Barol 10

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT BAROLE 10, BAROLE 20 (BAROLE 10, BAROLE 20)

Composition:

Active substance: rabeprazole;

1 capsule contains 10 mg or 20 mg of sodium rabeprazole (in the form of enteric-coated pellets);

Excipients: neutral pellets (No. 16–18) coated with magnesium carbonate; hypromellose; sodium hydroxide; light magnesium carbonate; talc; methacrylic acid copolymer (type C); macrogol 6000; titanium dioxide (E 171); iron oxide red (E 172); iron oxide black (E 172).

Pharmaceutical form. Enteric-coated capsules.

Main physicochemical properties:

10 mg capsules: hard, opaque, red/white gelatin capsules No. 5, containing spherical or oval brown-colored pellets;

20 mg capsules: hard, opaque, red/brown gelatin capsules No. 3, containing spherical or oval brown-colored pellets.

Pharmacotherapeutic group.

Drugs affecting the digestive tract and metabolism. Drugs for treatment of disorders related to acid imbalance. Antiulcer drugs and drugs for treatment of gastroesophageal reflux disease. Proton pump inhibitors. Rabeprazole. ATC code A02BC04.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action. Sodium rabeprazole belongs to the class of antisecretory compounds substituted benzimidazoles. It has no anticholinergic properties and is not a histamine H2-receptor antagonist, but it inhibits gastric acid secretion by specifically inhibiting the H+/K+-ATPase enzyme at the secretory surface of gastric parietal cells (the acid or proton pump). The effect is dose-dependent and results in inhibition of both basal and stimulated acid secretion, regardless of the stimulus. Animal studies have shown that after administration, sodium rabeprazole rapidly disappears from both plasma and gastric mucosa. Sodium rabeprazole has weakly basic properties, is rapidly absorbed in all doses, and accumulates in parietal cells. Sodium rabeprazole is converted into its active sulfenamide form via protonation and thereby reacts with accessible cysteine residues of the proton pump.

After oral administration of 20 mg of sodium rabeprazole, the antisecretory effect begins within 1 hour and reaches its maximum within 2–4 hours. The inhibition of basal acid secretion and food-stimulated acid secretion 23 hours after the first dose of sodium rabeprazole was 69% and 82%, respectively, with the duration of this effect lasting up to 48 hours. The acid-suppressing efficacy of sodium rabeprazole slightly increases during daily administration of 1 tablet, but stable suppression of acid secretion is achieved within 3 days of starting treatment. After discontinuation of sodium rabeprazole, secretory activity returns to normal within 2–3 days.

Reduction of gastric acidity, regardless of the cause, including proton pump inhibitors such as rabeprazole, increases the number of bacteria in the gastrointestinal tract. Treatment with proton pump inhibitors increases the risk of gastrointestinal infections such as Salmonella, Campylobacter, and Clostridium difficile.

In clinical studies, patients received 10 or 20 mg of sodium rabeprazole once daily for 4–36 months. During the first 2–8 weeks of therapy, serum gastrin concentration increased, reflecting acid secretion inhibition. Gastrin concentrations generally returned to baseline levels within 1–2 weeks after discontinuation of treatment.

Examination of biopsy samples from the gastric fundus and antrum in patients who received rabeprazole or a comparator drug for 8 weeks revealed no histological changes, no significant gastritis, no increased frequency of atrophic gastritis, intestinal metaplasia, or spread of H. pylori infection. Long-term treatment for up to 36 months in more than 250 patients showed no significant changes in these parameters.

Currently, there are no data on systemic effects on the central nervous system, cardiovascular system, or respiratory system caused by sodium rabeprazole. Oral administration of 20 mg of sodium rabeprazole daily for 2 weeks did not affect thyroid function, carbohydrate metabolism, or plasma concentrations of parathyroid hormone, cortisol, estrogen, testosterone, prolactin, cholecystokinin, secretin, glucagon, follicle-stimulating hormone, luteinizing hormone, renin, aldosterone, or growth hormone.

Studies in healthy volunteers showed no clinically significant interactions between rabeprazole and amoxicillin.

Rabeprazole has no negative effect on plasma levels of amoxicillin and clarithromycin when administered concomitantly for the eradication of H. pylori infection in the upper gastrointestinal tract.

During treatment with antisecretory drugs, serum gastrin levels increase in response to reduced acid secretion. Additionally, due to decreased gastric acidity, serum chromogranin A levels increase. Elevated chromogranin A levels may affect diagnostic testing for neuroendocrine tumors.

Available published data indicate that proton pump inhibitors should be discontinued 2 weeks to 5 days before measuring chromogranin A levels to allow levels to return to reference values if elevated during proton pump inhibitor therapy.

Pharmacokinetics.

Absorption. Barol is a medicinal product containing sodium rabeprazole as the active substance, formulated as enteric-coated capsules. This dosage form is necessary because sodium rabeprazole is susceptible to degradation by gastric acid. Absorption of sodium rabeprazole begins only after the capsule passes through the stomach. Sodium rabeprazole is rapidly absorbed from the intestine. Peak plasma concentrations (Cmax) of rabeprazole are reached approximately 3.5 hours after a 20 mg dose. Peak plasma concentrations (Cmax) and area under the concentration-time curve (AUC) of rabeprazole are linear within the dose range of 10–40 mg. Absolute bioavailability after oral administration of 20 mg (compared to intravenous administration) is approximately 52%, primarily due to first-pass metabolism. Furthermore, bioavailability does not increase with repeated administration of sodium rabeprazole. In healthy volunteers, the plasma elimination half-life is approximately 1 hour (ranging from 0.7 to 1.5 hours), and total clearance is estimated at 283 ± 98 mL/min. No clinically significant interaction with food has been observed. Neither the type of food nor the time of day affects the absorption of sodium rabeprazole.

Distribution. In humans, the plasma protein binding of sodium rabeprazole is approximately 97%.

Metabolism and excretion. Like other proton pump inhibitors, rabeprazole is metabolized by the hepatic cytochrome P450 (CYP450) drug metabolism system. In vitro studies using human liver microsomes have shown that sodium rabeprazole is metabolized by CYP450 isoenzymes (CYP2C19 and CYP3A4). At expected human plasma concentrations, rabeprazole does not induce or inhibit CYP3A4. However, in vitro results cannot always be extrapolated to in vivo situations. These results suggest that interaction between rabeprazole and cyclosporine is not expected. In humans, the main metabolites present in plasma are thioether (M1) and carboxylic acid (M6), while minor metabolites present at low concentrations include sulfone (M2), dimethylthioether (M4), and mercapturic acid conjugate (M5). Only the dimethyl metabolite (M3) has slight antisecretory activity, but it is not present in plasma.

After a single 20 mg dose of 14C-labeled sodium rabeprazole, unchanged rabeprazole was not detected in urine. Approximately 90% of the administered dose was eliminated in urine, primarily as two metabolites: mercapturic acid conjugate (M5) and carboxylic acid (M6). The remainder of the dose was recovered in feces.

Gender differences. Since the single 20 mg dose of sodium rabeprazole is adjusted according to body weight and height, gender does not influence pharmacokinetic parameters.

Renal impairment. In patients with end-stage chronic renal failure undergoing maintenance hemodialysis (creatinine clearance < 5 mL/min/1.73 m²), the disposition of sodium rabeprazole was very similar to that in healthy volunteers. AUC and Cmax of sodium rabeprazole were approximately 35% higher in these patients compared to healthy volunteers. The mean elimination half-life was 0.82 hours in healthy volunteers, 0.95 hours in hemodialysis patients, and 3.6 hours in post-dialysis patients. Drug clearance in hemodialysis patients with renal impairment was approximately twice that in healthy volunteers.

Hepatic impairment. After a single 20 mg dose of sodium rabeprazole in patients with moderate chronic liver disease, AUC was doubled, and the elimination half-life of rabeprazole was 2–3 times longer compared to healthy volunteers. Thus, with daily administration of 20 mg for 7 days, AUC should increase by at least 1.5-fold, and changes in peak plasma concentrations (Cmax) should be up to 1.2-fold. The elimination half-life of sodium rabeprazole in patients with liver disease was 12.3 hours compared to 2.1 hours in healthy volunteers. Pharmacodynamic response (gastric pH-metry) was similar between both patient groups in terms of therapeutic parameters.

Elderly patients. Elimination of sodium rabeprazole is slightly reduced in elderly patients. After 7 days of 20 mg daily dosing, AUC was approximately twice as high, Cmax increased by 60%, and elimination half-life increased by 30% compared to young healthy volunteers. However, there were no signs of sodium rabeprazole accumulation.

CYP2C19 polymorphism. When administering a daily dose of 20 mg of rabeprazole for 7 days, patients with slow CYP2C19 metabolism had AUC and elimination half-life values approximately 1.9 and 1.6 times higher, respectively, compared to patients with rapid metabolism; meanwhile, Cmax increased by only 40%.

Clinical characteristics.

Indications.

• Active duodenal peptic ulcer;
• active benign gastric ulcer;
• erosive or ulcerative gastroesophageal reflux disease (GERD);
• long-term treatment of gastroesophageal reflux disease (maintenance therapy for GERD);
• symptomatic treatment of moderate to very severe gastroesophageal reflux disease (symptomatic treatment of GERD);
• Zollinger–Ellison syndrome;
• in combination with appropriate antibacterial therapeutic regimens for eradication of Helicobacter pylori in patients with gastric and duodenal peptic ulcers.

Contraindications.

Hypersensitivity to rabeprazole, substituted benzimidazoles, or to any other component of the medicinal product. Concomitant use with atazanavir. Pregnancy or breastfeeding period.

Interaction with other medicinal products and other forms of interaction.

CYP450 system

Rabeprazole sodium is metabolized by the hepatic CYP450 enzyme system, specifically CYP2C19 and CYP3A4.

Studies have shown that rabeprazole sodium does not have pharmacokinetic or clinically significant interactions with warfarin, phenytoin, theophylline, or diazepam, each of which is metabolized by CYP450.

Interactions due to inhibition of gastric acid secretion

Rabeprazole sodium causes a strong and prolonged reduction in gastric acid production. Therefore, rabeprazole may interact with drugs whose absorption is dependent on the pH of gastric contents. Concomitant use of rabeprazole sodium with ketoconazole or itraconazole may lead to decreased plasma concentrations of the latter, while co-administration with digoxin may lead to increased digoxin concentration. Therefore, individual patients receiving these agents concomitantly with Barol should be monitored by a physician to determine whether dose adjustment is necessary.

Antacids

During clinical trials, patients received antacids as needed concomitantly with Barol; in a specific study, no interaction between the drug and antacids such as aluminum or magnesium hydroxide was observed.

Atazanavir

Concomitant administration of atazanavir 300 mg / ritonavir 100 mg with omeprazole (40 mg once daily) or atazanavir 400 mg with lansoprazole (60 mg once daily) in healthy volunteers resulted in a significant reduction in atazanavir exposure. Atazanavir absorption is pH-dependent. Although no studies have been conducted, similar results are expected with other proton pump inhibitors. Proton pump inhibitors, including rabeprazole, should not be used in combination with atazanavir (see section "Special precautions for use").

Methotrexate

Case reports of adverse reactions, published population pharmacokinetic studies, and retrospective analyses suggest that concomitant use of methotrexate and proton pump inhibitors (particularly at high doses) may lead to increased serum levels of methotrexate and/or its metabolite hydroxymethotrexate. However, no formal studies have been conducted.

Clopidogrel

Concomitant administration of clopidogrel and rabeprazole in healthy volunteers had no clinically significant effect on concentrations of the active metabolite of clopidogrel. Dose adjustment is not required.

Food

Studies have shown that consumption of a low-fat meal does not affect the absorption of rabeprazole sodium. Administration of rabeprazole sodium with a fatty meal may delay absorption by 4 hours or more, but maximum concentration and extent of absorption remain unchanged.

Cyclosporine

In vitro studies have shown that rabeprazole sodium inhibits the metabolism of cyclosporine. This level of inhibition is comparable to that observed with omeprazole.

Medicinal products not recommended for concomitant use with rabeprazole

Medicinal products that should be prescribed with caution

Special precautions for use.

Caution should be exercised when prescribing rabeprazole to patients with hypersensitivity to drugs. The risk of cross-hypersensitivity with other proton pump inhibitors or substituted benzimidazoles cannot be excluded.

Use in elderly patients

Rabeprazole is metabolized exclusively in the liver. Since hepatic physiological function may decline with age, adverse reactions may occur in elderly patients. Therefore, elderly patients should be closely monitored and dosing recommendations and treatment duration should be strictly followed.

Symptomatic improvement with rabeprazole treatment does not exclude the presence of gastric or esophageal malignancy; therefore, malignancy should be ruled out before initiating rabeprazole therapy.

Patients undergoing long-term treatment (especially those treated for more than 1 year) should be regularly monitored.

The risk of cross-hypersensitivity reactions when used concomitantly with other proton pump inhibitors or substituted benzimidazoles cannot be excluded.

Patients should be advised that Barol capsules must not be chewed or crushed but should be swallowed whole.

Rabeprazole is not recommended for use in children, as there is no experience with use in this patient population.

Blood abnormalities (thrombocytopenia and neutropenia) have been reported. In most cases, no other etiology was identified; hematological changes were uncomplicated and resolved after discontinuation of rabeprazole.

Abnormalities in liver enzymes have been observed both during clinical trials and in the post-marketing period. In most cases, no other etiology was identified; abnormalities were uncomplicated and resolved after discontinuation of rabeprazole.

During studies, no significant difference in the frequency of adverse effects was observed in patients with mild or moderate hepatic impairment compared to the control group matched for sex and age. Physicians should exercise caution when prescribing rabeprazole during the initial stages of therapy to patients with severe hepatic impairment, as clinical data on use in this patient group are lacking.

During rabeprazole treatment, periodic hematological and biochemical testing is recommended.

Concomitant use of atazanavir and rabeprazole is not recommended (see section "Interaction with other medicinal products and other forms of interaction").

Treatment with proton pump inhibitors, including rabeprazole, increases the risk of gastrointestinal infections such as Salmonella, Campylobacter, and Clostridium difficile (see section "Pharmacodynamics").

Risk of fractures

Proton pump inhibitors, particularly when used at high doses and for prolonged periods (more than 1 year), increase the risk of fractures of the hip, wrist, and spine, primarily in elderly patients or those with other risk factors. Observational studies suggest that proton pump inhibitors increase the overall risk of fractures by 10–40%. The risk may also be increased due to other factors. Patients at risk of osteoporosis should receive appropriate treatment and take vitamin D and calcium supplements.

Hypomagnesemia

Cases of severe hypomagnesemia have been reported in patients taking proton pump inhibitors for at least 3 months, mostly during a year of treatment. Severe manifestations of hypomagnesemia such as weakness, tetany, delirium, seizures, dizziness, and ventricular arrhythmia may occur unexpectedly and may go undetected. In most patients, hypomagnesemia resolved after discontinuation of proton pump inhibitors and magnesium replacement therapy.

In patients receiving long-term concomitant treatment with digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), serum magnesium levels should be monitored before and periodically during treatment.

Concomitant use of rabeprazole with methotrexate

Published data suggest that concomitant use of proton pump inhibitors and methotrexate (particularly at high doses) may increase serum levels of methotrexate and/or its metabolites, potentially leading to methotrexate-related toxicity. When high-dose methotrexate is required, consideration should be given to discontinuing proton pump inhibitor therapy.

Thyroid function

Monitoring of thyroid function is recommended during rabeprazole treatment.

Particularities of performing breath tests

Results of C-urea breath tests may be falsely negative during treatment with proton pump inhibitors such as rabeprazole and antibiotics such as amoxicillin, clarithromycin, and metronidazole. Therefore, breath tests to detect Helicobacter pylori should be performed no earlier than 4 weeks after discontinuation of these medications.

Treatment of non-erosive reflux disease is indicated in patients with recurrent reflux symptoms, particularly heartburn and acid regurgitation (approximately twice a week). Rabeprazole treatment may mask symptoms of malignancy (e.g., gastric or intestinal cancer) and other gastrointestinal disorders. Therefore, the presence of such conditions should be excluded before initiating rabeprazole therapy.

When rabeprazole is prescribed for a patient with non-erosive reflux disease, the physician should assess treatment efficacy after 2 weeks of therapy. If symptoms do not resolve, reflux disease may not be the cause. In such cases, the physician should consider alternative treatment approaches.

When rabeprazole is prescribed for Helicobacter pylori eradication, attention should be paid to contraindications, special precautions, clinically significant adverse reactions, and other warnings described in the instructions for medical use of other medications used for eradication.

According to some data, concomitant use of proton pump inhibitors and methotrexate (particularly at high doses) may increase serum levels of methotrexate and/or its metabolites, potentially leading to methotrexate-related toxicity. When high-dose methotrexate is required, consideration should be given to discontinuing proton pump inhibitor therapy.

Effect on vitamin B12 absorption

Rabeprazole sodium, like all drugs that suppress gastric acid secretion, may reduce absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be considered in patients with low body weight or risk factors for reduced vitamin B12 absorption during long-term treatment, or in the presence of relevant clinical symptoms.

Subacute cutaneous lupus erythematosus

Use of proton pump inhibitors has been associated with very rare cases of subacute cutaneous lupus erythematosus. If skin lesions develop, particularly in sun-exposed areas, accompanied by arthralgia, patients should seek immediate medical attention, and physicians should consider discontinuing rabeprazole sodium therapy. Development of subacute cutaneous lupus erythematosus after prior treatment with a proton pump inhibitor is a risk factor for its occurrence with other proton pump inhibitors (PPIs).

Renal function impairment

Acute tubulointerstitial nephritis (ATIN) has been observed in patients taking rabeprazole and may occur at any time during rabeprazole therapy (see section "Adverse reactions"). Acute tubulointerstitial nephritis may progress to renal failure.

If ATIN is suspected, rabeprazole should be discontinued and appropriate treatment initiated immediately.

Effect on laboratory test results

Elevated chromogranin A (CgA) levels may interfere with the detection of neuroendocrine tumors. To avoid this effect, treatment with the drug should be discontinued at least 5 days before measuring chromogranin A levels. If chromogranin A and gastrin levels have not returned to the reference range after initial measurement, the test should be repeated 14 days after discontinuation of PPI therapy.

Use during pregnancy or breastfeeding

Pregnancy. There are no data on the safety of rabeprazole use during pregnancy. Reproductive function studies in animals did not show evidence of impaired fertility or fetal harm associated with rabeprazole sodium; however, in rats, a small amount of the drug was found to cross the placenta.

Barol is contraindicated during pregnancy.

Breastfeeding. It is unknown whether rabeprazole sodium passes into human breast milk. Appropriate studies have not been conducted. Rabeprazole sodium passes into the breast milk of rats.

Therefore, Barol should not be prescribed to women during breastfeeding.

Ability to affect reaction speed when driving or operating machinery

Based on the pharmacodynamics of rabeprazole sodium and its known adverse effect profile, Barol is not expected to negatively affect the ability to drive or operate machinery. However, if drowsiness occurs, driving or operating machinery should be avoided.

Method of administration and dosage

Adults, including elderly patients

Active duodenal ulcer and active benign gastric ulcer: The recommended dose for these conditions is 20 mg once daily in the morning.

In most patients with active duodenal ulcer, healing occurs within 4 weeks. However, some patients may require an additional 4 weeks of treatment. In most patients with active benign gastric ulcer, healing occurs within 6 weeks, but some patients unresponsive to treatment may require an additional 6 weeks of therapy.

Erosive or ulcerative gastroesophageal reflux disease: The recommended dose for these conditions is 20 mg once daily for 4–8 weeks.

Long-term treatment of gastroesophageal reflux disease (maintenance therapy for GERD): For long-term treatment, maintenance doses of 10 mg or 20 mg once daily may be used (depending on treatment efficacy).

Symptomatic treatment of moderate to very severe GERD: Patients without esophagitis should be prescribed 10 mg once daily. If symptoms do not resolve after 4 weeks of treatment, further patient evaluation is required. Once symptoms resolve, symptom control can be maintained using an "on-demand" regimen: 10 mg once daily as needed.

Zollinger–Ellison syndrome: The dose should be individually adjusted.

The recommended initial dose is 60 mg once daily. The dose may be gradually increased up to 120 mg daily if clinically necessary. A single dose of up to 100 mg daily may be used. If a daily dose of 120 mg is required, the dose should be divided into two 60 mg doses. Treatment duration depends on clinical need.

Eradication of H. pylori: Patients with H. pylori should receive appropriate combinations of the drug with antibiotics. The recommended regimen is 7 days of:

• Barol 20 mg twice daily + clarithromycin 500 mg twice daily and amoxicillin 1 g twice daily.

For indications requiring once-daily dosing, tablets should be taken in the morning before meals. Although neither daytime administration nor food intake has demonstrated an effect on rabeprazole sodium activity, this regimen is considered more favorable for treatment. Tablets must not be chewed or crushed—they should be swallowed whole.

Renal and hepatic impairment. Patients with renal or hepatic impairment do not require dose adjustment. For treatment of patients with severe hepatic impairment, see section "Special precautions for use."

Children

Barol is not used in children, as there is no experience with use in this patient population.

Overdose

Experience with intentional or accidental overdose is limited. The maximum studied dose did not exceed 60 mg of rabeprazole sodium twice daily or 160 mg of rabeprazole sodium once daily. Symptoms occurring with overdose are generally minimal, typical of the known adverse effect profile, and resolve without further medical intervention. There is no specific antidote for Barol. Rabeprazole sodium is highly protein-bound and is not removed by dialysis. In case of overdose, symptomatic and supportive therapy should be administered.

Adverse Reactions

The most commonly reported adverse reactions were headache, diarrhea, abdominal pain, asthenia, flatulence, rash, and dry mouth. The observed adverse effects were generally mild, moderate, and transient.

The following adverse reactions have been reported during clinical trials and in the post-marketing period.

Frequency is defined as: common (> 1/100, < 1/10), uncommon (> 1/1000, < 1/100), rare (> 1/10000, < 1/1000), very rare (< 1/10000), not known (cannot be estimated from available data).

Infections and infestations:

common – infections.

Blood and lymphatic system disorders:

rare – neutropenia, leukopenia, thrombocytopenia, leukocytosis.

Immune system disorders:

rare – hypersensitivity^1,2.

Metabolism and nutrition disorders:

rare – anorexia;

not known – hyponatremia, hypomagnesemia⁴.

Psychiatric disorders:

common – insomnia;

uncommon – restlessness;

rare – depression;

not known – confusion.

Nervous system disorders:

common – headache, dizziness;

uncommon – somnolence.

Eye disorders:

rare – visual disturbances.

Vascular disorders:

not known – peripheral edema.

Respiratory, thoracic and mediastinal disorders:

common – cough, pharyngitis, rhinitis;

uncommon – bronchitis, sinusitis.

Gastrointestinal disorders:

common – diarrhea, vomiting, nausea, abdominal pain, constipation, flatulence, benign fundic gland polyp;

uncommon – dyspepsia, dry mouth, belching;

rare – gastritis, stomatitis, taste disturbance;

not known – microscopic colitis.

Hepatobiliary disorders:

rare – hepatitis, jaundice, hepatic encephalopathy³.

Skin and subcutaneous tissue disorders:

uncommon – rash, erythema²;

rare – pruritus, sweating, bullous reactions²;

very rare – erythema multiforme, toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome;

not known – subacute cutaneous lupus erythematosus⁴.

Musculoskeletal and connective tissue disorders:

common – non-specific pain, back pain;

uncommon – myalgia, leg cramps, arthralgia, fracture of the femoral neck, wrist or spine⁴.

Renal and urinary disorders:

uncommon – urinary tract infections;

rare – tubulointerstitial nephritis (with possible progression to renal failure).

Reproductive system disorders:

not known – gynecomastia.

General disorders and administration site conditions:

common – asthenia, influenza-like illness;

uncommon – chest pain, chills, pyrexia.

Investigations:

uncommon – increased liver enzymes³;

rare – weight gain.

1 Includes facial swelling, hypotension, and dyspnea.

2 Erythema, bullous reactions, and hypersensitivity reactions usually resolved after discontinuation of treatment.

3 Hepatic encephalopathy has been observed in isolated cases in patients with liver cirrhosis. Caution should be exercised when prescribing Pariet® to patients with severe hepatic impairment (see section "Special precautions for use").

4 See section "Special precautions for use".

Adverse reactions of clinical significance:

• Anaphylactic reactions and shock;
• Pancytopenia, leukopenia, agranulocytosis, and hemolytic anemia;
• Fulminant hepatitis, hepatic dysfunction, jaundice;
• Interstitial pneumonia;
• Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme;
• Acute renal failure, interstitial nephritis;
• Hyponatremia;
• Rhabdomyolysis.

Adverse reactions of clinical significance associated with proton pump inhibitors:

• Visual disturbances;
• Angioedema, bronchospasm;
• Confusion.

Reporting suspected adverse reactions after drug registration is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.

Shelf life. 2 years.

Storage conditions.

Store at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging.

10 capsules in a blister; 3 blisters in a cardboard box.

14 capsules in a blister; 1 blister in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

Inventia Healthcare Ltd, India.

Manufacturer's address.

F1-F1/1-F75/1, Edisenel Ambernath, M.I.D.C., Ambernath (East), 421506, District Thane, Maharashtra, India.

Marketing Authorization Holder.

Mega Lifesciences (Australia) Pty Ltd.

Address of the Marketing Authorization Holder.

60 National Avenue, Pakenham, Victoria 3810, Australia