Ranitidine Information
Ranitidine ()
Ranitidine () Description
The active ingredient in Ranitidine () Injection USP, is Ranitidine () hydrochloride (HCl), a histamine H-receptor antagonist. Chemically it is -[2-[[[5-[(Dimethylamino)methyl]-2-furanyl]methyl]thio]ethyl]-N-methyl-2-nitro-1,1-ethenediamine, hydrochloride. It has the following structural formula:
The molecular formula is CHNOS • HCl, representing a molecular weight of 350.87.
Ranitidine () hydrochloride is a white to pale yellow, granular substance that is soluble in water.
Ranitidine () Injection, USP is a clear, colorless to yellow, sterile, nonpyrogenic liquid. The yellow color of the liquid tends to intensify without adversely affecting potency. The pH of the injection solution is 6.7 to 7.3.
Each 1 mL of aqueous solution contains Ranitidine () 25 mg (as the hydrochloride); phenol 5 mg as a preservative; 0.96 mg of monobasic potassium phosphate and 2.4 mg of dibasic sodium phosphate as buffers. Hydrochloric acid used to adjust pH.
Ranitidine () Clinical Pharmacology
Ranitidine () is a competitive, reversible inhibitor of the action of histamine at the histamine H-receptors, including receptors on the gastric cells. Ranitidine () does not lower serum Ca++ in hypercalcemic states. Ranitidine () is not an anticholinergic agent.
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 () IV 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 pH4 after a 2 mg/kg dose and remained above 4 for at least 15 hours.
Ranitidine () Indications And Usage
Ranitidine () injection is indicated in some hospitalized patients with pathological hypersecretory conditions or intractable duodenal ulcers, or as an alternative to the oral dosage form for short-term use in patients who are unable to take oral medication.
Ranitidine () Contraindications
Ranitidine () injection is contraindicated for patients known to have hypersensitivity to the drug.
Ranitidine () Precautions
Ranitidine () has been reported to affect the bioavailability of other drugs through several different mechanisms such as competition for renal tubular secretion, alteration of gastric pH, and inhibition of cytochrome P450 enzymes.
Ranitidine () may alter the absorption of drugs in which gastric pH is an important determinant of bioavailability. This can result in either an increase in absorption (e.g., triazolam, midazolam, glipizide) or a decrease in absorption (e.g., ketoconazole, atazanavir, delavirdine, gefitinib). Appropriate clinical monitoring is recommended.
atazanavir label for specific recommendations.
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There was no indication of tumorigenic or carcinogenic effects in life-span studies in mice and rats at oral dosages up to 2,000 mg/kg per day.
Ranitidine () was not mutagenic in standard bacterial tests () for mutagenicity at concentrations up to the maximum recommended for these assays.
In a dominant lethal assay, a single oral dose of 1,000 mg/kg to male rats was without effect on the outcome of two matings per week for the next 9 weeks.
Safety and effectiveness of Ranitidine () injection have been established in the age-group of 1 month to 16 years for the treatment of duodenal ulcer. Use of Ranitidine () in this age-group is supported by adequate and well-controlled studies in adults, as well as additional pharmacokinetic data in pediatric patients, and an analysis of the published literature.
Safety and effectiveness in pediatric patients for the treatment of pathological hypersecretory conditions have not been established.
Limited data in neonatal patients (less than one month of age) receiving ECMO suggest that Ranitidine () may be useful and safe for increasing gastric pH for patients at risk of gastrointestinal hemorrhage.
Clinical studies of Ranitidine () injection did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently from younger subjects. However, in clinical studies of oral formulations of Ranitidine () , of the total number of subjects enrolled in US and foreign controlled clinical trials, for which there were subgroup analyses, 4,197 were 65 and over, while 899 were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
This drug is known to be substantially excreted by the kidney and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, caution should be exercised in dose selection, and it may be useful to monitor renal function (see : : and : ).
Ranitidine () Adverse Reactions
Transient pain at the site of IM injection has been reported. Transient local burning or itching has been reported with IV administration of Ranitidine () .
The following have been reported as events in clinical trials or in the routine management of patients treated with oral or parenteral Ranitidine () . The relationship to therapy with rantitidine has been unclear in many cases. Headache, sometimes severe, seems to be related to administration of Ranitidine () .
Ranitidine () Overdosage
There has been virtually no experience with overdosage with Ranitidine () injection and limited experience with oral doses of Ranitidine () . Reported acute ingestions of up to 18 g orally have been associated with transient adverse effects similar to those encountered in normal clinical experience (see ). In addition, abnormalities of gait and hypotension have been reported.
When overdosage occurs, clinical monitoring and supportive therapy should be employed.
Studies in dogs receiving dosages of Ranitidine () in excess of 225 mg/kg per day have shown muscular tremors, vomiting, and rapid respiration. Single oral doses of 1,000 mg/kg in mice and rats were not lethal. Intravenous LD values in mice and rats were 77 and 83 mg/kg, respectively.
Ranitidine () Dosage And Administration
In some hospitalized patients with pathological hypersecretory conditions or intractable duodenal ulcers, or in patients who are unable to take oral medication, Ranitidine () may be administered parenterally according to the following recommendations:
Stability
Stability
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.
Stability
For Zollinger-Ellison patients, dilute Ranitidine () injection in 5% dextrose injection or other compatible IV solution (see ) to a concentration no greater than 2.5 mg/mL. Start the infusion at a rate of 1 mg/kg per hour. If after 4 hours either a measured gastric acid output is >10 mEq/h or the patient becomes symptomatic, the dose should be adjusted upward in 0.5-mg/kg per hour increments, and the acid output should be remeasured. Dosages up to 2.5 mg/kg per hour and infusion rates as high as 220 mg/h have been used.
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 () , the recommended dosage in patients with a creatinine clearance
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 : : and : ).
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 IV solutions, e.g., 0.9% sodium chloride injection, 5% dextrose injection, 10% dextrose injection, lactated ringer’s injection, or 5% sodium bicarbonate injection.
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Ranitidine () How Supplied
Ranitidine () Injection USP, 25 mg/mL, containing phenol 0.5% as preservative, is available as:
Store at 20° to 25°C (68° to 77°F). See USP controlled room temperature. Protect from freezing.
Manufactured by Manufactured for
Ben Venue Laboratories, Inc. Bedford Laboratories™
Bedford, OH 44146 Bedford, OH 44146
November 2009 RNPP03
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