RABEPRAZOLE ACCORD Gastro-resistant tablet Ref.[7344] Active ingredients: Rabeprazole

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.

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.

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).

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.

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.

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.

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).

Infections and infestations

Common: Infection

Blood and lymphatic system disorders

Rare: Neutropenia, Leucopenia, Thrombocytopenia, Leucocytosis

Immune system disorders

Rare: Hypersensitivity^1,2

Metabolism and nutrition disorders

Rare: Anorexia

Not known: Hyponatremia, Hypomagnesaemia⁴

Psychiatric disorders

Common: Insomnia

Uncommon: Nervousness

Rare: Depression

Not known: Confusion

Nervous system disorders

Common: Headache, Dizziness

Uncommon: Somnolence

Eye disorders

Rare: Visual disturbance

Vascular disorders

Not known: Peripheral oedema

Respiratory, thoracic and mediastinal disorders

Common: Cough, Pharyngitis, Rhinitis

Uncommon: Bronchitis, Sinusitis

Gastrointestinal disorders

Common: Diarrhoea, Vomiting, Nausea, Abdominal pain, Constipation, Flatulence, Fundic gland polyps (benign)

Uncommon: Dyspepsia, Dry mouth, Eructation

Rare: Gastritis, Stomatitis, Taste disturbance

Not known: Microscopic colitis

Hepatobiliary disorders

Rare: Hepatitis, Jaundice, Hepatic encephalopathy³

Skin and subcutaneous tissue disorders

Uncommon: Rash, Erythema²

Rare: Pruritus, Sweating, Bullous reactions²

Very Rare: Erythema multiforme, toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS)

Not known: Subacute cutaneous lupus erythematosus (see section 4.4)

Musculoskeletal and connective tissue disorders

Common: Non-specific pain, Back pain

Uncommon: Myalgia, Leg cramps, Arthralgia, Fracture of the hip, wrist or spine (see section 4.4)

Renal and urinary disorders

Uncommon: Urinary tract infection

Rare: Interstitial nephritis

Reproductive system and breast disorders

Not known: Gynecomastia

General disorders and administration site conditions

Common: Asthenia, Influenza like illness

Uncommon: Chest pain, Chills, Pyrexia

Investigations

Uncommon: Increased hepatic enzymes³

Rare: Weight 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. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme; website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Not applicable.