- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
PosologyAdults/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 sodium 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 sodium 20 mg twice daily + clarithromycin 500 mg twice daily and amoxicillin 1 g twice daily.Renal and hepatic impairment: No dosage adjustment is necessary for patients with renal or hepatic impairment.See section 4.4 Special Warnings and Precautions for Use of Rabeprazole sodium in the treatment of patients with severe hepatic impairment.
Paediatric populationRabeprazole sodium is not recommended for use in children, as there is no experience of its use in this group.
Method of administrationFor indications requiring once daily treatment Rabeprazole sodium 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 sodium tablets should not be chewed or crushed, but should be swallowed whole.
Paediatric populationRabeprazole 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). 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 sodium is first initiated in such patients.Co-administration of atazanavir with Rabeprazole sodium is not recommended (see section 4.5).Treatment with proton pump inhibitors, including Rabeprazole sodium, may possibly increase the risk of gastrointestinal infections such as Salmonella, Campylobacter and Clostridium difficile (see section 5.1).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 1040%. 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.
PregnancyThere 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 sodium is contraindicated during pregnancy.
Breast-feedingIt 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 sodium should not be used during breast feeding.
|System Organ Class||Common||Uncommon||Rare||Very rare||Not known|
|Infections and infestations||infection|
|Blood and lymphatic system disorders||neutropenia, leucopenia, thrombocytopenia, leucocytosis|
|Immune system disorders||hypersensitivity1,2|
|Metabolism and nutrition disorders||anorexia||hyponatremia, hypomagnesaemia (see section 4.4)|
|Nervous system disorders||headache, dizziness||somnolence|
|Eye disorders||visual disturbance|
|Vascular disorders||peripheral oedema|
|Respiratory, thoracic and mediastinal disorders||cough, pharyngitis, rhinitis||bronchitis, sinusitis|
|Gastrointestinal disorders||diarrhoea, vomiting, nausea, abdominal pain, constipation, flatulence||dyspepsia, dry mouth, eructation||gastritis, stomatitis, taste disturbance|
|Hepato-biliary disorders||hepatitis, jaundice, hepatic encephalopathy3|
|Skin and subcutaneous tissue disorders||rash, erythema2||pruritus, sweating, bullous reactions2||erythema multiforme, toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS)|
|Musculoskeletal, connective tissue and bone disorders||non-specific pain, back pain||myalgia, leg cramps, arthralgia, fracture of the hip, wrist or spine (see section 4.4)|
|Renal and urinary disorders||urinary tract infection||interstitial nephritis|
|Reproductive system and breast disorders||gynaecomastia|
|General disorders and administration site conditions||asthenia, influenza like illness||chest pain, chills, pyrexia|
|Investigations||increased hepatic enzymes3||weight increased|
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:Yellow Card SchemeWebsite: www.mhra.gov.uk/yellowcard.
Mechanism of actionRabeprazole 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.Pharmacodynamic effectsAnti-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.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.
Clinical efficacy and safetyStudies 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.
Other special populationsCYP2C19 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%.
Tablet core:Mannitol (E421)Magnesium oxide, light (E530)Hydroxypropylcellulose (E463)Hydroxypropylcellulose, low-substituted (E463)Magnesium stearate (E572)
Coating:Ethylcellulose (E462)Magnesium oxide, light (E530)Hypromellose phthalateDiacetylated monoglycerides (E472a)Talc (E553b)Titanium dioxide (E171)Red iron oxide (E172)
Consilient Health Ltd
No. 1 Church Road, Richmond upon Thames, Surrey, TW9 2QE, UK
+44(0)20 3751 1889
+44(0) 20 3751 1888