodium is one of the antisecretory substances (a group of benzimidazole derivatives). Through specific inhibition of the enzyme hydrogen-potassium adenosine triphosphatase (H + / K + -ATPase) on the secretory surface of the parietal cells of the stomach, the substance inhibits the secretion of gastric juice. Because the H + / K + -ATPase enzyme is a protein complex that functions as a proton pump, Ulcernil is a proton pump inhibitor (PPI) and blocks the last stage of acid production. This effect depends on the dose of the drug and serves to suppress basal and stimulated acid secretion, regardless of the stimulus. The anticholinergic effect does not belong to the properties of rabeprazole sodium.
After oral administration of a 20 mg tablet, the development of an antisecretory effect is observed for 1 hour. 23 hours after taking the first dose, inhibition of basal and stimulated acid secretion is 69% and 82%, respectively, it lasts up to 48 hours. This duration of pharmacodynamic action is higher than predicted by half-life (about 1 hour). This effect can be explained by the long -term binding of the substance to the H + / K + -ATPase of gastric parietal cells. After 3 days of taking the drug, the magnitude of its inhibitory effect on acid secretion reaches a plateau. When the therapy is canceled, secretory activity is restored within 1-2 days.
In ongoing clinical trials, patients received tablets of 10 or 20 mg every day for a period of up to 43 months. In the range of the first 2–8 weeks, an increase in the level of gastrin in blood plasma was noted, which reflects an inhibitory effect on acid secretion. The gastrin content returned to its initial values in most cases within 1-2 weeks after the withdrawal of Ulcernil.
The obtained samples from the study of gastric biopsy from the fundus and antrum from 500 patients taking rabeprazole sodium or a reference drug for 8 weeks did not show stable changes in the spread of Helicobacter pylori infection, the frequency of atrophic gastritis, intestinal metaplasia, the severity of gastritis and the morphological structure of enterochromaffin-like cells …
In 400 volunteers who received the drug at a dose of 10 or 20 mg per day for a period of up to 1 year, the incidence of hyperplasia was low and comparable to that for omeprazole (20 mg per 1 kg of body weight). There were no cases of carcinoid neoplasms or adenomatous changes noted in rats.
Currently, the systemic effects of Ulcernil in relation to the respiratory, cardiovascular and central nervous systems have not been recorded. Oral administration of 20 mg tablets per day for 2 weeks does not lead to a change in the level of parathyroid, growth hormone, luteinizing and follicle-stimulating hormones, aldosterone, renin, glucagon, prolactin, testosterone, estrogen and cortisol, as well as carbohydrate metabolism and thyroid function.
Pharmacokinetics
Rabeprazole is characterized by a rapid rate of absorption from the intestine. The maximum plasma concentration (C max) is observed 3.5 hours after oral administration of 20 mg of the substance. Changes in its maximum content in blood plasma and the area under the concentration-time curve (AUC) are linear in the dose range of 10–40 mg. The absolute bioavailability after taking 20 mg of the drug orally in comparison with its intravenous administration is approximately 52%. With repeated administration of Ulcernil, the indicator does not change.
The half-life of blood plasma in healthy individuals is about 1 hour (varies from 0.7 to 1.5 hours), and the total clearance is 3.8 ml per minute per 1 kg of body weight. Against the background of chronic liver damage, AUC increases by 2 times in comparison with this indicator in healthy volunteers, which indicates a decrease in the first pass metabolism, the half-life from blood plasma is increased by 2–3 times.
The absorption of the drug does not depend on the time of application during the day and antacids. Simultaneous intake of fatty foods slows down its absorption by 4 hours or more, but neither the degree of absorption nor C max changes.
The degree of binding of a substance to blood plasma proteins in humans is approximately 97%.
After a single oral dose of 20 mg of the drug in healthy people, 14 C-labeled sodium rabeprazole in unchanged form was not observed in the urine. Almost 90% of the substance is excreted in the urine, mostly in the form of two metabolites - the conjugate of mercapturic acid (M5) and carboxylic acid (M6), as well as in the form of two unknown metabolites, which were identified during toxicological analysis. The remainder of the dose taken is excreted in the feces.
The total excretion is 99.8%, which indicates a small excretion of drug metabolites in the bile. The main metabolite of sodium rabeprazole is thioether (M1), the only active metabolite is desmethyl (M3), which, however, was detected in low concentrations in only one volunteer after 80 mg of the drug.
Against the background of stable renal failure in the terminal stage, in which maintenance hemodialysis is required (creatinine clearance <5 ml per minute per 1.73 m 2), excretion of the substance was similar to that in healthy individuals. Its half-life averaged 0.82 hours in healthy volunteers, 0.95 during hemodialysis and 3.6 hours after hemodialysis. The clearance of rabeprazole sodium in kidney pathologies requiring hemodialysis was almost 2 times higher than that in healthy volunteers.
Patients with chronic compensated liver cirrhosis tolerate rabeprazole sodium in a daily dose of 20 mg, but their C max and AUC are doubled by 50% in comparison with healthy individuals of the corresponding sex.
Elimination of Ulcernil in elderly patients is somewhat slowed down. After 7 days of using tablets in a daily dose of 20 mg, AUC in elderly patients was almost 2 times higher, and Cmax was increased by 60% in comparison with young healthy volunteers. No signs of accumulation of the substance were observed.
With a slow metabolism of CYP2C19, after 1 week of application of rabeprazole in a daily dose of 20 mg, AUC increases 1.9 times, and the half-life is 1.6 times compared with the same parameters in fast metabolizers, while C max increases by 40% …
Indications for use
Ulcernil tablets in a dosage of 10 mg are prescribed for the treatment of manifestations of dyspepsia associated with increased acidity of gastric juice, including symptoms of gastroesophageal reflux disease (acid belching, heartburn).
Ulcernil 20 mg tablets are used to treat the following conditions / diseases:
- exacerbation of duodenal ulcer;
- exacerbation of gastric ulcer, anastomotic ulcer;
- reflux esophagitis, peptic ulcer and erosive gastroesophageal reflux disease (GERD);
- GERD (for maintenance treatment);
- non-erosive gastroesophageal reflux disease (NERD);
- Zollinger-Ellison syndrome or other conditions characterized by pathological hypersecretion;
- peptic ulcer (for the eradication of Helicobacter pylori in combination with appropriate antibiotic therapy).
Contraindications
Absolute:
- pregnancy;
- lactation period;
- children and adolescents up to 12 and 18 years old (for tablets 20 and 10 mg, respectively);
- established hypersensitivity to the components of the drug.
Relative (taking Ulcernil requires special care and careful medical supervision): severe renal / hepatic failure; children's age (for tablets 10 mg).
Ulcernil, instructions for use: method and dosage
Ulcernil tablets are intended for oral administration.
A single dose should be taken in the morning, before meals, whole, without crushing or chewing the tablets. It was found that food and the time of day have no effect on the activity of rabeprazole sodium, but the recommended time of administration of the drug (morning) promotes better patient compliance with the therapy regimen.
Ulcernil 10 mg tablets are taken 1 pc. in a day. If there is no effect during the first 3 days of treatment, a specialist examination is necessary. The maximum duration of therapy without consulting a doctor should not exceed 14 days.
The recommended dosing regimen for Ulcernil 20 mg tablets, depending on the indication:
- exacerbation of gastric ulcer, anastomotic ulcer: 1 pc. in a day. In most cases, 42 days of treatment is enough, however, the duration of the drug intake, if necessary, can be increased by another 42 days;
- exacerbation of duodenal ulcer: 1 pc. per day for a period from 14 to 28 days. If necessary, it is allowed to increase the duration of taking the drug by another 28 days;
- GERD, reflux esophagitis: 1 pc. per day for 28-56 days, with a possible increase in the duration of taking Ulcernil by another 56 days (if necessary);
- supportive treatment for GERD: 1 pc. in a day. The duration of therapy is set individually, depending on the patient's condition;
- NERD without esophagitis: 1 pc. in a day. The duration of Ulcernil's use depends on the patient's condition. In cases where, after 28 days of treatment, the manifestations of pathology do not disappear, an additional study of the patient should be carried out. After the disappearance of symptoms in order to prevent their subsequent development, the drug should be taken on demand once a day;
- Zollinger-Ellison syndrome and other conditions characterized by pathological hypersecretion: the dose of rabeprazole is selected on an individual basis. The initial dose is 3 pcs. per day, in the future it is increased to 5 pcs. per day at one time or 3 pcs. 2 times a day. In some cases, fractional dosing is preferable. Taking Ulcernil continues as clinically necessary. In some patients, the duration of therapy was up to 1 year;
- eradication of Helicobacter pylori: 1 pc. 2 times a day according to a specific schedule with an appropriate combination of antibacterial agents. The duration of treatment is 7 days.
In renal / hepatic insufficiency, dose adjustment of Ulcernil is not required. The content of rabeprazole sodium in the blood in patients with mild to moderate hepatic insufficiency is usually higher than in healthy individuals. With extreme caution, the drug should be prescribed for severe hepatic impairment.
For elderly patients, dose adjustments are not performed.
The efficacy and safety of the use of Ulcernil 20 mg tablets in children aged 12 years and older for short-term (up to 8 weeks) treatment of GERD has been confirmed by extrapolation of the results of adequate and well-controlled studies supporting the therapeutic efficacy of Ulcernil for adults, and safety and pharmacokinetic studies for children. In patients aged 12 years and older, the drug is used in a daily dose of 20 mg for a period of up to 8 weeks. The safety and efficacy profile of rabeprazole sodium for the treatment of GERD and other conditions / diseases in children under 12 years of age has not been established.
Side effects
Ulcernil is usually well tolerated by patients, as evidenced by the experience of clinical trials. Adverse events are generally mild or moderate, and are transient.
During clinical trials, side effects were noted in the form of peripheral edema, rash, dizziness, headache, dry mouth, constipation, flatulence, diarrhea, and abdominal pain.
Possible side effects of Ulcernil [> 10% - very common; (> 1% and 0.1% and 0.01% and <0.1%) - rarely; <0.01% - very rare; frequency cannot be established from the available data - with an unspecified frequency]:
- immune system: rarely - acute systemic allergic reactions;
- blood and lymphatic system: rarely - leukopenia, neutropenia, thrombocytopenia;
- metabolism and nutrition: rarely - hypomagnesemia;
- liver and biliary tract: increased activity of liver enzymes; rarely - hepatic encephalopathy, jaundice, hepatitis;
- kidneys and urinary tract: very rarely - interstitial nephritis;
- skin and subcutaneous tissue: rarely - urticaria, bullous rash; very rarely - Steven-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme;
- musculoskeletal system: rarely - arthralgia, myalgia;
- reproductive system: very rarely - gynecomastia.
There were no changes in laboratory parameters. Based on the available data from post-registration studies, the use of PPIs is accompanied by an increased risk of fractures.
Overdose
There are few reports of intentional or accidental overdose of rabeprazole. Cases of severe overdose have not been recorded.
Therapy: symptomatic and supportive. The specific antidote is unknown. Since Ulcernil binds well to blood plasma proteins, it is not excreted through dialysis.
special instructions
A positive response of the patient to treatment with Ulcernil does not exclude the presence of malignant tumors in the stomach.
It should be borne in mind that the tablets must be swallowed whole, not crushed or chewed. It was found that the activity of the drug does not depend on the regimen and diet, as well as the time of day.
The study of the appointment of Ulcernil for mild or moderate liver dysfunction did not find any special differences in the frequency of adverse events from that in age-matched healthy volunteers. However, despite this, it is important to be careful when first administering rabeprazole sodium to patients with severe hepatic dysfunction. AUC of the substance in such cases is approximately 2 times higher than in healthy individuals.
Correction of the dosage regimen of Ulcernil with impaired renal or liver function is not carried out.
PPI use for at least 3 months is rarely associated with asymptomatic and symptomatic hypomagnesemia. Typically, reports of the development of this condition were received 1 year after treatment. Serious adverse events included seizures, arrhythmias, and tetany. In most cases, hypomagnesemia therapy was required, which included magnesium replacement and withdrawal of PPIs. In patients who plan to take Ulcernil for a long time, as well as taking PPIs in combination with digoxin or drugs that can cause hypomagnesemia (for example, diuretics), medical personnel should monitor the magnesium content before starting PPI use and during treatment.
Ulcernil should not be taken in combination with other drugs that lower acidity (for example, PPI or H2-receptor blockers).
Observational evidence suggests that PPI use may increase the risk of osteoporosis-related fractures of the spine, wrist, or hip. The likelihood of fractures was increased with long-term high doses of PPIs (1 year or more).
The combined use of PPIs with methotrexate, especially in high doses, according to the literature, can lead to an increase in the content of the latter and / or its metabolite (hydroxymethotrexate) and the half-life, which is sometimes accompanied by manifestations of toxicity. If high doses of methotrexate are needed, temporary discontinuation of PPIs may be considered.
PPI use can increase the risk of gastrointestinal infections, including Clostridium difficile.
With short-term symptomatic use of Ulcernil for the treatment of symptoms of NERD and GERD (for example, heartburn) without a prescription, the patient should seek medical help in the following cases:
- the use of drugs to relieve symptoms of heartburn and digestive disorders for 28 days or more;
- the emergence of new or change in previously noted signs in patients aged 55 years;
- a history of stomach ulcers or gastric surgery, jaundice, etc. (including impaired liver and kidney function);
- unintentional weight loss, persistent vomiting or vomiting of blood and stomach contents, pain when swallowing, dysphagia, bleeding in the gastrointestinal tract, anemia.
Patients suffering from repeated manifestations of indigestion or heartburn for a long time should be under regular medical supervision. Patients over the age of 55 who receive daily medication to relieve symptoms of digestive disorders and heartburn should inform their doctor about this.
In combination with Ulcernil, you cannot take other drugs that lower acidity, for example, PPIs or H2 receptor blockers.
When treating with other drugs, patients are advised to consult with a pharmacist or doctor prior to taking over-the-counter rabeprazole sodium.
Before starting therapy with Ulcernil, patients should inform their doctor if an endoscopic examination is prescribed.
The drug should be avoided prior to the urea breath test.
For severely impaired liver function, it is important for patients to see a doctor for short-term symptomatic treatment of signs of NERD and GERD (for example, heartburn) before using over-the-counter tablets.
Influence on the ability to drive vehicles and complex mechanisms
If during the period of therapy with Ulcernil, drowsiness is noted, drive vehicles, as well as perform other work associated with increased attention, should be used with caution.
Application during pregnancy and lactation
Ulcernil is not prescribed during pregnancy and during breastfeeding, since there is no data on the safety of its use in these cases.
Reproductive studies conducted in rabbits and rats did not reveal manifestations of impaired fertility or fetal developmental defects caused by Ulcernil. However, in small amounts in rats, rabeprazole penetrated the placental barrier. The drug should not be used during pregnancy, unless the expected therapeutic effect for the mother is higher than the potential harm to the fetus.
It has not been established whether the substance is excreted in breast milk, since appropriate studies have not been carried out in women. However, rabeprazole has been found in the milk of lactating rats, which is why it is not recommended for use during lactation in women.
Pediatric use
The use of Ulcernil in the form of tablets of 10 and 20 mg in children under the age of 18 and 12 years (respectively) is contraindicated.
For children and older adolescents, 20 mg tablets should be used with caution, as the safety and efficacy profile is not well understood.
With impaired renal function
Severe renal failure is a relative contraindication to the use of Ulcernil.
For violations of liver function
Severe liver failure is a relative contraindication to the use of Ulcernil.
Drug interactions
Like other PPIs, rabeprazole is metabolized in the liver with the participation of the cytochrome P450 (CYP450) system. In vitro studies on human liver microsomes have shown that the substance is metabolized by isoenzymes CYP3A4 and CYP2C19. At the same time, no pharmacokinetic or clinically significant interactions with other drugs metabolized by this system, such as diazepam, theophylline, phenytoin and warfarin, were observed in healthy individuals.
A four-way crossover study of combination treatment with rabeprazole and antibiotics was conducted in 16 healthy volunteers. They received daily 20 mg of rabeprazole, 1000 mg of amoxicillin and 500 mg of clarithromycin, or a combination of the three. The AUC and C max of clarithromycin and amoxicillin were similar when comparing combination therapy with monotherapy. These indicators for Ulcernil increased by 11% and 34%, respectively, and for the active metabolite of clarithromycin (14-hydroxyclarithromycin) increased by 42% and 46%, respectively, for combined use compared to monotherapy. This increase in rates for rabeprazole and clarithromycin is not clinically significant.
Rabeprazole sodium causes sustained and prolonged suppression of gastric acid secretion. This can lead to interactions with substances whose absorption depends on the pH. In cases of simultaneous use with ketoconazole / digoxin, the absorption of each of them is accordingly reduced by 30% / increased by 22%. Based on this, some patients should be monitored to make a decision on the need to adjust the dose when using Ulcernil with the substances in question or other drugs, the absorption of which depends on the pH.
When combined treatment with atazanavir (300 mg) / ritonavir (100 mg) with omeprazole (40 mg once a day) or with atazanavir (400 mg) with lansoprazole (60 mg once a day) in healthy individuals, there was a significant decrease in atazanavir exposure. Its absorption is pH dependent. Although combined use with rabeprazole has not been studied, similar results are expected for other PPIs as well. Thus, concomitant administration of atazanavir with PPIs, including Ulcernil, is contraindicated.
There were no clinically significant interactions of rabeprazole sodium with aluminum or magnesium hydroxide in the form of a gel, as well as with a diet depleted in fat. The use of Ulcernil with food enriched with fats can slow down its absorption up to 4 hours or more, however, C max and AUC do not change.
According to an in vitro experiment using human liver microsomes, rabeprazole inhibits the metabolism of cyclosporin with an IC50 of 62 μmol, that is, at a concentration 50 times higher than C max for healthy individuals after 20 days of taking 20 mg of the drug. The degree of inhibition is similar to that of omeprazole at equivalent concentrations.
The available reports of side effects, data from published pharmacokinetic studies and retrospective analyzes suggest that the use of a combination of PPI and methotrexate, especially in high doses, may be accompanied by an increase in the content of the latter and / or its metabolite in blood plasma and increase the half-life. However, there have been no specific studies of the interaction between PPI and methotrexate.
Analogs
The analogues of Ulcernil are Khairabezol, Rabelok, Zulbeks, Rabeprazol-SZ, Rabeprazole, Rabeprazole-VERTEX, Ulblok, Bereta, Pariet, Razo, Noflux, Ontaym, Rabiet.
Terms and conditions of storage
Store at temperatures up to 25 ° C. Keep out of the reach of children.
The shelf life is 3 years.
Terms of dispensing from pharmacies
10 mg tablets are available without a prescription, 20 mg tablets are available with a prescription.
Reviews about Ulzernil
There are few reviews about Ulcernil, confirming the effectiveness of the drug.
In one case, the use of tablets in a dosage of 10 mg was accompanied by the development of side effects from the stomach. Among the shortcomings, the rare presence of the drug in the pharmacy network is also noted.
The price of Ulcernil in pharmacies
The approximate price for Ulcernil for a package containing 28 tablets is: dosage 10 mg - 326 rubles; dosage 20 mg - 436 rubles.
Ulcernil: prices in online pharmacies
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Drug name Price Pharmacy |
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Ulcernil intestinal tablets. p.p. 10mg 28 pcs. 344 r Buy |
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Ulcernil 10 mg 28 pcs. 344 r Buy |
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Ulcernil 20 mg 28 pcs. 437 r Buy |
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Ulcernil intestinal tablets. p.p. 20mg 28 pcs. RUB 470 Buy |
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
