PRESCRIBING INFORMATION ZANTAC ® (ranitidine hydrochloride) Injection ZANTAC®
(ranitidine hydrochloride) Injection Premixed
DESCRIPTION The active ingredient in ZANTAC Injection and ZANTAC Injection Premixed is ranitidine hydrochloride (HCl), a histamine H2-receptor antagonist. Chemically it is N[2-[[[5[(dimethylamino)methyl]-2-furanyl]methyl]thio]ethyl]-N-methyl-2-nitro-1,1-ethenediamine, hydrochloride. It has the following structure: The empirical formula is C13H22N4O3SHCl, representing a molecular weight of 350.87. Ranitidine HCl is a white to pale yellow, granular substance that is soluble in water. ZANTAC Injection is a clear, colorless to yellow, 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. Sterile Injection for Intramuscular or Intravenous Administration: Each 1 mL of aqueous solution contains ranitidine 25 mg (as the hydrochloride); phenol 5 mg as preservative; and 0.96 mg of monobasic potassium phosphate and 2.4 mg of dibasic sodium phosphate as buffers. Sterile, Premixed Solution for Intravenous Administration in Single-Dose, Flexible Plastic Containers: Each 50 mL contains ranitidine HCl equivalent to 50 mg of ranitidine, sodium chloride 225 mg, and citric acid 15 mg and dibasic sodium phosphate 90 mg as buffers in water for injection. It contains no preservatives. The osmolarity of this solution is 180 mOsm/L (approx.), and the pH is 6.7 to 7.3. The flexible plastic container is fabricated from a specially formulated, nonplasticized, thermoplastic co-polyester (CR3). Water can permeate from inside the container into the overwrap but not in amounts sufficient to affect the solution significantly. Solutions inside the plastic container also can leach out certain of the chemical components in very small amounts before the expiration period is attained. However, the safety of the plastic has been confirmed by tests in animals according to USP biological standards for plastic containers. 1 CLINICAL PHARMACOLOGY ZANTAC is a competitive, reversible inhibitor of the action of histamine at the histamine H2-receptors, including receptors on the gastric cells. ZANTAC does not lower serum Ca++ in hypercalcemic states. ZANTAC is not an anticholinergic agent. Pharmacokinetics: Absorption: ZANTAC is absorbed very rapidly after intramuscular (IM) injection. Mean peak levels of 576 ng/mL occur within 15 minutes or less following a 50-mg IM dose. Absorption from IM sites is virtually complete, with a bioavailability of 90% to 100% compared with intravenous (IV) administration. Following oral administration, the bioavailability of ZANTAC Tablets is 50%. Distribution: The volume of distribution is about 1.4 L/kg. Serum protein binding averages 15%. Metabolism: In humans, the N-oxide is the principal metabolite in the urine; however, this amounts 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. ZANTAC Injection Premixed in Flexible Plastic Containers: Instructions for Use: To Open: Tear outer wrap at notch and remove solution container. Check for minute leaks by squeezing container firmly. If leaks are found, discard unit as sterility may be impaired. Preparation for Administration: Use aseptic technique. 1. Close flow control clamp of administration set. 2. Remove cover from outlet port at bottom of container. 3. Insert piercing pin of administration set into port with a twisting motion until the pin is firmly seated. NOTE: See full directions on administration set carton. 4. Suspend container from hanger. 5. Squeeze and release drip chamber to establish proper fluid level in chamber during infusion of ZANTAC Injection Premixed. 6. Open flow control clamp to expel air from set. Close clamp. 7. Attach set to venipuncture device. If device is not indwelling, prime and make venipuncture. 8. Perform venipuncture. 9. Regulate rate of administration with flow control clamp. Caution: ZANTAC Injection Premixed in flexible plastic containers is to be administered by slow IV drip infusion only. Additives should not be introduced into this solution. If used with 10 a primary IV fluid system, the primary solution should be discontinued during infusion of ZANTAC Injection Premixed. Do not administer unless solution is clear and container is undamaged. Warning: Do not use flexible plastic container in series connections. 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 ZANTAC, the recommended dosage in patients with a creatinine clearance