9883042
PEPCID
®
(FAMOTIDINE) TABLETS
DESCRIPTION
The active ingredient in PEPCID
®
(famotidine) is a histamine H
2
-receptor antagonist. Famotidine is N
′
-
(aminosulfonyl)-3-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]propanimidamide. The empirical
f
ormula of famotidine is C
8
H
15
N
7
O
2
S
3
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.
CLINICAL PHARMACOLOGY IN ADULTS
GI Effects
PEPCID is a competitive inhibitor of histamine H
2
-receptors. The primary clinically important
pharmacologic activity of PEPCID is inhibition of gastric secretion. Both the acid concentration and
volume of gastric secretion are suppressed by PEPCID, while changes in pepsin secretion are
proportional to volume output.
In normal volunteers and hypersecretors, PEPCID 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 to mean values of 5.0 and 6.4, respectively. When PEPCID was given after breakfast, the basal
daytime interdigestive pH at 3 and 8 hours after 20 or 40 mg of PEPCID was raised to about 5.
PEPCID had little or no effect on fasting or postprandial serum gastrin levels. Gastric emptying and
exocrine pancreatic function were not affected by PEPCID.
Other Effects
Systemic effects of PEPCID in the CNS, cardiovascular, respiratory or endocrine systems were not
noted in clinical pharmacology studies. Also, no antiandrogenic effects were noted. (See ADVERSE
REACTIONS.) Serum hormone levels, including prolactin, cortisol, thyroxine (T
4
), and testosterone, were
not altered after treatment with PEPCID.
Pharmacokinetics
PEPCID 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 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 in plasma is protein bound. PEPCID has an elimination half-life of 2.5-3.5 hours. PEPCID
Reference ID: 2954009
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PEPCID
®
(famotidine) Tablets 9883042
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. In patients with severe renal insufficiency, i.e., creatinine clearance less than 10 mL/min, the
elimination half-life of PEPCID may exceed 20 hours and adjustment of dose or dosing intervals in
moderate and severe renal insufficiency may be necessary (see PRECAUTIONS, DOSAGE AND
ADMINISTRATION).
In elderly patients, there are no clinically significant age-related changes in the pharmacokinetics of
PEPCID. However, in elderly patients with decreased renal function, the clearance of the drug may be
decreased (see PRECAUTIONS, Geriatric Use).
Clinical Studies
Duodenal Ulcer
In a U.S. multicenter, double-blind study in outpatients with endoscopically confirmed duodenal ulcer,
orally administered PEPCID was compared to placebo. As shown in Table 1, 70% of patients treated with
P
EPCID 40 mg h.s. were healed by week 4.
Table 1
Outpatients with Endoscopically
Confirmed Healed Duodenal Ulcers
PEPCID PEPCID Placebo
40 mg h.s. 20 mg b.i.d. h.s.
(N = 89) (N = 84) (N = 97)
Week 2
**
32%
**
38% 17%
Week 4
**
70%
**
67% 31%
**
Statistically significantly different than placebo (p<0.001)
Patients not healed by week 4 were continued in the study. By week 8, 83% of patients treated with
PEPCID had healed versus 45% of patients treated with placebo. The incidence of ulcer healing with
PEPCID 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 than for patients receiving placebo; patients receiving PEPCID also took less antacid than the
patients receiving placebo.
Long-Term Maintenance
Treatment of Duodenal Ulcers
PEPCID, 20 mg p.o. h.s., was compared to placebo h.s. as maintenance therapy in two double-blind,
multicenter studies of patients with endoscopically confirmed healed duodenal ulcers. In the U.S. study
the observed ulcer incidence within 12 months in patients treated with placebo was 2.4 times greater than
in the patients treated with PEPCID. The 89 patients treated with PEPCID had a cumulative observed
ulcer incidence of 23.4% compared to an observed ulcer incidence of 56.6% in the 89 patients receiving
placebo (p<0.01). These results were confirmed in an international study where the cumulative observed
ulcer incidence within 12 months in the 307 patients treated with PEPCID was 35.7%, compared to an
incidence of 75.5% in the 325 patients treated with placebo (p<0.01).
Gastric Ulcer
In both a U.S. and an international multicenter, double-blind study in patients with endoscopically
confirmed active benign gastric ulcer, orally administered PEPCID, 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 and placebo groups. As shown in Table 2, the incidence of ulcer healing (dropouts counted
as unhealed) with PEPCID 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,
c
onfirmed by endoscopy.
2
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PEPCID
®
(famotidine) Tablets 9883042
Table 2
Patients with Endoscopically
Confirmed Healed Gastric Ulcers
U.S. Study International Study
PEPCID Placebo PEPCID Placebo
40 mg h.s. h.s. 40 mg h.s. h.s.
(N=74) (N=75) (N=149) (N=145)
Week 4 45% 39%
†
47% 31%
Week 6
†
66% 44%
†
65% 46%
Week 8
***
78% 64%
†
80% 54%
***,†
Statistically significantly better than placebo (p≤0.05, p≤0.01 respectively)
Time to complete relief of daytime and nighttime pain was statistically significantly shorter for patients
receiving PEPCID 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).
Gastroesophageal Reflux Disease (GERD)
Orally administered PEPCID 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
20 mg b.i.d. was statistically significantly superior to 40 mg h.s. and to placebo in providing a successful
s
ymptomatic outcome, defined as moderate or excellent improvement of symptoms (Table 3).
Table 3
% Successful Symptomatic Outcome
PEPCID PEPCID
20 mg b.i.d. 40 mg h.s. Placebo
(N=154) (N=149) (N=73)
Week 6 82
††
69 62
††
p≤0.01 vs Placebo
By two weeks of treatment, symptomatic success was observed in a greater percentage of patients
taking PEPCID 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 40 mg p.o. b.i.d. to placebo and PEPCID 20 mg p.o.
b.i.d. showed a significantly greater percentage of healing for PEPCID 40 mg b.i.d. at weeks 6 and 12
(Table 4).
Table 4
% Endoscopic Healing - U.S. Study
PEPCID PEPCID
40 mg b.i.d. 20 mg b.i.d. Placebo
(N=127) (N=125) (N=66)
48
†††,‡‡
Week 12 54
†††
29
Week 6 32 18
69
†††,‡
†††
p≤0.01 vs Placebo
‡
p≤0.05 vs PEPCID 20 mg b.i.d.
‡‡
p≤0.01 vs PEPCID 20 mg b.i.d.
As compared to placebo, patients who received PEPCID 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 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 40 mg b.i.d. at
w
eek 12 (Table 5). There was, however, no significant difference among treatments in symptom relief.
3
Reference ID: 2954009
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This label may not be the latest approved by FDA.
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PEPCID
®
(famotidine) Tablets 9883042
Table 7
Pharmacodynamics of famotidine using the sigmoid E
max
model
EC
50
(ng/mL)*
Pediatric Patients 26 ± 13
Data from one study
a) healthy adult subjects 26.5 ± 10.3
b) adult patients with upper GI bleeding 18.7 ± 10.8
*Serum concentration of famotidine associated with 50% maximum gastric acid reduction. Values are presented as means ± SD.
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:
Table 8
Dosage Route Effect
a
Number of Patients
(age range)
0.5 mg/kg, single dose I.V. gastric pH >4 for 19.5 hours (17.3, 11 (5-19 days)
21.8)
c
b
0.3 mg/kg, single dose I.V. gastric pH >3.5 for 8.7 ± 4.7 hours 6 (2-7 years)
0.4-0.8 mg/kg I.V. gastric pH >4 for 6-9 hours 18 (2-69 months)
0.5 mg/kg, single dose I.V. a >2 pH unit increase above 9 (2-13 years)
baseline in gastric pH for >8 hours
b
0.5 mg/kg b.i.d. I.V. gastric pH >5 for 13.5 ± 1.8
b
hours 4 (6-15 years)
0.5 mg/kg b.i.d. oral gastric pH >5 for 5.0 ± 1.1 hours 4 (11-15 years)
a
Values reported in published literature.
b
Means ± SD.
c
Mean (95% confidence interval).
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 <1 month of age than in older pediatric patients. This longer
duration of gastric acid suppression is consistent with the decreased clearance in pediatric patients
<3 months of age (see Table 6).
INDICATIONS AND USAGE
PEPCID is indicated in:
1. Short-term treatment of active duodenal ulcer. Most adult patients heal within 4 weeks; there is
rarely reason to use PEPCID at full dosage for longer than 6 to 8 weeks. Studies have not assessed the
safety of famotidine in uncomplicated active duodenal ulcer for periods of more than eight weeks.
2. Maintenance therapy for duodenal ulcer patients at reduced dosage after healing of an active ulcer.
Controlled studies in adults have not extended beyond one year.
3. Short-term treatment of active benign gastric ulcer. Most adult patients heal within 6 weeks. Studies
have not assessed the safety or efficacy of famotidine in uncomplicated active benign gastric ulcer for
periods of more than 8 weeks.
4. Short-term treatment of gastroesophageal reflux disease (GERD). PEPCID is indicated for short-
term treatment of patients with symptoms of GERD (see CLINICAL PHARMACOLOGY IN ADULTS,
Clinical Studies).
PEPCID is also indicated for the short-term treatment of esophagitis due to GERD including erosive or
ulcerative disease diagnosed by endoscopy (see CLINICAL PHARMACOLOGY IN ADULTS, Clinical
Studies).
5. Treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison Syndrome, multiple
endocrine adenomas) (see CLINICAL PHARMACOLOGY IN ADULTS, Clinical Studies).
CONTRAINDICATIONS
Hypersensitivity to any component of these products. Cross sensitivity in this class of compounds has
been observed. Therefore, PEPCID should not be administered to patients with a history of
hypersensitivity to other H
2
-receptor antagonists.
5
Reference ID: 2954009
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PEPCID
®
(famotidine) Tablets 9883042
PRECAUTIONS
General
Symptomatic response to therapy with PEPCID does not preclude the presence of gastric malignancy.
Patients with Moderate or Severe Renal Insufficiency
Since CNS adverse effects have been reported in patients with moderate and severe renal
insufficiency, longer intervals between doses or lower doses may need to be used in patients with
moderate (creatinine clearance <50 mL/min) or severe (creatinine clearance <10 mL/min) renal
insufficiency to adjust for the longer elimination half-life of famotidine (see CLINICAL PHARMACOLOGY
IN ADULTS and DOSAGE AND ADMINISTRATION). Prolonged QT interval has been reported very
rarely in patients with impaired renal function whose dose/dosing interval of famotidine may not have
been adjusted appropriately.
Drug Interactions
No drug interactions have been identified. Studies with famotidine in man, in animal models, and in
vitro have shown no significant interference with the disposition of compounds metabolized by the hepatic
microsomal enzymes, e.g., cytochrome P450 system. Compounds tested in man include warfarin,
theophylline, phenytoin, diazepam, aminopyrine and antipyrine. Indocyanine green as an index of hepatic
drug extraction has been tested and no significant effects have been found.
Carcinogenesis, Mutagenesis, Impairment of Fertility
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 was negative in the microbial mutagen test (Ames test) using Salmonella typhimurium and
Escherichia coli with or without rat liver enzyme activation at concentrations up to 10,000 mcg/plate. In in
vivo 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.
Pregnancy
Pregnancy Category B
Reproductive studies have been performed in rats and rabbits at oral doses of up to 2000 and
500 mg/kg/day, respectively, and in both species at I.V. doses of up to 200 mg/kg/day, and have revealed
no significant evidence of impaired fertility or harm to the fetus due to PEPCID. While no direct fetotoxic
effects have been observed, sporadic abortions occurring only in mothers displaying marked decreased
food intake were seen in some rabbits at oral doses of 200 mg/kg/day (250 times the usual human dose)
or higher. There are, however, no adequate or well-controlled studies in pregnant women. Because
animal reproductive studies are not always predictive of human response, this drug should be used
during pregnancy only if clearly needed.
Nursing Mothers
Studies performed in lactating rats have shown that famotidine is secreted into breast milk. Transient
growth depression was observed in young rats suckling from mothers treated with maternotoxic doses of
at least 600 times the usual human dose. Famotidine is detectable in human milk. Because of the
potential for serious adverse reactions in nursing infants from PEPCID, a decision should be made
whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to
the mother.
Pediatric Patients <1 year of age
Use of PEPCID in pediatric patients <1 year of age is supported by evidence from adequate and
well-controlled studies of PEPCID in adults, and by the following studies in pediatric patients <1 year of
age.
Two pharmacokinetic studies in pediatric patients <1 year of age (N=48) demonstrated that clearance
of famotidine in 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
6
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PEPCID
®
(famotidine) Tablets 9883042
show that the mean bioavailability in pediatric patients <1 year of age after oral dosing is similar to older
pediatric patients and adults. Pharmacodynamic data in pediatric patients 0-3 months of age suggest that
the duration of acid suppression is longer compared with older pediatric patients, consistent with the
longer famotidine half-life in pediatric patients 0-3 months of age. (See CLINICAL PHARMACOLOGY IN
PEDIATRIC PATIENTS, Pharmacokinetics and Pharmacodynamics.)
In a double-blind, randomized, treatment-withdrawal study, 35 pediatric patients <1 year of age who
were diagnosed as having gastroesophageal reflux disease were treated for up to 4 weeks with
famotidine oral suspension (0.5 mg/kg/dose or 1 mg/kg/dose). Although an intravenous famotidine
formulation was available, no patients were treated with intravenous famotidine in this study. Also,
caregivers were instructed to provide conservative treatment including thickened feedings. Enrolled
patients were diagnosed primarily by history of vomiting (spitting up) and irritability (fussiness). The
famotidine dosing regimen was once daily for patients <3 months of age and twice daily for patients
≥3 months of age. After 4 weeks of treatment, patients were randomly withdrawn from the treatment and
followed an additional 4 weeks for adverse events and symptomatology. Patients were evaluated for
vomiting (spitting up), irritability (fussiness) and global assessments of improvement. The study patients
ranged in age at entry from 1.3 to 10.5 months (mean 5.6 ± 2.9 months), 57% were female, 91% were
white and 6% were black. Most patients (27/35) continued into the treatment-withdrawal phase of the
study. Two patients discontinued famotidine due to adverse events. Most patients improved during the
initial treatment phase of the study. Results of the treatment-withdrawal phase were difficult to interpret
because of small numbers of patients. Of the 35 patients enrolled in the study, agitation was observed in
5 patients on famotidine that resolved when the medication was discontinued; agitation was not observed
in patients on placebo (see ADVERSE REACTIONS, 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 <3 months of age and twice
daily in patients 3 months to <1 year of age; the safety and benefit of famotidine treatment beyond
4 weeks have not been established. Famotidine should be considered for the treatment of GERD only if
conservative measures (e.g., thickened feedings) are used concurrently and if the potential benefit
outweighs the risk.
Pediatric Patients 1-16 years of age
Use of PEPCID in pediatric patients 1-16 years of age is supported by evidence from adequate and
well-controlled studies of PEPCID 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 - 0.5 mg/kg/day p.o. at bedtime or divided b.i.d. up to 40 mg/day.
Gastroesophageal Reflux Disease with or without esophagitis including erosions and ulcerations -
1.0 mg/kg/day p.o. divided b.i.d. up to 40 mg b.i.d.
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.
Geriatric Use
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
7
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PEPCID
®
(famotidine) Tablets 9883042
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 CLINICAL PHARMACOLOGY IN ADULTS,
Pharmacokinetics). 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 PRECAUTIONS, Patients with Moderate or Severe Renal Insufficiency and DOSAGE
AND ADMINISTRATION, Dosage Adjustment for Patients with Moderate or Severe Renal Insufficiency).
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 Tablets were compared
to placebo, the incidence of adverse experiences in the group which received PEPCID 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 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 has been unclear in many cases. Within
each category the adverse reactions are listed in order of decreasing severity:
Body as a Whole: fever, asthenia, fatigue
Cardiovascular: arrhythmia, AV block, palpitation. Prolonged QT interval, in patients with impaired
renal function, has been reported very rarely.
Gastrointestinal: cholestatic jaundice, hepatitis, liver enzyme abnormalities, vomiting, nausea,
abdominal discomfort, anorexia, dry mouth
Hematologic: rare cases of agranulocytosis, pancytopenia, leukopenia, thrombocytopenia
Hypersensitivity: anaphylaxis, angioedema, orbital or facial edema, urticaria, rash, conjunctival
injection
Musculoskeletal: musculoskeletal pain including muscle cramps, arthralgia
Nervous System/Psychiatric: grand mal seizure; psychic disturbances, which were reversible in cases
for which follow-up was obtained, including hallucinations, confusion, agitation, depression, anxiety,
decreased libido; paresthesia; insomnia; somnolence. Convulsions, in patients with impaired renal
function, have been reported very rarely.
Respiratory: bronchospasm, interstitial pneumonia
Skin: toxic epidermal necrolysis/Stevens-Johnson syndrome (very rare), alopecia, acne, pruritus, dry
skin, flushing
Special Senses: tinnitus, taste disorder
Other: rare cases of impotence and rare cases of gynecomastia have been reported; however, in
controlled clinical trials, the incidences were not greater than those seen with placebo.
The adverse reactions reported for PEPCID Tablets may also occur with PEPCID for Oral
Suspension.
Pediatric Patients
In a clinical study in 35 pediatric patients <1 year of age with GERD symptoms [e.g., vomiting (spitting
up), irritability (fussing)], agitation was observed in 5 patients on famotidine that resolved when the
medication was discontinued.
OVERDOSAGE
The adverse reactions in overdose cases are similar to the adverse reactions encountered in normal
clinical experience (see ADVERSE REACTIONS). 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
8
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PEPCID
®
(famotidine) Tablets 9883042
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
50
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
50
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.
DOSAGE AND ADMINISTRATION
Duodenal Ulcer
Acute Therapy: The recommended adult oral dosage for active duodenal ulcer is 40 mg once a day at
bedtime. Most patients heal within 4 weeks; there is rarely reason to use PEPCID at full dosage for longer
than 6 to 8 weeks. A regimen of 20 mg b.i.d. is also effective.
Maintenance Therapy: The recommended adult oral dose is 20 mg once a day at bedtime.
Benign Gastric Ulcer
Acute Therapy: The recommended adult oral dosage for active benign gastric ulcer is 40 mg once a
day at bedtime.
Gastroesophageal Reflux Disease (GERD)
The recommended oral dosage for treatment of adult patients with symptoms of GERD is 20 mg b.i.d.
for up to 6 weeks. The recommended oral dosage for the treatment of adult patients with esophagitis
including erosions and ulcerations and accompanying symptoms due to GERD is 20 or 40 mg b.i.d. for up
to 12 weeks (see CLINICAL PHARMACOLOGY IN ADULTS, Clinical Studies).
Dosage for Pediatric Patients <1 year of age Gastroesophageal Reflux Disease (GERD)
See PRECAUTIONS, Pediatric Patients <1 year of age.
The studies described in PRECAUTIONS, Pediatric Patients <1 year of age suggest the following
starting doses in pediatric patients <1 year of age: Gastroesophageal Reflux Disease (GERD) -
0.5 mg/kg/dose of famotidine oral suspension for the treatment of GERD for up to 8 weeks once daily in
patients <3 months of age and 0.5 mg/kg/dose twice daily in patients 3 months to <1 year of age. Patients
should also be receiving conservative measures (e.g., thickened feedings). The use of intravenous
famotidine in pediatric patients <1 year of age with GERD has not been adequately studied.
Dosage for Pediatric Patients 1-16 years of age
See PRECAUTIONS, Pediatric Patients 1-16 years of age.
The studies described in PRECAUTIONS, Pediatric Patients 1-16 years of age suggest the following
starting doses in pediatric patients 1-16 years of age:
Peptic ulcer - 0.5 mg/kg/day p.o. at bedtime or divided b.i.d. up to 40 mg/day.
Gastroesophageal Reflux Disease with or without esophagitis including erosions and ulcerations -
1.0 mg/kg/day p.o. divided b.i.d. up to 40 mg b.i.d.
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.
Pathological Hypersecretory Conditions (e.g., Zollinger-Ellison Syndrome, Multiple Endocrine Adenomas)
The dosage of PEPCID in patients with pathological hypersecretory conditions varies with the
individual patient. The recommended adult oral starting dose for pathological hypersecretory conditions is
20 mg q 6 h. In some patients, a higher starting dose may be required. Doses should be adjusted to
9
Reference ID: 2954009
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
PEPCID
®
(famotidine) Tablets 9883042
individual patient needs and should continue as long as clinically indicated. Doses up to 160 mg q 6 h
have been administered to some adult patients with severe Zollinger-Ellison Syndrome.
Concomitant Use of Antacids
Antacids may be given concomitantly if needed.
Dosage Adjustment for Patients with Moderate or Severe Renal Insufficiency
In adult patients with moderate (creatinine clearance <50 mL/min) or severe (creatinine clearance
<10 mL/min) renal insufficiency, the elimination half-life of PEPCID is increased. For patients with severe
renal insufficiency, it may exceed 20 hours, reaching approximately 24 hours in anuric patients. Since
CNS adverse effects have been reported in patients with moderate and severe renal insufficiency, to
avoid excess accumulation of the drug in patients with moderate or severe renal insufficiency, the dose of
PEPCID may be reduced to half the dose or the dosing interval may be prolonged to 36-48 hours as
indicated by the patient's clinical response.
Based on the comparison of pharmacokinetic parameters for PEPCID in adults and pediatric patients,
dosage adjustment in pediatric patients with moderate or severe renal insufficiency should be considered.
HOW SUPPLIED
No. 9786 — PEPCID Tablets, 20 mg, are beige colored, rounded square shaped, film-coated tablets
coded MSD 963 on one side and plain on the other. They are supplied as follows:
NDC 0006-0963-31 unit of use bottles of 30
NDC 0006-0963-58 unit of use bottles of 100.
No. 9788 — PEPCID Tablets, 40 mg, are tan, rounded square shaped, film-coated tablets coded
MSD 964 on one side and plain on the other. They are supplied as follows:
NDC 0006-0964-31 unit of use bottles of 30
NDC 0006-0964-58 unit of use bottles of 100.
Storage
Preserve in well-closed, light-resistant containers. Store at controlled room temperature.
PEPCID (famotidine) Tablets 20 mg and Tablets 40 mg are manufactured for:
By:
MERCK SHARP & DOHME Pty., Ltd.
South Granville, NSW, Australia 2142.
Issued June 2011
Printed in USA
Copyright © 1986, 1988, 1991, 1995, 1996 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
All rights reserved
10
Reference ID: 2954009
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda