Raaz

Rx                  RAAZ

COMPOSITION

Each Capsule contains                        

Rabeprazole ……………20mg

 DESCRIPTION

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. This medication is prescribed for duodenal ulcer, gastro esophageal reflux disease (GERD) including heartburn, acid regurgitation, nausea, and Zollinger-Ellison (gastric acid hyper secretion) syndrome thus allows to heal and prevents from  further damage. It was developed by Eisai Co. and is marketed by Janssen-Cilag as the sodium salt under the brand names AcipHex in the US, Pariet in Europe, Brazil, Canada, Japan, Russia and Australia.

  

Pharmacology

Pharmacodynamics

Rabeprazole 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.

Antisecretory Activity: The antisecretory effect begins within one hour after oral administration of 20 mg rabeprazole. The median inhibitory effect of rabeprazole on 24 hour

gastric acidity is 88% of maximal after the first dose. Rabeprazole 20 mg inhibits basal and peptone meal-stimulated acid secretion versus placebo by 86% and 95%, respectively, and increases the percent of a 24-hour period that the gastric pH>3 from 10% to 65%  This relatively prolonged Pharmacodynamics action compared to the short pharmacokinetic half-life (1-2 hours) reflects the sustained inactivation of the H+, K+ATPase.

Pharmacokinetic

Absorption: After oral administration of 20 mg rabeprazole, peak plasma concentrations (Cmax) of rabeprazole occur over a range of 2.0 to 5.0 hours (Tmax) The plasma half-life ranges from 1 to 2 hours. Oral bioavailability is approximately 52%. Rabeprazole may be taken without regard to timing of meals.

Distribution: Protein binding is 96.3%.

Metabolism: Extensively metabolized in liver by cytochrome P4503A(CYP 3A) to sulphone metabolite and cytochrome P450 2C19(CYP2C19) to desmethyl rabeprazole. Thioether and sulphone metabolites are formed by reduction of rabeprazole

Excretion: Plasma half-life is 1 to 2 h. Eliminated in urine (90% as thioether carboxylic acid, glucuronide, and mercapturic acid); remainder recovered in feces. No unchanged drug recovered.

Special population

Renal Function Impairment

No pharmacokinetic differences in ESRD compared with healthy volunteers.

Hepatic Function Impairment

For chronic mild to moderate hepatic impairment, AUC approximately doubled and elimination half-life was 2- to 3-fold higher, total Cl decreased to less than half. For mild to moderate hepatic impairment, C max increased approximately 20% (not significant).

Elderly

AUC values doubled; C max increased 60%.

Children

Pharmacokinetics in patients 12 to 16 y of age with gastroesophageal reflux disease (GERD) were within the range observed in healthy adults.

Gender

Pharmacokinetics did not differ between men and women.

Race

Values for AUC for healthy Japanese men were approximately 50% to 60% higher than values for healthy men in the United States.

Indications

·         Gastric ulcer (GU)

·         Peptic ulcer disease (PUD)

·         Maintenance of healing of erosive or ulcerative GORD

·         Healing of erosive and ulcerative GORD

·         Healing of duodenal ulcers.

·         Treatment of symptomatic GORD

·         Treatment of pathological hypersecretory conditions (Zollinger-Ellison syndrome)

·         Helicobacter pylori eradication to reduce risk of duodenal ulcer recurrence

           

UNLABELLED USES

Prevention of GI bleeding in patients receiving antiplatelets

DOSAGE AND ADMINISTRATION

·         Duodenal Ulcers
Adults

PO 20 mg/day after the morning meal for 4 wk; additional therapy may be required for some patients.

·         Short-Term Treatment of GERD
Adults and Children 12 y and older

PO 20 mg once daily for up to 8 wk.

·         Erosive or Ulcerative GERD
Adults

PO 20 mg/day for 4 to 8 wk; an additional 8 wk may be considered for patients who do not heal. For the maintenance healing of GERD, 20 mg/day.

·         Pathological Hypersecretory Conditions
Adults

PO 60 mg/day. Adjust dose to individual patient needs. Dosages up to 100 mg daily or 60 mg twice daily have been administered.

·         H. Pylori Eradication
Adults

PO Rabeprazole 20 mg plus amoxicillin 1,000 mg plus clarithromycin 500 mg twice daily for 7 days with morning and evening meals.

General Advice

·         Tablets should be swallowed whole; do not chew, crush, or split.

·         May take with or without food.

Drug Interactions

·         Rabeprazole decreases the concentration of ketoconazole in the plasma (in 33%), increases the concentration of digoxin (in 22%), and does not interact with liquid antacids

·         . Rabeprazole is compatible with any medicine metabolized by the CYP450(theophylline, warfarin, diazepam, phenytoin).

·         Compounds dependent on gastric pH for absorption

·         Concomitant use of atazanavir and proton pump inhibitors is not recommended. Co-administration of atazanavir with proton pump inhibitors is expected to substantially decrease atazanavir plasma concentrations and thereby reduce its therapeutic effect.

CONTRA-INDICATIONS

•                     Hypersensitivity to rabeprazole, substituted benzimidazoles or any of components of its pharmaceutical forms

·         It should not be used whenever stimulation of gastric motility is to be avoided or could be harmful, e.g. in the presence of gastrointestinal hemorrhage, obstruction or perforation.

·          It is also contra-indicated in patients with a prolactin-releasing pituitary tumor (prolactinoma)

Restriction of usage

•   Acute hepatic failure

•     Pediatric use in patients under 18 years of age (there are insufficient data about safety and efficiency of rabeprazole in this group of patients)

Side effects:

·         Central Nervous System- Headache, dizziness, disorientation/delirium.

·         Skin- Skin eruptions, severe allergic reactions.

·         Eye and ENT- Inflammation of pharynx.

·         Gastrointestinal- Diarrhea, nausea, abdominal pain, vomiting, flatulence, constipation, abdominal pain, dry mouth.

·         Genitourinary- Kidney disorder.

·         Liver- Occurrence of confusion, altered level of consciousness and coma as a result of liver failure (hepatic encephalopathy), inflammation of liver, increased liver enzymes, jaundice.

·         Blood- Decrease in white blood cells, anemia.

·         Metabolic- Excess ammonia in blood, thyroid stimulating hormone elevations.

·        Musculoskeletal- Joint pain, muscle pain, rapid breakdown of skeletal muscle.

·         Respiratory- Inflammation of lung tissue.

·        Miscellaneous- Pain, infection, rapid swelling of dermis, coma, sudden death.

PRECAUTION AND WARNING

Pregnancy: Category B

Caution should be exercised in patients with history of bleeding ulcer, such as black, tarry stools or vomit that looks like coffee grounds, or if  experience throat pain, chest pain, severe stomach pain, or trouble swallowing discontinue the drug. May increase the risk of GI infections due to acid suppressive effects, liver damage, and gastric tumor.

Overdosage

Studies in mice and rats indicated the symptoms of acute toxicity due to overdose included: hypoactivity, labored respiration,convulsion, diarrhea, tremor, and coma. A study in dogs indicated that a dose of 2000mg/kg was not lethal.

Storage Conditions: Oral: Store at 15-30°C. Store it in an airtight container and keep away from children.