Bereta^® (Tablets) Instructions for Use

Marketing Authorization Holder

Veropharm, JSC (Russia)

ATC Code

A02BC04 (Rabeprazole)

Active Substance

Rabeprazole (Rec.INN WHO registered)

Dosage Forms

Bereta®		Tablets, enteric-coated, 10 mg: 14, 20, or 28 pcs.
		Tablets, enteric-coated, 20 mg: 14, 20, or 28 pcs.

Dosage Form, Packaging, and Composition

Tablets, enteric-coated dark pink, round, biconvex; a cross-section shows two layers, the inner layer is white or white with a yellowish tint.

Excipients : mannitol (Mannogem EZ Spray Dried) – 28 mg, low-substituted hydroxypropyl cellulose (L-HPC) – 13 mg, hydroxypropyl cellulose (Klucel) – 4 mg, magnesium oxide (Marinco OH) – 44 mg, magnesium stearate – 1 mg.

Inner coating composition (subcoat) ethylcellulose – 1 mg, magnesium oxide (Marinco OH) – 1 mg.

Enteric coating composition acryl-iz pink [methacrylic acid copolymer, talc, titanium dioxide, sodium bicarbonate, sodium lauryl sulfate, aluminum lake based on dye azorubine, aluminum lake based on dye sunset yellow] – 14.72 mg, triethyl citrate – 1.28 mg.

7 pcs. – contour cell blisters (2) – cardboard packs.
7 pcs. – contour cell blisters (4) – cardboard packs.
10 pcs. – contour cell blisters (2) – cardboard packs.
14 pcs. – contour cell blisters (1) – cardboard packs.
14 pcs. – contour cell blisters (2) – cardboard packs.
14 pcs. – polymer bottles (1) – cardboard packs.
20 pcs. – polymer bottles (1) – cardboard packs.
28 pcs. – polymer bottles (1) – cardboard packs.

Tablets, enteric-coated yellow with a grayish tint, round, biconvex; a cross-section shows two layers, the inner layer is white or white with a yellowish tint.

Excipients : mannitol (Mannogem EZ Spray Dried) – 56 mg, low-substituted hydroxypropyl cellulose (L-HPC) – 26 mg, hydroxypropyl cellulose (Klucel) – 8 mg, magnesium oxide (Marinco OH) – 88 mg, magnesium stearate – 2 mg.

Inner coating composition (subcoat) ethylcellulose – 2 mg, magnesium oxide (Marinco OH) – 2 mg.

Enteric coating composition acryl-iz yellow [methacrylic acid copolymer, talc, titanium dioxide, colloidal silicon dioxide, sodium bicarbonate, sodium lauryl sulfate, dye yellow iron oxide] – 29.44 mg, triethyl citrate – 2.56 mg.

7 pcs. – contour cell blisters (2) – cardboard packs.
7 pcs. – contour cell blisters (4) – cardboard packs.
10 pcs. – contour cell blisters (2) – cardboard packs.
14 pcs. – contour cell blisters (1) – cardboard packs.
14 pcs. – contour cell blisters (2) – cardboard packs.
14 pcs. – polymer bottles (1) – cardboard packs.
20 pcs. – polymer bottles (1) – cardboard packs.
28 pcs. – polymer bottles (1) – cardboard packs.

Clinical-Pharmacological Group

H⁺-K⁺-ATPase inhibitor. Antiulcer drug

Pharmacotherapeutic Group

Gastric secretion reducing agent – proton pump inhibitor

Pharmacological Action

Proton pump inhibitor. Rabeprazole belongs to the class of antisecretory agents that are chemically substituted benzimidazoles. Rabeprazole inhibits the activity of the H+/K+ ATPase enzyme (proton pump), thereby blocking the final stage of hydrochloric acid synthesis. This effect is dose-dependent and leads to inhibition of both basal and stimulated secretion of hydrochloric acid, regardless of the stimulus. It does not possess anticholinergic properties.

Pharmacokinetics

After oral administration, it is absorbed from the gastrointestinal tract. At a dose of 20 mg, C_max is reached in 3.5 hours. Changes in C_max and AUC are linear (in the dose range from 10 to 40 mg). Absolute bioavailability is about 52% due to the first-pass effect through the liver. The bioavailability of rabeprazole does not increase with repeated administration.

Food intake and time of day do not affect the absorption of rabeprazole.

Plasma protein binding is 97%.

Rabeprazole sodium undergoes a first-pass effect. It is metabolized in the liver with the participation of CYP isoenzymes.

Main metabolites (thioether and carboxylic acid) and minor metabolites (sulfone, dimethyl thioether, and mercapturic acid conjugate) are present in low concentrations.

Indications

Adults aged 18 years and older: gastric ulcer in the acute phase and anastomotic ulcer; duodenal ulcer in the acute phase; erosive and GERD or reflux esophagitis, maintenance therapy for GERD, non-erosive GERD; Zollinger-Ellison syndrome and other conditions characterized by pathological hypersecretion; in combination with antibacterial therapy for the eradication of Helicobacter pylori in patients with peptic ulcer disease.

Adolescents aged 12 years and older: GERD.

ICD codes

Dosage Regimen

Administer orally, swallowing the tablet whole. Do not chew or crush the enteric-coated tablet.

Take in the morning, before a meal. The dosage is set individually based on the indication and treatment regimen.

For duodenal ulcer: 20 mg once daily for 4 weeks. For gastric ulcer: 20 mg once daily for 6 weeks.

For erosive GERD or reflux esophagitis: 20 mg once daily for 4-8 weeks. For long-term maintenance therapy of GERD: 10 mg or 20 mg once daily.

For non-erosive GERD: 10 mg once daily for 4 weeks. If symptoms persist, consider another 4 weeks.

For Zollinger-Ellison syndrome: start with 60 mg once daily. Adjust the dose individually; some patients require divided doses. Doses up to 100 mg daily or 60 mg twice daily have been used.

For Helicobacter pylori eradication: use as part of combination therapy. A common regimen is rabeprazole 20 mg twice daily with amoxicillin 1000 mg twice daily and clarithromycin 500 mg twice daily for 7 days.

For adolescents aged 12 years and older with GERD: 10 mg once daily for up to 8 weeks. For inadequate response, increase to 20 mg once daily.

No dose adjustment is required for elderly patients or those with mild to moderate renal or hepatic impairment. Use with caution in patients with severe hepatic impairment.

If a dose is missed, take it as soon as remembered. If it is near the time of the next dose, skip the missed dose. Do not double the dose to catch up.

Adverse Reactions

Immune system disorders: rarely – acute systemic allergic reactions.

Blood and lymphatic system disorders: rarely – thrombocytopenia, neutropenia, leukopenia.

Metabolism and nutrition disorders: rarely – hypomagnesemia.

Hepatobiliary disorders: infrequently – increased activity of liver enzymes; rarely – hepatitis, jaundice, hepatic encephalopathy.

Renal and urinary disorders: very rarely – interstitial nephritis.

Skin and subcutaneous tissue disorders: rarely – bullous eruptions, urticaria; very rarely – erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome;

Musculoskeletal and connective tissue disorders: rarely – myalgia, arthralgia.

Reproductive system and breast disorders: very rarely – gynecomastia.

Contraindications

Hypersensitivity to rabeprazole or substituted benzimidazoles; pregnancy, breastfeeding period; children under 12 years of age (for all indications), children and adolescents under 18 years of age (except for indications for adolescents over 12 years).

With caution severe renal failure.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

No dose adjustment is required for patients with impaired liver function; however, Rabeprazole should be used with caution in patients with severe liver impairment.

Use in Renal Impairment

Should be used with caution in patients with severe renal impairment.

Pediatric Use

Contraindicated for use for all indications in children under 12 years of age.

Contraindicated for use in children and adolescents under 18 years of age (except for indications for adolescents over 12 years).

Geriatric Use

Patients aged 55 years and older should consult a doctor if symptoms appear or change during therapy with rabeprazole.

Special Precautions

Before starting therapy, it is necessary to exclude malignant neoplasms of the stomach, because the use of rabeprazole can mask symptoms and delay correct diagnosis.

No dose adjustment is required for patients with impaired liver or kidney function; however, Rabeprazole is recommended to be used with caution in patients with severe liver impairment.

Proton pump inhibitor therapy may lead to an increased risk of gastrointestinal infections caused by Clostridium difficile.

When used concomitantly with rabeprazole, doses of ketoconazole and digoxin should be adjusted.

Patients with long-term recurring symptoms of indigestion or heartburn should be regularly monitored by a doctor. Patients over 55 years of age who daily take over-the-counter medications to relieve symptoms of heartburn and indigestion should inform their doctor about this.

Other acid-reducing agents, such as H₂-receptor blockers or proton pump inhibitors, should not be used concomitantly with rabeprazole.

In experimental studies, no carcinogenic effect of rabeprazole was established, but ambiguous results were obtained in mutagenicity studies. Tests on mouse lymphoma cells were positive, while the in vivo micronucleus test and the in vivo and in vitro DNA repair tests were negative.

Drug Interactions

With simultaneous use with digoxin, a slight to moderate increase in the plasma concentration of digoxin is possible.

With simultaneous use with ketoconazole, its bioavailability decreases.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.