Pepcid Information
Pepcid (Famotidine) Description
The active ingredient in Pepcid (Famotidine) is a histamine H-receptor antagonist. Famotidine is -(aminosulfonyl)-3-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]propanimidamide. The empirical formula of famotidine is CHNOS and its molecular weight is 337.43. Its structural formula is:
Famotidine is a white to pale yellow crystalline compound that is freely soluble in glacial acetic acid, slightly soluble in methanol, very slightly soluble in water, and practically insoluble in ethanol.
Each tablet for oral administration contains either 20 mg or 40 mg of famotidine and the following inactive ingredients: hydroxypropyl cellulose, hypromellose, iron oxides, magnesium stearate, microcrystalline cellulose, corn starch, talc, titanium dioxide, and carnauba wax.
Pepcid (Famotidine) Clinical Pharmacology In Adults
Pepcid (Famotidine) is a competitive inhibitor of histamine H-receptors. The primary clinically important pharmacologic activity of Pepcid (Famotidine) is inhibition of gastric secretion. Both the acid concentration and volume of gastric secretion are suppressed by Pepcid (Famotidine) , while changes in pepsin secretion are proportional to volume output.
In normal volunteers and hypersecretors, Pepcid (Famotidine) inhibited basal and nocturnal gastric secretion, as well as secretion stimulated by food and pentagastrin. After oral administration, the onset of the antisecretory effect occurred within one hour; the maximum effect was dose-dependent, occurring within one to three hours. Duration of inhibition of secretion by doses of 20 and 40 mg was 10 to 12 hours.
Single evening oral doses of 20 and 40 mg inhibited basal and nocturnal acid secretion in all subjects; mean nocturnal gastric acid secretion was inhibited by 86% and 94%, respectively, for a period of at least 10 hours. The same doses given in the morning suppressed food-stimulated acid secretion in all subjects. The mean suppression was 76% and 84%, respectively, 3 to 5 hours after administration, and 25% and 30%, respectively, 8 to 10 hours after administration. In some subjects who received the 20-mg dose, however, the antisecretory effect was dissipated within 6-8 hours. There was no cumulative effect with repeated doses. The nocturnal intragastric pH was raised by evening doses of 20 and 40 mg of Pepcid (Famotidine) to mean values of 5.0 and 6.4, respectively. When Pepcid (Famotidine) was given after breakfast, the basal daytime interdigestive pH at 3 and 8 hours after 20 or 40 mg of Pepcid (Famotidine) was raised to about 5.
Pepcid (Famotidine) had little or no effect on fasting or postprandial serum gastrin levels. Gastric emptying and exocrine pancreatic function were not affected by Pepcid (Famotidine) .
Pepcid (Famotidine) is incompletely absorbed. The bioavailability of oral doses is 40-45%. Bioavailability may be slightly increased by food, or slightly decreased by antacids; however, these effects are of no clinical consequence. Pepcid (Famotidine) undergoes minimal first-pass metabolism. After oral doses, peak plasma levels occur in 1-3 hours. Plasma levels after multiple doses are similar to those after single doses. Fifteen to 20% of Pepcid (Famotidine) in plasma is protein bound. Pepcid (Famotidine) has an elimination half-life of 2.5-3.5 hours. Pepcid (Famotidine) is eliminated by renal (65-70%) and metabolic (30-35%) routes. Renal clearance is 250-450 mL/min, indicating some tubular excretion. Twenty-five to 30% of an oral dose and 65-70% of an intravenous dose are recovered in the urine as unchanged compound. The only metabolite identified in man is the S-oxide.
There is a close relationship between creatinine clearance values and the elimination half-life of Pepcid (Famotidine) . In patients with severe renal insufficiency, i.e., creatinine clearance less than 10 mL/min, the elimination half-life of Pepcid (Famotidine) may exceed 20 hours and adjustment of dose or dosing intervals in moderate and severe renal insufficiency may be necessary (see , ).
In elderly patients, there are no clinically significant age-related changes in the pharmacokinetics of Pepcid (Famotidine) . However, in elderly patients with decreased renal function, the clearance of the drug may be decreased (see ).
In a U.S. multicenter, double-blind study in outpatients with endoscopically confirmed duodenal ulcer, orally administered Pepcid (Famotidine) was compared to placebo. As shown in Table 1, 70% of patients treated with Pepcid (Famotidine) 40 mg h.s. were healed by week 4.
Patients not healed by week 4 were continued in the study. By week 8, 83% of patients treated with Pepcid (Famotidine) had healed versus 45% of patients treated with placebo. The incidence of ulcer healing with Pepcid (Famotidine) was significantly higher than with placebo at each time point based on proportion of endoscopically confirmed healed ulcers.
In this study, time to relief of daytime and nocturnal pain was significantly shorter for patients receiving Pepcid (Famotidine) than for patients receiving placebo; patients receiving Pepcid (Famotidine) also took less antacid than the patients receiving placebo.
In both a U.S. and an international multicenter, double-blind study in patients with endoscopically confirmed active benign gastric ulcer, orally administered Pepcid (Famotidine) , 40 mg h.s., was compared to placebo h.s. Antacids were permitted during the studies, but consumption was not significantly different between the Pepcid (Famotidine) and placebo groups. As shown in Table 2, the incidence of ulcer healing (dropouts counted as unhealed) with Pepcid (Famotidine) was statistically significantly better than placebo at weeks 6 and 8 in the U.S. study, and at weeks 4, 6 and 8 in the international study, based on the number of ulcers that healed, confirmed by endoscopy.
Time to complete relief of daytime and nighttime pain was statistically significantly shorter for patients receiving Pepcid (Famotidine) than for patients receiving placebo; however, in neither study was there a statistically significant difference in the proportion of patients whose pain was relieved by the end of the study (week 8).
Orally administered Pepcid (Famotidine) was compared to placebo in a U.S. study that enrolled patients with symptoms of GERD and without endoscopic evidence of erosion or ulceration of the esophagus. Pepcid (Famotidine) 20 mg b.i.d. was statistically significantly superior to 40 mg h.s. and to placebo in providing a successful symptomatic outcome, defined as moderate or excellent improvement of symptoms (Table 3).
By two weeks of treatment, symptomatic success was observed in a greater percentage of patients taking Pepcid (Famotidine) 20 mg b.i.d. compared to placebo (p≤0.01).
Symptomatic improvement and healing of endoscopically verified erosion and ulceration were studied in two additional trials. Healing was defined as complete resolution of all erosions or ulcerations visible with endoscopy. The U.S. study comparing Pepcid (Famotidine) 40 mg p.o. b.i.d. to placebo and Pepcid (Famotidine) 20 mg p.o. b.i.d. showed a significantly greater percentage of healing for Pepcid (Famotidine) 40 mg b.i.d. at weeks 6 and 12 (Table 4).
As compared to placebo, patients who received Pepcid (Famotidine) had faster relief of daytime and nighttime heartburn and a greater percentage of patients experienced complete relief of nighttime heartburn. These differences were statistically significant.
In the international study, when Pepcid (Famotidine) 40 mg p.o. b.i.d. was compared to ranitidine 150 mg p.o. b.i.d., a statistically significantly greater percentage of healing was observed with Pepcid (Famotidine) 40 mg b.i.d. at week 12 (Table 5). There was, however, no significant difference among treatments in symptom relief.
Pepcid (Famotidine) Clinical Pharmacology In Pediatric Patients
Table 6 presents pharmacokinetic data from clinical trials and a published study in pediatric patients (
Plasma clearance is reduced and elimination half-life is prolonged in pediatric patients 0-3 months of age compared to older pediatric patients. The pharmacokinetic parameters for pediatric patients, ages >3 months-15 years, are comparable to those obtained for adults.
Bioavailability studies of 8 pediatric patients (11-15 years of age) showed a mean oral bioavailability of 0.5 compared to adult values of 0.42 to 0.49. Oral doses of 0.5 mg/kg achieved AUCs of 645 ± 249 ng-hr/mL and 580 ± 60 ng-hr/mL in pediatric patients
Pharmacodynamics of famotidine were evaluated in 5 pediatric patients 2-13 years of age using the sigmoid E model. These data suggest that the relationship between serum concentration of famotidine and gastric acid suppression is similar to that observed in one study of adults (Table 7).
Five published studies (Table 8) examined the effect of famotidine on gastric pH and duration of acid suppression in pediatric patients. While each study had a different design, acid suppression data over time are summarized as follows:
The duration of effect of famotidine I.V. 0.5 mg/kg on gastric pH and acid suppression was shown in one study to be longer in pediatric patients
Pepcid (Famotidine) Indications And Usage
Pepcid (Famotidine) is indicated in:
Pepcid (Famotidine) Contraindications
Hypersensitivity to any component of these products. Cross sensitivity in this class of compounds has been observed. Therefore, Pepcid (Famotidine) should not be administered to patients with a history of hypersensitivity to other H-receptor antagonists.
Pepcid (Famotidine) Precautions
In a 106-week study in rats and a 92-week study in mice given oral doses of up to 2000 mg/kg/day (approximately 2500 times the recommended human dose for active duodenal ulcer), there was no evidence of carcinogenic potential for Pepcid (Famotidine) .
Famotidine was negative in the microbial mutagen test (Ames test) using and with or without rat liver enzyme activation at concentrations up to 10,000 mcg/plate. In studies in mice, with a micronucleus test and a chromosomal aberration test, no evidence of a mutagenic effect was observed.
In studies with rats given oral doses of up to 2000 mg/kg/day or intravenous doses of up to 200 mg/kg/day, fertility and reproductive performance were not affected.
Use of Pepcid (Famotidine) in pediatric patients
Two pharmacokinetic studies in pediatric patients 3 months to 1 year of age is similar to that seen in older pediatric patients (1-15 years of age) and adults. In contrast, pediatric patients 0-3 months of age had famotidine clearance values that were 2- to 4-fold less than those in older pediatric patients and adults. These studies also show that the mean bioavailability in pediatric patients
In a double-blind, randomized, treatment-withdrawal study, 35 pediatric patients
These studies suggest that a starting dose of 0.5 mg/kg/dose of famotidine oral suspension may be of benefit for the treatment of GERD for up to 4 weeks once daily in patients
Use of Pepcid (Famotidine) in pediatric patients 1-16 years of age is supported by evidence from adequate and well-controlled studies of Pepcid (Famotidine) in adults, and by the following studies in pediatric patients: In published studies in small numbers of pediatric patients 1-15 years of age, clearance of famotidine was similar to that seen in adults. In pediatric patients 11-15 years of age, oral doses of 0.5 mg/kg were associated with a mean area under the curve (AUC) similar to that seen in adults treated orally with 40 mg. Similarly, in pediatric patients 1-15 years of age, intravenous doses of 0.5 mg/kg were associated with a mean AUC similar to that seen in adults treated intravenously with 40 mg. Limited published studies also suggest that the relationship between serum concentration and acid suppression is similar in pediatric patients 1-15 years of age as compared with adults. These studies suggest a starting dose for pediatric patients 1-16 years of age as follows:
Peptic ulcer
Gastroesophageal Reflux Disease with or without esophagitis including erosions and ulcerations
While published uncontrolled studies suggest effectiveness of famotidine in the treatment of gastroesophageal reflux disease and peptic ulcer, data in pediatric patients are insufficient to establish percent response with dose and duration of therapy. Therefore, treatment duration (initially based on adult duration recommendations) and dose should be individualized based on clinical response and/or pH determination (gastric or esophageal) and endoscopy. Published uncontrolled clinical studies in pediatric patients have employed doses up to 1 mg/kg/day for peptic ulcer and 2 mg/kg/day for GERD with or without esophagitis including erosions and ulcerations.
Of the 4,966 subjects in clinical studies who were treated with famotidine, 488 subjects (9.8%) were 65 and older, and 88 subjects (1.7%) were greater than 75 years of age. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. However, greater sensitivity of some older individuals cannot be ruled out.
No dosage adjustment is required based on age (see ). 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, care should be taken in dose selection, and it may be useful to monitor renal function. Dosage adjustment in the case of moderate or severe renal impairment is necessary (see and ).
Pepcid (Famotidine) Adverse Reactions
The adverse reactions listed below have been reported during domestic and international clinical trials in approximately 2500 patients. In those controlled clinical trials in which Pepcid (Famotidine) Tablets were compared to placebo, the incidence of adverse experiences in the group which received Pepcid (Famotidine) Tablets, 40 mg at bedtime, was similar to that in the placebo group.
The following adverse reactions have been reported to occur in more than 1% of patients on therapy with Pepcid (Famotidine) in controlled clinical trials, and may be causally related to the drug: headache (4.7%), dizziness (1.3%), constipation (1.2%) and diarrhea (1.7%).
The following other adverse reactions have been reported infrequently in clinical trials or since the drug was marketed. The relationship to therapy with Pepcid (Famotidine) has been unclear in many cases. Within each category the adverse reactions are listed in order of decreasing severity:
The adverse reactions reported for Pepcid (Famotidine) Tablets may also occur with Pepcid (Famotidine) for Oral Suspension.
Pepcid (Famotidine) Overdosage
The adverse reactions in overdose cases are similar to the adverse reactions encountered in normal clinical experience (see ). Oral doses of up to 640 mg/day have been given to adult patients with pathological hypersecretory conditions with no serious adverse effects. In the event of overdosage, treatment should be symptomatic and supportive. Unabsorbed material should be removed from the gastrointestinal tract, the patient should be monitored, and supportive therapy should be employed.
The oral LD of famotidine in male and female rats and mice was greater than 3000 mg/kg and the minimum lethal acute oral dose in dogs exceeded 2000 mg/kg. Famotidine did not produce overt effects at high oral doses in mice, rats, cats and dogs, but induced significant anorexia and growth depression in rabbits starting with 200 mg/kg/day orally. The intravenous LD of famotidine for mice and rats ranged from 254-563 mg/kg and the minimum lethal single I.V. dose in dogs was approximately 300 mg/kg. Signs of acute intoxication in I.V. treated dogs were emesis, restlessness, pallor of mucous membranes or redness of mouth and ears, hypotension, tachycardia and collapse.
Pepcid (Famotidine) Dosage And Administration
Acute Therapy:
Maintenance Therapy:
Acute Therapy:
See .
The studies described in suggest the following starting doses in pediatric patients
See .
The studies described in suggest the following starting doses in pediatric patients 1-16 years of age:
Peptic ulcer
Gastroesophageal Reflux Disease with or without esophagitis including erosions and ulcerations
While published uncontrolled studies suggest effectiveness of famotidine in the treatment of gastroesophageal reflux disease and peptic ulcer, data in pediatric patients are insufficient to establish percent response with dose and duration of therapy. Therefore, treatment duration (initially based on adult duration recommendations) and dose should be individualized based on clinical response and/or pH determination (gastric or esophageal) and endoscopy. Published uncontrolled clinical studies in pediatric patients 1-16 years of age have employed doses up to 1 mg/kg/day for peptic ulcer and 2 mg/kg/day for GERD with or without esophagitis including erosions and ulcerations.
In adult patients with moderate (creatinine clearance
Based on the comparison of pharmacokinetic parameters for Pepcid (Famotidine) in adults and pediatric patients, dosage adjustment in pediatric patients with moderate or severe renal insufficiency should be considered.
Pepcid (Famotidine) How Supplied
Pepcid (Famotidine) Tablets, 20 mg, are beige colored, rounded square shaped, film-coated tablets coded MSD on one side and plain on the other. They are supplied as follows:
Pepcid (Famotidine) Tablets, 40 mg, are tan, rounded square shaped, film-coated tablets coded MSD on one side and plain on the other. They are supplied as follows:
Pepcid (Famotidine)
Pepcid (Famotidine)
