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Famotidine


General


Pronunciation

(fa MOE ti deen)


Brand Names: U.S.

  • Acid Reducer Maximum Strength [OTC]
  • Acid Reducer [OTC]
  • Heartburn Relief Max St [OTC]
  • Heartburn Relief [OTC]
  • Pepcid

Indications


Use: Labeled Indications

Maintenance therapy and treatment of duodenal ulcer; treatment of gastroesophageal reflux disease (GERD), active benign gastric ulcer; pathological hypersecretory conditions

OTC labeling: Relief of heartburn, acid indigestion, and sour stomach


Contraindications


Hypersensitivity to famotidine, other H2 antagonists, or any component of the formulation


Dosing and Administration


Dosing: Adult

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

Peptic ulcer disease: Eradication ofHelicobacter pylori(off-label use): Oral: 40 mg once daily; requires combination therapy with antibiotics

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 suggest the use of proton pump inhibitors rather than H2 antagonist therapy (Dellinger, 2013).

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

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


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Treatment duration and dose should be individualized

Peptic ulcer: 1-16 years:

Oral: 0.5 mg/kg/day at bedtime or divided twice daily (maximum dose: 40 mg/day); doses of up to 1 mg/kg/day have been used in clinical studies

IV: 0.25 mg/kg every 12 hours (maximum dose: 40 mg/day); doses of up to 0.5 mg/kg have been used in clinical studies

GERD: Oral:

<3 months: 0.5 mg/kg once daily

3-12 months: 0.5 mg/kg twice daily

1-16 years: 1 mg/kg/day divided twice daily (maximum dose: 40 mg twice daily); doses of up to 2 mg/kg/day have been used in clinical studies

Heartburn, indigestion, sour stomach: OTC labeling: Oral: Children ≥12 years: Refer to adult dosing.


Dosing: Renal Impairment

CrCl <50 mL/minute: Manufacturers labeling: Administer 50% of dose or increase the dosing interval to every 36 to 48 hours (to limit potential CNS adverse effects).


Reconstitution

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.


Administration

Oral: May administer with antacids.

Suspension: Shake vigorously before use. May be taken without regard to meals.

Tablet: May be taken without regard to meals.

IV:

IV push: Inject over at least 2 minutes.

Solution for infusion: Administer over 15-30 minutes.


Dietary Considerations

May be taken without regard to meals.


Storage

Oral:

Powder for oral suspension: Prior to mixing, dry powder should be stored at controlled room temperature of 25 � �C (77 � �F). Reconstituted oral suspension is stable for 30 days at room temperature; do not freeze.

Tablet: Store controlled room temperature. Protect from moisture.

IV:

Solution for injection: Prior to use, store at 2 � �C to 8 � �C (36 � �F to 46 � �F). If solution freezes, allow to solubilize at controlled room temperature. May be stored at room temperature for up to 3 months (data on file [Bedford Laboratories, 2011]).

IV push: Following preparation, solutions for IV push should be used immediately, or may be stored in refrigerator and used within 48 hours.

Infusion: Following dilution In D5W, D10W, NS or LR, the manufacturer states may be stored for up to 48 hours under refrigeration; however, solutions for infusion have been found to be physically and chemically stable for 7 days at room temperature (maintains at least 90% of initial potency).

Solution for injection, premixed bags: Store at controlled room temperature of 25 � �C (77 � �F); avoid excessive heat.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Generic: 20 mg (50 mL); 20 mg/2 mL (2 mL); 40 mg/4 mL (4 mL); 200 mg/20 mL (20 mL); 500 mg/50 mL (50 mL)

Solution, Intravenous [preservative free]:

Generic: 20 mg/2 mL (2 mL); 40 mg/4 mL (4 mL [DSC])

Suspension Reconstituted, Oral:

Pepcid: 40 mg/5 mL (50 mL) [contains methylparaben sodium, propylparaben sodium, sodium benzoate; cherry banana mint flavor]

Generic: 40 mg/5 mL (50 mL)

Tablet, Oral:

Acid Reducer: 10 mg

Acid Reducer Maximum Strength: 20 mg

Heartburn Relief: 10 mg

Heartburn Relief Max St: 20 mg

Pepcid: 20 mg

Pepcid: 20 mg [DSC] [scored]

Pepcid: 40 mg

Pepcid: 40 mg [DSC] [scored]

Generic: 10 mg, 20 mg, 40 mg


Extemporaneously Prepared

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.

Dentinger PJ, Swenson CF, and Anaizi NH, "Stability of Famotidine in an Extemporaneously Compounded Oral Liquid," Am J Health Syst Pharm, 2000, 57(14):1340-2.[PMID: 10918924]

Compatibility

Stable in D5W, D10W, LR, fat emulsion 10%, NS, sodium bicarbonate 5%.

Y-site administration: Incompatible with amphotericin B cholesteryl sulfate complex, azithromycin, cefepime, piperacillin/tazobactam, sulfamethoxazole/trimethoprim.

Compatibility in syringe: Incompatible with ceftriaxone, dexamethasone sodium phosphate.


Drug Interactions

Atazanavir: H2-Antagonists may decrease the serum concentration of Atazanavir. Management: Specific dose limitations and administration guidelines exist; consult full interaction monograph or atazanavir prescribing information. Consider therapy modification

Bosutinib: H2-Antagonists may decrease the serum concentration of Bosutinib. Management: Administer histamine H2 receptor antagonists more than 2 hours before or after bosutinib. Consider therapy modification

BuPROPion: May increase the serum concentration of OCT2 Substrates. Monitor therapy

Cefditoren: H2-Antagonists may decrease the serum concentration of Cefditoren. Management: Concomitant use of cefditoren with H2-antagonists and antacids is not recommended. Consider alternative methods to control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of H2-antagonists can not be avoided. Consider therapy modification

Cefpodoxime: H2-Antagonists may decrease the absorption of Cefpodoxime. Separate oral doses by at least 2 hours. Monitor therapy

Cefuroxime: H2-Antagonists may decrease the absorption of Cefuroxime. Separate oral doses by at least 2 hours. Monitor therapy

Cysteamine (Systemic): H2-Antagonists may diminish the therapeutic effect of Cysteamine (Systemic). Monitor therapy

Dabrafenib: H2-Antagonists may decrease the serum concentration of Dabrafenib. Monitor therapy

Dasatinib: H2-Antagonists may decrease the absorption of Dasatinib. Management: Antacids (taken 2 hours before or after dasatinib administration) can be used in place of H2-antagonists if some acid-reducing therapy is needed. Avoid combination

Delavirdine: H2-Antagonists may decrease the serum concentration of Delavirdine. Management: Chronic therapy with H2-antagonists should be avoided in patients who are being treated with delavirdine. The clinical significance of short-term H2-antagonist therapy with delavirdine is uncertain, but such therapy should be undertaken with caution. Avoid combination

Dexmethylphenidate: H2-Antagonists may increase the absorption of Dexmethylphenidate. Specifically, H2-antagonists may interfere with the normal release of drug from the extended-release capsules (Focalin XR brand), which could result in both increased absorption (early) and decreased delayed absorption. Monitor therapy

Erlotinib: H2-Antagonists may decrease the serum concentration of Erlotinib. Management: Avoid H2-antagonists in patients receiving erlotinib when possible. If concomitant treatment cannot be avoided, erlotinib should be dosed once daily, 10 hours after and at least 2 hours before H2-antagonist dosing. Consider therapy modification

Fosamprenavir: H2-Antagonists may decrease the serum concentration of Fosamprenavir. Cimetidine may also inhibit the metabolism of the active metabolite amprenavir, making its effects on fosamprenavir/amprenavir concentrations difficult to predict. Monitor therapy

Gefitinib: H2-Antagonists may decrease the serum concentration of Gefitinib. Management: Administer gefitinib at least 6 hours before or after administration of a histamine H2-antagonist, and closely monitor clinical response to gefitinib. Consider therapy modification

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Indinavir: H2-Antagonists may decrease the serum concentration of Indinavir. Monitor therapy

Iron Salts: H2-Antagonists may decrease the absorption of Iron Salts. Exceptions: Ferric Carboxymaltose; Ferric Citrate; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Monitor therapy

Itraconazole: H2-Antagonists may decrease the serum concentration of Itraconazole. Management: When this combination is used, the itraconazole should be administered with a cola beverage (8 ounces). Itraconazole oral suspension may be less sensitive to this interaction. Monitor patient response to itraconazole closely. Consider therapy modification

Ketoconazole (Systemic): H2-Antagonists may decrease the serum concentration of Ketoconazole (Systemic). Management: Administer oral ketoconazole at least 2 hours prior to use of any H2-receptor antagonist. Monitor patients closely for signs of inadequate clinical response to ketoconazole. Consider therapy modification

Ledipasvir: H2-Antagonists may decrease the serum concentration of Ledipasvir. Consider therapy modification

Mesalamine: H2-Antagonists may diminish the therapeutic effect of Mesalamine. Histamine H2-Antagonist-mediated increases in gastrointestinal pH may cause the premature release of mesalamine from specific sustained-release mesalamine products. Management: Consider avoiding concurrent administration of high-dose histamine H2-receptor antagonists with sustained-release mesalamine products. Consider therapy modification

Methylphenidate: H2-Antagonists may increase the absorption of Methylphenidate. Specifically, H2-antagonists may interfere with the normal release of drug from the extended-release capsules (Ritalin LA brand), which could result in both increased absorption (early) and decreased delayed absorption. Monitor therapy

MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): H2-Antagonists may decrease the serum concentration of Multivitamins/Minerals (with ADEK, Folate, Iron). Specifically, the absorption of iron may be impaired by H2-antagonists. Monitor therapy

Nelfinavir: H2-Antagonists may decrease the serum concentration of Nelfinavir. Concentrations of the active M8 metabolite may also be reduced. Monitor therapy

Nilotinib: H2-Antagonists may decrease the serum concentration of Nilotinib. Management: The nilotinib dose should be given 10 hours after or 2 hours before the H2 receptor antagonist in order to minimize the risk of a significant interaction. Consider therapy modification

PAZOPanib: H2-Antagonists may decrease the serum concentration of PAZOPanib. Management: Avoid the use of histamine H2-antagonists in combination with pazopanib. Strategies to minimize the expected interaction between these agents (eg, dose separation) have not been investigated. Avoid combination

Posaconazole: H2-Antagonists may decrease the serum concentration of Posaconazole. Management: Avoid concurrent use of oral suspension with H2-antagonists whenever possible. Monitor patients closely for decreased antifungal effects if this combination is used. Delayed-release posaconazole tablets may be less likely to interact. Consider therapy modification

Rilpivirine: H2-Antagonists may decrease the serum concentration of Rilpivirine. Management: Administer histamine H2 receptor antagonists at least 12 hours before or 4 hours after rilpivirine. Consider therapy modification

Risedronate: H2-Antagonists may increase the serum concentration of Risedronate. This applies specifically to delayed-release risedronate. Avoid combination

Saquinavir: H2-Antagonists may increase the serum concentration of Saquinavir. Monitor therapy

Varenicline: H2-Antagonists may increase the serum concentration of Varenicline. Management: Monitor for increased varenicline adverse effects with concomitant use of cimetidine or other H2-antagonists, particularly in patients with severe renal impairment. International product labeling recommendations vary. Consult appropriate labeling. Monitor therapy

Velpatasvir: H2-Antagonists may decrease the serum concentration of Velpatasvir. Monitor therapy


Adverse Reactions


>10%:

Central nervous system: Agitation (<1 year of age: ≤14%)

Gastrointestinal: Vomiting (<1 year of age: ≤14%)

1% to 10%:

Central nervous system: Headache (5%), dizziness (1%)

Gastrointestinal: Diarrhea (2%), constipation (1%), necrotizing enterocolitis (very low birth weight neonates; Guillet 2006)

<1% (Limited to important or life-threatening): Abdominal distress, acne vulgaris, agranulocytosis, alopecia, anaphylaxis, angioedema, anorexia, anxiety, arthralgia, atrioventricular block, bronchospasm, cardiac arrhythmia, cholestatic jaundice, confusion, conjunctival injection, decreased libido, depression, drowsiness, dysgeusia, facial edema, fatigue, fever, flushing, hallucination, hepatitis, hypersensitivity reaction, increased liver enzymes, injection site reaction, insomnia, interstitial pneumonitis, leukopenia, muscle cramps, nausea, palpitations, pancytopenia, paresthesia, prolonged Q-T interval on ECG, pruritus, rhabdomyolysis, seizure, skin rash, Stevens-Johnson syndrome, thrombocytopenia, tinnitus, torsades de pointes, toxic epidermal necrolysis, urticaria, weakness, xeroderma, xerostomia


Warnings/Precautions


Concerns related to adverse effects.

- Confusion: Reversible confusional states, usually clearing within 3-4 days after discontinuation, have been linked to use. Increased age (>50 years) and renal or hepatic impairment are thought to be associated.

- ECG changes: Prolonged QT interval has been reported in patients with renal dysfunction. The FDA has received reports of torsade de pointes occurring with famotidine (Poluzzi, 2009).

- Vitamin B12 deficiency: Prolonged treatment ( ≥2 years) may lead to vitamin B12 malabsorption and subsequent vitamin B12 deficiency. The magnitude of the deficiency is dose-related and the association is stronger in females and those younger in age (<30 years); prevalence is decreased after discontinuation of therapy (Lam, 2013).

Disease-related concerns:

- Gastric malignancy: Relief of symptoms does not preclude the presence of a gastric malignancy.

- Renal impairment: Use with caution in patients with moderate-to-severe renal impairment (CrCl <50 mL/minute); dosage adjustment recommended.

Dosage form specific issues:

- Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol and/or sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol ( ≥99 mg/kg/day) have been associated with a potentially fatal toxicity ( "gasping syndrome " �) in neonates; the "gasping syndrome " � consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP [Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol and/or benzyl alcohol derivative with caution in neonates. See manufacturer 's labeling.

Other warnings/precautions:

- OTC labeling: When used for self-medication, patients should be instructed not to use if they have difficulty swallowing, are vomiting blood, or have bloody or black stools. Not for use with other acid reducers.


Pregnancy Risk Factor

B


Pregnancy Considerations

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.


Actions


Pharmacology

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


Onset of Action

Antisecretory effect: Oral: Within 1 hour; IV: Within 30 minutes; Peak effect: Antisecretory effect: Oral: Within 1 to 3 hours (dose-dependent)


Time to Peak

Serum: Oral: ~1 to 3 hours;orally disintegrating tablet: 2.5 hours


Duration of Action

Antisecretory effect: IV, Oral: 10 to 12 hours


Half-Life Elimination

Infants: 0 to 3 months: 8.1 � � 3.5 hours to 10.5 � � 5.4 hours; >3 to 12 months: 4.5 � � 1.1 hours

Children: 3.3 � � 2.5 hours

Adolescents: 2.3 � � 0.4 hours

Adults: 2.5 to 3.5 hours; prolonged with renal impairment; Oliguria: >20 hours; Anuria: 24 hours


Protein Binding

15% to 20%


Patient and Family Education


Patient Education

- 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, diarrhea, or constipation. Have patient report immediately to prescriber black, tarry, or bloody stools; vomiting blood; dysphagia; difficulty speaking; severe nausea; severe vomiting; severe dizziness; passing out; confusion; angina; tachycardia; bruising; bleeding; or injection site irritation (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 healthcare 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.

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