Ranitidine

Comparative studies

Effervescent ranitidine 150 mg bd has been compared with as-needed calcium carbonate antacids 750 mg in a randomized study in 115 subjects who frequently self-treated heartburn [ ]. Effervescent ranitidine was significantly more effective than antacids in reducing heartburn, healing erosive esophagitis, alleviating pain, and improving quality of life. The overall incidences of adverse events were not significantly different in the two groups; 12% in the antacid group and 3% in the ranitidine group had adverse events related to the gastrointestinal system: nausea, vomiting, diarrhea, constipation, gas, fecal incontinence; and 1% in the antacid group and 4% in the ranitidine group had adverse events related to the central nervous system: headache, dizziness, insomnia, malaise, fatigue, weakness, nervousness.

A large multicenter comparison of intravenous pantoprazole and intravenous ranitidine in the prevention of ulcer rebleeding was terminated early after only 149 had been entered, owing to slow enrolment [ ]. The results showed a numerical but non-significant advantage with intravenous pantoprazole. There were adverse events in both groups, including headaches, abdominal pain, anemia, and pain with pantoprazole, and abdominal pain, headache, anemia, and infection with ranitidine. Non-bleeding serious adverse events were not significantly different between the groups and were all thought to be non-drug-related.

Placebo-controlled studies

The efficacy of low-dose ranitidine for the relief of heartburn has been studied in a double-blind, placebo-controlled trial [ ]. Subjects with heartburn were randomized to ranitidine 75 mg (n = 491), ranitidine 25 mg (n = 504), or placebo (n = 494), to be taken as needed up to four times a day for 2 weeks. Ranitidine 75 mg was significantly more effective than placebo and provided prompt relief of heartburn lasting up to 12 hours. The most common adverse effects were nausea, diarrhea, and headache, which occurred in under 2% of patients in each group.

In a randomized, placebo-controlled, four-way, crossover study of the effects of low-dose ranitidine and an antacid on meal-induced heartburn and acidity in 26 subjects, ranitidine 75 mg significantly reduced gastric but not esophageal acidity, calcium carbonate 420 mg significantly reduced esophageal but not gastric acidity, and ranitidine plus calcium carbonate reduced both esophageal and gastric acidity [ ]. Both drugs given alone reduced heartburn severity compared with placebo.

Cardiovascular

Atrioventricular block has been attributed to ranitidine [ ].

• A 20-year-old man taking ranitidine 300 mg/day had a brief episode of syncope. The only abnormal finding was first-degree atrioventricular block, which disappeared after withdrawal of ranitidine. Rechallenges on two separate occasions produced recurrence of asymptomatic first-degree atrioventricular block, but cimetidine 400–800 mg/day and famotidine 40–80 mg/day caused no electrocardiographic abnormalities.

The authors hypothesized that this patient may have been abnormally susceptible to the cholinergic or cholinergic-like effect of ranitidine, unrelated to its histamine H ₂ blocking action. However, the ability of ranitidine to release histamine may also have contributed.

Bradycardia occurred in a 4-day-old full-term male neonate 2 hours after the intravenous injection of ranitidine and resolved over 24 hours [ ].

Respiratory

Histamine H ₂ receptor antagonists can increase the risk of respiratory infections, and the possible significance of this effect has been studied best with ranitidine; there seems to be no reason for concern in most patients, but the risk can be considerable in some older patients with pre-existing health problems rendering them unduly susceptible to infection [ ].