Continuing Education Activity

Famotidine reduces gastric acid secretion in individuals, and its pharmacological properties are utilized in treating gastrointestinal conditions related to excessive acid production. Famotidine can be obtained through a prescription or bought over-the-counter (OTC). The U.S. Food and Drug Administration (FDA) has approved famotidine as a prescription medication for treating duodenal ulcers, gastric ulcers, and gastroesophageal reflux disease (GERD) in adults and children, as well as pathological hypersecretory conditions in adults. The drug has also received FDA approval for OTC usage for treating and preventing heartburn caused by GERD in adults and pediatric populations. The drug is also off-label to treat refractory urticaria, prevent stress ulcers in critically ill patients, and provide symptomatic relief for gastritis. This activity outlines the indications, mechanisms of action, administration methods, significant adverse effects, contraindications, monitoring recommendations, and toxicity of famotidine to enhance the competence of healthcare providers, empowering providers to customize patient therapy and ensure favorable treatment outcomes effectively.

Objectives:

• Identify appropriate indications for famotidine therapy, distinguishing between FDA-approved uses and off-label applications.
• Screen patients for contraindications and potential drug interactions before initiating famotidine therapy.
• Select appropriate administration methods for famotidine based on patient factors, including oral and intravenous routes, and educate patients on OTC usage.
• Communicate effectively with patients about famotidine therapy, including dosing instructions, potential adverse effects, and self-monitoring guidelines.

Indications

Famotidine reduces gastric acid secretion in individuals, and its pharmacological properties are utilized in treating gastrointestinal conditions related to excessive acid production.[1][2]

Famotidine can be obtained through a prescription or bought over-the-counter (OTC). The U.S. Food and Drug Administration (FDA) has approved famotidine as a prescription medication for treating duodenal ulcers, gastric ulcers, and gastroesophageal reflux disease (GERD) in adults and children, as well as pathological hypersecretory conditions in adults.[3] The drug has also received FDA approval for OTC usage for treating and preventing heartburn caused by GERD in adults and pediatric populations.[4] 

Famotidine is used off-label in mitigating the gastrointestinal risks associated with nonsteroidal anti-inflammatory drugs (NSAIDs).[5] The drug is also used off-label to treat refractory urticaria, prevent stress ulcers in critically ill patients, and provide symptomatic relief for gastritis.[6] A fixed-dose combination of ibuprofen, which is an NSAID, and famotidine is accessible to reduce the risk of gastrointestinal adverse effects.[7][8]

Mechanism of Action

Famotidine is a competitive histamine-2 (H2) receptor antagonist that selectively binds to H2 receptors situated on the basolateral membrane of the parietal cells in the stomach. This interaction proficiently obstructs the actions mediated by histamine. The drug's pharmacological activity inhibits gastric secretion by concurrently suppressing the acidity levels and the volume of gastric secretions. Famotidine also inhibits basal and nocturnal gastric acid secretion while lowering gastric volume, acidity, and secretions triggered by food, caffeine, insulin, and pentagastrin.[9][10][11]

Pharmacokinetics

Absorption: The bioavailability of oral famotidine ranges from 40% to 45%. Upon oral administration, famotidine exhibits an onset of action within 1 hour and reaches its peak effect within 1 to 3 hours. Intravenous (IV) administration of the drug results in a peak effect within approximately 30 minutes. The antisecretory effect of famotidine typically persists for around 10 to 12 hours.

Distribution: Famotidine exhibits a plasma protein binding of 15% to 20%, accompanied by a relatively small volume of distribution between 1.0 and 1.3 L/kg.[12]

Metabolism: Famotidine undergoes minimal first-pass metabolism and is primarily metabolized by the cytochrome P450 system, specifically CYP1A2.[13]

Elimination: Famotidine's elimination half-life ranges from 2.5 to 3.5 hours. Notably, around 65% to 70% of famotidine is excreted unchanged in the urine. In severe renal insufficiency cases, characterized by a creatinine clearance <10 mL/min, famotidine's elimination half-life could extend beyond 20 hours, necessitating dosage adjustments. Pediatric patients with chronic renal insufficiency experience significant alterations in the pharmacokinetics of famotidine.[14]

Administration

Available Dosage Forms and Strengths

The manufacturer's package insert states that famotidine can be prescribed in various forms, including IV solution, oral suspension, and tablets in strengths of 10 mg, 20 mg, and 40 mg. The IV solution of famotidine can be administered as either an IV push over at least 2 minutes or an IV infusion lasting 15 to 30 minutes. The suspension formulation of the medication should be shaken vigorously before administration. The oral famotidine tablets can be administered without considering meals. The OTC formulations of the drug are available in gel capsules, tablets, and chewable tablets, with strengths of 10 or 20 mg. Physicians recommend not to chew the OTC tablet formulation of famotidine. In addition, the OTC tablet should be taken 10 to 60 minutes before consuming food or drinks that may cause heartburn. Unless specifically instructed by their healthcare provider, patients should refrain from using OTC formulations of famotidine for more than 2 weeks. The combination product contains famotidine 10 mg, calcium carbonate 800 mg, and magnesium hydroxide 165 mg.[15] 

According to the American College of Gastroenterology guidelines, H2-receptor antagonist (H2RA) therapy, including famotidine, is appropriate for nonerosive, symptomatic GERD disease maintenance treatment. In instances where concrete evidence of nighttime reflux is present, the addition of bedtime H2RA therapy can be considered with daytime proton pump inhibitor (PPI) therapy if deemed necessary.[16]

Adult Dosage

Active duodenal ulcer: For active duodenal ulcers, the recommended oral dosage of famotidine is 40 mg, administered at bedtime for up to 8 weeks. Alternatively, patients are advised to take 20 mg of famotidine either orally and twice daily or via IV route every 12 hours. In cases where a patient cannot take oral medication, IV administration should only be used for short-term treatment.

Maintenance treatment for duodenal ulcers: For maintenance treatment of duodenal ulcers, the recommended famotidine dosage is 20 mg administered at bedtime.

Active gastric ulcer: The typical dosage of famotidine for patients with gastric ulcers is 40 mg orally, taken at bedtime for a maximum of 8 weeks. Alternatively, an IV dosage of 20 mg every 12 hours can be considered. In cases where oral administration is not feasible, IV administration should only be used for short-term treatment.

Nonerosive, symptomatic GERD: For nonerosive, symptomatic GERD, the standard famotidine dosage is 20 mg taken orally twice daily, with a treatment duration of up to 6 weeks.

GERD with erosive esophagitis: The recommended famotidine dosage ranges from 20 to 40 mg taken orally twice daily, with a treatment duration of up to 12 weeks. Alternatively, an IV dosage of 20 mg every 12 hours can be considered. In cases where a patient cannot take oral medication, IV administration should only be used for short-term treatment.

Hypersecretory conditions: The suggested famotidine dosage for patients with hypersecretory conditions ranges from 20 to 60 mg orally every 6 hours. Physicians advise to commence the treatment with an initial dosage of 20 mg administered orally every 6 hours. 

Intractable ulcer: The recommended dosage for intractable ulcers is 20 mg of famotidine administered intravenously every 12 hours.

Specific Patient Populations

Hepatic impairment: The manufacturer's labeling does not specify any dosage adjustments for famotidine in cases of hepatic impairment.

Renal impairment: The elimination half-life of famotidine increases in adults with moderate-to-severe renal insufficiency, exceeding 20 hours. In patients with anuria, the half-life can extend to around 24 hours, which may cause adverse effects on the central nervous system (CNS). When the creatinine clearance is below 50 mL/min, the famotidine dosage can be reduced by 50%, or the dosing interval can be extended to 36 to 48 hours.[17] 

Pregnancy considerations: Famotidine can traverse the placental barrier.[18] The American Society of Anesthesiologists (ASA) supports the utilization of famotidine in obstetric anesthesia for prophylaxis against aspiration.[19] Managing GERD in pregnant women involves adopting lifestyle and dietary modifications as the initial approach. The primary drug therapy options in the first-line method encompass using antacids. If symptoms persist even after implementing these measures, the potential use of famotidine can be considered following a comprehensive assessment of the risk-benefit profile.[20]

Breastfeeding considerations: Famotidine is detectable in breast milk. Per the product labeling, engaging in a shared decision-making process concerning the usage of famotidine during lactation is recommended due to the potential adverse reactions in nursing infants. Based on the existing evidence, famotidine is not anticipated to induce adverse effects in breastfed infants, and thus, no particular precautions are deemed necessary.[21]

Older patients: According to the American Geriatrics Society 2023 Beers Criteria, older patients should refrain from using famotidine if their creatinine clearance is less than 50 mL/min. Famotidine should also not be administered to older patients experiencing delirium.[22]

Pediatric patients: For pediatric patients, the recommended daily famotidine dose is 1 mg/kg, to be administered twice daily, divided into 2 equally divided doses of 0.5 mg/kg each.[23] The administration of H2RA, including famotidine, to preterm infants has been associated with a higher occurrence of necrotizing enterocolitis and increased susceptibility to late-onset infections. These outcomes could potentially be linked to changes in the intestinal microbiome. Famotidine should be used cautiously in preterm infants.[24]

Adverse Effects

The adverse effects of the IV formulation of famotidine are primarily local, as it could irritate the injection site. Nonetheless, the exact frequency of occurrence has not been determined. The most common adverse effects of famotidine include agitation (14% in infants and less than 1% in adults), headache (5%), dizziness (1%), diarrhea (2%), and constipation (1%). To minimize the adverse effects of CNS, adjusting famotidine dosage may involve longer intervals or lower doses due to its extended elimination half-life.[25][12][26] 

An increased risk of developing community-acquired pneumonia and acute gastroenteritis has been associated with using famotidine and other gastric acid inhibitors in the pediatric population.[27]

Individuals using OTC famotidine must notify their healthcare provider if they experience frequent chest pain and wheezing, particularly with heartburn, unexplained weight loss, persistent stomach pain, heartburn lasting more than 3 months, or heartburn with lightheadedness, sweating, or dizziness. Patients should discontinue using OTC famotidine if their heartburn persists or worsens or if they use the medication for more than 14 days unless a healthcare professional directs otherwise.[28] 

Cases of famotidine-induced thrombocytopenia have been reported in individuals where this condition led to prolonged hospital stays and elevated injury severity scores. The mechanism is likely attributed to bone marrow suppression or the development of platelet autoantibodies. Patients are advised to regularly monitor their complete blood count (CBC) with differential. Physicians recommend discontinuing famotidine use and transitioning to PPI if there are indications of thrombocytopenia.[29][30][31][32]

Drug-Drug Interactions

Famotidine undergoes hepatic metabolism by cytochrome P450 enzymes, yet it exerts only minimal inhibitory effects on the metabolism of most other drugs.[33] Coadministering famotidine with other drugs can decrease the absorption of those medications, potentially leading to diminished effectiveness of the concurrent treatment. Per the manufacturer's package insert, famotidine should not be used simultaneously with the following medications: cefuroxime, dasatinib, delavirdine, neratinib, pazopanib, and risedronate.[34]

Famotidine acts as a mild inhibitor of the CYP1A2 enzyme, leading to a notable increase in the blood levels of tizanidine, a substrate of CYP1A2. The concurrent use of famotidine with tizanidine should be avoided. If coadministration of the drugs is necessary, it is essential to monitor patients for signs of hypotension, bradycardia, and excessive drowsiness. The case report also outlines an instance of tizanidine-induced acute severe cystitis due to famotidine.[13]

Contraindications

Famotidine is contraindicated for patients with hypersensitivity to famotidine or any of its formulation components. Due to observed cross-sensitivity among H2RAs, famotidine should not be prescribed to patients with a history of hypersensitivity to cimetidine.[35] Furthermore, OTC tablets should not be used by patients experiencing difficulties or pain while swallowing food, exhibiting vomiting with blood, or noticing the presence of bloody or black stools. The OTC famotidine tablets should also not be administered to patients who are allergic to or are currently taking other acid reducers, as well as those with renal impairment.

Box Warnings/Precautions

Famotidine injection containing benzyl alcohol should not be used in neonates and pregnant women due to the risk of developing gasping syndrome. Neonates receiving IV solutions containing benzyl alcohol are at risk of developing gasping syndrome after administering the medication. This syndrome is characterized by sudden gasping respiration, hypotension, bradycardia, and cardiovascular collapse. Benzyl alcohol can readily cross the placental and blood-brain barriers. Famotidine injection from multiple-dose vials containing benzyl alcohol must be avoided in pregnant women and neonates. Healthcare professionals responsible for administering this medication through this route should consult the excipient information before proceeding with the treatment.[36][37]

Monitoring

As famotidine is primarily eliminated through the kidneys, healthcare professionals may consider monitoring renal function in patients, particularly in older populations. In patients experiencing gastrointestinal bleeding, it is recommended to monitor their CBC, measure their gastric pH, and observe for the presence of occult blood.

Toxicity

As famotidine is primarily eliminated through the kidneys, the risk of toxicity could be heightened in individuals with compromised renal function. Consequently, dosage adjustments are imperative for patients with moderate-to-severe renal impairment.[12][26] As per famotidine's package insert, oral doses exceeding FDA-approved limits, reaching up to 640 mg/d, have been administered to adult patients with pathological hypersecretory conditions. Notably, this usage has not led to any serious adverse outcomes. Drug overdose cases share similarities with those seen in routine clinical practice.

Managing a drug overdose necessitates the following actions: eliminating unabsorbed medications from the gastrointestinal tract, closely monitoring the patient, and delivering appropriate supportive therapy. Famotidine is classified as a pregnancy category B drug and should be used during pregnancy only when the potential benefits outweigh the associated risks. Famotidine is detectable in breast milk. Hence, when a mother is undergoing therapy, the decision to breastfeed her infant should consider both the benefits to the mother and the potential risks to the infant. Compared to other H2RAs, famotidine shows notably lower concentrations in breast milk, making it a potentially preferable choice in such situations.[20][38]

Enhancing Healthcare Team Outcomes

In 1999, the American Society of Health-System Pharmacists (ASHP) published a guideline to prevent stress ulcers in medical, surgical, respiratory, and pediatric intensive care units (ICUs) patients. Since then, and in recent years, stress ulcer prophylaxis has been increasingly used beyond ICUs and general medical settings despite limited evidence supporting its effectiveness.

In hospital settings, up to 71% of patients on general medicine wards receive acid-suppressive therapy (AST) without a suitable indication. Furthermore, a significant number of patients continue on AST even after being discharged from the hospital. This continuation can result in escalated medical expenses and an increased risk of adverse drug reactions among patients.

The interprofessional healthcare team is critical in enhancing patient safety by actively working to reduce the inappropriate utilization of AST. Physicians and advanced practice practitioners should meticulously assess the necessity of AST for patients in the general medicine ward. In addition, pharmacists can collaborate by communicating with prescribers and inquiring about the unnecessary use of AST. While administering the medication, the nursing staff should remain vigilant regarding potential adverse events of the drug and communicate any concerns related to the therapy to the prescribing or ordering clinician. Educating patients on the appropriate utilization of ACT in ICU settings as per ASHP recommendations will mitigate its unwarranted usage.[39][40][41]

The OTC use of famotidine mandates interprofessional care coordination to ensure effective patient counseling on accurate drug dosing and self-monitoring for potential adverse events. This collaborative interprofessional approach is poised to yield optimal outcomes while minimizing adverse events.

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References

1.

McCullough AJ, Graham DY, Knuff TE, Lanza FL, Levenson HL, Lyon DT, Munsell WP, Perozza J, Roufail WM, Sinar DR. Suppression of nocturnal acid secretion with famotidine accelerates gastric ulcer healing. Gastroenterology. 1989 Oct;97(4):860-6. [PubMed: 2570730]

2.

Vinayek R, Howard JM, Maton PN, Wank SA, Slaff JI, Gardner JD, Jensen RT. Famotidine in the therapy of gastric hypersecretory states. Am J Med. 1986 Oct 24;81(4B):49-59. [PubMed: 2877575]

3.

Keithley JK. Histamine H2-receptor antagonists. Nurs Clin North Am. 1991 Jun;26(2):361-73. [PubMed: 1675461]

4.

Nonprescription version of famotidine wins FDA approval. Am J Health Syst Pharm. 1995 Jul 01;52(13):1377. [PubMed: 7671034]

5.

Hudson N, Taha AS, Russell RI, Trye P, Cottrell J, Mann SG, Swanell AJ, Sturrock RD, Hawkey CJ. Famotidine for healing and maintenance in nonsteroidal anti-inflammatory drug-associated gastroduodenal ulceration. Gastroenterology. 1997 Jun;112(6):1817-22. [PubMed: 9178671]

6.

Inalöz SS, Goral V, Sari I, Canberk Y, Ulak G. Omeprazole, nitrendipine, famotidine and stress-induced ulcers. Acta Gastroenterol Belg. 1997 Jul-Sep;60(3):192-6. [PubMed: 9396173]

7.

Bello AE. DUEXIS(®) (ibuprofen 800 mg, famotidine 26.6 mg): a new approach to gastroprotection for patients with chronic pain and inflammation who require treatment with a nonsteroidal anti-inflammatory drug. Ther Adv Musculoskelet Dis. 2012 Oct;4(5):327-39. [PMC free article: PMC3458616] [PubMed: 23024710]

8.

Deeks ED. Fixed-dose ibuprofen/famotidine: a review of its use to reduce the risk of gastric and duodenal ulcers in patients requiring NSAID therapy. Clin Drug Investig. 2013 Sep;33(9):689-97. [PubMed: 23881568]

9.

Talke PO, Solanki DR. Dose-response study of oral famotidine for reduction of gastric acidity and volume in outpatients and inpatients. Anesth Analg. 1993 Dec;77(6):1143-8. [PubMed: 8250305]

10.

Berlin RG, Clineschmidt BV, Majka JA. Famotidine: an appraisal of its mode of action and safety. Am J Med. 1986 Oct 24;81(4B):8-12. [PubMed: 2877577]

11.

Miyata K, Kamato T, Nishida A, Honda K. Studies on the mechanism for the gastric mucosal protection by famotidine in rats. Jpn J Pharmacol. 1991 Feb;55(2):211-22. [PubMed: 2067140]

12.

Echizen H, Ishizaki T. Clinical pharmacokinetics of famotidine. Clin Pharmacokinet. 1991 Sep;21(3):178-94. [PubMed: 1764869]

13.

Poudel RR, Kafle NK. Tizanidine-induced acute severe cystitis in a female taking famotidine. Clin Pharmacol. 2015;7:83-5. [PMC free article: PMC4524377] [PubMed: 26251632]

14.

Maples HD, James LP, Stowe CD, Jones DP, Hak EB, Blumer JL, Vogt B, Wilson JT, Kearns GL, Wells TG., Network of Pediatric Pharmacology Research Units. Famotidine disposition in children and adolescents with chronic renal insufficiency. J Clin Pharmacol. 2003 Jan;43(1):7-14. [PubMed: 12520622]

15.

Garg V, Narang P, Taneja R. Antacids revisited: review on contemporary facts and relevance for self-management. J Int Med Res. 2022 Mar;50(3):3000605221086457. [PMC free article: PMC8966100] [PubMed: 35343261]

16.

Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013 Mar;108(3):308-28; quiz 329. [PubMed: 23419381]

17.

Harada R, Ishikura K, Shinozuka S, Mikami N, Hamada R, Hataya H, Morikawa Y, Omori T, Takahashi H, Hamasaki Y, Kaneko T, Iijima K, Honda M. Ensuring safe drug administration to pediatric patients with renal dysfunction: a multicenter study. Clin Exp Nephrol. 2018 Aug;22(4):938-946. [PubMed: 29411162]

18.

Wang X, Rytting E, Abdelrahman DR, Nanovskaya TN, Hankins GD, Ahmed MS. Quantitative determination of famotidine in human maternal plasma, umbilical cord plasma and urine using high-performance liquid chromatography-mass spectrometry. Biomed Chromatogr. 2013 Jul;27(7):866-73. [PMC free article: PMC3872971] [PubMed: 23401067]

19.

Practice Guidelines for Obstetric Anesthesia: An Updated Report by the American Society of Anesthesiologists Task Force on Obstetric Anesthesia and the Society for Obstetric Anesthesia and Perinatology. Anesthesiology. 2016 Feb;124(2):270-300. [PubMed: 26580836]

20.

Richter JE. Review article: the management of heartburn in pregnancy. Aliment Pharmacol Ther. 2005 Nov 01;22(9):749-57. [PubMed: 16225482]

21.

Drugs and Lactation Database (LactMed®) [Internet]. National Institute of Child Health and Human Development; Bethesda (MD): Aug 15, 2024. Famotidine. [PubMed: 30000326]

22.

By the 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023 Jul;71(7):2052-2081. [PubMed: 37139824]

23.

Rosen R, Vandenplas Y, Singendonk M, Cabana M, DiLorenzo C, Gottrand F, Gupta S, Langendam M, Staiano A, Thapar N, Tipnis N, Tabbers M. Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2018 Mar;66(3):516-554. [PMC free article: PMC5958910] [PubMed: 29470322]

24.

Eichenwald EC., COMMITTEE ON FETUS AND NEWBORN. Diagnosis and Management of Gastroesophageal Reflux in Preterm Infants. Pediatrics. 2018 Jul;142(1) [PubMed: 29915158]

25.

Poluzzi E, Raschi E, Moretti U, De Ponti F. Drug-induced torsades de pointes: data mining of the public version of the FDA Adverse Event Reporting System (AERS). Pharmacoepidemiol Drug Saf. 2009 Jun;18(6):512-8. [PubMed: 19358226]

26.

Lin JH, Chremos AN, Yeh KC, Antonello J, Hessey GA. Effects of age and chronic renal failure on the urinary excretion kinetics of famotidine in man. Eur J Clin Pharmacol. 1988;34(1):41-6. [PubMed: 2896129]

27.

Canani RB, Cirillo P, Roggero P, Romano C, Malamisura B, Terrin G, Passariello A, Manguso F, Morelli L, Guarino A., Working Group on Intestinal Infections of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP). Therapy with gastric acidity inhibitors increases the risk of acute gastroenteritis and community-acquired pneumonia in children. Pediatrics. 2006 May;117(5):e817-20. [PubMed: 16651285]

28.

McRorie JW, Kirby JA, Miner PB. Histamine2-receptor antagonists: Rapid development of tachyphylaxis with repeat dosing. World J Gastrointest Pharmacol Ther. 2014 May 06;5(2):57-62. [PMC free article: PMC4023325] [PubMed: 24868486]

29.

Compoginis JM, Gaspard D, Obaid A. Famotidine use and thrombocytopenia in the trauma patient. Am Surg. 2011 Dec;77(12):1580-3. [PubMed: 22273212]

30.

Harinstein LM, Kane-Gill SL, Smithburger PL, Culley CM, Reddy VK, Seybert AL. Use of an abnormal laboratory value-drug combination alert to detect drug-induced thrombocytopenia in critically Ill patients. J Crit Care. 2012 Jun;27(3):242-9. [PubMed: 22520497]

31.

Wade EE, Rebuck JA, Healey MA, Rogers FB. H(2) antagonist-induced thrombocytopenia: is this a real phenomenon? Intensive Care Med. 2002 Apr;28(4):459-65. [PubMed: 11967601]

32.

Ecker RD, Wijdicks EF, Wix K, McClelland R. Does famotidine induce thrombocytopenia in neurosurgical patients? J Neurosurg Anesthesiol. 2004 Oct;16(4):291-3. [PubMed: 15557833]

33.

LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. National Institute of Diabetes and Digestive and Kidney Diseases; Bethesda (MD): Jan 25, 2018. Famotidine. [PMC free article: PMC547852] [PubMed: 31643553]

34.

Patel D, Bertz R, Ren S, Boulton DW, Någård M. A Systematic Review of Gastric Acid-Reducing Agent-Mediated Drug-Drug Interactions with Orally Administered Medications. Clin Pharmacokinet. 2020 Apr;59(4):447-462. [PMC free article: PMC7109143] [PubMed: 31788764]

35.

Song WJ, Kim MH, Lee SM, Kwon YE, Kim SH, Cho SH, Min KU, Kim YY, Chang YS. Two cases of h(2)-receptor antagonist hypersensitivity and cross-reactivity. Allergy Asthma Immunol Res. 2011 Apr;3(2):128-31. [PMC free article: PMC3062792] [PubMed: 21461253]

36.

Hutchinson HM, Sayre BE, Prettyman T, King E. Evaluating Sterility of Single Dose Vials on an Automated Compounding Device. Hosp Pharm. 2017 Apr;52(4):286-293. [PMC free article: PMC5424833] [PubMed: 28515508]

37.

Fukuda H, Kamidani R, Okada H, Kitagawa Y, Yoshida T, Yoshida S, Ogura S. Complex poisoning mainly with benzyl alcohol complicated by paralytic ileus: a case report. Int J Emerg Med. 2022 Jul 04;15(1):31. [PMC free article: PMC9251944] [PubMed: 35787785]

38.

Garbis H, Elefant E, Diav-Citrin O, Mastroiacovo P, Schaefer C, Vial T, Clementi M, Valti E, McElhatton P, Smorlesi C, Rodriguez EP, Robert-Gnansia E, Merlob P, Peiker G, Pexieder T, Schueler L, Ritvanen A, Mathieu-Nolf M. Pregnancy outcome after exposure to ranitidine and other H2-blockers. A collaborative study of the European Network of Teratology Information Services. Reprod Toxicol. 2005 Mar-Apr;19(4):453-8. [PubMed: 15749258]

39.

Grube RR, May DB. Stress ulcer prophylaxis in hospitalized patients not in intensive care units. Am J Health Syst Pharm. 2007 Jul 01;64(13):1396-400. [PubMed: 17592004]

40.

Farrell CP, Mercogliano G, Kuntz CL. Overuse of stress ulcer prophylaxis in the critical care setting and beyond. J Crit Care. 2010 Jun;25(2):214-20. [PubMed: 19683892]

41.

Liberman JD, Whelan CT. Brief report: Reducing inappropriate usage of stress ulcer prophylaxis among internal medicine residents. A practice-based educational intervention. J Gen Intern Med. 2006 May;21(5):498-500. [PMC free article: PMC1484795] [PubMed: 16704396]

Disclosure: Kim Nguyen declares no relevant financial relationships with ineligible companies.

Disclosure: Graham Dersnah declares no relevant financial relationships with ineligible companies.

Disclosure: Preeti Patel declares no relevant financial relationships with ineligible companies.

Disclosure: Rajni Ahlawat declares no relevant financial relationships with ineligible companies.