Side Effects of Ranitidine

Abstract

Ranitidine was first marketed in 1981; since then many patients have been treated such that much experience has been accumulated on the safety of this histamine H2-receptor antagonist in the treatment of gastroduodenal disease. A wide array of ranitidine-associated side effects has been described, but infrequently. As so much information is now available, the aim of this review is to assess the weight of evidence for a causal link between ranitidine and the reported side effects. Overall, ranitidine is well tolerated. The incidence of general side effects at less than 2% is very similar to placebo. Headaches, tiredness, dizziness and mild gastrointestinal disturbance (e.g. diarrhoea, constipation and nausea) are among the most frequent complaints, but have very seldom resulted in stopping treatment. Cardiovascular side effects are extremely rare and unpredictable with the usual doses of oral ranitidine (at most 1 in 1 million patients). They mostly comprise sinusal bradycardia and atrioventricular blockade, especially after rapid intravenous administration, receding after cessation of the drug. Clinical studies, however, have not shown a significant pharmacological effect of ranitidine on the cardiovascular system via H2-receptors, even though individual sensitivities cannot be ruled out in a few isolated reports. Ranitidine is unlikely to be directly hepatotoxic: a transient change in liver function tests has been noted in only 1 in 100 to 1 in 1000 patients. Several cases of mixed hepatitis have been reported, but very few were fully documented. The incidence of ranitidine-associated acute hepatitis has been estimated to be less than 1 in 100,000 patients. Neuropsychiatric complications may be less common and clinically quite similar to those reported with cimetidine, i.e. confusion, disorientation, hallucinations, delirium. These side effects have occurred especially in critically ill and multiple-therapy patients, or patients with chronic renal or hepatic failure, so that the direct causal link with ranitidine treatment was often difficult to ascertain. Even though an H2-receptor-mediated effect is an attractive hypothesis (since similar complications were noted with other H2-receptor antagonists), other mechanisms have been suggested to play a role, e.g. cholinergic or histaminic effects. The overall incidence of neuropsychiatric complications is probably markedly less than 1%. White cell injury (i.e. agranulocytosis) appears to be the most frequent haematological complication, even though case reports are very few and poorly documented.(ABSTRACT TRUNCATED AT 400 WORDS)

Ranitidine Treatment during a Modest Inflammatory Response Precipitates Idiosyncrasy-Like Liver Injury in Rats

“…These modes of action have been proposed for RAN idiosyncrasy (Vial et al, 1991), but supporting evidence is lacking, and neither seems to explain easily all features observed in clinical cases of RAN hepatotoxicity. For example, time of onset of hepatotoxicity relative to the initiation of RAN therapy varies greatly: some episodes occur as early as 1 week, whereas others do not occur until months after the start of maintenance therapy (Halparin, 1984;Hiesse et al, 1985;Ramrakhiani et al, 1998).…”

“…for treatment of duodenal ulcers, gastric hypersecretory diseases, and gastroesophageal reflux disease. Idiosyncratic RAN hepatotoxicity occurs in less than 0.1% of people taking the drug (Vial et al, 1991). Most liver reactions are mild and reversible; however, extensive liver damage and death have occurred in individuals undergoing RAN therapy (Ribeiro et al, 2000).…”

Inflammatory Stress and Idiosyncratic Hepatotoxicity: Hints from Animal Models

“…RAN is available over the counter for oral administration or by prescription for parenteral administration for treatment of duodenal ulcers, gastric hypersecretory diseases, and gastroesophageal reflux disease. Idiosyncratic hepatotoxicity occurs in less than 0.1% of people taking RAN (Vial et al, 1991). A summary of numerous published case reports appears in Table 3.…”

Coagulation-Mediated Hypoxia and Neutrophil-Dependent Hepatic Injury in Rats Given Lipopolysaccharide and Ranitidine

“…RAN is associated with idiosyncratic hepatotoxicity in a small fraction (estimated at Ͻ0.1%) of people taking the drug (Vial et al, 1991). Although the mechanism of RAN-induced hepatotoxicity is not understood, inflammation might be a predisposing factor for idiosyncratic hepatotoxicity from this drug and others Ganey et al, 2004).…”