Rabeprazole Other names: Rabeprazole sodium

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.

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.

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, although low foeto-placental transfer occurs in rats. Rabeprazole is contraindicated during pregnancy.

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

Based on the pharmacodynamic properties and the adverse events profile, it is unlikely that rabeprazole 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, Hypomagnesaemia

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

Musculoskeletal and connective tissue disorders

Common: Non-specific pain, Back pain

Uncommon: Myalgia, Leg cramps, Arthralgia, Fracture of the hip, wrist or spine

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 is first initiated in such patients.