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.
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%.
The volume of distribution is about 1.4 L/kg. Serum protein
binding averages 15%.
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,
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
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).
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).
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
| Peptic ulcer disease
( < 6 years)
||1.25 or 2.5
| (6–11.9 years)
||1.25 or 2.5
| ( > 12 years)
||1.25 or 2.5
|Peptic ulcer disease
|Children in intensive care
(1 day–12.6 years)
|Neonates receiving ECMO
|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.
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.
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
||Time After Dose, hours
||% Inhibition of Gastric Acid Output by Intravenous Dose,
||Up to 2
||Up to 3
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
Gastric bacterial flora -increase in nitrate-reducing
organisms, significance not known.
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.
Other pituitary hormones-no effect on serum
gonadotropins, TSH, or GH. Possible impairment of vasopressin release.
No change in cortisol, aldosterone, androgen, or estrogen
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 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.
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
|*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 : Â Mean Daily Doses of Antacid
||Ulcer Not Healed
Pathological Hypersecretory Conditions (such as
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.