These Highlights Do Not Include All The Information Needed To Use Famotidine For Oral Suspension Safely And Effectively. See Full Prescribing Information For Famotidine For Oral Suspension.

Preparation of Constituted Suspension by a Healthcare Provider Prior to Dispensing

• Prior to dispensing, constitute famotidine for oral suspension, USP by slowly adding below volume of purified water to the bottle.
• Shake vigorously for 5 to 10 seconds immediately after adding the water.
• The constituted suspension contains 40 mg of famotidine, USP per 5 mL, and should be a smooth, mobile, white to off-white, and homogeneous suspension.

  Bottle Size	Volume of Purified Water for Reconstitution
  50 mL	46 mL
  100 mL	92 mL
  150 mL	138 mL

Storage

Store famotidine for oral suspension dry powder and constituted suspension at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Protect from freezing. Discard unused constituted suspension after 30 days.

Dispense in a USP tight, light-resistant container.

The types of adverse reactions in overdosage of famotidine are similar to the adverse reactions encountered with use of recommended dosages [see Adverse Reactions (6.1)] .

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.

Due to low binding to plasma proteins, famotidine is eliminated by hemodialysis. There is limited experience on the usefulness of hemodialysis as a treatment for famotidine overdosage.

The active ingredient in famotidine for oral suspension, USP is a histamine-2 (H ₂) receptor antagonist. Famotidine, USP is N'-(aminosulfonyl)-3-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]propanimidamide. The empirical formula of famotidine, USP is C ₈H ₁₅N ₇O ₂S ₃and its molecular weight is 337.43. Its structural formula is:

Each 5 mL of famotidine for oral suspension, USP when prepared as directed contains 40 mg of famotidine, USP and the following inactive ingredients: carboxymethyl cellulose sodium, flavors (banana, cherry and peppermint), fumaric acid, microcrystalline cellulose, sucrose, xanthan gum. Added as preservatives are sodium benzoate 0.42%, sodium methyl paraben 0.08%, and sodium propyl paraben 0.02%.

Famotidine, USP is a white to pale yellow-white crystalline compound that is freely soluble in dimethylformamide and in glacial acetic acid, slightly soluble in methanol, very slightly soluble in water, and practically insoluble in ethanol, chloroform, ether and in ethyl acetate.

Of the 1,442 famotidine-treated patients in clinical studies, approximately 10% were 65 and older. In these studies, no overall differences in safety or effectiveness were observed between elderly and younger patients. In post marketing experience, CNS adverse reactions have been reported in elderly patients with and without renal impairment receiving famotidine [see Warnings and Precautions (5.1)] .

Famotidine is known to be substantially excreted by the kidney, and the risk of adverse reactions to famotidine for oral suspension may be greater in elderly patients, particularly those with impaired renal function [see Use in Specific Populations (8.6)] .

In general, use the lowest effective dose of famotidine for oral suspension for an elderly patient and monitor renal function [see Dosage and Administration (2.2)] .

The safety and effectiveness of famotidine for oral suspension have been established based on adequate and well-controlled studies of another oral famotidine product .The following is a summary of the efficacy results reported in those studies.

Famotidine for oral suspension is contraindicated in patients with a history of serious hypersensitivity reactions (e.g., anaphylaxis) to famotidine or other histamine-2 (H ₂) receptor antagonists.

The most common adverse reactions are: headache, dizziness, constipation, and diarrhea. ( 6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Upsher-Smith Laboratories, LLC at 1-855-899-9180 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Drugs Dependent on Gastric pH for Absorption: Systemic exposure of the concomitant drug may be significantly reduced leading to loss of efficacy. See full prescribing information for a list of interacting drugs. ( 7.1)
• Tizanidine (CYP1A2) Substrate: Potential for substantial increases in blood concentrations of tizanidine resulting in hypotension, bradycardia or excessive drowsiness; avoid concomitant use, if possible. ( 7.2)

CNS adverse reactions and prolonged QT intervals have been reported in patients with moderate and severe renal impairment [see Warnings and Precautions (5.1)] . The clearance of famotidine is reduced in adults with moderate and severe renal impairment compared to adults with normal renal function [see Clinical Pharmacology (12.3)] . No dosage adjustment is needed in adults with mild renal impairment (creatinine clearance greater than or equal to 60 mL/minute). Dosage reduction is recommended in adults with moderate or severe renal impairment (creatinine clearance less than 60 mL/minute) [see Dosage and Administration (2.3)] . Data are not available to establish a safe and effective dosage in pediatric patients with renal impairment.

Famotidine for oral suspension is indicated in adults for the treatment of:

• active duodenal ulcer (DU).
• active gastric ulcer (GU).
• symptomatic nonerosive gastroesophageal reflux disease (GERD).
• erosive esophagitis due to GERD, diagnosed by biopsy.
• treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome, multiple endocrine neoplasias).
• reduction of the risk of duodenal ulcer recurrence.

Famotidine for oral suspension is indicated in pediatric patients 1 year of age and older for the treatment of:

• peptic ulcer disease.
• GERD with or without esophagitis and ulcerations.

Famotidine for oral suspension is indicated in pediatric patients from birth to less than 1 year of age for the treatment of:

• GERD.

Famotidine is a competitive inhibitor of histamine-2 (H ₂) receptors. The primary clinically important pharmacologic activity of famotidine is inhibition of gastric secretion. Both the acid concentration and volume of gastric secretion are suppressed by famotidine, while changes in pepsin secretion are proportional to volume output.

In both a U.S. and an international multicenter, double-blind trials in patients with endoscopically confirmed active gastric ulcer (GU), orally administered famotidine 40 mg at bedtime was compared to placebo. Antacids were permitted during the trials, but consumption was not significantly different between the famotidine and placebo groups.

As shown in Table 7, the incidence of GU healing confirmed by endoscopy (dropouts counted as unhealed) with famotidine was greater than placebo at Weeks 6 and 8 in the U.S. trial, and at Weeks 4, 6 and 8 in the international trial.

In these trials, most famotidine-treated patients healed within 6 weeks. Trials have not assessed the safety of famotidine in uncomplicated active GU for periods of more than 8 weeks.

Time to complete relief of daytime and nighttime pain was statistically significantly shorter for patients receiving famotidine than for patients receiving placebo; however, neither trial demonstrated a statistically significant difference in the proportion of patients whose pain was relieved by the end of the trial (Week 8).

In a U.S. multicenter, double-blind trial in adult outpatients with endoscopically confirmed duodenal ulcer (DU), orally administered famotidine was compared to placebo. As shown in Table 6, 70% of patients treated with famotidine 40 mg at bedtime were healed by Week 4. Most patients' DU healed within 4 weeks.

Patients not healed by Week 4 were continued in the trial. By Week 8, 83% of patients treated with famotidine had healed DU, compared to 45% of patients treated with placebo. The incidence of DU healing with famotidine was greater than with placebo at each time point based on proportion of endoscopically confirmed healed DUs. Trials have not assessed the safety of famotidine in uncomplicated active DU for periods of more than 8 weeks.

In this study, time to relief of daytime and nocturnal pain was shorter for patients receiving famotidine than for patients receiving placebo; patients receiving famotidine also took less antacid than patients receiving placebo.

• Central Nervous System (CNS) Adverse Reactions: Elderly patients and patients with renal impairment at increased risk; reduce the dosage. ( 2.2, 5.1, 8.5, 8.6)
• GI Malignancy: Absence of GI symptoms does not preclude the presence of gastric malignancy; evaluate prior to initiating therapy. ( 5.2)

• Recommended adult dosage by indication ( 2.1):

  Active DU	40 mg once daily; or 20 mg twice daily
  Active GU	40 mg once daily
  Symptomatic Nonerosive GERD	20 mg twice daily
  Erosive Esophagitis due to GERD	20 mg twice daily; or 40 mg twice daily
  Pathological Hypersecretory Conditions	20 mg every 6 hours; adjust to patient needs; maximum 160 mg every 6 hours
  Risk Reduction of DU Recurrence	20 mg once daily

• Recommended pediatric dosage by indication ( 2.2):

  Peptic Ulcer Disease	1 year to less than 17 years Starting dosage 0.5 mg/kg once daily; or 0.25 mg/kg twice daily; may increase to 1 mg/kg once daily at bedtime or 0.5 mg/kg twice daily; Maximum of 40 mg per day
  GERD	Birth to less than 3 months Starting dosage 0.5 mg/kg once daily; may increase to 1 mg/kg once daily;
  3 months to less than 1 year Starting dosage 0.5 mg/kg twice daily; may increase to 1 mg/kg twice daily; Maximum of 40 mg per day
  GERD with or without esophagitis and ulcerations	1 year to less than 17 years 0.5 mg/kg twice daily Maximum of 40 mg twice daily

• See full prescribing information for complete dosing information in adults and pediatrics, recommended treatment duration by indication, and dosage adjustment for adult patients with renal impairment. ( 2.1, 2.2, 2.3)

Administration ( 2.3) :

• Take once daily before bedtime or twice daily in the morning and before bedtime with or without food.

Famotidine for oral suspension 400 mg, 800 mg and 1,200 mg is a white to off-white powder containing 40 mg of famotidine per 5 mL. When constituted as directed, famotidine for oral suspension is a smooth, mobile, white to off-white, homogeneous suspension with a cherry-banana-mint flavor,

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of famotidine for oral suspension has been established based on adequate and well-controlled studies of another oral famotidine product [see Clinical Studies (14)] . The following is a summary of the adverse reactions reported in those studies.

Oral famotidine was studied in 7 U.S. and international placebo- and active-controlled trials in approximately 2,500 patients [see Clinical Studies (14)] . A total of 1,442 patients were treated with famotidine, including 302 treated with 40 mg twice daily, 456 treated with 20 mg twice daily, 461 treated with 40 mg once daily, and 396 treated with 20 mg once daily. The population was 17 to 91 years old, fairly well distributed between sex and race; however, the predominant race was Caucasian.

The following adverse reactions occurred in greater than or equal to 1% of famotidine-treated patients: headache, dizziness and constipation.

The following other adverse reactions were reported in less than 1% of patients in clinical trials:

Body as a Whole:fever, asthenia, fatigue

Cardiovascular:palpitations

Gastrointestinal:elevated liver enzymes, vomiting, nausea, abdominal discomfort, anorexia, dry mouth

Hematologic:thrombocytopenia

Hypersensitivity:orbital edema, rash, conjunctival injection, bronchospasm

Musculoskeletal:musculoskeletal pain, arthralgia

Nervous System/Psychiatric:seizure, hallucinations, depression, anxiety, decreased libido, insomnia, somnolence

Skin:pruritus, dry skin, flushing

Special Senses:tinnitus, taste disorder

Other:impotence

The following adverse reactions have been identified during post-approval use of famotidine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiovascular:arrhythmia, AV block, prolonged QT interval

Gastrointestinal:cholestatic jaundice, hepatitis

Hematologic:agranulocytosis, pancytopenia, leukopenia

Hypersensitivity:anaphylaxis, angioedema, facial edema, urticaria

Musculoskeletal:rhabdomyolysis, muscle cramps

Nervous System/Psychiatric:confusion, agitation, paresthesia

Respiratory:interstitial pneumonia

Skin:toxic epidermal necrolysis/Stevens-Johnson syndrome

• Geriatric Use: Use the lowest effective dose for an elderly patient and monitor renal function. ( 2.2, 5.1, 8.5)
• Renal Impairment: Risk of CNS adverse reactions and QT prolongation in patients with moderate and severe renal impairment; reduce the dosage in adults. ( 2.2, 8.6)

The recommended dosage and duration of famotidine for oral suspension, USP in adults with normal renal function is shown in Table 1.

In adults, symptomatic response to therapy with famotidine for oral suspension does not preclude the presence of gastric malignancy. Consider evaluation for gastric malignancy in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with famotidine for oral suspension.

Although not studied clinically, famotidine is considered a weak CYP1A2 inhibitor and may lead to substantial increases in blood concentrations of tizanidine, a CYP1A2 substrate. Avoid concomitant use with famotidine for oral suspension. If concomitant use is necessary, monitor for hypotension, bradycardia or excessive drowsiness. Refer to the full prescribing information for tizanidine.

Healing of endoscopically verified erosion and symptomatic improvement were studied in a U.S. and an international double-blind trials. Healing was defined as complete resolution of all erosions visible with endoscopy. The U.S. trial comparing orally administered famotidine 40 mg twice daily to placebo and orally administered famotidine 20 mg twice daily showed a significantly greater percentage of healing of erosive esophagitis for famotidine 40 mg twice daily at Weeks 6 and 12 (Table 9).

As compared to placebo, patients in the U.S. trial who received famotidine had faster relief of daytime and nighttime heartburn, and a greater percentage of famotidine-treated patients experienced complete relief of nighttime heartburn. These differences were statistically significant.

In the international trial, when orally administered famotidine 40 mg twice daily was compared to orally administered ranitidine 150 mg twice daily, a statistically significantly greater percentage of healing of erosive esophagitis was observed with famotidine 40 mg twice daily at Week 12 (Table 10). There was, however, no significant difference in symptom relief among treatment groups.

Famotidine for oral suspension, USP 40 mg/5 mL is supplied as follows:

Prior to dispensing, constitute famotidine for oral suspension, USP [see Dosage and Administration (2.3)] .

In trials of patients with pathological hypersecretory conditions such as Zollinger-Ellison syndrome with or without multiple endocrine neoplasias, famotidine significantly inhibited gastric acid secretion and controlled associated symptoms. Orally administered famotidine dosages from 20 mg to 160 mg every 6 hours maintained basal acid secretion below 10 mEq/hour; initial dosages were titrated to the individual patient need and subsequent adjustments were necessary with time in some patients.

The recommended dosage and duration of famotidine for oral suspension, USP in pediatric patients with normal renal function is shown in Table 2.

Central nervous system (CNS) adverse reactions, including confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy, have been reported in elderly patients and patients with moderate and severe renal impairment treated with famotidine. Since famotidine blood levels are higher in patients with renal impairment than in patients with normal renal function, dosage adjustments are recommended in patients with renal impairment [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)] .

NDC 0832-6045-50

Famotidine for Oral

Suspension, USP

40 mg/5 mL

400 mg of famotidine

When reconstituted as directed, each teaspoonful

(5 mL) contains famotidine, USP 40 mg.

FOR ORAL USE ONLY

SHAKE WELL BEFORE EACH USE

50 mL (when reconstituted)

Rx only

UPSHER-SMITH

NDC 0832-6045-10

Famotidine for Oral

Suspension, USP

40 mg/5 mL

800 mg of famotidine

When reconstituted as directed, each teaspoonful

(5 mL) contains famotidine, USP 40 mg.

FOR ORAL USE ONLY

SHAKE WELL BEFORE EACH USE

100 mL (when reconstituted)

Rx only

UPSHER-SMITH

NDC 0832-6045-15

Famotidine for Oral

Suspension, USP

40 mg/5 mL

1,200 mg of famotidine

When reconstituted as directed, each teaspoonful

(5 mL) contains famotidine, USP 40 mg.

FOR ORAL USE ONLY

SHAKE WELL BEFORE EACH USE

150 mL (when reconstituted)

Rx only

UPSHER-SMITH

Two randomized, double-blind, multicenter trials in patients with endoscopically confirmed healed DUs demonstrated that patients receiving treatment with orally administered famotidine 20 mg at bedtime had lower rates of DU recurrence, as compared with placebo.

• In the U.S. trial, DU recurrence within 12 months was 2.4 times greater in patients treated with placebo than in the patients treated with famotidine. The 89 famotidine-treated patients had a cumulative observed DU recurrence rate of 23%, compared to a 57% in the 89 patients receiving placebo (p<0.01).
• In the international trial, the cumulative observed DU recurrence within 12 months in the 307 famotidine-treated patients was 36%, compared to 76% in the 325 patients who received placebo (p<0.01).

Controlled trials have not extended beyond one year.

Famotidine can reduce the absorption of other drugs, due to its effect on reducing intragastric acidity, leading to loss of efficacy of the concomitant drug.

Concomitant administration of famotidine for oral suspension with dasatinib, delavirdine mesylate, cefditoren, and fosamprenavir is not recommended.

See the prescribing information for other drugs dependent on gastric pH for absorption for administration instructions, including atazanavir, erlotinib, ketoconazole, itraconazole, ledipasvir/sofosbuvir, nilotinib, and rilpivirine.

Recommended dosage adjustments for adults with moderate to severe renal impairment (creatinine clearance less than 60 mL/min) by indication are shown in Table 3. Use the lowest effective dosage [see Use in Specific Populations (8.6)] .

A safe and effective dosage has not been established in pediatric patients with renal impairment.

Orally administered famotidine was compared to placebo in a U.S. trial that enrolled patients with symptoms of GERD and without endoscopic evidence of esophageal erosion or ulceration. As shown in Table 8, patients treated with famotidine 20 mg twice daily had greater improvement in symptomatic GERD than patients treated with 40 mg at bedtime or placebo.

In a double-blind, randomized, treatment-withdrawal study, 35 pediatric patients less than 1 year of age who were diagnosed with GERD, primarily by history of vomiting (spitting up) and irritability (fussiness), were treated for up to 4 weeks with famotidine oral suspension 0.5 mg/kg or 1 mg/kg administered once daily for patients less than 3 months of age and administered twice daily for patients 3 months to less than 12 months of age. Caregivers were instructed to provide conservative treatment including thickened feedings. After 4 weeks of treatment, patients were randomly withdrawn from the treatment and followed an additional 4 weeks 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. 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.

Carcinogenic potential of famotidine was assessed in a 106-week oral carcinogenicity study in rats and a 92-week oral carcinogenicity study in mice. In the 106-week study in rats and the 92-week study in mice at oral doses of up to 2,000 mg/kg/day (approximately 243 and 122 times, respectively, based on body surface area, the recommended human dose of 80 mg per day for the treatment of erosive esophagitis), there was no evidence of carcinogenic potential for famotidine.

Famotidine was negative in the microbial mutagen test (Ames test) using Salmonella typhimuriumand Escherichia coliwith or without rat liver enzyme activation at concentrations up to 10,000 mcg/plate. In in vivostudies 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 2,000 mg/kg/day (approximately 243 times, based on body surface area, the recommended human dose of 80 mg per day) fertility and reproductive performance were not affected.

Preparation of Constituted Suspension by a Healthcare Provider Prior to Dispensing

• Prior to dispensing, constitute famotidine for oral suspension, USP by slowly adding below volume of purified water to the bottle.
• Shake vigorously for 5 to 10 seconds immediately after adding the water.
• The constituted suspension contains 40 mg of famotidine, USP per 5 mL, and should be a smooth, mobile, white to off-white, and homogeneous suspension.

  Bottle Size	Volume of Purified Water for Reconstitution
  50 mL	46 mL
  100 mL	92 mL
  150 mL	138 mL

Storage

Store famotidine for oral suspension dry powder and constituted suspension at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Protect from freezing. Discard unused constituted suspension after 30 days.

Dispense in a USP tight, light-resistant container.

The types of adverse reactions in overdosage of famotidine are similar to the adverse reactions encountered with use of recommended dosages [see Adverse Reactions (6.1)] .

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.

Due to low binding to plasma proteins, famotidine is eliminated by hemodialysis. There is limited experience on the usefulness of hemodialysis as a treatment for famotidine overdosage.

The active ingredient in famotidine for oral suspension, USP is a histamine-2 (H ₂) receptor antagonist. Famotidine, USP is N'-(aminosulfonyl)-3-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]propanimidamide. The empirical formula of famotidine, USP is C ₈H ₁₅N ₇O ₂S ₃and its molecular weight is 337.43. Its structural formula is:

Each 5 mL of famotidine for oral suspension, USP when prepared as directed contains 40 mg of famotidine, USP and the following inactive ingredients: carboxymethyl cellulose sodium, flavors (banana, cherry and peppermint), fumaric acid, microcrystalline cellulose, sucrose, xanthan gum. Added as preservatives are sodium benzoate 0.42%, sodium methyl paraben 0.08%, and sodium propyl paraben 0.02%.

Famotidine, USP is a white to pale yellow-white crystalline compound that is freely soluble in dimethylformamide and in glacial acetic acid, slightly soluble in methanol, very slightly soluble in water, and practically insoluble in ethanol, chloroform, ether and in ethyl acetate.

Of the 1,442 famotidine-treated patients in clinical studies, approximately 10% were 65 and older. In these studies, no overall differences in safety or effectiveness were observed between elderly and younger patients. In post marketing experience, CNS adverse reactions have been reported in elderly patients with and without renal impairment receiving famotidine [see Warnings and Precautions (5.1)] .

Famotidine is known to be substantially excreted by the kidney, and the risk of adverse reactions to famotidine for oral suspension may be greater in elderly patients, particularly those with impaired renal function [see Use in Specific Populations (8.6)] .

In general, use the lowest effective dose of famotidine for oral suspension for an elderly patient and monitor renal function [see Dosage and Administration (2.2)] .

The safety and effectiveness of famotidine for oral suspension have been established based on adequate and well-controlled studies of another oral famotidine product .The following is a summary of the efficacy results reported in those studies.

Famotidine for oral suspension is contraindicated in patients with a history of serious hypersensitivity reactions (e.g., anaphylaxis) to famotidine or other histamine-2 (H ₂) receptor antagonists.

The most common adverse reactions are: headache, dizziness, constipation, and diarrhea. ( 6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Upsher-Smith Laboratories, LLC at 1-855-899-9180 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Drugs Dependent on Gastric pH for Absorption: Systemic exposure of the concomitant drug may be significantly reduced leading to loss of efficacy. See full prescribing information for a list of interacting drugs. ( 7.1)
• Tizanidine (CYP1A2) Substrate: Potential for substantial increases in blood concentrations of tizanidine resulting in hypotension, bradycardia or excessive drowsiness; avoid concomitant use, if possible. ( 7.2)

CNS adverse reactions and prolonged QT intervals have been reported in patients with moderate and severe renal impairment [see Warnings and Precautions (5.1)] . The clearance of famotidine is reduced in adults with moderate and severe renal impairment compared to adults with normal renal function [see Clinical Pharmacology (12.3)] . No dosage adjustment is needed in adults with mild renal impairment (creatinine clearance greater than or equal to 60 mL/minute). Dosage reduction is recommended in adults with moderate or severe renal impairment (creatinine clearance less than 60 mL/minute) [see Dosage and Administration (2.3)] . Data are not available to establish a safe and effective dosage in pediatric patients with renal impairment.

Famotidine for oral suspension is indicated in adults for the treatment of:

• active duodenal ulcer (DU).
• active gastric ulcer (GU).
• symptomatic nonerosive gastroesophageal reflux disease (GERD).
• erosive esophagitis due to GERD, diagnosed by biopsy.
• treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome, multiple endocrine neoplasias).
• reduction of the risk of duodenal ulcer recurrence.

Famotidine for oral suspension is indicated in pediatric patients 1 year of age and older for the treatment of:

• peptic ulcer disease.
• GERD with or without esophagitis and ulcerations.

Famotidine for oral suspension is indicated in pediatric patients from birth to less than 1 year of age for the treatment of:

• GERD.

Famotidine is a competitive inhibitor of histamine-2 (H ₂) receptors. The primary clinically important pharmacologic activity of famotidine is inhibition of gastric secretion. Both the acid concentration and volume of gastric secretion are suppressed by famotidine, while changes in pepsin secretion are proportional to volume output.

In both a U.S. and an international multicenter, double-blind trials in patients with endoscopically confirmed active gastric ulcer (GU), orally administered famotidine 40 mg at bedtime was compared to placebo. Antacids were permitted during the trials, but consumption was not significantly different between the famotidine and placebo groups.

As shown in Table 7, the incidence of GU healing confirmed by endoscopy (dropouts counted as unhealed) with famotidine was greater than placebo at Weeks 6 and 8 in the U.S. trial, and at Weeks 4, 6 and 8 in the international trial.

In these trials, most famotidine-treated patients healed within 6 weeks. Trials have not assessed the safety of famotidine in uncomplicated active GU for periods of more than 8 weeks.

Time to complete relief of daytime and nighttime pain was statistically significantly shorter for patients receiving famotidine than for patients receiving placebo; however, neither trial demonstrated a statistically significant difference in the proportion of patients whose pain was relieved by the end of the trial (Week 8).

In a U.S. multicenter, double-blind trial in adult outpatients with endoscopically confirmed duodenal ulcer (DU), orally administered famotidine was compared to placebo. As shown in Table 6, 70% of patients treated with famotidine 40 mg at bedtime were healed by Week 4. Most patients' DU healed within 4 weeks.

Patients not healed by Week 4 were continued in the trial. By Week 8, 83% of patients treated with famotidine had healed DU, compared to 45% of patients treated with placebo. The incidence of DU healing with famotidine was greater than with placebo at each time point based on proportion of endoscopically confirmed healed DUs. Trials have not assessed the safety of famotidine in uncomplicated active DU for periods of more than 8 weeks.

In this study, time to relief of daytime and nocturnal pain was shorter for patients receiving famotidine than for patients receiving placebo; patients receiving famotidine also took less antacid than patients receiving placebo.

• Central Nervous System (CNS) Adverse Reactions: Elderly patients and patients with renal impairment at increased risk; reduce the dosage. ( 2.2, 5.1, 8.5, 8.6)
• GI Malignancy: Absence of GI symptoms does not preclude the presence of gastric malignancy; evaluate prior to initiating therapy. ( 5.2)

• Recommended adult dosage by indication ( 2.1):

  Active DU	40 mg once daily; or 20 mg twice daily
  Active GU	40 mg once daily
  Symptomatic Nonerosive GERD	20 mg twice daily
  Erosive Esophagitis due to GERD	20 mg twice daily; or 40 mg twice daily
  Pathological Hypersecretory Conditions	20 mg every 6 hours; adjust to patient needs; maximum 160 mg every 6 hours
  Risk Reduction of DU Recurrence	20 mg once daily

• Recommended pediatric dosage by indication ( 2.2):

  Peptic Ulcer Disease	1 year to less than 17 years Starting dosage 0.5 mg/kg once daily; or 0.25 mg/kg twice daily; may increase to 1 mg/kg once daily at bedtime or 0.5 mg/kg twice daily; Maximum of 40 mg per day
  GERD	Birth to less than 3 months Starting dosage 0.5 mg/kg once daily; may increase to 1 mg/kg once daily;
  3 months to less than 1 year Starting dosage 0.5 mg/kg twice daily; may increase to 1 mg/kg twice daily; Maximum of 40 mg per day
  GERD with or without esophagitis and ulcerations	1 year to less than 17 years 0.5 mg/kg twice daily Maximum of 40 mg twice daily

• See full prescribing information for complete dosing information in adults and pediatrics, recommended treatment duration by indication, and dosage adjustment for adult patients with renal impairment. ( 2.1, 2.2, 2.3)

Administration ( 2.3) :

• Take once daily before bedtime or twice daily in the morning and before bedtime with or without food.

Famotidine for oral suspension 400 mg, 800 mg and 1,200 mg is a white to off-white powder containing 40 mg of famotidine per 5 mL. When constituted as directed, famotidine for oral suspension is a smooth, mobile, white to off-white, homogeneous suspension with a cherry-banana-mint flavor,

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of famotidine for oral suspension has been established based on adequate and well-controlled studies of another oral famotidine product [see Clinical Studies (14)] . The following is a summary of the adverse reactions reported in those studies.

Oral famotidine was studied in 7 U.S. and international placebo- and active-controlled trials in approximately 2,500 patients [see Clinical Studies (14)] . A total of 1,442 patients were treated with famotidine, including 302 treated with 40 mg twice daily, 456 treated with 20 mg twice daily, 461 treated with 40 mg once daily, and 396 treated with 20 mg once daily. The population was 17 to 91 years old, fairly well distributed between sex and race; however, the predominant race was Caucasian.

The following adverse reactions occurred in greater than or equal to 1% of famotidine-treated patients: headache, dizziness and constipation.

The following other adverse reactions were reported in less than 1% of patients in clinical trials:

Body as a Whole:fever, asthenia, fatigue

Cardiovascular:palpitations

Gastrointestinal:elevated liver enzymes, vomiting, nausea, abdominal discomfort, anorexia, dry mouth

Hematologic:thrombocytopenia

Hypersensitivity:orbital edema, rash, conjunctival injection, bronchospasm

Musculoskeletal:musculoskeletal pain, arthralgia

Nervous System/Psychiatric:seizure, hallucinations, depression, anxiety, decreased libido, insomnia, somnolence

Skin:pruritus, dry skin, flushing

Special Senses:tinnitus, taste disorder

Other:impotence

The following adverse reactions have been identified during post-approval use of famotidine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiovascular:arrhythmia, AV block, prolonged QT interval

Gastrointestinal:cholestatic jaundice, hepatitis

Hematologic:agranulocytosis, pancytopenia, leukopenia

Hypersensitivity:anaphylaxis, angioedema, facial edema, urticaria

Musculoskeletal:rhabdomyolysis, muscle cramps

Nervous System/Psychiatric:confusion, agitation, paresthesia

Respiratory:interstitial pneumonia

Skin:toxic epidermal necrolysis/Stevens-Johnson syndrome

• Geriatric Use: Use the lowest effective dose for an elderly patient and monitor renal function. ( 2.2, 5.1, 8.5)
• Renal Impairment: Risk of CNS adverse reactions and QT prolongation in patients with moderate and severe renal impairment; reduce the dosage in adults. ( 2.2, 8.6)

The recommended dosage and duration of famotidine for oral suspension, USP in adults with normal renal function is shown in Table 1.

In adults, symptomatic response to therapy with famotidine for oral suspension does not preclude the presence of gastric malignancy. Consider evaluation for gastric malignancy in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with famotidine for oral suspension.

Although not studied clinically, famotidine is considered a weak CYP1A2 inhibitor and may lead to substantial increases in blood concentrations of tizanidine, a CYP1A2 substrate. Avoid concomitant use with famotidine for oral suspension. If concomitant use is necessary, monitor for hypotension, bradycardia or excessive drowsiness. Refer to the full prescribing information for tizanidine.

Healing of endoscopically verified erosion and symptomatic improvement were studied in a U.S. and an international double-blind trials. Healing was defined as complete resolution of all erosions visible with endoscopy. The U.S. trial comparing orally administered famotidine 40 mg twice daily to placebo and orally administered famotidine 20 mg twice daily showed a significantly greater percentage of healing of erosive esophagitis for famotidine 40 mg twice daily at Weeks 6 and 12 (Table 9).

As compared to placebo, patients in the U.S. trial who received famotidine had faster relief of daytime and nighttime heartburn, and a greater percentage of famotidine-treated patients experienced complete relief of nighttime heartburn. These differences were statistically significant.

In the international trial, when orally administered famotidine 40 mg twice daily was compared to orally administered ranitidine 150 mg twice daily, a statistically significantly greater percentage of healing of erosive esophagitis was observed with famotidine 40 mg twice daily at Week 12 (Table 10). There was, however, no significant difference in symptom relief among treatment groups.

Famotidine for oral suspension, USP 40 mg/5 mL is supplied as follows:

Prior to dispensing, constitute famotidine for oral suspension, USP [see Dosage and Administration (2.3)] .

In trials of patients with pathological hypersecretory conditions such as Zollinger-Ellison syndrome with or without multiple endocrine neoplasias, famotidine significantly inhibited gastric acid secretion and controlled associated symptoms. Orally administered famotidine dosages from 20 mg to 160 mg every 6 hours maintained basal acid secretion below 10 mEq/hour; initial dosages were titrated to the individual patient need and subsequent adjustments were necessary with time in some patients.

The recommended dosage and duration of famotidine for oral suspension, USP in pediatric patients with normal renal function is shown in Table 2.

Central nervous system (CNS) adverse reactions, including confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy, have been reported in elderly patients and patients with moderate and severe renal impairment treated with famotidine. Since famotidine blood levels are higher in patients with renal impairment than in patients with normal renal function, dosage adjustments are recommended in patients with renal impairment [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)] .

NDC 0832-6045-50

Famotidine for Oral

Suspension, USP

40 mg/5 mL

400 mg of famotidine

When reconstituted as directed, each teaspoonful

(5 mL) contains famotidine, USP 40 mg.

FOR ORAL USE ONLY

SHAKE WELL BEFORE EACH USE

50 mL (when reconstituted)

Rx only

UPSHER-SMITH

NDC 0832-6045-10

Famotidine for Oral

Suspension, USP

40 mg/5 mL

800 mg of famotidine

When reconstituted as directed, each teaspoonful

(5 mL) contains famotidine, USP 40 mg.

FOR ORAL USE ONLY

SHAKE WELL BEFORE EACH USE

100 mL (when reconstituted)

Rx only

UPSHER-SMITH

NDC 0832-6045-15

Famotidine for Oral

Suspension, USP

40 mg/5 mL

1,200 mg of famotidine

When reconstituted as directed, each teaspoonful

(5 mL) contains famotidine, USP 40 mg.

FOR ORAL USE ONLY

SHAKE WELL BEFORE EACH USE

150 mL (when reconstituted)

Rx only

UPSHER-SMITH

Two randomized, double-blind, multicenter trials in patients with endoscopically confirmed healed DUs demonstrated that patients receiving treatment with orally administered famotidine 20 mg at bedtime had lower rates of DU recurrence, as compared with placebo.

• In the U.S. trial, DU recurrence within 12 months was 2.4 times greater in patients treated with placebo than in the patients treated with famotidine. The 89 famotidine-treated patients had a cumulative observed DU recurrence rate of 23%, compared to a 57% in the 89 patients receiving placebo (p<0.01).
• In the international trial, the cumulative observed DU recurrence within 12 months in the 307 famotidine-treated patients was 36%, compared to 76% in the 325 patients who received placebo (p<0.01).

Controlled trials have not extended beyond one year.

Famotidine can reduce the absorption of other drugs, due to its effect on reducing intragastric acidity, leading to loss of efficacy of the concomitant drug.

Concomitant administration of famotidine for oral suspension with dasatinib, delavirdine mesylate, cefditoren, and fosamprenavir is not recommended.

See the prescribing information for other drugs dependent on gastric pH for absorption for administration instructions, including atazanavir, erlotinib, ketoconazole, itraconazole, ledipasvir/sofosbuvir, nilotinib, and rilpivirine.

Recommended dosage adjustments for adults with moderate to severe renal impairment (creatinine clearance less than 60 mL/min) by indication are shown in Table 3. Use the lowest effective dosage [see Use in Specific Populations (8.6)] .

A safe and effective dosage has not been established in pediatric patients with renal impairment.

Orally administered famotidine was compared to placebo in a U.S. trial that enrolled patients with symptoms of GERD and without endoscopic evidence of esophageal erosion or ulceration. As shown in Table 8, patients treated with famotidine 20 mg twice daily had greater improvement in symptomatic GERD than patients treated with 40 mg at bedtime or placebo.

In a double-blind, randomized, treatment-withdrawal study, 35 pediatric patients less than 1 year of age who were diagnosed with GERD, primarily by history of vomiting (spitting up) and irritability (fussiness), were treated for up to 4 weeks with famotidine oral suspension 0.5 mg/kg or 1 mg/kg administered once daily for patients less than 3 months of age and administered twice daily for patients 3 months to less than 12 months of age. Caregivers were instructed to provide conservative treatment including thickened feedings. After 4 weeks of treatment, patients were randomly withdrawn from the treatment and followed an additional 4 weeks 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. 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.

Carcinogenic potential of famotidine was assessed in a 106-week oral carcinogenicity study in rats and a 92-week oral carcinogenicity study in mice. In the 106-week study in rats and the 92-week study in mice at oral doses of up to 2,000 mg/kg/day (approximately 243 and 122 times, respectively, based on body surface area, the recommended human dose of 80 mg per day for the treatment of erosive esophagitis), there was no evidence of carcinogenic potential for famotidine.

Famotidine was negative in the microbial mutagen test (Ames test) using Salmonella typhimuriumand Escherichia coliwith or without rat liver enzyme activation at concentrations up to 10,000 mcg/plate. In in vivostudies 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 2,000 mg/kg/day (approximately 243 times, based on body surface area, the recommended human dose of 80 mg per day) fertility and reproductive performance were not affected.