Famotidine

Class: Histamine H2-Antagonists
VA Class: GA301
Chemical Name: 3-[[[2-[(Aminoiminomethyl)amino]-4-thiazolyl]methyl]thio]-N-(aminosulfonyl)propanimidamide
Molecular Formula: C₈H₁₅N₇O₂S₃
CAS Number: 76824-35-6
Brands: Pepcid, Pepcid Complete

Introduction

Histamine H₂ receptor antagonist.^{1 3 4 6 23 46 48 114}

Uses for Famotidine

Duodenal Ulcer

Short-term treatment of active duodenal ulcer (endoscopically or radiographically confirmed).^{1 4 5 6 7 12 16 18 19 22 91 92 93 94 114 123 124 128 129 130 135}

Maintenance of healing and reduction in recurrence of duodenal ulcer.^{1 4 8 88 91 93 114}

Pathologic GI Hypersecretory Conditions

Treatment of Zollinger-Ellison syndrome, multiple endocrine adenomas.^{1 4 5 10 51 93 114 122 132}

Gastric Ulcer

Short-term treatment of active benign gastric ulcer.^{1 4 5 9 12 14 20 22 75 89 93 94 124 131 136 140}

Gastroesophageal Reflux (GERD)

Short-term treatment of symptomatic GERD.^{1 139 167 168 169 170 171 172 173 174 175}

Short-term treatment of esophagitis, including erosions or ulcers (endoscopically diagnosed) in patients with GERD.^{1 167 168 171}

Self-medication as initial therapy for less severe symptomatic GERD†.²⁶¹

Short-term self-medication for relief of heartburn symptoms in adults and adolescents ≥12 years of age.^{238 260}

Short-term self-medication for prevention of heartburn symptoms associated with acid indigestion and sour stomach brought on by ingestion of certain foods and beverages in adults and children ≥12 years of age.^{238 260}

Famotidine Dosage and Administration

Administration

Administered orally,¹ or by slow IV injection or intermittent IV infusion in hospitalized patients with pathological GI hypersecretory conditions or intractable duodenal ulcer, or when oral therapy is not feasible.²⁴⁰

Oral Administration

Administer with or without food; administration with food may slightly enhance bioavailabilty.^{1 3 47 114}

Antacids may be used as necessary for pain relief.^{1 4 6 7 16 18 19 49 94}

Tablet for self-medication should be administered with a glass of water.^{c d}

Chewable tablets (Pepcid AC Chewable, Pepcid Complete) for self-medication should be chewed thoroughly before swallowing.^{238 260}

For duodenal ulcer treatment, the advantage of administration once daily at bedtime (when convenience is important for compliance) over twice-daily administration has not been determined.^{4 7 16 18 93 130}

For gastric ulcer treatment in adults, administer once daily at bedtime.^{1 9 22 93 131 136}

For gastroesophageal reflux, once daily dosage not considered appropriate.²⁶¹

Oral Suspension

Add 46 mL of water to bottle containing 400 mg of famotidine for 40 mg/5mL suspension.^{1 3 14}

Shake oral suspension vigorously for 5–10 seconds after reconstitution and before each use.¹

Intermittent Direct IV Injection

Dilution

Dilute 20 mg to 5–10 mL with 0.9% sodium chloride injection or other compatible IV solution before direct IV injection.²⁴⁰

Rate of Administration

Inject over not less than 2 minutes (no faster than 10 mg/minute).²⁴⁰

Intermittent IV infusion

Dilution

Dilute 20 mg in at least 100 mL of 5% dextrose injection or other compatible IV solution.²⁴⁰

No additional dilution required for commercially available infusion solution (20 mg famotidine in 50 mL of 0.9% sodium chloride injection).²⁴⁰

Rate of Administration

Over 15–30 minutes.²⁴⁰

Dosage

Pediatric Patients

General Parenteral Dosage

May administer IV in hospitalized pediatric patients with pathologic hypersecretory conditions, intractable ulcer, or for short-term use when oral therapy is not feasible.^b

Safety and efficacy have not been established in children <1 year of age.^b

Treatment of Children 1–16 Years of Age

Individualize duration and dosage based on clinical response and/or gastric or esophageal pH determination and endoscopy.^{1 240}

Intermittent Direct IV Injection

Initially, 0.25 mg/kg (15-minute infusion) every 12 hours (maximum 40 mg daily).²⁴⁰ Up to 0.5 mg/kg every 12 hours has provided gastric acid suppression.^b

Intermittent IV Infusion

Initially, 0.25 mg/kg (over not less than 2 minutes) every 12 hours (maximum 40 mg daily).²⁴⁰ Up to 0.5 mg/kg every 12 hours has provided gastric acid suppression^b

Gastroesophageal Reflux

Treatment of GERD in Infants <3 Months of Age

Oral

0.5 mg/kg once daily for up to 4 weeks.^a

Infants should also be receiving conservative measures (e.g., thickened feedings).^a

IV

Safety and efficacy not established.^b

Treatment of GERD in Infants 3 Months to <1 Year of Age

Oral

0.5 mg/kg twice daily for up to 4 weeks.^a

Infants should also be receiving conservative measures (e.g., thickened feedings).^a

IV

Safety and efficacy not established.^b

Treatment of GERD in Children 1–16 Years of Age

Oral

1 mg/kg daily in 2 divided doses (maximum 40 mg twice daily); up to 2 mg/kg daily has been used.^a

Individualize duration and dosage based on clinical response and/or gastric or esophageal pH determination and endoscopy.^{1 240 b}

IV

Dosage not established.^b

Treatment of Esophagitis in Children 1- 16 Years of Age

Oral

1 mg/kg daily in 2 divided doses (maximum 40 mg twice daily); up to 2 mg/kg daily has been used.^a

Individualize duration and dosage based on clinical response and/or gastric or esophageal pH determination and endoscopy.^{1 240 b}

IV

Dosage not established.^b

Self-medication for Heartburn in Adolescents ≥12 Years of Age

Oral

10-mg tablets: 10 mg once or twice daily (maximum 20 mg in 24 hours continuously for 2 weeks) or as directed by clinician.^{238 239 260 267 268 269}

Chewable tablets: 10 mg once or twice daily (maximum 20 mg in 24 hours continuously for 2 weeks) or as directed by clinician.^{238 260} Do not swallow whole; chew completely before swallowing.^{238 260}

20-mg tablets: 20 mg once or twice daily (maximum 40 mg in 24 hours continuously for 2 weeks) or as directed by clinician.^{238 239 260 267 268 269}

Fixed combination of famotidine, calcium carbonate, and magnesium hydroxide (Pepcid Complete): 1 tablet (10 mg of famotidine) once or twice daily (maximum 2 tablets in 24 hours continuously for 2 weeks).^e Do not swallow whole; chew completely before swallowing.^e

Self-medication for Prevention of Heartburn In Adolescents ≥12 Years of Age

Oral

10-mg tablets: 10 mg once or twice daily (15–60 minutes before ingestion of causative food or beverage); maximum 20 mg in 24 hours continuously for 2 weeks or as directed by clinician.^{238 239 260 267 268 269}

10-mg chewable tablets: 10 mg once or twice daily (15–60 minutes before ingestion of causative food or beverage); maximum 20 mg in 24 hours continuously for 2 weeks or as directed by clinician.^{238 260} Do not swallow whole; chew completely before swallowing.^{238 260}

20-mg tablets: 20 mg once or twice daily (10–60 minutes before ingestion of causative food or beverage); maximum 40 mg in 24 hours continuously for 2 weeks or as directed by clinician.^d

Duodenal Ulcer

Treatment of Duodenal Ulcer in Children 1–16 Years of Age

Oral

0.5 mg/kg once daily at bedtime or in 2 divided doses daily (maximum 40 mg daily);¹ up to 1 mg/kg daily has been used.^{1 240}

Individualize duration and dosage based on clinical response and/or gastric or esophageal pH determination and endoscopy.^{1 240}

Gastric Ulcer

Treatment of Gastric Ulcer in Children 1–16 Years of Age

Oral

0.5 mg/kg once daily at bedtime or in 2 divided doses daily (maximum 40 mg daily);¹ up to 1 mg/kg daily has been used.^{1 240}

Individualize duration and dosage based on clinical response and/or gastric or esophageal pH determination and endoscopy.¹

Adults

General Parenteral Dosage

May administer IV in hospitalized adults with pathologic hypersecretory conditions, intractable ulcer, or for short-term use when oral therapy is not feasible.^b

Dosage for parenteral administration in patients with GERD has not been established.^b

Intermittent Direct IV Injection

20 mg every 12 hours (maximum 40 mg daily).^{2 114 240}

Intermittent IV Infusion

20 mg every 12 hours (maximum 40 mg daily).^{2 114 240}

Gastroesophageal Reflux

Treatment of GERD

Oral

20 mg twice daily for up to 6 weeks.^{1 167 173 174}

40 mg once daily at bedtime also has been used, but is less effective^{1 139 167 168} and not considered appropriate therapy.²⁶¹

Treatment of Esophagitis

Oral

20 or 40 mg twice daily for up to 12 weeks.^{1 167 168 171}

Self-medication for Heartburn

Oral

10-mg tablets: 10 mg once or twice daily (maximum 20 mg in 24 hours continuously for 2 weeks) or as directed by clinician.^{238 239 260 267 268 269}

Chewable tablets: 10 mg once or twice daily (maximum 20 mg in 24 hours continuously for 2 weeks) or as directed by clinician.^{238 260} Do not swallow whole; chew completely before swallowing.^{238 260}

Fixed combination of famotidine, calcium carbonate, and magnesium hydroxide (Pepcid Complete): 1 tablet (10 mg of famotidine) once or twice daily (maximum 2 tablets in 24 hours continuously for 2 weeks).^e Do not swallow whole; chew completely before swallowing.^e

20-mg tablets: 20 mg once or twice daily (maximum 40 mg in 24 hours continuously for 2 weeks) or as directed by clinician.^{238 239 260 267 268 269}

Self-medication for Prevention of Heartburn

Oral

10-mg tablets: 10 mg once or twice daily (15–60 minutes before ingestion of causative food or beverage); maximum 20 mg in 24 hours continuously for 2 weeks or as directed by clinician.^{238 239 260 267 268 269}

Chewable tablets: 10 mg once or twice daily (15–60 minutes before ingestion of causative food or beverage); maximum 20 mg in 24 hours continuously for 2 weeks or as directed by clinician.^{238 260} Do not swallow whole; chew completely before swallowing.^{238 260}

20-mg tablets: 20 mg once or twice daily (10–60 minutes before ingestion of causative food or beverage); maximum 40 mg in 24 hours continuously for 2 weeks or as directed by clinician .^d

Duodenal Ulcer

Treatment of Active Duodenal Ulcer

Oral

40 mg once daily at bedtime, or 20 mg twice daily.^{1 2 4 7 16 18 19 22 92 114 129 130}

Healing may occur within 2 weeks in some, ^{1 4 6 16 18 19 22} and within 4 weeks in most patients;^{1 4 6 7 16 18 19 22 93 114 129} some patients may benefit from an additional 4 weeks of therapy.^{1 4 7 16 18 19 22 129}

Occasionally may be necessary to continue full-dose therapy for >6–8 weeks.^{1 114 116}

Safety and efficacy of continuing full-dose therapy for >8 weeks have not been established.^{1 4}

Maintenance of Healing of Duodenal Ulcer

Oral

20 mg once daily at bedtime.^{1 4 8 114}

Gastric Ulcer

Oral

40 mg daily at bedtime for up to 8 weeks.^{1 9 22 93 131 136}

Complete healing of gastric ulcers usually occurs within 8 weeks.^{9 22 131 136}

Safety and efficacy of therapy for >8 weeks have not been established.¹

Pathologic GI Hypersecretory Conditions

Zollinger-Ellison Syndrome

Oral

20 mg every 6 hours.^{1 4 114} Higher doses administered more frequently may be necessary; adjust dosage according to response and tolerance and continue as long as necessary.^{1 4 10 114 122 141}

20–160 mg every 6 hours generally has been necessary to maintain basal gastric acid secretion at <10 mEq/hour.^{1 10 51 114 123 141}

Up to 160 mg every 6 hours,¹ or 800 mg daily in divided doses, ^{2 3 4 10 122} has been used in severe disease.

Intermittent IV Infusion

20 mg every 12 hours.^b Higher initial dosage may be required;^{10 114 115 116 240} adjust to individual needs and continue as long as necessary.^{115 116 240 b}

Prescribing Limits

Pediatric Patients

General Parenteral Dosage

Treatment of children 1–16 Years of Age

Intermittent Direct IV Injection

Maximum 40 mg daily.²⁴⁰

Intermittent IV Infusion

Maximum 40 mg daily.²⁴⁰

Gastroesophageal Reflux

Treatment of GERD in Infants <1 Year of Age

Oral

Safety and efficacy for >4 weeks not established.^a

Treatment of GERD without Esophagitis in Children 1–16 Years of Age

Oral

Maximum 40 mg twice daily.^a

Treatment of Esophagitis (including Erosions, Ulcerations) in Children 1- 16 Years of Age

Oral

Maximum 40 mg twice daily.^a

Self-Medication For Heartburn in Adolescents ≥12 Years of Age

Oral

Maximum 20 or 40 mg in 24 hours continuously for 2 weeks.^{238 260 267 268 269}

Self-medication for Prevention of Heartburn in Adolescents ≥12 Years of Age

Oral

Maximum 20 or 40 mg in 24 hours continuously for 2 weeks.^{238 260 267 268 269}

Duodenal Ulcer

Treatment of Active Duodenal Ulcer in Children 1–16 Years of Age

Oral

Maximum 40 mg daily.¹

Gastric Ulcer

Treatment of Gastric Ulcer in Children 1–16 Years of Age

Oral

Maximum 40 mg daily.¹

Adults

General Parenteral Dosage

Intermittent Direct IV Injection

Maximum 40 mg daily.²⁴⁰

Intermittent IV Infusion

Maximum 40 mg daily.²⁴⁰

Gastroesophageal Reflux

Treatment of Symptomatic GERD

Oral

Safety and efficacy for >6 weeks not established.^{1 167 173 174}

Treatment of Esophagitis

Oral

Safety and efficacy for >12 weeks not established.^{1 167 168 171}

Self-medication for Heartburn

Oral

Maximum 20 or 40 mg in 24 hours continuously for 2 weeks.^{238 260 238 260 267 268 269}

Self-medication for Prevention of Heartburn

Maximum 20 or 40 mg in 24 hours continuously for 2 weeks.^{238 260 267 268 269}

Duodenal Ulcer

Treatment of Active Duodenal Ulcer

Oral

Safety for >8 weeks not established.^{1 4}

Gastric Ulcer

Short-term Treatment of Active Benign Gastric Ulcer

Oral

Safety and efficacy for >8 weeks not established.¹

Pathologic GI Hypersecretory Conditions (e.g., Zollinger-Ellison Syndrome)

Oral

Up to 160 mg every 6 hours,¹ or 800 mg daily in divided doses.^{2 3 4 10 122}

Special Populations

Renal Impairment

Pediatric Patients

Consider dosage adjustment in children with moderate or severe renal impairment.^{1 240}

Adults

In adults, modify dose and/or frequency of administration to the degree of renal impairment; adverse CNS effects have been reported.^{1 4 86 114}

Moderate (Cl_cr<50 mL/minute) or Severe (Cl_cr< 10 mL/minute)

Oral

Decrease to 50% of usual dosage.^{1 114 115}

Alternatively, increase dosing interval to 36–48 hours according to response.^{1 114 115}

IV

Decrease to 50% of usual dosage.^b

Alternatively, increase dosing interval to 36–48 hours according to response.^b

Cl_cr of 30–60 mL/minute per 1.48 m²

50% of usual adult dosage has been recommended.^{4 86}

Cl_cr < 30 mL/minute per 1.48 m²

25% of usual adult dosage has been recommended.^{4 86}

Cautions for Famotidine

Contraindications

• 
  

  Known hypersensitivity to famotidine, any ingredient in the formulation, or to other histamine H₂ antagonists (i.e., cimetidine, nizatidine, ranitidine).^{1 240}

  
  

Warnings/Precautions

General Precautions

Gastric Malignancy

Response to famotidine does not preclude presence of gastric malignancy.¹

Phenylketonuria

Pepcid AC chewable tablets contain aspartame (Nutrasweet), which is metabolized in the GI tract to provide 1.4 mg of phenylalanine per tablet.^c

Respiratory Effects

Administration of H₂-receptor antagonists has been associated with an increased risk for developing certain infections (e.g., community-acquired pneumonia).^{270 271}

Use of Fixed Combination

When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.

Specific Populations

Pregnancy

Category B.^{1 3}

Self-medication in pregnant women: consult clinician before using.²³⁸

Lactation

Distributed into milk.¹ Discontinue nursing or the drug.¹

Self-medication in nursing women: consult clinician before using.²³⁸

Pediatric Use

Infants <1 year of age: Consider for GERD treatment only if other conservative measures (e.g., thickened feedings) are used concurrently and potential benefits outweigh risks.^{a b}

Safety and efficacy for self-medication not established in children <12 years of age; do not use unless directed by clinician.^{238 239 260}

Renal Impairment

Use with caution.^{1 3 114 240} Dosage adjustments necessary in patients with severe renal impairment.^{1 3 114 240} (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Headache, dizziness, constipation, diarrhea.^{1 4 5 7 9 13 22 123 130}

Interactions for Famotidine

Does not appear to inhibit hepatic metabolism of drugs by hepatic CYP isoenzymes.^{1 3 4 21 39 40 41 42 45 46 93 114 118 125 127}

Antacids appear to cause slight but clinically unimportant decrease in bioavailability.^{1 3 47 114} May concomitantly administer with antacids.^{1 4 6 7 16 18 19 47 49 94}

Famotidine Pharmacokinetics

Absorption

Bioavailability

Oral: about 40–50%.^{1 3 4 11 46 85 114 118} Similar (50%) in children 11–15 years of age.¹

Tablets and oral suspension reportedly are bioequivalent.^{1 2 3 114}

Onset

Gastric acid inhibition within 1 hour after IV or oral administration.^{1 2 11 118} Peak inhibition within 0.5–3 hours following IV,^{1 11 114 118} 1–4 hours following oral^{1 10 11 46 51 114} administration.

Duration

Dose-dependent inhibition of gastric acid secretion.^{1 4 11 46 48 60 61 62 63 65 81 118}

Inhibition of basal and nocturnal secretion for 10–12 hours after single oral 20-^{1 2 11 61 62 63 81} or 40-mg^{1 2 46 61 62} dose.^{1 2 11 46 61 62 63 81 93 114 118}

Inhibition of food-stimulated secretion generally persists for 8–10 hours after morning administration, but may dissipate within 6–8 hours after a 20-mg oral dose in some patients.^{1 4 81}

Inhibition of nocturnal gastric acid secretion is 10–15 hours after single 10- or 20-mg IV dose.^{1 2 11}

Food

May slightly enhance bioavailability.^{1 3 47 114}

Distribution

Extent

Widely distributed, highest concentrations in the kidney, liver, pancreas, and submandibular gland.^{4 84}

Distributed into human milk.^{a b}

Does not cross the placenta in animal studies;² not known if famotidine crosses the placenta in humans.²

Plasma Protein Binding

15–20%.^{1 3 4 114 118}

Elimination

Metabolism

Metabolized in the liver¹¹⁵ to inactive famotidine S-oxide (S-famotidine).^{1 2 3 82 84 114}

Minimal first-pass metabolism.^{1 3 114 118}

Elimination Route

Excreted principally in urine;^{1 2 3 4 53 86 114 118} 25–30% excreted unchanged within 24 hours after oral administration,^{1 2 3 4 65 81 83 114} 65–80%^{1 2 3 4 85 86 114} after IV administration.^{1 2 3 4 83 85 86} Small fraction of orally administered dose is excreted in urine as famotidine S-oxide.^{4 83} Remainder of orally administered dose eliminated in feces.⁴

Interindividual variation in metabolism and excretion.^{4 83 118}

Half-life

2.5–4 hours (adults).^{1 2 4 11 65 81 83 85 86 93 118}

Special Populations

In patients with renal impairment, close correlation between Cl_cr and elimination half-life;^{a b} >20 hours when Cl_cr <10 mL/minute,^{1 3 4 86 114} 24 hours in anuric patients.¹

Does not appear to be removed by hemodialysis.⁴

Stability

Storage

Oral

Tablets

20 and 40 mg film-coated tablets: 25°C (may be exposed to 15–30°C) in tight, light-resistant containers.^{1 2 3 152}

Tablets for Self-medication

10 mg tablets, chewable tablets, film-coated tablets: 25–30°C.^{238 267 268}

10 mg chewable tablets in combination with calcium carbonate and magnesium hydroxide: 25–30°C.^e

20 mg film-coated tablets: 20–30°C.^d

Protect from moisture.^{238 267 268 d e}

For Suspension

Reconstituted suspension or dry powder: 25°C (may be exposed to 15–30°C) in tight containers.^a

Suspension may be refrigerated;¹¹⁵ protect from freezing.^{1 2 3}

Discard unused suspension after 30 days.^{1 2 3}

Parenteral

Injection

2–8°C;^{1 2} expiration date of 24 months following the date of manufacture when stored at this temperature.^{2 3} If freezing occurs, thaw at room temperature,^{1 3} or in warm water bath, or under running hot tap water;¹¹⁵ allow sufficient time for dissolution of all ingredients.^{1 3} Do not thaw by microwave because of potential hazard of rapidly increased temperature and vapor pressure in a closed system. Diluted solutions of famotidine not used immediately after preparation should be refrigerated and used within 48 hours.^{b 115}

Injection for IV infusion only

25°C.²⁴¹ Protect from excessive heat; brief exposure up to 35°C will not adversely affect the stability of the solution.²⁴⁰ Stable for 15 months when stored as recommended.²⁴¹

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility^HID

Compatible
Amino acids
Dextrose 5% in water
Fat emulsion 10%, IV
Sodium chloride 0.9%

Drug Compatibility

Admixture CompatibilityHID

Compatible
Cefazolin sodium
Flumazenil
Vancomycin HCl

Y-Site CompatibilityHID

Compatible
Acyclovir sodium
Allopurinol sodium
Amifostine
Aminophylline
Amiodarone HCl
Ampicillin sodium
Ampicillin sodium–sulbactam sodium
Amsacrine
Anakinra
Atropine sulfate
Aztreonam
Bivalirudin
Bretylium tosylate
Calcium gluconate
Cefazolin sodium
Cefotaxime sodium
Cefoxitin sodium
Ceftazidime
Ceftizoxime sodium
Ceftriaxone sodium
Cefuroxime sodium
Chlorpromazine HCl
Cisplatin
Cladribine
Cyclophosphamide
Cytarabine
Dexamethasone sodium phosphate
Dexmedetomidine HCl
Dextran 40
Digoxin
Diphenhydramine HCl
Dobutamine HCl
Docetaxel
Dopamine HCl
Doxorubicin HCl
Doxorubicin HCl liposome injection
Droperidol
Enalaprilat
Epinephrine HCl
Erythromycin lactobionate
Esmolol HCl
Etoposide phosphate
Fenoldopam mesylate
Filgrastim
Fluconazole
Fludarabine phosphate
Folic acid
Gemcitabine HCl
Gentamicin sulfate
Granisetron HCl
Haloperidol lactate
Heparin sodium
Hetastarch in lactated electrolyte injection (Hextend)
Hydrocortisone
Hydrocortisone sodium succinate
Hydromorphone HCl
Hydroxyzine HCl
Imipenem–cilastatin sodium
Inamrinone lactate
Isoproterenol HCl
Labetalol HCl
Lidocaine HCl
Linezolid
Lorazepam
Magnesium sulfate
Melphalan HCl
Meperidine HCl
Methotrexate sodium
Methylprednisolone sodium succinate
Metoclopramide HCl
Midazolam HCl
Morphine sulfate
Nafcillin sodium
Nicardipine HCl
Nitroglycerin
Norepinephrine bitartrate
Ondansetron HCl
Oxacillin sodium
Oxalipatin
Paclitaxel
Pemetrexed disodium
Perphenazine
Phenylephrine HCl