GENERIC NAME OF THE MEDICINAL PRODUCT:

Rabeprazole Gastro-resistant Tablets 10mg
Rabeprazole Gastro-resistant Tablets 20mg
Rabeprazole Gastro-resistant Tablets 40mg

QUALITATIVE AND QUANTITATIVE COMPOSITION:

a) Each Rabeprazole Gastro Resistant Tablets IP 10mg (Rabtaj) Taj Pharma Contains:
Rabeprazole           10mg
Excipients            q.s.
b) Each Rabeprazole Gastro Resistant Tablets IP 20mg (Rabtaj) Taj Pharma Contains:
Rabeprazole         20mg
Excipients          q.s.
b) Each Rabeprazole Gastro Resistant Tablets IP 20mg (Rabtaj) Taj Pharma Contains:
Rabeprazole         40mg
Excipients          q.s.

THERAPEUTIC INDICATIONS:

For the treatment of acid-reflux disorders (GERD), peptic ulcer disease, H. pylori eradication, and prevention of gastroinetestinal bleeds with NSAID use.

DIRECTION OF USE:

Do not swallow whole or chew.
Take this medicine on an empty stomach.

CAUTION & SCHEDULE:

CAUTION: KEEP OUT OF REACH AND SIGHT OF CHILDREN.
SCHEDULE: SCHEDULE ‘H’ DRUG – To be sold by retail on the prescription of a Registered Medical Practitioner only.

STORAGE & DOSAGE:

STORAGE: Preserve in tight container.
Keep in cool & dry place.
Protect from light & moisture.
DOSAGE: As directed by Physician.

Rabeprazole Gastro Resistant Tablets IP 20mg (Rabtaj) Taj Pharma

Overview

INTRODUCTION

Rabtaj 20mg Injection is a medicine which reduces the amount of acid produced in your stomach. It is used to treat heartburn, acid reflux and problems in your food pipe. It is also used to prevent and treat stomach ulcers.

You should take Rabtaj 20mg Injection as your doctor advises. The dose will depend on what you are being treated for, but it should be the lowest dose for the shortest amount of time needed to treat your condition. It should be given as an injection into the vein by a healthcare professional. It may take up to a few weeks to work properly but your doctor will tell you how long you need to be taking it for. You should keep on taking it as prescribed even if your symptoms disappear quickly. If you are taking this medicine for a long time, your doctor may carry out regular tests to check your levels of magnesium which can fall with this medicine.

Common side effects include vomiting, headache, diarrhoea, nausea, stomach pain and feeling or being sick. These tend to be mild but talk to your doctor if they bother you or do not go away. The risk of side effects may increase the longer you take this medicine. Serious side effects are rare, but some need immediate medical attention. Ask your doctor what these are. You may be more likely to have a broken bone if you take it for a long time. It is best to avoid foods that seem to make your symptoms worse, such as rich, spicy and fatty foods. It also helps to cut down on caffeinated drinks, such as tea, coffee and cola, as well as alcohol.

Rabtaj 20mg Injection is not suitable for some people. Before taking this medicine, you need to tell your doctor if you have severe liver problems, are taking medicines for HIV, have had an allergic reaction to similar medicines in the past or have osteoporosis. Alcohol does not interfere with the way Rabtaj 20mg Injection works. However, drinking alcohol makes your stomach produce more acid than normal. This medicine can make you feel dizzy, sleepy, or affect your vision. If this happens, do not drive, cycle or use machinery or tools until you feel better. It is not usually recommended during pregnancy and breastfeeding.

SIDE EFFECTS OF RABTAJ POWDER FOR INJECTION

Common
  • Vomiting
  • Headache
  • Stomach pain
  • Nausea
  • Flatulence
  • Diarrhea

HOW TO USE RABTAJ POWDER FOR INJECTION

Your doctor or nurse will give you this medicine. Kindly do not self administer.

HOW RABTAJ POWDER FOR INJECTION WORKS

Rabtaj 20mg Injection is a proton pump inhibitor (PPI). It works by reducing the amount of acid in the stomach which helps in relief of acid related indigestion and heartburn.

SAFETY ADVICE

warnings

Alcohol

CAUTION
Caution is advised when consuming alcohol with Rabtaj 20mg Injection. Please consult your doctor.
warnings

Pregnancy

CONSULT YOUR DOCTOR
Rabtaj 20mg Injection may be unsafe to use during pregnancy. Although there are limited studies in humans, animal studies have shown harmful effects on the developing baby. Your doctor will weigh the benefits and any potential risks before prescribing it to you. Please consult your doctor.
warnings

Breastfeeding

CONSULT YOUR DOCTOR
Rabtaj 20mg Injection is probably unsafe to use during breastfeeding. Limited human data suggests that the drug may pass into the breastmilk and harm the baby.
warnings

Driving

UNSAFE
Rabtaj 20mg Injection may decrease alertness, affect your vision or make you feel sleepy and dizzy. Do not drive if these symptoms occur.
warnings

Kidney

SAFE IF PRESCRIBED
Rabtaj 20mg Injection is safe to use in patients with kidney disease. No dose adjustment of Rabtaj 20mg Injection is recommended.
warnings

Liver

CAUTION
Rabtaj 20mg Injection should be used with caution in patients with severe liver disease. Dose adjustment of Rabtaj 20mg Injection may be needed. Please consult your doctor.

WHAT IF YOU FORGET TO TAKE RABTAJ POWDER FOR INJECTION?

If you miss a dose of Rabtaj 20mg Injection, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular schedule. Do not double the dose.

Rabeprazole Gastro Resistant Tablets IP 20mg (Rabtaj) Taj Pharma

1. Name of the medicinal product

a) Rabeprazole Gastro Resistant Tablets IP 10mg (Rabtaj) Taj Pharma
b) Rabeprazole Gastro Resistant Tablets IP 20mg (Rabtaj) Taj Pharma
c) Rabeprazole Gastro Resistant Tablets IP 40mg (Rabtaj) Taj Pharma

2. Qualitative and quantitative composition

a) Each Rabeprazole Gastro Resistant Tablets IP 10mg (Rabtaj) Taj Pharma Contains:
Rabeprazole           10mg
Excipients                q.s.

b) Each Rabeprazole Gastro Resistant Tablets IP 20mg (Rabtaj) Taj Pharma Contains:
Rabeprazole         20mg
Excipients              q.s.

b) Each Rabeprazole Gastro Resistant Tablets IP 20mg (Rabtaj) Taj Pharma Contains:
Rabeprazole         40mg
Excipients              q.s.

  1. Pharmaceutical form

Gastro-resistant tablet.

biconvex tablet.

  1. Clinical particulars

4.1 Therapeutic indications

Rabeprazole 10mg Gastro-resistant Tablets are indicated for the treatment of:

  • Active duodenal ulcer
  • Active benign gastric ulcer
  • Symptomatic erosive or ulcerative gastro-oesophageal reflux disease (GORD).
  • Gastro-Oesophageal Reflux Disease Long-term Management (GORD Maintenance)
  • Symptomatic treatment of moderate to very severe gastro-oesophageal reflux disease (symptomatic GORD)
  • Zollinger-Ellison Syndrome
  • In combination with appropriate antibacterial therapeutic regimens for the eradication of Helicobacter pylori in patients with peptic ulcer disease. See section 4.2

4.2 Posology and method of administration

Posology

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 20 mg to be taken once daily in the morning.

Most patients with active duodenal ulcer heal within four weeks. However a few patients may require an additional four weeks of therapy to achieve healing. Most patients with active benign gastric ulcer heal within six weeks. However again a few patients may require an additional six weeks of therapy to achieve healing.

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

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

Symptomatic treatment of moderate to very severe gastro-oesophageal reflux disease (symptomatic GORD): 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 10 mg once daily when needed.

Zollinger-Ellison Syndrome: The recommended adult starting dose is 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. pylori infection should be treated with eradication therapy. The following combination given for 7 days is recommended.

Rabeprazole 20 mg twice daily + clarithromycin 500 mg twice daily and amoxicillin 1 g twice daily.

Special populations

Renal and hepatic impairment: No dosage adjustment is necessary for patients with renal or hepatic impairment.

See section 4.4 for the use of Rabeprazole tablets in the treatment of patients with severe hepatic impairment.

Paediatric population

Rabeprazole tablets are not recommended for use in children due to a lack of data on safety and efficacy.

Method of administration

For indications requiring once daily treatment Rabeprazole tablets 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.

Patients should be cautioned that the Rabeprazole tablets should not be chewed or crushed, but should be swallowed whole.

4.3 Contraindications

– Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

– Pregnancy.

– Breast feeding.

4.4 Special warnings and precautions for use

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 10mg Gastro-resistant Tablets.

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.

Patients should be cautioned that Rabeprazole 10mg Gastro-resistant Tablets should not be chewed or crushed, but should be swallowed whole.

Paediatric population

Rabeprazole 10mg Gastro-resistant Tablets is not recommended for use in children due to a lack of data on safety and efficacy.

There have been post marketing reports of blood dyscrasias (thrombocytopenia and neutropenia). In the majority of cases where an alternative aetiology cannot be identified, the events were uncomplicated and resolved on discontinuation of rabeprazole.

Hepatic enzyme abnormalities have been seen in clinical trials and have also been reported since market authorisation. 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 in the treatment of patients with severe hepatic dysfunction the prescriber is advised to exercise caution when treatment with Rabeprazole 10mg Gastro-resistant Tablets is first initiated in such patients.

Co-administration of atazanavir with rabeprazole is not recommended (see section 4.5).

Treatment with proton pump inhibitors, including rabeprazole, may possibly increase the risk of gastrointestinal infections such as Salmonella, Campylobacter and Clostridium difficile (see section 5.1).

Hypomagnesaemia

Severe hypomagnesaemia has been reported in patients treated with PPIs like rabeprazole for at least three months, and in most cases for a year. Serious manifestations of hypomagnesaemia such as fatigue, tetany, delirium, convulsions, dizziness and ventricular arrhythmia can occur but they may begin insidiously and be overlooked. In most affected patients, hypomagnesaemia improved after magnesium replacement and discontinuation of the PPI.

For patients expected to be on prolonged treatment or who take PPIs with digoxin or drugs that may cause hypomagnesaemia (e.g., diuretics), health care professionals should consider measuring magnesium levels before starting PPI treatment and periodically during treatment.

Proton pump inhibitors, especially if used in high doses and over long durations (>1 year), may modestly increase the risk of hip, wrist and spine fracture, predominantly in the elderly or in presence of other recognised risk factors. Observational studies suggest that proton pump inhibitors may increase the overall risk of fracture by 10–40%. Some of this increase may be due to other risk factors. Patients at risk of osteoporosis should receive care according to current clinical guidelines and they should have an adequate intake of vitamin D and calcium.

Influence on vitamin B12 absorption

Rabeprazole sodium, as all acid-blocking medicines, may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or a- chlorhydria. This should be considered in patients with reduced body stores or risk factors for reduced vitamin B12 absorption on long-term therapy or if respective clinical symptoms are observed.

Subacute cutaneous lupus erythematosus (SCLE)

Proton pump inhibitors are associated with very infrequent cases of SCLE. If lesions occur, especially in sun-exposed areas of the skin, and if accompanied by arthralgia, the patient should seek medical help promptly and the health care professional should consider stopping Rabeprazole. SCLE after previous treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors.

Interference with laboratory tests

Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. To avoid this interference, Rabeprazole 10mg Gastro-resistant Tablets treatment should be stopped for at least 5 days before CgA measurements (see section 5.1). If CgA and gastrin levels have not returned to reference range after initial measurement, measurements should be repeated 14 days after cessation of proton pump inhibitor treatment.

4.5 Interaction with other medicinal products and other forms of interaction

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 with rabeprazole.

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 300 mg/ritonavir 10 mg with omeprazole (40 mg once daily) or atazanavir 400 mg with lansoprazole (60 mg 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 PPIs, including rabeprazole, should not be co-administered with atazanavir (see section 4.4).

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no data on the safety of rabeprazole in human pregnancy. Reproduction studies performed in rats and rabbits have revealed no evidence of impaired fertility or harm to the foetus due to rabeprazole sodium, although low foeto-placental transfer occurs in rats. Rabeprazole 10mg Gastro-resistant Tablets is contraindicated during pregnancy.

Breastfeeding

It is not known whether rabeprazole sodium is excreted in human breast milk. No studies in lactating women have been performed. Rabeprazole sodium is however excreted in rat mammary secretions. Therefore Rabeprazole 10mg Gastro-resistant Tablets must not be used during breast feeding.

4.7 Effects on ability to drive and use machines

Based on the pharmacodynamic properties and the adverse events profile, it is unlikely that Rabeprazole 10mg Gastro-resistant Tablets 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.

4.8 Undesirable effects

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 majority of adverse events experienced during clinical studies were mild or moderate in severity, and transient in nature.

The following adverse events have been reported from clinical trial and post-marketed experience.

Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data)

System Organ ClassCommonUncommonRare Very RareNot known
Infections and infestationsInfection
Blood and lymphatic system disordersNeutropenia

Leucopenia

Thrombocytopenia

Leucocytosis

Immune system disorders Hypersensitivity1,2
Metabolism and nutrition disordersAnorexiaHyponatremia

Hypomagnesaemia4

Psychiatric disordersInsomniaNervousnessDepressionConfusion
Nervous system disordersHeadache

Dizziness

Somnolence
Eye disordersVisual disturbance
Vascular disordersPeripheral oedema
Respiratory, thoracic and mediastinal disordersCough

Pharyngitis

Rhinitis

Bronchitis

Sinusitis

Gastrointestinal disordersDiarrhoea

Vomiting

Nausea

Abdominal pain

Constipation

Flatulence

Fundic gland polyps (benign)

Dyspepsia

Dry mouth

Eructation

Gastritis

Stomatitis

Taste disturbance

Microscopic colitis
Hepatobiliary disorders Hepatitis

Jaundice

Hepatic encephalopathy3

Skin and subcutaneous tissue disordersRash

Erythema2

Pruritus

Sweating

Bullous reactions2

Erythema multiforme, toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS)Subacute cutaneous lupus erythematosus (see section 4.4)
Musculoskeletal and connective tissue disordersNon-specific pain

Back pain

Myalgia

Leg cramps

Arthralgia

Fracture of the hip,wrist or spine (see section 4.4)

Renal and urinary disordersUrinary tract infectionInterstitial nephritis
Reproductive system and breast disordersGynecomastia
General disorders and administration site conditionsAsthenia

Influenza like illness

Chest pain

Chills

Pyrexia

InvestigationsIncreased hepatic enzymes3Weight increased

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 the prescriber is advised to exercise caution when treatment with Rabeprazole 10mg Gastro-resistant Tablets is first initiated in such patients (see section 4.4).

4 See Special warnings and precautions for use (section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

4.9 Overdose

Experience to date with deliberate or accidental overdose is limited. The maximum established exposure has not exceeded 60 mg twice daily, or 160 mg 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 dialysable. As in any case of overdose, treatment should be symptomatic and general supportive measures should be utilised.

  1. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Drugs for peptic ulcer and gastro-oesophageal reflux disease (GORD), proton pump inhibitors.

Mechanism of action

Rabeprazole sodium belongs to the class of anti-secretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or H2 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.

Clinical efficacy and safety

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 normalises 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 20 mg 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.

During treatment with antisecretory medicinal products, serum gastrin increases in response to the decreased acid secretion. Also CgA increases due to decreased gastric acidity. The increased CgA level may interfere with investigations for neuroendocrine tumours.

Available published evidence suggests that proton pump inhibitors should be discontinued between 5 days and 2 weeks prior to CgA measurements. This is to allow CgA levels that might be spuriously elevated following PPI treatment to return to reference range.

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 20 mg for 2 weeks, had no effect on thyroid function, carbohydrate metabolism, or circulating levels of parathyroid hormone, cortisol, oestrogen, 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.

5.2 Pharmacokinetic properties

Absorption

Rabeprazole 10mg Gastro-resistant Tablet 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 20 mg dose. Peak plasma concentrations (Cmax) of rabeprazole and AUC are linear over the dose range of 10 mg to 40 mg. Absolute bioavailability of an oral 20 mg 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 ml/min. 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.

Biotransformation and elimination

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), desmethyl-thioether (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.

Following a single 20 mg 14C 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 20 mg dose of rabeprazole.

Renal dysfunction

In patients with stable, end-stage, renal failure requiring maintenance haemodialysis (creatinine clearance ≤5 ml/min/1.73 m2), the disposition of rabeprazole was very similar to that in healthy volunteers. The AUC and the Cmax in these 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 haemodialysis and 3.6 hours post dialysis. The clearance of the drug in patients with renal disease requiring maintenance haemodialysis was approximately twice that in healthy volunteers.

Hepatic dysfunction

Following a single 20 mg 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 20 mg dose daily for 7 days the AUC had increased to only 1.5-fold and the Cmax 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 20 mg of rabeprazole sodium, the AUC approximately doubled, the Cmax increased by 60 % and t½ increased by approximately 30 % as compared to young healthy volunteers. However there was no evidence of rabeprazole accumulation.

CYP2C19 Polymorphism

Following a 20 mg daily dose of rabeprazole for 7 days, CYP2C19 slow metabolisers, had AUC and t½ which were approximately 1.9 and 1.6 times the corresponding parameters in extensive metabolisers whilst Cmax had increased by only 40 %.

5.3 Preclinical safety data

Non-clinical effects were observed only at exposures sufficiently in excess of the maximum human exposure that make concerns for human safety negligible in respect of animal data.

Studies on mutagenicity gave equivocal results. Tests in mouse lymphoma cell line were positive, but in vivo micronucleus and in vivo and in vitro DNA repair tests were negative. Carcinogenicity studies revealed no special hazard for humans.

  1. Pharmaceutical particulars

6.1 List of excipients

Tablet core:

Povidone, Hydroxypropyl cellulose, low subst.

Magnesium oxide, light, Mannitol,  Magnesium stearate,

Undercoating:

Ethyl cellulose, Magnesium oxide, light

Enteric coating:

Methacrylic acid-ethyl acrylate copolymer

Talc, Polysorbate 80, Sodium laurilsulfate

Propylene glycol, Iron oxide yellow, Titanium dioxide, Iron oxide red (10 mg tablets only)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years

6.4 Special precautions for storage

Blister packs: Store below 25°C. Store in the original package in order to protect from moisture.

Tablet containers: Store below 25°C. Keep the container tightly closed in order to protect from moisture.

6.5 Nature and contents of container

Blister packs (Al-OPA-PVC/Al).

Tablet cotainers (HDPE) with plastic closure (LDPE) and a desiccant.

Tablet containers (HDPE) with a plastic screw cap with an integrated desiccant.

Pack sizes:

Blister packs: 7, 14, 20, 28, 30, 56, 60, 98, 100 and 120 tablets.

Tablet containers: 30, 100 and 250 tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements

7. Manufactured in India By:
TAJ PHARMACEUTICALS LTD.
29, Xcelon Industrial Park-1,
Behind Intas Pharmaceuticals,
At & Po Vasna – Chacharwadi,
Tal- Sanand, Dist- Ahmedabad-382213,
Gujarat, India

Rabeprazole Gastro Resistant Tablets IP 20mg (Rabtaj) Taj Pharma

Package leaflet: Information for the user

a) Rabeprazole Gastro Resistant Tablets IP 10mg
b) Rabeprazole Gastro Resistant Tablets IP 20mg

Rabeprazole sodium

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor or pharmacist.
  • This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
  • If you get any side effects talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

  1. What Rabtaj is and what it is used for
    2. What you need to know before you take Rabtaj
    3. How to take Rabtaj
    4. Possible side effects
    5. How to store Rabtaj
    6. Contents of the pack and other information
  2. What Rabtaj is and what it is used for

Rabtaj tablets contain the active ingredient rabeprazole sodium. This belongs to a group of medicines called ‘Proton Pump Inhibitors’ (PPIs). They work by lowering the amount of acid that your stomach produces.

Rabtaj tablets are used to treat the following conditions:

  • ‘Gastro-oesophageal reflux disease’ (GORD), which can include heartburn. GORD is caused when acid and food from your stomach escapes into your food pipe (oesophagus).
  • Ulcers in your stomach or the upper part of your gut (intestine). If these ulcers are infected with bacteria called ‘Helicobacter pylori’ (H. Pylori), you will also be given antibiotics. Using Rabtaj tablets and antibiotics together gets rid of the infection and makes the ulcer heal. It also stops the infection and ulcer from coming back
  • Zollinger-Ellison Syndrome where your stomach produces too much acid
  1. What you need to know before you take Rabtaj

Do not take Rabtaj if

  • You are allergic (hypersensitive) to rabeprazole sodium, or any of the other ingredients of this medicine (listed in Section 6).
  • You are pregnant or think that you are pregnant
  • You are breast feeding

Do not use Rabtaj if any of the above applies to you. If you are not sure, talk to your doctor or pharmacist before using Rabtaj

Warnings and precautions

Talk to your doctor or pharmacist before taking Rabtaj if:

  • You are allergic to other proton pump inhibitor medicines or ‘substituted benzimidazoles’.
  • Blood and liver problems have been seen in some patients but often get better when Rabtaj is stopped.
  • You have a stomach tumour.
  • You have ever had liver problems.
  • If you are taking atazanavir- for HIV infection.
  • If you have reduced body stores or risk factors for reduced vitamin B12 and receive long term treatment with rabeprazole sodium. As with all acid reducing agents, rabeprazole sodium may lead to a reduced absorption of vitamin B12.
    • If you have ever had a skin reaction after treatment with a medicine similar to Rabtaj that reduces stomach acid.
    • If you get a rash on your skin, especially in areas exposed to the sun tell your doctor as soon as you can, as you may need to stop your treatment with Rabtaj. Remember to also mention any other ill-effects like pain in your joints.
  • You are due to have a specific blood test (Chromogranin A).

If you are not sure if any of the above applies to you, talk to your doctor or pharmacist before using Rabtaj.

Children

Rabtaj should not be used in children.

If you experience severe (watery or bloody) diarrhoea with symptoms such as fever, abdominal pain or tenderness, stop taking Rabtaj and see a doctor straight away.

Taking a proton pump inhibitor like Rabtaj, especially over a period of more than one year, may slightly increase your risk of fracture in the hip, wrist or spine. Tell your doctor if you have osteoporosis or if you are taking corticosteroids (which can increase the risk of osteoporosis).

Other medicines and Rabtaj

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines. This includes medicines obtained without a prescription, including herbal medicines.

In particular, tell your doctor or pharmacist if you are taking any of the following medicines:

  • Ketoconazole or itraconazole – used to treat infections caused by a fungus. Rabtaj may lower the amount of this type of medicine in your blood. Your doctor may need to adjust your dose.
  • Atazanavir– used to treat HIV-infection. Rabtaj may lower the amount of this type of medicine in your blood and they should not be used together.
  • Methotrexate (a chemotherapy medicine used in high doses to treat cancer) – if you are taking a high dose of methotrexate, your doctor may temporarily stop your Rabtaj treatment.

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before using Rabtaj.

Pregnancy, breast feeding and fertility

  • Do not use Rabtaj if you are pregnant or think you may be pregnant
  • Do not use Rabtaj if you are breast-feeding or planning to breast-feed

If you are pregnant or breast feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

You may feel sleepy while taking Rabtaj. If this happens, do not drive or use any tools or machines.

  1. How to take Rabtaj

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Taking this medicine

  • Only remove a tablet from the blister strip when it is time to take your medicine.
  • Swallow your tablets whole with a drink of water. Do not chew or crush the tablets.
  • Your doctor will tell you how many tablets to take and how long to take them for. This will depend on your condition.
  • If you are taking this medicine for a long time, your doctor will want to monitor you.

Adults and older people

For ‘gastro-oesophageal reflux disease’ (GORD)

Treatment of moderate to severe symptoms (symptomatic GORD)

  • The usual dose is one Rabtaj 10 mg tablet once a day for up to 4 weeks
  • Take the tablet in the morning before eating
  • If your condition returns after 4 weeks treatment, your doctor may tell you to take one Rabtaj 10 mg tablet as and when you require it

Treatment of more severe symptoms (erosive or ulcerative GORD)

  • The usual dose is one Rabtaj 20 mg tablet once a day for 4 to 8 weeks
  • Take the tablet in the morning before eating

Long-term treatment of symptoms (GORD maintenance)

  • The usual dose is one Rabtaj 10 mg or 20 mg tablet once a day for as long as your doctor has told you
  • Take the tablet in the morning before eating
  • Your doctor will want to see you at regular intervals to check your symptoms and dosage

For ulcers of the stomach (peptic ulcers)

  • The usual dose is one Rabtaj 20 mg tablet once a day for 6 weeks
  • Take the tablet in the morning before eating
  • Your doctor may tell you to take Rabtaj for another 6 weeks if your condition does not improve

For ulcers of the intestine (duodenal ulcers)

  • The usual dose is one Rabtaj 20 mg tablet once a day for 4 weeks
  • Take the tablet in the morning before eating
  • Your doctor may tell you to take Rabtaj for another 4 weeks if your condition does not improve

For ulcers caused by H. Pylori infection and to stop them coming back

  • The usual dose is one Rabtaj 20 mg tablet twice a day for seven days
  • Your doctor will also tell you to take antibiotics called amoxicillin and clarithromycin

For further information on the other medicines used for the H. Pylori treatment, see the individual product information leaflets.

Zollinger-Ellison Syndrome where excess acid is produced in the stomach

  • The usual dose is three Rabtaj 20 mg tablets once a day to start with
  • The dose may then be adjusted by your doctor depending on how you respond to the treatment

If you are on long-term treatment you will need to see your doctor at regular intervals for review of your tablets and symptoms.

Patients with liver problems. You should consult your doctor who will take special care when beginning treatment with Rabtaj and while you continue to be treated with Rabtaj.

If you take more Rabtaj than you should

If you take more Rabtaj than you should, talk to a doctor or go to a hospital straight away. Take the medicine pack with you.

If you forget to take Rabtaj

  • If you forget to take a dose, take it as soon as you remember it. However, if it is almost time for your next dose, skip the missed dose and continue as usual
  • If you forget to take your medicine for more than 5 days, talk to your doctor before taking any more medicine
  • Do not take a double dose (two doses at the same time) to make up for a forgotten dose

If you stop taking Rabtaj

Relief of symptoms will normally occur before the ulcer has completely healed. It is important that you do not stop taking the tablets until told to do so by your doctor.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

  1. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The side effects are usually mild and improve without you having to stop taking this medicine.

Stop taking Rabtaj and see a doctor straight away if you notice any of the following side effects – you may need urgent medical treatment:

  • Allergic reactions – the signs may include: sudden swelling of your face, difficulty breathing or low blood pressure which may cause fainting or collapse
  • Frequent infections, such as a sore throat or high temperature (fever), or ulcers in your mouth or throat
  • Bruising or bleeding easily

These side effects are rare (affect less than 1 in 1,000 people).

  • Severe skin blistering, or soreness or ulcers in your mouth and throat

These side effects are very rare (affect less than 1 in 10, 000 people).

Other possible side effects:

Common (affect less than 1 in 10 people)

  • Infections
  • Difficulty sleeping
  • Headache or feeling dizzy
  • Cough, runny nose or sore throat (pharyngitis)
  • Effects on your stomach or gut such as stomach pain, diarrhoea, wind (flatulence), feeling sick (nausea), being sick (vomiting) or constipation
  • Aches or back pain
  • Weakness or flu-like symptoms
  • Benign polyps in the stomach.

Uncommon (affect less than 1 in 100 people)

  • Feeling nervous or drowsy
  • Chest infection (bronchitis)
  • Painful and blocked sinuses (sinusitis)
  • Dry mouth
  • Indigestion or belching
  • Skin rash or redness
  • Muscle, leg or joint pain
  • Fractures of the hip, wrist and spine
  • Bladder infection (urinary tract infection)
  • Chest pain
  • Chills or fever
  • Changes in how your liver is working (shown in blood tests)

Rare (affect less than 1 in 1,000 people)

  • Loss of appetite (Anorexia)
  • Depression
  • Hypersensitivity (includes allergic reactions)
  • Visual disturbance
  • Sore mouth (stomatitis) or taste disturbance
  • Upset stomach or stomach pain
  • Liver problems including yellowing of your skin and whites of your eyes (jaundice)
  • Itchy rash or blistering skin
  • Sweating
  • Kidney problems
  • Weight gain
  • Changes in white blood cells (shown in blood tests) which may result in frequent infection
  • Reduction in blood platelets resulting in bleeding or bruising more easily than normal

Other possible side effects (unknown frequency)

  • Breast swelling in men
  • Fluid retention
  • Inflammation of the gut (leading to diarrhoea)
  • Low blood levels of sodium which can cause tiredness and confusion, muscle twitching, fits and coma
  • Patients who have previously had liver problems may very rarely get encephalopathy (a brain disease)”
  • Rash, possibly with pain in the joints

If you are on Rabtaj for more than three months it is possible that the levels of magnesium in your blood may fall. Low levels of magnesium can be seen as fatigue, involuntary muscle contractions, disorientation, convulsions, dizziness, increased heart rate. If you get any of these symptoms, please tell your doctor promptly. Low levels of magnesium can also lead to a reduction in potassium or calcium levels in the blood. Your doctor may decide to perform regular blood tests to monitor your levels of magnesium.

Do not be concerned by this list of side effects. You may not get any of them.

Reporting of side effects

If you get any side effects talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

  1. How to store Rabtaj

Keep out of the sight and reach of children.

Do not store this medicine above 25°C.

Do not refrigerate.

Do not use Rabtaj after the expiry date which is stated on the carton and blister foil. The expiry date refers to the last day of that month.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer required. These measures will help to protect the environment.

  1. Contents of the pack and other information

What Rabtaj contains

Each Rabtaj 10 mg tablet contains 10 mg of the active substance rabeprazole sodium.

The other ingredients it contains:

mannitol, magnesium oxide, low-substituted hyprolose, hyprolose, magnesium stearate, ethylcellulose, hypromellose phthalate, diacetylated monoglycerides, talc, titanium dioxide, red iron oxide, Carnauba wax and ink (white shellac, black iron oxide), dehydrated ethyl alcohol, 1-butanol.

Each Rabtaj 20 mg tablet contains 20 mg of the active substance rabeprazole sodium.

The other ingredients it contains:

mannitol, magnesium oxide, low-substituted hyprolose, hyprolose, magnesium stearate, ethylcellulose, hypromellose phthalate, diacetylated monoglycerides, talc, titanium dioxide, yellow iron oxide, Carnauba wax and ink (white shellac, red iron oxide), glycerine fatty acid ester, dehydrated ethyl alcohol, 1-butanol.

What Rabtaj looks like and contents of the pack

Rabtaj 10 mg gastro-resistant tablet is a biconvex tablet.

Rabtaj 20 mg gastro-resistant tablet biconvex tablet.

The tablets are packed in blister strips and come in pack sizes that contain: 1, 5, 7, 14, 15, 25, 28, 30, 50, 56, 75, 98, 112 or 120 tablets.

Not all pack sizes may be marketed.

7. Manufactured in India By:
TAJ PHARMACEUTICALS LTD.
29, Xcelon Industrial Park-1,
Behind Intas Pharmaceuticals,
At & Po Vasna – Chacharwadi,
Tal- Sanand, Dist- Ahmedabad-382213,
Gujarat, India