RABELIX-DSR

(Rabeprazole sodium Delayed-Release Tablets 20mg & Domperidone 30mg SR Capsules)

RABELIX DSR COMPOSITION:

Each capsule contains

Rabeprazole sodium :20 mg(as enteric coated pellets)
Domperidone :30 mg (as sustained release pellets)

DESCRIPTION

Rabeprazole belongs to a class of antisecretory compounds (substituted benzimidazole proton-pump inhibitors) that do not exhibit anticholinergic or histamine H 2 –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. Domperidone is a derivative of benzimidazole that possesses both prokinetic and antiemetic properties due to its inhibitory action at dopamine D 2 receptors.

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.

Domperidone

Domperidone is a dopamine antagonist with anti-emetic properties domperidone does not readily cross the blood-brain barrier. In domperidone users, especially in adults, extrapyramidal side effects are very rare, but domperidone promotes the release of prolactin from the pituitary. Its anti-emetic effect may be due to a combination of peripheral (gastrokinetic) effects and antagonism of dopamine receptors in the chemoreceptor trigger zone, which lies outside the blood-brain barrier in the area postrema. Animal studies, together with the low concentrations found in the brain, indicate a predominantly peripheral effect of domperidone on dopamine receptors. Studies in man have shown oral domperidone to increase lower esophaegeal pressure, improve antroduodenal motility and accelerate gastric emptying. There is no effect on gastric secretion.

Absorption

In fasting subjects, domperidone is rapidly absorbed after oral administration, with peak plasma concentrations at 30 to 60 minutes. The low absolute bioavailability of oral domperidone (approximately 15%) is due to an extensive first-pass metabolism in the gut wall and liver. Although domperidone`s bioavailability is enhanced in normal subjects when taken after a meal, patients with gastro-intestinal complaints should take Domperidone 15-30 minutes before a meal. Reduced gastric acidity impairs the absorption of domperidone.

Oral bioavailability is decreased by prior concomitant administration of cimetidine and sodium bicarbonate. The time of peak absorption is slightly delayed and the AUC somewhat increased when the oral drug is taken after a meal.

Distribution

Oral domperidone does not appear to accumulate or induce its own metabolism; a peak plasma level after 90 minutes of 21 ng/ml after two weeks oral administration of 30 mg per day was almost the same as that of 18 ng/ml after the first dose. Domperidone is 91-93% bound to plasma proteins. Distribution studies with radio labelled drug in animals have shown wide tissue distribution, but low brain concentration. Small amounts of drug cross the placenta in rats.

INDICATIONS

RABELIX DSR is indicated for the relief of symptoms of

• Dyspepsia
• GERD
• Nausea associated with acid peptic disorders
• Post-operative nausea and vomiting
• Chronic gastritis

DOSAGE AND ADMINISTRATION

Once daily.

CONTRAINDICATIONS

RABELIX DSR is contraindicated in patients with known hypersensitivity to rabeprazole, substituted benzimidazole, domperidone or to any component of the formulation. It should not be used whenever stimulation of gastric motility is to be avoided or could be harmful, e.g. in the presence of gastro-intestinal hemorrhage, obstruction or perforation. It is also contra-indicated in patients with a prolactin-releasing pituitary tumor (prolactinoma).