Side effects and drug interactions.
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-marketing experience. Frequencies are defined as: common (> 1/100, < 1/10), uncommon (> 1/1,000, < 1/100), rare (>1/10,000, <1/1000) very rare (<1/10,000), not known (cannot be estimated from the available data).
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 RAVSID is first initiated in such patients (see section
4.4). 4 See Special warnings and precautions for use.
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 RAVSID. In clinical trials, antacids were used concomitantly with the administration of RAVSID and, in a specific drug-drug interaction study, no interaction with liquid antacids was observed. Co-administration of atazanavir 300 mg/ritonavir 100 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). Methotrexate Case reports, published population pharmacokinetic studies, and retrospective analyses suggest that concomitant administration of PPIs and methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate. However, no formal drug interaction studies of methotrexate with PPIs have been conducted.
Administration during pregnancy or breast-feeding.
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. RAVSID is contraindicated during pregnancy. Breast-feeding: It is not known whether rabeprazole sodium is excreted in human breast milk. No studies in breast-feeding women have been performed. Rabeprazole sodium is however excreted in rat mammary secretions. Therefore RAVSID should not be used during breast-feeding.
RAVSID is not recommended for use in children, as there is no experience of its use in this group.
Experience to date with deliberate or accidental overdose is limited. The maximum established exposure has not exceeded 60mg twice daily, or 160mg 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. Ability to influence reaction velocity while driving or operating any other mechanisms. Based on the pharmacodynamic properties and the adverse events profile, it is unlikely that RAVSID 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.