in (15 to 20 minutes). in some patients it may be necessary to increase dosage. when this is necessary, the increases should be made by more frequent administration of the dose, but generally should not exceed 400 mg/day. continuous intravenous infusion add ranitidine injection to 5% dextrose injection or other compatible intravenous solution (see stability ). deliver at a rate of 6.25 mg/hour (e.g., 150 mg [6 ml] of ranitidine injection in 250 ml of 5% dextrose injection at 10.7 ml/hour). for zollinger-ellison patients, dilute ranitidine injection in 5% dextrose injection or other compatible intravenous solution (see stability ) to a concentration no greater than 2.5 mg/ml. start the infusion at a rate of 1.0 mg/kg/hour. if after 4 hours either a measured gastric acid output is >10 meq/hour or the patient becomes symptomatic, the dose should be adjusted upward in 0.5 mg/kg/hour increments, and the acid output should be remeasured. dosages up to 2.5 mg/kg/hour and infusion rates as high as 220 mg/hour have been used. pediatric use while limited data exist on the administration of intravenous ranitidine to children, the recommended dose in pediatric patients is for a total daily dose of 2 to 4 mg/kg, to be divided and administered every 6 to 8 hours, up to a maximum of 50 mg given every 6 to 8 hours. this recommendation is derived from adult clinical studies and pharmacokinetic data in pediatric patients. limited data in neonatal patients (less than 1 month of age) receiving ecmo have shown that a dose of 2 mg/kg is usually sufficient to increase gastric ph to >4 for at least 15 hours. therefore, doses of 2 mg/kg given every 12 to 24 hours or as a continuous infusion should be considered. dosage adjustment for patients with impaired renal function the administration of ranitidine as a continuous infusion has not been evaluated in patients with impaired renal function. on the basis of experience with a group of subjects with severely impaired renal function treated with ranitidine hydrochloride, the recommended dosage in patients with a creatinine clearance <50 ml/min is 50 mg every 18 to 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: geriatric use and precautions: geriatric use ). stability undiluted, ranitidine injection tends to exhibit a yellow color that may intensify over time without adversely affecting potency. ranitidine injection is stable for 48 hours at room temperature when added to or diluted with most commonly used intravenous solutions, e.g., 0.9% sodium chloride injection, 5% dextrose injection, 10% dextrose injection, lactated ringer's injection, or 5% sodium bicarbonate injection. note parenteral drug products should be inspected visually for particulate matter and discoloration before administration whenever solution and container permit. directions for dispensing pharmacy bulk package - not for direct infusion the pharmacy bulk package is for use in a pharmacy admixture service only under a laminar flow hood. the closure should be penetrated only once with a sterile transfer set or other sterile dispensing device, which allows measured distribution of the contents, and the contents dispensed in aliquots using aseptic technique. contents should be used as soon as possible following initial closure puncture. discard any unused portion within 24 hours of first entry. following closure puncture, container should be maintained below 30°c (86°f) under a laminar flow hood until contents are dispensed.

-blockers, rare reports of arrhythmias such as tachycardia, bradycardia, asystole, atrioventricular block, and premature ventricular beats. gastrointestinal constipation, diarrhea, nausea/vomiting, abdominal discomfort/pain, and rare reports of pancreatitis. hepatic 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. 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. 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 humans have shown no stimulation of any pituitary hormone by ranitidine hydrochloride and no antiandrogenic activity, and cimetidine-induced gynecomastia and impotence in hypersecretory patients have resolved when ranitidine hydrochloride has been substituted. however, occasional cases of impotence and loss of libido have been reported in male patients receiving ranitidine hydrochloride, 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 (h 2 ras) compared to patients who had stopped h 2 ra treatment, with an observed adjusted relative risk of 1.63 (95% ci, 1.07 to 2.48). however, a causal relationship between use of h 2 ras 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. to report suspected adverse reactions , contact zydus pharmaceuticals (usa) inc. at 1-877-993-8779 or fda at 1-800-fda-1088 or www.fda.gov/medwatch.

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 following intravenous injection, approximately 70% of the dose is recovered in the urine as unchanged drug. renal clearance averages 530 ml/min, with a total clearance of 760 ml/min. the elimination half-life is 2.0 to 2.5 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 3.1 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 pharmacokinetics of ranitidine hydrochloride in pediatric patients are summarized in table 1. table 1 ranitidine pharmacokinetics in pediatric patients following intravenous dosing t ½ = terminal half-life; clp = plasma clearance of ranitidine. ecmo = extracorporeal membrane oxygenation. population (age) n dose (mg/kg) t ½ (hours) vd (l/kg) clp (ml/min/kg) peptic ulcer disease (<6 years) (6 to 11.9 years) (>12 years) adults 6 11 6 6 1.25 or 2.5 1.25 or 2.5 1.25 or 2.5 2.5 2.2 2.1 1.7 1.9 1.29 1.14 0.98 1.04 11.41 8.96 9.89 8.77 peptic ulcer disease (3.5–16 years) 12 0.13 to 0.80 1.8 2.3 795 ml/min/1.73/m 2 children in intensive care (1 day–12.6 years) 17 1.0 2.4 2 11.7 neonates receiving ecmo 12 2 6.6 1.8 4.3 plasma clearance in neonatal patients (less than 1 month of age) receiving ecmo was considerably lower (3 to 4 ml/min/kg) than observed in children or adults. the elimination half-life in neonates averaged 6.6 hours as compared to approximately 2 hours in adults and pediatric patients. pharmacodynamics serum concentrations necessary to inhibit 50% of stimulated gastric acid secretion are estimated to be 36 to 94 ng/ml. following single intravenous or intramuscular 50 mg doses, serum concentrations of ranitidine are in this range for 6 to 8 hours. antisecretory activity 1. effects on acid secretion ranitidine injection inhibits basal gastric acid secretion as well as gastric acid secretion stimulated by betazole and pentagastrin, as shown in table 2. table 2 effect of intravenous ranitidine hydrochloride on gastric acid secretion time after dose, hours % inhibition of gastric acid output by intravenous dose, mg 20 mg 60 mg 100 mg betazole up to 2 93 99 99 pentagastrin up to 3 47 66 77 in a group of 10 known hypersecretors, ranitidine plasma levels of 71, 180, and 376 ng/ml inhibited basal acid secretion by 76%, 90%, and 99.5%, respectively. it appears that basal- and betazole-stimulated secretions are most sensitive to inhibition by ranitidine hydrochloride, while pentagastrin-stimulated secretion is more difficult to suppress. 2. effects on other gastrointestinal secretions pepsin ranitidine hydrochloride does not affect pepsin secretion. total pepsin output is reduced in proportion to the decrease in volume of gastric juice. intrinsic factor ranitidine hydrochloride has no significant effect on pentagastrin-stimulated intrinsic factor secretion. serum gastrin ranitidine hydrochloride has little or no effect on fasting or postprandial serum gastrin. other pharmacologic actions gastric bacterial flora - increase in nitrate-reducing organisms, significance not known. prolactin levels - no effect in recommended oral or intravenous dosage, but small, transient, dose-related increases in serum prolactin have been reported after intravenous bolus injections of 100 mg or more. other pituitary hormones - no effect on serum gonadotropins, tsh, or gh. possible impairment of vasopressin release. no change in cortisol, aldosterone, androgen, or estrogen levels. no antiandrogenic action. no effect on count, motility, or morphology of sperm. pediatrics the ranitidine concentration necessary to suppress basal acid secretion by at least 90% has been reported to be 40 to 60 ng/ml in pediatric patients with duodenal or gastric ulcers. in a study of 20 critically ill pediatric patients receiving ranitidine intravenous at 1 mg/kg every 6 hours, 10 patients with a baseline ph ≥ 4 maintained this baseline throughout the study. eight of the remaining 10 patients with a baseline of ph ≤ 2 achieved ph ≥ 4 throughout varying periods after dosing. it should be noted, however, that because these pharmacodynamic parameters were assessed in critically ill pediatric patients, the data should be interpreted with caution when dosing recommendations are made for a less seriously ill pediatric population. in another small study of neonatal patients (n = 5) receiving ecmo, gastric ph < 4 pretreatment increased to > 4 after a 2 mg/kg dose and remained above 4 for at least 15 hours. clinical trials active duodenal ulcer in a multicenter, double-blind, controlled, us study of endoscopically diagnosed duodenal ulcers, earlier healing was seen in the patients treated with oral ranitidine hydrochloride as shown in table 3. table 3 duodenal ulcer patient healing rates * all patients were permitted antacids as needed for relief of pain. † p <0.0001 oral ranitidine hydrochloride * oral placebo * number entered healed/ evaluable number entered healed/ evaluable outpatients week 2 195 69/182 (38%) † 188 31/164 (19%) week 4 137/187 (73%) † 76/168 (45%) in these studies, patients treated with oral ranitidine hydrochloride reported a reduction in both daytime and nocturnal pain, and they also consumed less antacid than the placebo-treated patients. table 4 mean daily doses of antacid ulcer healed ulcer not healed oral ranitidine hydrochloride 0.06 0.71 oral placebo 0.71 1.43 pathological hypersecretory conditions (such as zollinger-ellison syndrome) ranitidine hydrochloride inhibits gastric acid secretion and reduces occurrence of diarrhea, anorexia, and pain in patients with pathological hypersecretion associated with zollinger-ellison syndrome, systemic mastocytosis, and other pathological hypersecretory conditions (e.g., postoperative, "short-gut" syndrome, idiopathic). use of oral ranitidine hydrochloride was followed by healing of ulcers in 8 of 19 (42%) patients who were intractable to previous therapy. in a retrospective review of 52 zollinger-ellison patients given ranitidine hydrochloride as a continuous intravenous infusion for up to 15 days, no patients developed complications of acid-peptic disease such as bleeding or perforation. acid output was controlled to ≤10 meq/h.