Safety Of Ranitidine Research Articles

The Safety and Efficacy of Acid Suppression Therapy in Neonatal GERD

Gastroesophageal reflux (GER) is a common physiologic process in infants that often resolves with growth and maturation, while gastroesophageal reflux disease (GERD) is a serious and common referral disease in infants and neonates. The first-line treatment for both GER and GERD is conservative therapy. H2RAs and PPIs are the two basic pharmacologic agents in the treatment of GERD in pediatrics and adults. The efficacy of PPIs is higher than that of H2RAs in GERD treatment. There are controversies in the pharmacologic treatment of neonatal GERD, and performing more clinical trials to survey the effect of PPIs and H2RAs and compare them with each other is necessary in this age group. We conducted three different clinical trials to compare the efficacy and safety of ranitidine with omeprazole or lansoprazole in refractory neonatal GERD.

Clinical Use of Gastric Antisecretory Drugs in Hospitalized Pediatric Patients.

Antisecretory drugs are frequently used in the treatment of pediatric gastrointestinal disorders. This study was aimed to assess the prescribing patterns and the safety of ranitidine and proton pump inhibitors (PPIs) in a cohort of Italian pediatric patients. Children aged >1 month to <16 years that were admitted to our Pediatric Clinic between 2016 and 2018 were enrolled in this retrospective observational study. All data were obtained from medical records and a parent telephone questionnaire. The exclusion criteria included the use of antisecretory therapy at hospital admission, failure to collect the relevant clinical data, and failure to administer the questionnaire. This study included 461 subjects, who were divided into four age groups: <2 years, 2−5 years, 6−11 years, and ≥12 years. Ranitidine was prescribed in 396 (85.9%) patients, mainly for the acute treatment of gastrointestinal symptoms, and a PPI was given to 65 (14.1%) children to treat gastroesophageal reflux disease, gastritis/ulcer, or for gastroprotection. During the study period, the percentage of patients treated with ranitidine progressively increased, except in the 2−5-year age group. We observed eighty-seven adverse drug reactions (ADRs), 61 of which occurred in the ranitidine group and 26 in the PPI group. The most common ADR was constipation (n = 35), which occurred more frequently in children treated with PPIs and in the 6−11-year age group. Ranitidine was the most used antisecretory drug in all the age groups, especially for acute treatment. Conversely, PPIs were the drugs of choice for prolonged treatments. Further research should be focused on developing an effective and safer alternative to ranitidine.

Ranitidine use in pediatrics: current evidence-based review and recommendations

Ranitidine plays a pivotal role in routine pediatric practice. The multi-dimensional use and safety of ranitidine are not supported by any practical guidelines, which led to recommendations convened by a group of experts based on evidence and the clinical experience of experts. A group of general pediatricians and pediatric gastroenterologists from India were part of this panel. This group of experts reviewed the literature on topics that were unanimously agreed upon, for which no recommendations were available. The Delphi method was implemented to reach unified decisions, which led to the development of evidence-based recommendations. Gastritis and gastroesophageal reflux disease (GERD) are common conditions seen in pediatric practice. Ranitidine has a rapid onset of action compared to proton pump inhibitors (PPIs). It is a preferred drug for on-demand use for gastritis and managing stress-induced gastric lesions in critically ill pediatric patients. Ranitidine has an established role in the management of GERD, and it also prevents nocturnal acid reflux effectively. It helps in reducing gastric fluid volume when used as preoperative prophylaxis. Also, ranitidine has a better safety profile in comparison to PPIs. Recommendations on the use and safety of ranitidine in pediatrics were developed which will be a guiding tool for all practicing clinicians, highlighting the strength and benefits of ranitidine as a better and safe alternative to PPIs in short-term acid suppression for multiple indications.

The Safety and Efficacy of Lansoprazole plus Metoclopramide among Neonates with Gastroesophageal Reflux Disease Resistant to Conservative Therapy and Monotherapy: A Clinical Trial.

Background Gastroesophageal reflux disease (GERD) is one of the most common problems in neonates. The main clinical manifestations of neonatal GERD are frequent regurgitation or vomiting associated with irritability, crying, anorexia or feeding refusal, failure to thrive, arching of the back, and sleep disturbance. Aims The efficacy and safety of ranitidine plus metoclopramide and lansoprazole plus metoclopramide in reducing clinical GERD symptoms based on I-GERQ-R scores in neonatal GERD resistant to conservative and monotherapy. Study Design. This study was a randomized clinical trial of term neonates with GERD diagnosis (according to the final version of the I-GERQ-R), resistant to conservative and monotherapy admitted to Bahrami Children Hospital during 2017-2019. Totally, 120 term neonates (mean age 10.91 ± 7.17 days; girls 54.63%) were randomly assigned to a double-blind trial with either oral ranitidine plus metoclopramide (group A) or oral lansoprazole plus metoclopramide (group B). The changes of the symptoms and signs were recorded after one week and one month. At the end, fifty-four neonates in each group completed the study and their data were analyzed. Results There was no significant difference in demographic and baseline characteristics between the two groups. The response rate of “lansoprazole plus metoclopramide” was significantly higher than “ranitidine plus metoclopramide” (7.44 ± 3.86 score vs. 9.3 ± 4.57 score, p = 0.018) after one week and (2.41 ± 3.06 score vs. 4.5 ± 4.12 score, p = 0.003) after one month (primary outcome). There were no drug adverse effects in either group during intervention (secondary outcome). Conclusions The response rate was significant in each group after one week and one month of treatment, but it was significantly higher in the “lansoprazole plus metoclopramide” group compared with the “ranitidine plus metoclopramide” group. The combination of each acid suppressant with metoclopramide led to a higher response rate in comparison with monotherapy used before intervention. This study has been registered at the Iranian Registry of Clinical Trails (RCT20160827029535N3).

The safety of ranitidine in over a decade of use.

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. 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. 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. 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.

An evaluation of the safety of ranitidine during seven years daily oral administration to beagle dogs.

1. Ranitidine hydrochloride was administered orally to Beagles at doses equivalent to 50 mg once daily, or 5 mg twice daily, of ranitidine base/kg for more than 7 years. 2. Apart from looseness of faeces, seen mainly after doses of 50 mg/kg and only rarely after the first year of such treatment, there were no adverse clinical effects. There were no deaths related to treatment. 3. Periodic gastroscopy revealed nothing abnormal. 4. Peak plasma levels of ranitidine occurred within 2 h of dosing; levels were proportional to the doses administered. 5. There were no major differences in fasting plasma gastrin levels between treated and untreated dogs; the expected increase occurred in response to the provision of food and, predictably, this was greater following a dose of ranitidine. 6. A normal histamine-induced gastric secretory response was demonstrated. 7. Necropsy revealed no lesions of toxicological significance. Macroscopically the stomachs appeared normal but microscopic examination showed some gastritis in both treated and control dogs. No changes in enterochromaffin-like (ECL) cells were detected. Electron microscopy showed unimpaired secretory activity of parietal cells. 8. Thus, after more than 7 years administration to beagle dogs of doses in excess of the normal daily therapeutic dose, the stomachs showed no changes attributable to treatment and their secretory capacity was unimpaired.

Single blind comparative study of ranitidine and cimetidine in patients with gastric ulcer. The Belgian Peptic Ulcer Study Group.

In a single blind multicentre study, the efficacy and safety of ranitidine was compared with cimetidine in patients with gastric ulcer confirmed by endoscopy. Patients were randomly allocated to receive either 150 mg ranitidine twice daily, or 200 mg cimetidine three times a day and 400 mg at night for four weeks; patients with unhealed ulcers continued the same treatment for a further two weeks. Out of 260 patients, 197 were analysed. Of the ranitidine treated patients, 66% were healed after four weeks and 78% after six weeks and of the cimetidine treated patients 62% were healed after four weeks and 87% after six weeks. These differences are not significant. These results confirmed that ranitidine is as effective as cimetidine in the acute treatment of gastric ulcer.