Capsule Presentation

Each hard gelatin capsule contains:
Levosulpiride                   75 mg
(SR Pellets)

Rabeprazole Sodium    20 mg
(EC Pellets)


GERD
Gastroesophageal reflux disease (GERD), gastric reflux disease, is a chronic symptom of mucosal damage caused by stomach acid coming up from the stomach into the esophagus.

PATHOPHYSIOLOGY
GERD is thought to have a multifactorial etiology rather than a single cause. Contributing factors include the caustic materials that are refluxed, a breakdown in the defense mechanisms of the esophagus and a functional abnormality that results in reflux.

ETIOLOGY
Gastroesophageal relux disease results when the lower esophageal sphincter—the muscle that acts as a valve between the esophagus and stomach—becomes weak or relaxes when it should not, causing stomach contents to rise up into the esophagus. Abnormalities in the body such as hiatal hernias may also cause GERD. Other factors that may contribute to GERD include obesity, pregnancy, smoking, Common foods that can worsen reflux symptoms include citrus fruits, chocolate drinks, caffeine or alcohol fatty and fried foods , garlic and onions mint flavorings spicy foods tomato-based foods, like spaghetti sauce, salsa, chili, and pizza.

Indications

  • For the treatment of Gastro-oesophageal Reflux Disease (GERD).
  • Healing of Erosive or Ulcerative Gastroesophageal Reflux Disease (GERD).
  • Maintenance of Healing of Erosive or Ulcerative Gastroesophageal Reflux Disease (GERD).
  • Healing of Duodenal Ulcers.
  • Treatment of Pathological Hypersecretory Conditions, Including Zollinger-Ellison Syndrome.
  • Irritable bowel syndrome.

About combination

Rabeprazole Sodium belongs to proton pump inhibitors group of drugs. It is used to reduce acidity in the stomach. It is also used to treat Gastroesophageal reflux disease and Zollinger Ellison syndrome. Rabeprazole is also given to treat gastric ulcers caused by H.pylori infection.
Levosulpiride is a sulpiride isomer that exerts its prokinetic action through a dual mechanism: 1) as a D(2) dopamine receptor antagonist and 2) as a serotonin 5HT(4) receptor agonist, conferring this drug with a cholinergic effect.
It has been demonstrated by recent studies concomitant administration of a Rabeprazole and Levosulpiride shows significantly better improvement of GERD.

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 (hydrogen-potassium adenosine triphosphatase) 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.
Levosulpiride is a sulpiride isomer that exerts its prokinetic action through a dual mechanism: 1) as a D(2) dopamine receptor antagonist and 2) as a serotonin 5HT(4) receptor agonist, conferring this drug with a cholinergic effect. It helps in relieving the eoshophagitis associated with GERD .

Drug Interactions

It inhibits gastric acid secretion and may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (e.g., ketoconazole, iron salts and digoxin).
It may reduce the plasma levels of atazanavir .
Antacids and Sucralfate: They can decrease the absorption of the drug from the intestine. So, these medicines should not be taken along with levosulpiride. There should be a minimum 2 hour time lag between the two medicines.
Alcohol: There is increased chance of sedation.
Antihypertensive Medications: Concomitant use may enhance the hypotensive effect seen with the drug.
Anticholinergics: Increased incidence of anticholinergic side effects.
Increased INR and prothrombin times have been reported with concomitant use with warfarin. Patients need to be monitored.

Pharmacodynamics

Rabeprazole Sodium

Prevents the production of acid in the stomach. It reduces symptoms and prevents injury to the esophagus or stomach in patients with gastroesophageal reflux disease (GERD) or ulcers. Rabeprazole is a selective and irreversible proton pump inhibitor, suppresses gastric acid secretion by specific inhibition of the H+, K+ -ATPase, which is found at the secretory surface of parietal cells. In doing so, it inhibits the final transport of hydrogen ions (via exchange with potassium ions) into the gastric lumen.

Levosulpiride

It is a substituted benzamide, which exerts antidopaminergic (selective dopamine D2 receptors) activity on both central and peripheral levels. It a typical neuroloptic and also acts as prokinetic agent by acting as antagonist to dopamine receptor and acting as agonist to serotonin receptor.

Pharmacokinetics

Rabeprazole

Absorption: Absolute bioavailability is approximately 52%.
Route of Elimination: Following a single 20 mg oral dose of 14C-labeled rabeprazole, Approximately 90% of the drug was eliminated in the urine, primarily as thioether carboxylic acid; itslucuronide, and mercapturic acid metabolites.

Levosulpiride

Absorption: Oral bioavailability is about 30%; peak plasma concentrations after about 3hr.
Route of Elimination: Mainly via urine. Plasma half-life: 9.7 hr (oral);

Side Effects

  • Rash.
  • Swelling of tongue and face.
  • Headache.
  • Dizziness.
  • Dry mouth.
  • Diarrhea.
  • Constipation.

Contraindications

  • Caution when used during pregnancy.
  • Caution when used during lactation.
  • contraindicated in persons with a history of hypersensitivity.
  • History of epilepsy.
  • Alcohol intoxication.
  • Certain tumors like phaeochromocytoma andpituitary prolactinoma.
  • Hypokalemia.
  • Increased INR and prothrombin times have been reported with concomitant use with warfarin. Patients need to be monitored.
  • It inhibits gastric acid secretion and may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (e.g., ketoconazole, iron salts and digoxin).
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