The safety of ranitidine in over a decade of use.
BACKGROUND
Ranitidine hydrochloride (Zantac) is one of the most extensively studied and widely used drugs of all time. This has provided an excellent opportunity to define its safety profile.


METHODS
Data from 189 controlled clinical trials in which more than 26,000 patients received daily doses of ranitidine for 4 weeks or more were reviewed. More than 80% of patients were treated with up to 300 mg ranitidine daily; the remaining patients received doses of up to 1200 mg daily. Eighty-seven trials were placebo controlled. Analyses of post-marketing surveillance and a database of all spontaneously reported adverse events were also evaluated.


RESULTS
Overall in the clinical trial programme adverse events were reported by 20% of those receiving ranitidine compared with 27% of those receiving placebo. The pattern of events was similar in all treatment groups with no evidence of dose-related toxicity in regimens encompassing an eightfold range of therapeutic doses. Similarly in a programme of studies designed to evaluate a dose of ranitidine of 75 mg for non-prescription (over-the-counter) use in the treatment of heartburn, ranitidine was not associated with an adverse event profile distinct from that of placebo. Analysis of spontaneously reported adverse event data allowed identification of rare idiosyncratic events.


CONCLUSIONS
Review of data from a large population of controlled clinical trials with analyses of postmarketing surveillance studies and spontaneously reported adverse events confirmed the excellent safety profile of ranitidine.
Mills
J G
JG
Group Medical Operations, Glaxo Wellcome Research and Development, Uxbridge, UK.
Koch
K M
KM
Webster
C
C
Sirgo
M A
MA
Fitzgerald
K
K
Wood
J R
JR
D000897:Anti-Ulcer Agents / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D016208:Databases, Factual; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage; D006356:Heartburn / Q000188:drug therapy; D006635:Histamine H2 Antagonists / Q000009:adverse effects*; D006801:Humans; D011358:Product Surveillance, Postmarketing; D011899:Ranitidine / Q000009:adverse effects*; D013806:Theophylline / Q000008:administration & dosage; D014229:Triazolam / Q000008:administration & dosage; D014859:Warfarin / Q000008:administration & dosage
D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D014229:Triazolam; D000431:Ethanol; D014859:Warfarin; D011899:Ranitidine; D013806:Theophylline