Reloxa

Rabeprazole sodium.

Each enteric-coated tablet and vial contains Rabeprazole sodium 20 mg.

Pharmacology: Pharmacodynamics: Mechanism of Action: Rabeprazole belongs to a class of antisecretory compounds (substituted benzimidazole proton-pump inhibitors) that do not exhibit anticholinergic or histamine H2-receptor antagonist properties, but suppress gastric acid secretion by inhibiting the gastric H+, K+ ATPase at the secretory surface of the gastric parietal cell. Because this enzyme is regarded as the acid (proton) pump within the parietal cell, Rabeprazole has been characterized as a gastric proton-pump inhibitor. Rabeprazole blocks the final step of gastric acid secretion.
In gastric parietal cells, Rabeprazole is protonated, accumulates, and is transformed to an active sulfenamide.
When studied in vitro, Rabeprazole is chemically activated at pH 1.2 with a half-life of 78 seconds. It inhibits acid transport in porcine gastric vesicles with a half-life of 90 seconds.
Anti-secretory Activity: After oral administration of a 20 mg dose of Rabeprazole sodium, the onset of the anti-secretory effect occurs within one hour with the maximum effect occurring within two to four hours. Inhibition of basal and food stimulated acid secretion 23 hours after the first dose of Rabeprazole sodium are 69% and 82% respectively and the duration of inhibition lasts up to 48 hours. The inhibitory effect of Rabeprazole sodium on acid secretion increases slightly with repeated once-daily dosing, achieving steady state inhibition after three days. When the drug is discontinued, secretory activity normalizes over 2 to 3 days.
Serum Gastrin Effects: In clinical studies, patients were treated once daily with 10 or 20 mg Rabeprazole sodium, for up to 24 months duration. Serum gastrin levels increased during the first 2 to 8 weeks reflecting the inhibitory effects on acid secretion. Gastrin values returned to pre-treatment levels, usually within 1 to 2 weeks after discontinuation of therapy.
Pharmacokinetics: Rabeprazole is rapidly absorbed and peak plasma concentrations are reached about 3.5 hours after an oral dose.
The oral bioavailability is about 52% with the enteric-coated tablet formulation, because of first-pass metabolism, and does not appear to vary after single or repeated doses. Rabeprazole is about 97% bound to plasma proteins. It is extensively metabolised in the liver by cytochrome P450 isoenzymes CYP2C19 and CYP3A4 to the thioether carboxylic acid; sulfone and desmethylthioether. Metabolites are excreted principally in the urine (about 90%) with the remainder in the faeces. The plasma half-life is about 1 hour, increased two to threefold in hepatic impairment, 1.6 times in CYP2C19 slow metabolisers, and by 30% in the elderly.

Rabeprazole sodium (Reloxa) tablets are indicated for the treatment of: Active duodenal ulcer.
Active benign gastric ulcer.
Symptomatic erosive or ulcerative gastroesophageal reflux disease (GERD).
H. pylori-positive duodenal ulcers, as part of the eradication programme with appropriate antibiotics.
Maintenance treatment of healed erosive or ulcerative GERD.
Efficacy has not been demonstrated for periods exceeding 12 months.

Adults and Elderly: Severe (erosive or ulcerative) gastroesophageal reflux disease: The usual dose of Rabeprazole sodium is 20 mg once daily for 4 to 8 weeks; a further 8-week course may be needed for healing of erosive oesophagitis. Thereafter, maintenance therapy can be continued with 10 or 20 mg daily depending on the response. For symptomatic disease without erosive or ulcerative oesophagitis a dose of 10 or 20 mg may be given once daily for 4 weeks.
Active peptic ulcer disease: 20 mg daily is given for 4 to 8 weeks for duodenal ulcer and 6 to 12 weeks for gastric ulcer. For the eradication of Helicobacter pylori, Rabeprazole sodium may be combined with two antibacterials in a 1-week triple therapy regimen.
Effective regimens include 20 mg twice daily combined with clarithromycin 500 mg twice daily and amoxicillin 1 g twice daily, or combined with clarithromycin 250 mg twice daily and metronidazole 400 mg twice daily.
Zollinger-Ellison syndrome: The starting dose is 60 mg once daily, adjusted according to response. Doses up to 120 mg daily have been given; when the daily dose is more than 100 mg it should be given in 2 divided doses.
Children: Rabeprazole sodium (Reloxa) is not recommended for use in children, as there is no experience of its use in this group.
Renal and Hepatic Impairment: No dosage adjustment is necessary for patients with renal or hepatic impairment. Caution is however advised when Rabeprazole sodium (Reloxa) is first initiated in patients with severe hepatic dysfunction.

No specific antidote is known. Rabeprazole sodium is extensively protein bound and is therefore, not readily dialysable. Treatment should be supportive and symptomatic.

Rabeprazole sodium (Reloxa) is contraindicated in: Patients with known hypersensitivity to rabeprazole sodium, or to any excipient used in the formulation.
Pregnancy and lactation.

Symptomatic response to therapy with Rabeprazole sodium does not preclude the presence of gastric or oesophageal malignancy, therefore the possibility of malignancy should be excluded prior to commencing treatment. Although no evidence of significant drug related safety problems was seen in a study of patients with mild to moderate hepatic impairment versus normal age and sex matched controls, it is advised to be cautious when is first initiating Rabeprazole sodium (Reloxa) in patients with severe hepatic dysfunction.

The most common adverse effects are headache, diarrhea and nausea. Other adverse events are rhinitis, abdominal pain, asthenia, flatulence, pharyngitis, vomiting, non-specific pain/back pain, dizziness, flu syndrome, infection, cough, constipation and insomnia.
Further less frequent adverse events are rash, myalgia, chest pain, dry mouth, dyspepsia, nervousness, somnolence, bronchitis, sinusitis, chills, leg cramps, urinary tract infection, arthralgia and fever. In isolated cases, anorexia, gastritis, weight gain, depression, pruritus, vision or taste disturbances, stomatitis, sweating and leucocytosis have also been observed.
Increased hepatic enzymes have been observed in 2% of patients. There have been reports of thrombocytopenia, neutropenia and leukopenia. Bullous eruptions have been reported and other dermatological reactions including erythema have been reported.
Treatment should be stopped immediately at the recurrence of skin lesions.

Rabeprazole sodium, as is the case with other members of the proton pump inhibitors (PPI) class of compounds, is metabolised through the cytochrome P450 (CYP450) hepatic drug metabolising system.
Studies in healthy subjects have shown that Rabeprazole sodium does not have clinically significant interactions with other drugs metabolised by the CYP450 system, such as warfarin, phenytoin, theophylline or diazepam. Rabeprazole sodium produces a profound and long lasting inhibition of gastric acid secretion. An interaction with compounds whose absorption is pH dependent may occur therefore the potential for such interaction was investigated.
Coadministration of Rabeprazole sodium results in a 33% decrease in ketoconazole levels and a 22% increase in trough digoxin levels in normal subjects. Therefore, individual patients may need to be monitored to determine if a dosage adjustment is necessary when such drugs are taken concomitantly with Rabeprazole sodium (Reloxa). In clinical trials, antacids were used concomitantly with the administration of Rabeprazole sodium (Reloxa) and in a specific study designed to define this interaction, no interaction with liquid antacids was observed.
There was no clinically relevant interaction with food.

Store at temperatures not exceeding 30°C.

Antacids, Antireflux Agents & Antiulcerants

A02BC04 - rabeprazole ; Belongs to the class of proton pump inhibitors. Used in the treatment of peptic ulcer and gastro-oesophageal reflux disease (GERD).

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