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Zantac Injection

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Zantac Injection

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% 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

Following IV 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 ZANTAC in pediatric patients are summarized in Table 1.

Table 1 : Ranitidine Pharmacokinetics in Pediatric Patients Following IV Dosing

Population
(age)
n Dose
(mg/kg)

(hours)
Vd
(L/kg)
CLp
(mL/min/kg)
 Peptic ulcer disease
( < 6 years)
6 1.25 or 2.5 2.2 1.29 11.41
  (6–11.9 years) 11 1.25 or 2.5 2.1 1.14 8.96
  ( > 12 years) 6 1.25 or 2.5 1.7 0.98 9.89
  Adults 6 2.5 1.9 1.04 8.77
Peptic ulcer disease
(3.5–16 years)
12 0.13–0.80 1.8 2.3 795 mL/min/1.73/m²
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
T½ = Terminal half-life; CLp = Plasma clearance of ranitidine.
ECMO = extracorporeal membrane oxygenation.

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 IV or IM 50-mg doses, serum concentrations of ranitidine are in this range for 6 to 8 hours.

Antisecretory Activity

1. Effects on Acid Secretion: ZANTAC Injection (ranitidine hydrochloride 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 ZANTAC 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 ZANTAC, while pentagastrin-stimulated secretion is more difficult to suppress.

2. Effects on Other Gastrointestinal Secretions: Pepsin: ZANTAC does not affect pepsin secretion. Total pepsin output is reduced in proportion to the decrease in volume of gastric juice.

Intrinsic Factor: ZANTAC has no significant effect on pentagastrin-stimulated intrinsic factor secretion.

Serum Gastrin: ZANTAC has little or no effect on fasting or postprandial serum gastrin.

Other Pharmacologic Actions
  1. Gastric bacterial flora -increase in nitrate-reducing organisms, significance not known.
  2. Prolactin levels-no effect in recommended oral or IV dosage, but small, transient, dose-related increases in serum prolactin have been reported after IV bolus injections of 100 mg or more.
  3. Other pituitary hormones-no effect on serum gonadotropins, TSH, or GH. Possible impairment of vasopressin release.
  4. No change in cortisol, aldosterone, androgen, or estrogen levels.
  5. No antiandrogenic action.
  6. 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 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 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 ZANTAC as shown in Table 3.

Table 3 : Duodenal Ulcer Patient Healing Rates

Outpatients Oral Placebo* Oral ZANTAC*
Number Entered Healed/ Evaluable Number Entered Healed/ Evaluable
Week 2 195 69/182 (38%)† 188 31/164 (19%)
Week 4 137/187 (73%)† 76/168 (45%)
*All patients were permitted antacids as needed for relief of pain.
†P < 0.0001.

In these studies, patients treated with oral ZANTAC 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 ZANTAC 0.06 0.71
Oral placebo 0.71 1.43

Pathological Hypersecretory Conditions (such as Zollinger-Ellison syndrome)

ZANTAC 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 ZANTAC 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 ZANTAC as a continuous IV 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.

Last reviewed on RxList: 3/31/2009
This monograph has been modified to include the generic and brand name in many instances.

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Additional Zantac Injection Information

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