Famotidine

Pepcid, Pepcid AC, Acid Reducer, Heartburn Relief

• Tablets: 10, 20, and 40 mg.
• Tablets (Chewable): 10 and 20 mg.
• Suspension: 40 mg per 5 ml (teaspoon). Injection: 10 mg/ml.

Tablets and suspension should be stored at room temperature, 15 C - 30 C (59 F - 86 F). Injection should be stored between 2 C - 8 C (36 F - 46 F).

The active ingredient in PEPCID® (famotidine) is a histamine H2-receptor antagonist. Famotidine is N'(aminosulfonyl)-3-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]propanimidamide. The empirical formula of famotidine is C8H15N7O2S3 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 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).

Clinical Pharmacology In Adults

PEPCID is a competitive inhibitor of histamine H2-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.

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 (T4), and testosterone, were not altered after treatment with PEPCID.

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 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 PEPCID 40 mg h.s. were healed by week 4.

Table 1 : Outpatients with Endoscopically Confirmed Healed Duodenal Ulcers

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.

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, confirmed by endoscopy.

Table 2 : Patients with Endoscopically Confirmed Healed Gastric Ulcers

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 symptomatic outcome, defined as moderate or excellent improvement of symptoms (Table 3).

Table 3 : % Successful Symptomatic Outcome

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

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 week 12 (Table 5). There was, however, no significant difference among treatments in symptom relief.

Table 5 : % Endoscopic Healing - International Study

Pathological Hypersecretory Conditions (e.g., Zollinger-Ellison Syndrome, Multiple Endocrine Adenomas)

In studies of patients with pathological hypersecretory conditions such as Zollinger-Ellison Syndrome with or without multiple endocrine adenomas, PEPCID significantly inhibited gastric acid secretion and controlled associated symptoms. Orally administered doses from 20 to 160 mg q 6 h maintained basal acid secretion below 10 mEq/hr; initial doses were titrated to the individual patient need and subsequent adjustments were necessary with time in some patients. PEPCID was well tolerated at these high dose levels for prolonged periods (greater than 12 months) in eight patients, and there were no cases reported of gynecomastia, increased prolactin levels, or impotence which were considered to be due to the drug.

Clinical Pharmacology In Pediatric Patients

Table 6 presents pharmacokinetic data from clinical trials and a published study in pediatric patients ( < 1 year of age; N=27) given famotidine I.V. 0.5 mg/kg and from published studies of small numbers of pediatric patients (1-15 years of age) given famotidine intravenously. Areas under the curve (AUCs) are normalized to a dose of 0.5 mg/kg I.V. for pediatric patients 1-15 years of age and compared with an extrapolated 40 mg intravenous dose in adults (extrapolation based on results obtained with a 20 mg I.V. adult dose).

Table 6 : Pharmacokinetic Parametersa of Intravenous Famotidine

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 < 1 year of age (N=5) and in pediatric patients 11-15 years of age, respectively, compared to 482 ± 181 ng-hr/mL in adults treated with 40 mg orally.

Pharmacodynamics of famotidine were evaluated in 5 pediatric patients 2-13 years of age using the sigmoid Emax 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).

Table 7 : Pharmacodynamics of famotidine using the sigmoid Emax model

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

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).

If you take too much famotidine, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

Your pharmacist can provide more information about famotidine.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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Competitive inhibition of histamine at H2 receptors of the gastric parietal cells, which inhibits gastric acid secretion

Absorption

Oral: Incompletely absorbed

Distribution

Vd:

Infants: 0 to 3 months: 1.4 ± 0.4 L/kg to 1.8 ± 0.3 L/kg; >3 to 12 months: 2.3 ± 0.7 L/kg

Children: 2 ± 1.5 L/kg

Adolescents: 1.5 ± 0.4 L/kg

Adults: 0.94 to 1.33 L/kg

Metabolism

30% to 35%; minimal first-pass metabolism; forms one metabolite (S-oxide)

Excretion

Urine (25% to 30% [oral], 65% to 70% [IV] as unchanged drug)

Clearance:

Infants: 0 to 3 months: 0.13 to 0.21 ± 0.06 L/hour/kg; >3 to 12 months: 0.49 ± 0.17 L/hour/kg

Children 1 to 11 years: 0.54 ± 0.34 L/hour/kg

Adolescents: 0.48 ± 0.14 L/hour/kg

Adults: 0.39 ± 0.14 L/hour/kg

Duodenal ulcer: Oral: Acute therapy: 40 mg/day at bedtime (or 20 mg twice daily) for 4 to 8 weeks; maintenance therapy: 20 mg/day at bedtime

Gastric ulcer: Oral: Acute therapy: 40 mg/day at bedtime

GERD: Oral: 20 mg twice daily for 6 weeks

Hypersecretory conditions: Oral: Initial: 20 mg every 6 hours, may increase in increments up to 160 mg every 6 hours

Esophagitis and accompanying symptoms due to GERD: Oral: 20 mg or 40 mg twice daily for up to 12 weeks

Patients unable to take oral medication: IV: 20 mg every 12 hours

Heartburn, indigestion, sour stomach: OTC labeling: Oral: 10 to 20 mg every 12 hours; dose may be taken 15 to 60 minutes before eating foods known to cause heartburn

Reducing gastrointestinal risks of NSAIDs and antiplatelet therapies: Oral: 40 mg twice daily (Abraham 2010; Lanza 2009)

Refractory urticaria, treatment: Oral: 20 mg twice daily (Bernstein 2014)

Stress ulcer prophylaxis, ICU patients (off-label use): Oral, IV, or nasogastric (NG) tube: 20 mg twice daily (ASHP 1999; Baghaie 1995); Note: Intended for patients with associated risk factors (eg, coagulopathy, mechanical ventilation for >48 hours, severe sepsis); discontinue use once risk factors have resolved. The Surviving Sepsis Campaign guidelines recommend either an H2-receptor antagonist or a proton-pump inhibitor (PPI) when stress ulcer prophylaxis is indicated (Rhodes 2017).

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer's labeling.

Solution for injection:

IV push: Dilute famotidine with NS (or another compatible solution) to a total of 5 to 10 mL (may also administer undiluted [Lipsy, 1995])

Infusion: Dilute with D5W 100 mL or another compatible solution.

An 8 mg/mL oral suspension may be made with tablets. Crush seventy 40 mg tablets in a mortar and reduce to a fine powder. Add small portions of sterile water and mix to a uniform paste. Mix while adding a 1:1 mixture of Ora-Plus® and Ora-Sweet® in incremental proportions to almost 350 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 350 mL. Label "shake well". Stable for 95 days at room temperature.

Adverse events have not been observed in animal reproduction studies; therefore, famotidine is classified as pregnancy category B. Famotidine crosses the placenta. An increased risk of congenital malformations or adverse events in the newborn has generally not been observed following maternal use of famotidine during pregnancy. Histamine H2 antagonists have been evaluated for the treatment of gastroesophageal reflux disease (GERD), as well as gastric and duodenal ulcers, during pregnancy. Although if needed, famotidine is not the agent of choice. Histamine H2 antagonists may be used for aspiration prophylaxis prior to cesarean delivery.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Oral:
-Initial dose: 20 mg orally every 6 hours
-Maximum dose: 160 mg orally every 6 hours

Parenteral:
-Usual dose: 20 mg IV every 6 to 12 hours

Comments:
-Parenteral treatment should be limited to patients who cannot tolerate oral formulations.
-Dosing should be determined on an individual basis.
-Treatment should be continued for as long as clinically necessary.

Uses:
-Treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome and multiple endocrine adenomas
-Some hospitalized patients with pathological hypersecretory conditions

LESS THAN 3 MONTHS:
Oral:
-Initial dose: 0.5 mg/kg orally once a day
-Duration of therapy: Up to 8 weeks

3 MONTHS TO LESS THAN 1 YEAR:
Oral:
-Initial dose: 0.5 mg/kg orally 2 times a day
-Duration of therapy: Up to 8 weeks

1 YEAR TO 16 YEARS:
Oral:
-Usual dose: 0.5 mg/kg/day orally 2 times a day
-Maximum dose: Up to 40 mg/dose

Parenteral:
-Initial dose: 0.25 mg/kg IV injected over at least 2 minutes OR infused over 15 minutes every 12 hours
-Maximum dose: 40 mg/day

16 YEARS AND OLDER:
Oral:
-Usual dose: 20 mg orally 2 times day
-Duration of therapy: Up to 6 weeks

Parenteral:
-Usual dose: 20 mg IV every 12 hours

Comments:
-The concomitant use of conservative measures (e.g., thickened feedings) should be considered during treatment.
-Parenteral treatment should be limited to patients who cannot tolerate oral formulations.
-Uncontrolled clinical trials have used oral doses up to 2 mg/kg in patients 1 to 16 years of age with gastroesophageal reflux disease (GERD) with/without esophagitis (including erosions ad ulcerations).
-Oral dissolving tablets may be used in patients 6 years and older, but should be taken as an intact tablet.

Uses:
-Short-term treatment of esophagitis due to gastroesophageal reflux disease, including erosive/ulcerative disease diagnosed by endoscopy
-Alternative to the oral dosage forms for short-term use in specific hospitalized patients who are unable to take oral medication for GERD

12 YEARS AND OLDER:
Oral:
Over-the-Counter (OTC) Formulations:
-Treatment dose: 10 to 20 mg orally once
-Symptom prevention: 10 to 20 mg orally once 10 to 60 minutes prior to consuming food/beverages that cause heartburn
-Maximum dose: 2 tablets/day
-Maximum duration of therapy: 14 days

Comments:
-OTC formulations should be taken with a glass of water.
-Chewable tablet formulations should be chewed completely before swallowing.

Uses:
-Relief of heartburn associated with acid indigestion and sour stomach
-Prevention of heartburn associated with acid indigestion and sour stomach brought on by eating/drinking certain foods and beverages

Mild renal dysfunction (CrCl 50 to 90 mL/min): No adjustment recommended.
Moderate (CrCl less than 50 mL/min) to severe renal dysfunction (CrCl less than 10 mL/min): Reduce the dose by 50% and/or prolong the dosing interval to 36 to 48 hours

Famotidine is an acid suppressing agent that may be used to treat a wide range of gastric-acid related disorders including gastric ulcers, heartburn, and GERD. A headache is the most common side effect and it appears to interact with few other drugs.

Famotidine a histamine-2 blockers. Famotidine works by decreasing the amount of acid the stomach produces.

Famotidine is used to treat and prevent ulcers in the stomach and intestines. It also treats conditions in which the stomach produces too much acid, such as Zollinger-Ellison syndrome. Famotidine also treats gastroesophageal reflux disease (GERD) and other conditions in which acid backs up from the stomach into the esophagus, causing heartburn.

Famotidine may also be used for purposes not listed in this medication guide.

Other drugs may interact with famotidine, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.