Drug Class Description
Proton pump inhibitors (PPIs).

Generic Name
Rabeprazole

Drug Description
PARIET® 10mg gastro-resistant tabletPARIET® 20mg gastro-resistant tablet

Presentation
Gastro-resistant tablet.10mg: Pink, film coated biconvex tablet with 'E 241' printed on one side.20mg: Yellow, film coated biconvex tablet with 'E 243' printed on one side

Indications
PARIET 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.

Adult Dosage
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 20mg 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 20mg 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 PARIET 20mg or 10mg once daily can be used depending upon patient response.Symptomatic treatment of moderate to very severe gastro-oesophageal reflux disease (symptomatic GORD): 10mg 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 60 mg once a day. The dose may be titrated upwards to 120mg/day based on individual patient needs. Single daily doses up to 100mg/day may be given. 120mg dose may require divided doses, 60mg 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.PARIET 20mg twice daily + clarithromycin 500mg twice daily and amoxicillin 1g twice daily.For indications requiring once daily treatment PARIET 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 PARIET tablets should not be chewed or crushed, but should be swallowed whole.Renal and hepatic impairment: No dosage adjustment is necessary for patients with renal or hepatic impairment.

Child Dosage
PARIET is not recommended for use in children, as there is no experience of its use in this group.

Contra Indications
PARIET is contra-indicated in patients with known hypersensitivity to rabeprazole sodium, or to any excipient used in the formulation. PARIET is contra-indicated in pregnancy and during breast feeding.

Special 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 PARIET.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 PARIET tablets should not be chewed or crushed, but should be swallowed whole.PARIET 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 PARIET in the treatment of patients with severe hepatic dysfunction the prescriber is advised to exercise caution when treatment with PARIET is first initiated in such patients.

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 with PARIET.In clinical trials, antacids were used concomitantly with the administration of PARIET 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 PPIs, including rabeprazole, should not be co-administered with atazanavir

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 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: common (>1/100, <1/10), uncommon (> 1/1,000, <1/100), rare (>1/10,000, <1/1000) and very rare ( <1/10,000).System Organ ClassCommonUncommonRare Very RareNot KnownInfections and infestationsInfectionBlood and the lymphatic system disordersNeutropeniaLeucopeniaThrombocytopeniaLeucocytosisImmune system disorders Hypersensitivity1,2Metabolism and nutrition disordersAnorexiaHyponatremiaPsychiatric disordersInsomniaNervousnessDepressionConfusionNervous system disordersHeadacheDizzinessSomnolenceEye disordersVisual disturbanceVascular disordersPeripheral oedemaRespiratory, thoracic and mediastinal disordersCoughPharyngitisRhinitisBronchitisSinusitisGastrointestinal disordersDiarrhoeaVomitingNauseaAbdominal painConstipationFlatulenceDyspepsiaDry mouthEructationGastritisStomatitisTaste disturbanceHepato-biliary disorders HepatitisJaundiceHepatic encephalopathy3Skin and subcutaneous tissue disordersRashErythema2PruritusSweatingBullous reactions2Erythema multiforme, toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS)Musculoskeletal, connective tissue and bone disordersNon-specific painBack painMyalgiaLeg crampsArthralgiaRenal and urinary disordersUrinary tract infectionInterstitial nephritisReproductive system and breast disordersGynaecomastiaGeneral disorders and administration site conditionsAstheniaInfluenza like illnessChest painChillsPyrexiaInvestigationsIncreased hepatic enzymes3Weight increased1 Includes facial swelling, hypotension and dyspnoea2 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 PARIET is first initiated in such patients.

Manufacturer
Eisai Ltd

Drug Availability
(POM)

Updated
24 June 2009