te ulcers. placebo-controlled studies have been carried out for 1 year. treatment of gerd. symptomatic relief commonly occurs within 24 hours after starting therapy with ranitidine 150 mg twice daily. treatment of endoscopically diagnosed erosive esophagitis. symptomatic relief of heartburn commonly occurs within 24 hours of therapy initiation with ranitidine 150 mg 4 times daily. maintenance of healing of erosive esophagitis. placebo-controlled trials have been carried out for 48 weeks. concomitant antacids should be given as needed for pain relief to patients with active duodenal ulcer; active, benign gastric ulcer; hypersecretory states; gerd; and erosive esophagitis.

ance of healing of duodenal ulcers the current recommended adult oral dosage is 150 mg or 10 ml of oral solution (2 teaspoonfuls of oral solution equivalent to 150 mg of ranitidine) at bedtime. pathological hypersecretory conditions (such as zollinger-ellison syndrome) the current recommended adult oral dosage is 150 mg or 10 ml of oral solution (2 teaspoonfuls of oral solution equivalent to 150 mg of ranitidine) twice a day. in some patients it may be necessary to administer ranitidine 150 mg doses more frequently. dosages should be adjusted to individual patient needs, and should continue as long as clinically indicated. dosages up to 6 g/day have been employed in patients with severe disease. benign gastric ulcer the current recommended adult oral dosage is 150 mg or 10 ml of oral solution (2 teaspoonfuls of oral solution equivalent to 150 mg of ranitidine) twice a day. maintenance of healing of gastric ulcers the current recommended adult oral dosage is 150 mg or 10 ml of oral solution (2 teaspoonfuls of oral solution equivalent to 150 mg of ranitidine) at bedtime. gerd the current recommended adult oral dosage is 150 mg or 10 ml of oral solution (2 teaspoonfuls of oral solution equivalent to 150 mg of ranitidine) twice a day. erosive esophagitis the current recommended adult oral dosage is 150 mg or 10 ml of oral solution (2 teaspoonfuls of oral solution equivalent to 150 mg of ranitidine) four times a day. maintenance of healing of erosive esophagitis the current recommended adult oral dosage is 150 mg or 10 ml of oral solution (2 teaspoonfuls of oral solution equivalent to 150 mg of ranitidine) twice a day. pediatric use the safety and effectiveness of ranitidine have been established in the age-group of 1 month to 16 years. there is insufficient information about the pharmacokinetics of ranitidine in neonatal patients (less than 1 month of age) to make dosing recommendations. the following 3 subsections provide dosing information for each of the pediatric indications. treatment of duodenal and gastric ulcers the recommended oral dose for the treatment of active duodenal and gastric ulcers is 2 to 4 mg/kg twice daily to a maximum of 300 mg/day. this recommendation is derived from adult clinical studies and pharmacokinetic data in pediatric patients. maintenance of healing of duodenal and gastric ulcers the recommended oral dose for the maintenance of healing of duodenal and gastric ulcers is 2 to 4 mg/kg once daily to a maximum of 150 mg/day. this recommendation is derived from adult clinical studies and pharmacokinetic data in pediatric patients. treatment of gerd and erosive esophagitis although limited data exist for these conditions in pediatric patients, published literature supports a dosage of 5 to 10 mg/kg per day, usually given as two divided doses. dosage adjustment for patients with impaired renal function on the basis of experience with a group of subjects with severely impaired renal function treated with ranitidine, the recommended dosage in patients with a creatinine clearance <50 ml/min is 150 mg or 10 ml of oral solution (2 teaspoonfuls of oral solution equivalent to 150 mg of ranitidine) every 24 hours. should the patient's condition require, the frequency of dosing may be increased to every 12 hours or even further with caution. hemodialysis reduces the level of circulating ranitidine. ideally, the dosing schedule should be adjusted so that the timing of a scheduled dose coincides with the end of hemodialysis. elderly patients are more likely to have decreased renal function, therefore caution should be exercised in dose selection, and it may be useful to monitor renal function (see clinical pharmacology: pharmacokinetics: geriatrics and precautions: geriatric use).

hepatic there have been occasional reports of hepatocellular, cholestatic, or mixed hepatitis, with or without jaundice. in such circumstances, ranitidine should be immediately discontinued. these events are usually reversible, but in rare circumstances death has occurred. rare cases of hepatic failure have also been reported. in normal volunteers, sgpt values were increased to at least twice the pretreatment levels in 6 of 12 subjects receiving 100 mg intravenously 4 times daily for 7 days, and in 4 of 24 subjects receiving 50 mg intravenously 4 times daily for 5 days. musculoskeletal rare reports of arthralgias and myalgias. hematologic blood count changes (leukopenia, granulocytopenia, and thrombocytopenia) have occurred in a few patients. these were usually reversible. rare cases of agranulocytosis, pancytopenia, sometimes with marrow hypoplasia, and aplastic anemia and exceedingly rare cases of acquired immune hemolytic anemia have been reported. endocrine controlled studies in animals and man have shown no stimulation of any pituitary hormone by ranitidine and no antiandrogenic activity, and cimetidine-induced gynecomastia and impotence in hypersecretory patients have resolved when ranitidine has been substituted. however, occasional cases of impotence and loss of libido have been reported in male patients receiving ranitidine, but the incidence did not differ from that in the general population. rare cases of breast symptoms and conditions, including galactorrhea and gynecomastia, have been reported in both males and females. integumentary rash, including rare cases of erythema multiforme. rare cases of alopecia and vasculitis. respiratory a large epidemiological study suggested an increased risk of developing pneumonia in current users of histamine-2-receptor antagonists (h2ras) compared to patients who had stopped h2ra treatment, with an observed adjusted relative risk of 1.63 (95% ci 1.07-2.48). however, a causal relationship between use of h2ras and pneumonia has not been established. other rare cases of hypersensitivity reactions (e.g., bronchospasm, fever, rash, eosinophilia), anaphylaxis, angioneurotic edema, acute interstitial nephritis, and small increases in serum creatinine.

es 15%. metabolism in humans, the n-oxide is the principal metabolite in the urine; however, this amounts to <4% of the dose. other metabolites are the s-oxide (1%) and the desmethyl ranitidine (1%). the remainder of the administered dose is found in the stool. studies in patients with hepatic dysfunction (compensated cirrhosis) indicate that there are minor, but clinically insignificant, alterations in ranitidine half-life, distribution, clearance, and bioavailability. excretion the principal route of excretion is the urine, with approximately 30% of the orally administered dose collected in the urine as unchanged drug in 24 hours. renal clearance is about 410 ml/min, indicating active tubular excretion. the elimination half-life is 2.5 to 3 hours. four patients with clinically significant renal function impairment (creatinine clearance 25 to 35 ml/min) administered 50 mg of ranitidine intravenously had an average plasma half-life of 4.8 hours, a ranitidine clearance of 29 ml/min, and a volume of distribution of 1.76 l/kg. in general, these parameters appear to be altered in proportion to creatinine clearance (see dosage and administration). geriatrics the plasma half-life is prolonged and total clearance is reduced in the elderly population due to a decrease in renal function. the elimination half-life is 3 to 4 hours. peak levels average 526 ng/ml following a 150 mg twice daily dose and occur in about 3 hours (see precautions: geriatric use and dosage and administration: dosage adjustment for patients with impaired renal function). pediatrics there are no significant differences in the pharmacokinetic parameter values for ranitidine in pediatric patients (from 1 month up to 16 years of age) and healthy adults when correction is made for body weight. the average bioavailability of ranitidine given orally to pediatric patients is 48% which is comparable to the bioavailability of ranitidine in the adult population. all other pharmacokinetic parameter values (t1/2, vd, and cl) are similar to those observed with intravenous ranitidine use in pediatric patients. estimates of cmax and tmax are displayed in table 1. table 1: ranitidine pharmacokinetics in pediatric patients following oral dosing population (age) n dosage form (dose) cmax (ng/ml) tmax (hours) gastric or duodenal ulcer (3.5 to 16 years) 12 tablets (1 to 2 mg/kg) 54 to 492 2.0 otherwise healthy requiring ranitidine (0.7 to 14 years, single dose) 10 oral solution (2 mg/kg) 244 1.61 otherwise healthy requiring ranitidine (0.7 to 14 years, multiple dose) 10 oral solution (2 mg/kg) 320 1.66 plasma clearance measured in two neonatal patients (less than 1 month of age) was considerably lower (3 ml/min/kg) than children or adults and is likely due to reduced renal function observed in this population. (see precautions: pediatric use and dosage and administration: pediatric use). pharmacodynamics serum concentrations necessary to inhibit 50% of stimulated gastric acid secretion are estimated to be 36 to 94 ng/ml. following a single oral dose of 150 mg, serum concentrations of ranitidine are in this range up to 12 hours. however, blood levels bear no consistent relationship to dose or degree of acid inhibition. antisecretory activity 1. effects on acid secretion ranitidine inhibits both daytime and nocturnal basal gastric acid secretions as well as gastric acid secretion stimulated by food, betazole, and pentagastrin, as shown in table 2. table 2: effect of oral ranitidine syrup (ranitidine oral solution usp) on gastric acid secretion time after dose, h % inhibition of gastric acid output by dose, mg 75-80 100 150 200 basal up to 4 99 95 nocturnal up to 13 95 96 92 betazole up to 3 97 99 pentagastrin up to 5 58 72 72 80 meal up to 3 73 79 95 it appears that basal-, nocturnal-, and betazole-stimulated secretions are most sensitive to inhibition by ranitidine, responding almost completely to doses of 100 mg or less, while pentagastrin- and food-stimulated secretions are more difficult to suppress. 2. effects on other gastrointestinal secretions pepsin oral ranitidine does not affect pepsin secretion. total pepsin output is reduced in proportion to the decrease in volume of gastric juice. intrinsic factor oral ranitidine has no significant effect on pentagastrin-stimulated intrinsic factor secretion. serum gastrin ranitidine has little or no effect on fasting or postprandial serum gastrin. other pharmacologic actions a. gastric bacterial flora—increase in nitrate-reducing organisms, significance not known. b. prolactin levels—no effect in recommended oral or intravenous (iv) dosage, but small, transient, dose-related increases in serum prolactin have been reported after iv bolus injections of 100 mg or more. c. other pituitary hormones—no effect on serum gonadotropins, tsh, or gh. possible impairment of vasopressin release. d. no change in cortisol, aldosterone, androgen, or estrogen levels. e. no antiandrogenic action. f. no effect on count, motility, or morphology of sperm. pediatrics oral doses of 6 to 10 mg/kg per day in two or three divided doses maintain gastric ph>4 throughout most of the dosing interval.