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RABAKTIVE

Quick Overview

Our aim is to reach out to the globe withinshortest possible time frame. 


To promote this objective, not only we distribute and market our Gastroenterology range of products globally through our distribution channels but we also undertake ‘contract manufacturing’& ‘formulation development ’of our wide range of generic products such as Rabactive which contains Rabeprazole Sodium….20mg.


 

RABAKTIVE

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Details

 Each Enteric-Coated Tablet Contains:

Rabeprazole Sodium….20mg

Excipients     q.s

Colours: SunsetYellow FCF, Iron Oxide Yellow NF and Titanium Dioxide BP

Chemical Name: 2- M4-(3-methoxypropoxy)-3-methyl-2- pyridinyli-methyl] sulfiny1]-1H-benzimidazole sodium salt.

Category: Gastric proton-pump inhibitor

Description: Light yellow to yellow colour round shape enteric coated tablet plain on both sides.

PHARMACOLOGY

Pharmacodynamics Actions

Mechanism of Action:

Rabeprazole sodium belongs to the class of anti-secretory compounds, the substituted benzimidazoles, that do not exhibit anti-cholinergic or H, histamine antagonist properties, but suppress gastric acid secretion by the specific inhibition of the H±/K+-ATPase enzyme (the acid or proton pump) The effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus. Animal studies indicate that after administration, rabeprazole sodium rapidly disappears from both the plasma and gastric mucosa. As a weak base, rabeprazole is rapidly absorbed following all doses and is concentrated in the acid environment of the parietal cells. Rabeprazole is converted to the active sulphenamide form through protonation and it subsequently reacts with the available cysteines on the proton pump.

Anti-secretory Activity: After oral administration of a 20mg 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 to48 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.

Decreased gastric acidity due to any means, including proton pump inhibitors such as rabeprazole, increases counts of bacteria normally present in the gastrointestinal tract. Treatment with proton pump inhibitors may possibly increase the risk of gastrointestinal infections such as Salmonella, Campylobacter and Clostridium difficile.

Serum Gastrin Effects: In clinical studies patients were treated once daily with 10 or 20mg rabeprazole sodium, for up to 43 months duration. Serum gastrin levels increased during the first 2 to 8 weeks reflecting the inhibitory effects on acid secretion and remained stable while treatment was continued. Gastrin values returned to pre-treatment levels, usually within 1 to 2 weeks after discontinuation of therapy.

Human gastric biopsy specimens from the antrum and the fundus from over 500 patients receiving rabeprazole or comparator treatment for up to 8 weeks have not detected changes in ECL cell histology, degree of gastritis, incidence of atrophic gastritis, intestinal metaplasia or distribution of H. pylori infection. In over 250 patients followed for 36 months of continuous therapy, no significant change in findings present at baseline was observed.

Other Effects: Systemic effects of rabeprazole sodium in the CNS, cardiovascular and respiratory systems have not been found to date. Rabeprazole sodium, given in oral doses of 20mg for 2 weeks, had no effect on thyroid function, carbohydrate metabolism, or circulating levels of parathyroid hormone, cortisol, estrogen, testosterone, prolactin, cholecystokinin, secretin, glucagon, follicle stimulating hormone (FSH), luteinising hormone (LH), renin, aldosterone or somatotrophic hormone.

Studies in healthy subjects have shown that rabeprazole sodium does not have clinically significant interactions with amoxicillin. Rabeprazole does not adversely influence plasma concentrations of amoxicillin or clarithromycin when co-administered for the purpose of eradicating upper gastrointestinal H. pylori infection.

Pharmacokinetic Actions

Absorption: RABAKTIVE is an enteric-coated (gastro-resistant) tablet formulation of rabeprazole sodium. This presentation is necessary because rabeprazole is acid-labile. Absorption of rabeprazole therefore begins only after the tablet leaves the stomach. Absorption is rapid, with peak plasma levels of

rabeprazole occurring approximately 3.5 hours after a 20mg dose. Peak plasma concentrations (Cmax) of rabeprazole and AUC are linear over the dose range of 10mg to 40mg. Absolute bioavailability of an oral 20mg dose (compared to intravenous administration) is about 52% due in large part to pre-systemic metabolism. Additionally the bioavailability does not appear to increase with repeat administration. In healthy subjects the plasma half-life is approximately one hour (range 0.7 to 1.5 hours), and the total body clearance is estimated to be 283 ± 98 mVmin. There was no clinically relevant interaction with food. Neither food nor the time of day of administration of the treatment affect the absorption of rabeprazole sodium.

Distribution:

Rabeprazole is approximately 97% bound to human plasma proteins.

Metabolism:

Rabeprazole sodium, as is the case with other members of the proton pump inhibitor (PPI) class of compounds, is metabolised through the cytochrome P450 (CYP450) hepatic drug metabolising system. In vitro studies with human liver microsomes indicated that rabeprazole sodium is metabolised by isoenzymes of CYP450 (CYP2C19 and CYP3A4). In these studies, at expected human plasma concentrations rabeprazole neither induces nor inhibits CYP3A4; and although in vitro studies may not always be predictive of in vivo status these findings indicate that no interaction is expected between rabeprazole and cyclosporin. In humans the thioether (M1) and carboxylic acid (M6) are the main plasma metabolites with the sulphone (M2), desmethyl­thioether (M4) and mercapturic acid conjugate (M5) minor metabolites observed at lower levels. Only the desmethyl metabolite (M3) has a small amount of anti-secretory activity, but it is not present in plasma.

Elimination:

Following a single 20mg "C labelled oral dose of rabeprazole sodium, no unchanged drug was excreted in the urine. Approximately 90% of the dose was eliminated in urine mainly as the two metabolites: a mercapturic acid conjugate (M5) and a carboxylic acid (M6), plus two unknown metabolites. The remainder of the dose was recovered in faeces.

Gender:

 Adjusted for body mass and height, there are no significant gender differences in pharmacokinetic parameters following a single 20mg dose of rabeprazole.

Renal dysfunction: In patients with stable, end-stage, renal failure requiring maintenance hemodialysis (creatinine clearance  to that in healthy volunteers. The AUC and the Cinthese patients was about 35% lower than the corresponding parameters in healthy volunteers. The mean half-life of rabeprazole was 0.82 hours in healthy volunteers, 0.95 hours in patients during hemodialysis and 3.6 hours post dialysis. The clearance of the drug in patients with renal disease requiring maintenance hemodialysis was approximately twice that in healthy volunteers. Hepatic dysfunction: Following a single 20mg dose of rabeprazole to patients with chronic mild to moderate hepatic impairment the AUC doubled and there was a 2-3 fold increase in half-life of rabeprazole compared to the healthy volunteers. However, following a 20mg dose daily for 7 days the AU C had increased to only 1.5-fold and the Cma to only 1.2-fold. The half-life of rabeprazole in patients with hepatic impairment was 12.3 hours compared to 2.1 hours in healthy volunteers. The pharmacodynamic response (gastric pH control) in the two groups was clinically comparable.

Elderly:

Elimination of rabeprazole was somewhat decreased in the elderly. Following 7 days of daily dosing with 20mg of rabeprazole sodium, the AUC approximately doubled, the Cma„ increased by 60% and t1/2 increased by approximately 30% as compared to young healthy volunteers. However there was no evidence of rabeprazole accumulation.

CYP2C19 Polymorphism:

Following a 20mg daily dose of rabeprazole for 7 days, CYP2C19 slow metabolisers, had AUC and t1/2 which were approximately 1.9 and 1.6 times the corresponding parameters in extensive metabolisers whilst Cmax had increased by only 40%.

INDICATIONS AND USAGE

RABAKTIVE is indicated in the following conditions:-

  • Active duodenal ulcer
  • Active benign gastric ulcer
  • Symptomatic erosive or ulcerative Gastro-Esophageal Reflux Disease (GERD).
  • Long-term Management of Gastro-Esophageal Ref lux Disease (GERD Maintenance)
  • Symptomatic treatment of moderate to very severe gastro­oesophageal reflux disease
  • Zollinger-Ellison Syndrome

In combination with appropriate antibacterial therapeutic regimens for the eradication of Helicobacter pylon in patients with peptic ulcer disease.

DOSAGE AND ADMINISTRATION

Adults/Elderly:

Active Duodenal Ulcer and Active Benign Gastric Ulcer: The recommended oral dose for both active duodenal ulcer and active benign gastric ulcer is RABAKTIVE 20mg to be taken once daily in the morning. Most patients with active duodenal ulcer and active benign gastric ulcer heal within four weeks and six weeks respectively. However a few patients may require four weeks and six weeks of additional therapy to achieve healing.

Erosive or Ulcerative Gastro-Esophageal Reflux Disease (GERD): The recommended oral dose of RABAKTIVE for this condition is 20mg to be taken once daily for four to eight weeks.

Long-term Management of Gastro-Oesophageal Reflux Disease (GERD Maintenance): For long-term management, a maintenance dose of RABAKTIVE 20mg or 10mg once daily can be used depending upon patient response.

Symptomatic treatment of moderate to very severe Gastro­Oesophageal Reflux Disease (symptomatic GERD): RABAKTIVE 10 mg once daily in patients without oesophagitis. If symptom control has not been achieved during four weeks, the patient should be further investigated. Once symptoms have resolved, subsequent symptom control can be achieved using an on- demand regimen taking 10mg once daily when needed.

Zollinger-Ellison Syndrome: The recommended adult starting dose is RABAKTIVE 60 mg once a day. The dose may be titrated upwards to 120 mg/day based on individual patient needs. Single daily doses up to 100 mg/day may be given.120 mg dose may require divided doses, 60 mg twice daily. Treatment should continue for as long as clinically indicated.

Eradication of H. pylori: Patients with H. pylon infection should be treated with eradication therapy. The following combination given for 7 days is recommended.

RABAKTIVE 20 mg twice daily + Clarithromycin 500mg twice daily + Amoxycillin 1g twice daily.

For indications requiring once daily treatment RABAKTIVE should be taken in the morning, before eating; and although neither the time of day nor food intake was shown to have any effect on rabeprazole sodium activity, this regimen will facilitate treatment compliance.

Renal and hepatic impairment: No dosage adjustment is necessary for patients with renal or hepatic impairment. Children: RABAKTIVE is not recommended for use in children.  

CONTRAINDICATIONS

  • Contra-indicated in patients with known hypersensitivity to rabeprazole sodium, or to any excipients used in the formulation.
  • Contra-indicated in pregnancy and during breast feeding.

SPECIAL WARNINGS & PRECAUTIONS

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 with Rabeprazole Sodium. Patients on long-term treatment (particularly those treated for more than a year) should be kept under regular surveillance. A risk of cross- hypersensitivity reactions with other proton pump inhibitor or substituted benzimidazoles cannot be excluded. Rabeprazole Sodium is not recommended for use in children, as there is no experience of its use in this group. There have been post marketing reports of blood dyscrasias (thrombocytopenia and neutropenia) and Hepatic enzyme abnormalities. In the majority of cases where an alternative aetiology cannot be identified, the events were uncomplicated and resolved on discontinuation of rabeprazole. 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. However because there are no clinical data on the use of Rabeprazole Sodium in the treatment of patients with severe hepatic dysfunction it is advised to exercise caution when treatment is first initiated in such patients. Treatment with proton pump inhibitors, including Rabeprazole Sodium, may possibly increase the risk of gastrointestinal infections such as Salmonella, Campylobacter and Clostridium difficile.

Drug Interactions

Rabeprazole sodium produces a profound and long lasting inhibition of gastric acid secretion. An interaction with compounds whose absorption is pH dependent may occur. Co-administration of rabeprazole sodium with ketoconazole or itraconazole may result in a significant decrease in antifungal plasma levels. Therefore individual patients may need to be monitored to determine if a dosage adjustment is necessary when ketoconazole or itraconazole are taken concomitantly.

In clinical trials, antacids were used concomitantly with the administration of rabeprazole and, in a specific drug-drug interaction study, no interaction with liquid antacids was observed.

Co-administration of atazanavir 300mg/ritonavir 10mg with omeprazole (40 mg once daily) or atazanavir 400mg with lansoprazole (60mg once daily) to healthy volunteers resulted in a substantial reduction in atazanavir exposure. The absorption of atazanavir is pH dependent. Although not studied, similar results are expected with other proton pump inhibitors. Therefore PP15, including rabeprazole, should not be co-administered with atazanavir

Pregnancy & Lactation

There are no data on the safety of rabeprazole in human pregnancy. However Rabeprazole Sodium is contraindicated during pregnancy. It is not known whether rabeprazole sodium is excreted in human breast milk. No studies in lactating women have been performed. Therefore Rabeprazole Sodium should not be used during breast feeding.

Effect to Drive & Use the Machine

Based on the pharmacodynamic properties and the adverse events profile, it is unlikely that Rabeprazole Sodium would cause an impairment of driving performance or compromise the ability to use machinery. If however, alertness is impaired due to somnolence, it is recommended that driving and operating complex machinery be avoided.

ADVERSE REACTIONS

The most commonly reported adverse drug reactions, during controlled clinical trials with rabeprazole were headache, diarrhoea, abdominal pain, asthenia, flatulence, rash and dry mouth.

The following adverse events have been reported and the frequencies are defined as: common (>1/100, <1/10), uncommon (> 1/1,000, <1/100), rare (>1/10,000, <1/1000) and very rare (<1/10,000).

Common: Infection, Insomnia, Headache, Dizziness, Cough, Pharyngitis, Rhinitis, Diarrhoea, Vomiting, Nausea, Abdominal pain, Constipation, Flatulence, Non-specific pain & Back pain, Asthenia, Influenza like illness.

Uncommon: Nervousness, Somnolence, Bronchitis, Sinusitis, Dyspepsia, Dry mouth, Eructation, Rash, Erythema2, Myalgia, Leg cramps, Arthralgia, UTI, Chest pain, Chills, Pyrexia, Increased hepatic enzymes3.

Rare: Neutropenia, Leucopenia, Thrombocytopenia, Hypersensitivity1, 2 , Anorexia, Depression, Visual disturbance, Leucocytosis, Gastritis, Stomatitis, Taste disturbance, Hepatitis, Jaundice, Hepatic encephalopathy3, Pruritus, Sweating, Bullous

 

 

reactions2, Interstitial nephritis, Weight increase,

Very rare: Erythema multiforme, toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome.

1 Includes facial swelling, hypotension and dyspnoea

2 Erythema, Bullous reactions and hypersensitivity reactions have usually resolved after discontinuation of therapy.

3 Rare reports of hepatic encephalopathy have been received in patients with underlying cirrhosis. In treatment of patients with severe hepatic dysfunction it is advised to exercise caution when treatment is first initiated.

OVERDOSAGE

Experience to date with deliberate or accidental overdose is limited. The maximum established exposure has not exceeded 60mg twice daily, or 160mg once daily. Effects are generally minimal, representative of the known adverse event profile and reversible without further medical intervention. No specific antidote is known. Rabeprazole sodium is extensively protein bound and is, therefore, not dialyzable. As in any case of overdose, treatment should be symptomatic and general supportive measures should be utilized.

PACKING: 3 Blisters of 10 Tablets

STORAGE

Store in a cool and dry place below 30°C. Protect from light and moisture.

Keep out of reach of children.

SHELF LIFE: 36 Months from the date of Manufacturing.

 

 

 

 

 

 
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