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StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-.

StatPearls [Internet].

Show detailsTreasure Island (FL): StatPearls Publishing; 2025 Jan-.Search term H2 Blockers

Caitlin C. Nugent; Samuel R. Falkson; Jamie M. Terrell.

Author Information and Affiliations

Authors

Caitlin C. Nugent1; Samuel R. Falkson2; Jamie M. Terrell3.

Affiliations

1 University of Louisiana at Monroe2 Massachusetts General Hospital, Department of Anesthesia, Critical Care and Pain Medicine3 University of LA Monroe

Last Update: August 11, 2024.

Continuing Education Activity

H2 receptor blockers, or histamine-2 receptor antagonists (H2RAs), are gastric acid-suppressing agents frequently used to treat various gastric conditions. The U.S. Food and Drug Administration has approved the short-term administration of H2RAs for patients with uncomplicated gastroesophageal reflux disease (GERD), gastric or duodenal ulcers, gastric hypersecretion, and mild to infrequent heartburn or indigestion. H2RAs may also be used off-label for stress ulcer prophylaxis, esophagitis, gastritis, gastrointestinal bleeding, or urticaria. H2RAs are sometimes part of a multidrug regimen for Helicobacter pylori eradication.

In the United States, 3 H2RAs are FDA-approved and available either over-the-counter (OTC) or by prescription: famotidine, cimetidine, and nizatidine. Depending on the dose, famotidine and cimetidine may require a prescription. Higher doses of nizatidine require a prescription. A solid clinical understanding of H2RAs is crucial for effectively managing gastrointestinal disorders. This activity describes the pharmacological features of H2 blockers and emphasizes the interprofessional team's role in promoting their safety, equipping healthcare professionals with essential knowledge, and enhancing patient outcomes and care standards.

Objectives:

• Evaluate the mechanism of action of H2 receptor blockers.
• Assess the adverse drug reactions associated with H2 receptor blocker administration.
• Identify the indications for H2 receptor blocker therapy.
• Implement effective collaboration and communication among interprofessional team members to improve outcomes and treatment efficacy for patients who might benefit from H2 receptor blockers.

Access free multiple choice questions on this topic.

Indications

H2 receptor blockers, or H2 receptor antagonists (H2RAs), are gastric acid-suppressing agents frequently used in various gastric conditions. The FDA approves these drugs to treat uncomplicated gastroesophageal reflux disease (GERD), gastric or duodenal ulcers, gastric hypersecretion, and mild to infrequent heartburn or indigestion. H2 receptor antagonists may also be used off-label for stress ulcer prophylaxis, esophagitis, gastritis, gastrointestinal bleeding, or urticaria. These drugs are also sometimes included in a multidrug regimen for Helicobacter pylori eradication.[1] Currently, 3 FDA-approved H2RAs are available in the United States, either over-the-counter (OTC) or by prescription. Famotidine and cimetidine are available OTC or by prescription, depending on the dose. Low-dose nizatidine is also available in OTC, but higher doses require a prescription. Ranitidine was previously available but has been withdrawn in the United States and suspended in Europe and Australia for carcinogen contamination during manufacturing.[2][3] 

FDA-Approved Indications

H2 receptor antagonists are approved for short-term use in treating uncomplicated gastroesophageal reflux disease (GERD), gastric or duodenal ulcers, gastric hypersecretion, and mild to infrequent heartburn or indigestion. IV famotidine is approved for the short-term treatment of active duodenal and gastric ulcers, maintenance therapy for patients with duodenal ulcers, short-term treatment of gastroesophageal reflux disease, erosive or ulcerative esophagitis due to GERD, and hypersecretory conditions such as Zollinger-Ellison syndrome (ZES).

The American College of Gastroenterology (ACG) guidelines recommend adding bedtime H2RA for patients with persistent nocturnal symptoms while on proton pump inhibitors. In contrast, the ACG recommends proton pump inhibitors (PPIs) over H2 receptor antagonists (H2RAs) for the treatment of erosive esophagitis (EE).[4] ACG also advises the use of high-dose proton pump inhibitor (PPI) therapy, either continuously or intermittently, for 3 days following successful endoscopic hemostatic treatment of a bleeding ulcer.[5]

Off-Label Uses

H2 receptor antagonists can be used off-label for esophagitis, gastritis, gastrointestinal bleeding, urticaria, and stress ulcer prophylaxis.[6] These drugs are also sometimes included in a multidrug regimen for Helicobacter pylori eradication.[1] Although antacids are generally considered first-line agents for heartburn during pregnancy, H2 receptor antagonists may be used if needed.[7] H2RAs have been determined safe for use in children or adolescents with mild or infrequent heartburn symptoms that do not respond to lifestyle changes.[8] The overall therapeutic effectiveness of H2RAs significantly depends on the severity of the gastric disease, dosage regimen, and duration of therapy.

Mechanism of Action

H2RAs decrease gastric acid secretion by reversibly binding to histamine H2 receptors located on gastric parietal cells, inhibiting the binding and activity of the endogenous ligand histamine. H2 blockers thus function as competitive antagonists. Normally, gastrin stimulates histamine release from enterochromaffin-like cells after a meal, which then binds to histamine H2 receptors on gastric parietal cells, causing gastric acid release. This increase in gastric acid release occurs through the activation of adenylate cyclase, which raises intracellular cyclic adenosine monophosphate (cAMP) levels. Cyclic AMP then activates protein kinase A (PKA), which phosphorylates proteins involved in moving H+/K+ ATPase transporters to the plasma membrane. Increasing H+/K+ ATPase transporters at the plasma membrane allows more acid secretion from parietal cells.

By blocking the histamine receptor and thus histamine's stimulation of parietal cell acid secretion, H2RAs suppress stimulated and basal gastric acid secretion induced by histamine.[9] Studies have suggested that adding an H2RA improves nocturnal intragastric pH control.[10] The study indicates that H2RAs have a comparatively less pronounced impact on gut microbiota than PPIs, with minimal changes in oral-to-gut transmission and microbial composition. This suggests that H2RAs may have less effect on gut microbiome alteration than PPIs.[11]

Pharmacokinetics

Absorption: The onset of gastric relief provided by H2RAs is approximately 60 minutes with a duration of action that ranges from 4 to 10 hours, making them useful for the on-demand treatment of occasional symptoms. All H2RAs have similar efficacy in decreasing gastric acid secretion.[12] Famotidine is absorbed with an oral bioavailability of 40% to 45%. The presence of food may slightly increase its absorption, while antacids may slightly decrease it; these effects are not clinically significant. Peak plasma levels of famotidine are typically attained within 1 to 3 hours, and plasma levels after multiple doses are similar to those after single doses. Nizatidine has a higher oral bioavailability, often exceeding 70%. Antacids containing aluminum and magnesium hydroxides can reduce their absorption by about 10%, whereas food can increase AUC and Cmax by approximately 10%. Peak plasma concentrations of nizatidine occur within 0.5 to 3 hours after dosing. Cimetidine is rapidly absorbed, with peak plasma levels occurring within 45 to 90 minutes following oral administration. Blood concentrations of cimetidine remain high enough to inhibit 80% of basal gastric acid secretion for 4 to 5 hours.

Distribution: Approximately 15% to 20% of famotidine in the plasma is bound to proteins. Nizatidine has a volume of distribution ranging from 0.8 to 1.5 L/kg, with about 35% bound to plasma proteins, primarily α1-acid glycoprotein. Although specific distribution details for cimetidine are not well-documented, the drug is known to distribute widely throughout the body, including significant accumulation in the liver and kidneys.

Metabolism: The H2 receptor blockers are metabolized in the liver by the cytochrome P450 system. Among the H2RAs, cimetidine is unique because it inhibits the CYP1A2, CYP2C9, and CYP2D6, which can lead to significant drug interactions.[13]

Elimination: Famotidine has an elimination half-life of 2.5 to 3.5 hours. The drug is primarily excreted via the renal route (65% to 70%), with renal clearance ranging from 250 to 450 mL/min, indicating some tubular secretion. Nizatidine has a shorter elimination half-life of 1 to 2 hours, with plasma clearance between 40 and 60 L/h. Over 90% of the oral dose is excreted in the urine within 12 hours; about 60% of the drug is unchanged. Renal clearance is approximately 500 mL/min, reflecting active tubular secretion. Less than 6% of the dose is eliminated in the feces. In patients with renal impairment, the half-life of nizatidine is prolonged significantly, and its clearance is decreased, necessitating dose adjustments. Cimetidine has an elimination half-life of about 2 hours and is primarily excreted renally.

Administration

Available Dosage Forms and Strengths

H2 receptor antagonists are well-absorbed after oral administration, and all H2RAs are available as oral tablets. Nizatidine is also available as a capsule or an oral solution. Famotidine, one of the most commonly used agents, is available as a chewable tablet, oral powder for suspension, or in combination formulations containing calcium carbonate and magnesium hydroxide or ibuprofen.

Nizatidine is available in several formulations, including oral tablets in strengths of 150 mg and 300 mg and an over-the-counter (OTC) option of 75 mg. Cimetidine is available as an injectable solution (150 mg/mL), an oral solution (150 mg/5 mL), and oral tablets in multiple strengths: 200 mg, 300 mg, 400 mg, 600 mg, and 800 mg, with higher doses available only by prescription. Famotidine is available as an injectable solution in concentrations of 0.4 mg/mL and 10 mg/mL, an oral suspension (40 mg/5 mL), and various oral tablets and chewable tablets available via prescription or OTC in strengths of 10 mg, 20 mg, and 40 mg.

Adult Dosage

H2 receptor antagonists may relieve current gastric symptoms or be taken prophylactically 30 to 60 minutes before known food or beverage triggers. H2RAs may also be taken concomitantly with antacids if both quick relief of symptoms and a longer duration of action are desired. For best results, patients should take once-daily doses of H2RAs at bedtime. More common regimens involve twice-daily dosing: once in the morning and once in the evening.[12] Patients should not initially self-treat with H2RAs for longer than 2 weeks without consulting their primary care physician.

Famotidine 

• Active duodenal ulcer: 40 mg once daily or 20 mg twice daily. The recommended dosage for IV famotidine is 20 mg every 12 hours.
• Active gastric ulcer: 40 mg once daily. Malignancy should be excluded before treatment.
• GERD: 20 mg twice daily
• Erosive esophagitis: 20 to 40 mg twice daily
• Hypersecretion pathologies: 20 mg every 6 hours, with adjustments based on patient needs. The maximum dose is 160 mg every 6 hours.
• Maintenance of healed duodenal ulcer: 20 mg once daily to reduce the risk of duodenal ulcers.

Nizatidine

• Active duodenal ulcer: 300 mg once daily or 150 mg twice daily
• Maintenance of healed duodenal ulcer: 150 mg once daily (oral) at bedtime
• GERD: 150 mg twice daily (oral)
• Active benign gastric ulcer: 300 mg once daily at bedtime or 150 mg twice daily. Malignancy should be excluded before treatment.

Cimetidine

• Active duodenal ulcer: 800 mg at bedtime, which provides effective healing, pain relief, and convenience.
• Maintenance for duodenal ulcers: 400 mg (oral) at bedtime
• GERD: 1600 mg daily, divided into 800 mg twice or 400 mg 4 times daily, for up to 12 weeks.
• Hypersecretion pathologies: The initial dose is 300 mg 4 times daily. Dosages can be adjusted based on individual needs but should not exceed 2400 mg daily.

Specific Patient Populations

Hepatic impairment: The manufacturer's labeling for famotidine and nizatidine does not provide specific dosage adjustments for hepatic impairment. However, cimetidine should be used with caution in patients with hepatic impairment due to its potential for interactions.

Renal impairment: According to product labeling, famotidine doses should be reduced by 50% for patients with a creatinine clearance (CrCl) of less than 30 mL/min. For patients with similar creatinine clearances receiving cimetidine, dosing should not exceed 300 mg every 12 hours. No adjustment is necessary for nizatidine doses for patients with CrCl >50 mL/min. For patients with CrCl 20-50 mL/min, the recommended dose is 150 mg once daily. For patients with a CrCl <20 mL/min, the dose should be adjusted to 150 mg every other day.

Pregnancy considerations: Although antacids are generally considered first-line agents for heartburn during pregnancy, H2 receptor antagonists are pregnancy category B drugs. This means they are not well-studied in pregnant women but have no known teratogenic effects and may be administered if needed. The minimum effective dose should be used.[7] 

Breastfeeding considerations: Maternal doses of cimetidine ranging from 1000 to 1200 mg daily result in infant exposure levels considerably lower than the neonatal dosage of 5 to 10 mg/kg daily. Consequently, cimetidine is not expected to adversely affect breastfed infants, especially those older than 2 months old. However, other medications may be preferable due to their potential to inhibit hepatic enzymes. Cimetidine can increase serum prolactin levels and has been used, though not validated, as a galactagogue. With famotidine, the concentration in breast milk results in infant doses that are lower than those typically administered to newborns, suggesting that adverse effects in breastfed infants are unlikely. No special precautions are needed. Nizatidine is also minimally present in breast milk, resulting in small amounts ingested by the infant, and is not expected to cause adverse effects. No specific precautions are required for nizatidine. H2 receptor antagonists with more extensive clinical use might be preferable in newborns.[14][15][16]

Pediatric patients: H2RAs have also been determined safe for children or adolescents with mild or infrequent heartburn symptoms that do not respond to lifestyle changes.[8] According to the American Academy of Pediatrics (AAP), GERD syrup/suspension formulations are preferred. Cimetidine is dosed at 30 to 40 mg/kg per day, divided into 4 doses, for patients aged 16 years and older. Famotidine is administered at 1 mg/kg daily, divided into 2 doses, for children aged 12 months to 16 years. The maximum dose of famotidine is 40 mg per day. Nizatidine is dosed at 10 mg/kg per day, divided into 2 doses, for individuals aged 12 years and older.[17]

Older patients: H2RA dosing is similar to adult dosing. As explained above, adjustment for renal function is necessary. Previous studies have investigated the potential link between dementia and long-term use of H2RAs. A recent study, however, found no significant association between H2RA use and cognitive impairment or dementia. Further research is required to understand this relationship better.[18]

Adverse Effects

H2 receptor antagonists are generally well-tolerated. Mild side effects may include headache, drowsiness, fatigue, abdominal pain, constipation, or diarrhea.[19] The administration of H2RAs to patients with renal impairment, hepatic impairment, or who are older than 50 is associated with central nervous system side effects such as delirium, confusion, hallucinations, and slurred speech. Cimetidine is generally considered the most likely H2 blocker to cause these symptoms, although similar effects have also occurred with famotidine administration.[20][21][22]

Using H2 receptor antagonists regularly may result in tachyphylaxis or tolerance, limiting their use as maintenance therapy for GERD symptoms. Tolerance to these effects can occur after 7 to 14 days of continued treatment. Intermittent or as-needed administration may help prevent the development of tachyphylaxis.[23]

H2RAs have a relatively minor risk of developing bacterial overgrowth and infections compared to PPIs.[24] Recent studies indicate an association between rosacea and H2RAs; further research is required.[25] 

Drug-Drug Interactions

As a result of the intended elevation in gastric pH, drugs requiring an acidic environment for dissolution and absorption may become less effective. Cimetidine is a potent cytochrome P450 (CYP450) enzyme inhibitor and should be avoided with other medications metabolized by CYP450 enzymes, such as theophylline, selective serotonin reuptake inhibitors, or warfarin. Prolonged, high doses of cimetidine have also been linked to gynecomastia, reduced sperm count, and impotence in men, as well as galactorrhea in women. These conditions typically resolve with drug discontinuation. Clinicians generally avoid cimetidine as a treatment for gastric symptoms.[26] Excessive use of histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) may predispose individuals to iron deficiency anemia, although direct clinical evidence is limited.[27] A case-control study using Korean National Health Insurance data from 2014 to 2020 found that the combined use of PPIs and H2RAs was associated with an increased risk of osteoporotic fractures; further research is required. However, this combination should be used cautiously.[28]

Contraindications

There are currently no absolute contraindications to H2RA therapy. However, these drugs should not be used in patients with known hypersensitivity to any H2RA or formulation components.[29] Cross-sensitivity has been reported. Patients should stop using OTC H2RAs if they experience difficulty or pain when swallowing, vomiting with blood, or bloody or black stools. These patients should seek immediate medical attention.

Warnings and Precautions

Prior recalls of ranitidine: The FDA recalled ranitidine tablets due to unacceptable levels of N-nitrosodimethylamine (NDMA), a potential carcinogen.[30]

Monitoring

Patients using H2RAs should be monitored for endoscopic improvement and decreased gastric symptoms to assess the clinical effectiveness and need for therapy adjustments. Patients should also be monitored for adverse effects and possible drug interactions, especially when taking cimetidine.

Famotidine and nizatidine require dose adjustment for patients with a creatine clearance of less than 50 mL/min. Cimetidine doses should be reduced for patients with a creatine clearance of less than 30 mL/min. The half-life of cimetidine may become prolonged in patients with hepatic impairment, but for all H2RAs, no dose adjustments are required for hepatic impairment unless also accompanied by renal impairment.

Rarely, QT-prolongation or central nervous system effects have been observed in patients with impaired renal function receiving standard doses. Famotidine use requires caution during renal impairment and in combination with other QT-prolonging medications or conditions. Older patients should also be monitored for adverse central nervous system effects such as dizziness or confusion resulting from decreased drug clearance.[31]

Toxicity

Signs and Symptoms of Overdose

H2 receptor antagonists have a broad therapeutic index; severe toxicity is rare. Toxic H2RA levels may cause inhibition of H2 receptors in the myocardium and central nervous system. Central nervous system depression, hypotension, and bradycardia are rare but have been observed after rapid intravenous H2RA infusion.

Management of Overdose

Treatment for H2RA overdose typically involves discontinuation of the drug and supportive care measures and may include decontamination with gastric lavage or activated charcoal.

Enhancing Healthcare Team Outcomes

Many H2 blockers are available over the counter. While these drugs are relatively safe, they may produce severe adverse effects when combined with other CNS drugs. Patient education by the interprofessional healthcare team is critical to preventing toxicity and improving outcomes for patients receiving H2 receptor-blocking therapy. Pharmacists should check for drug interactions and inquire of patients in the retail setting if they encounter a patient purchasing H2 receptor antagonists as an over-the-counter option. Patients should be advised not to combine these agents with other CNS drugs or alcohol and refrain from taking them for prolonged periods.[32] An interprofessional team approach and communication among clinicians (MD, DO, NP, PA), pharmacists, and nurses are crucial to decreasing potential adverse effects and improving patient outcomes related to H2 blockers.

Review Questions

• Access free multiple choice questions on this topic.
• Comment on this article.

References

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[PMC free article: PMC8754510] [PubMed: 34807007]5.Laine L, Barkun AN, Saltzman JR, Martel M, Leontiadis GI. ACG Clinical Guideline: Upper Gastrointestinal and Ulcer Bleeding. Am J Gastroenterol. 2021 May 01;116(5):899-917. [PubMed: 33929377]6.Song MJ, Kim S, Boo D, Park C, Yoo S, Yoon HI, Cho YJ. Comparison of proton pump inhibitors and histamine 2 receptor antagonists for stress ulcer prophylaxis in the intensive care unit. Sci Rep. 2021 Sep 16;11(1):18467. [PMC free article: PMC8446063] [PubMed: 34531488]7.Servey J, Chang J. Over-the-Counter Medications in Pregnancy. Am Fam Physician. 2014 Oct 15;90(8):548-55. [PubMed: 25369643]8.Mattos ÂZ, Marchese GM, Fonseca BB, Kupski C, Machado MB. ANTISECRETORY TREATMENT FOR PEDIATRIC GASTROESOPHAGEAL REFLUX DISEASE - A SYSTEMATIC REVIEW. Arq Gastroenterol. 2017 Dec;54(4):271-280. [PubMed: 28954042]9.MacFarlane B. Management of gastroesophageal reflux disease in adults: a pharmacist's perspective. Integr Pharm Res Pract. 2018;7:41-52. [PMC free article: PMC5993040] [PubMed: 29892570]10.Mainie I, Tutuian R, Castell DO. Addition of a H2 receptor antagonist to PPI improves acid control and decreases nocturnal acid breakthrough. J Clin Gastroenterol. 2008 Jul;42(6):676-9. [PubMed: 18496394]11.Zhu J, Sun C, Li M, Hu G, Zhao XM, Chen WH. Compared to histamine-2 receptor antagonist, proton pump inhibitor induces stronger oral-to-gut microbial transmission and gut microbiome alterations: a randomised controlled trial. Gut. 2024 Jun 06;73(7):1087-1097. [PMC free article: PMC11187400] [PubMed: 38050061]12.Pettit M. Treatment of gastroesophageal reflux disease. Pharm World Sci. 2005 Dec;27(6):432-5. [PubMed: 16341949]13.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. Histamine Type-2 Receptor Antagonists (H2 Blockers) [PubMed: 31643264]14.Drugs and Lactation Database (LactMed®) [Internet]. National Institute of Child Health and Human Development; Bethesda (MD): Feb 15, 2021. Nizatidine. [PubMed: 30000299]15.Drugs and Lactation Database (LactMed®) [Internet]. National Institute of Child Health and Human Development; Bethesda (MD): Aug 15, 2024. Famotidine. [PubMed: 30000326]16.Drugs and Lactation Database (LactMed®) [Internet]. National Institute of Child Health and Human Development; Bethesda (MD): Sep 15, 2024. Cimetidine. [PubMed: 30000265]17.Lightdale JR, Gremse DA., Section on Gastroenterology, Hepatology, and Nutrition. Gastroesophageal reflux: management guidance for the pediatrician. Pediatrics. 2013 May;131(5):e1684-95. [PubMed: 23629618]18.Mehta RS, Kochar B, Zhou Z, Broder JC, Chung P, Yang K, Lockery J, Fravel M, Ryan J, Mahady S, Orchard SG, McNeil JJ, Murray A, Woods RL, Ernst ME, Chan AT. Association of Proton Pump Inhibitor Use With Incident Dementia and Cognitive Decline in Older Adults: A Prospective Cohort Study. Gastroenterology. 2023 Sep;165(3):564-572.e1. [PMC free article: PMC10527011] [PubMed: 37315867]19.Pinto-Sanchez MI, Yuan Y, Bercik P, Moayyedi P. Proton pump inhibitors for functional dyspepsia. Cochrane Database Syst Rev. 2017 Mar 08;3(3):CD011194. [PMC free article: PMC6464600] [PubMed: 28271513]20.von Einsiedel RW, Roesch-Ely D, Diebold K, Sartor K, Mundt C, Bergemann N. H(2)-histamine antagonist (famotidine) induced adverse CNS reactions with long-standing secondary mania and epileptic seizures. Pharmacopsychiatry. 2002 Jul;35(4):152-4. [PubMed: 12163986]21.Hamano T, Takano A, Miyao S, Teramoto J. Reversible adverse effects on the CNS induced by histamine H2 receptor antagonists. Eur Neurol. 1998;39(4):242. [PubMed: 9635477]22.Werbel T, Cohen PR. Ranitidine-Associated Sleep Disturbance: Case Report and Review of H2 Antihistamine-Related Central Nervous System Adverse Effects. Cureus. 2018 Apr 03;10(4):e2414. [PMC free article: PMC5984261] [PubMed: 29872595]23.Fox RK, Muniraj T. Pharmacologic Therapies in Gastrointestinal Diseases. Med Clin North Am. 2016 Jul;100(4):827-50. [PubMed: 27235617]24.Untersmayr E. Acid suppression therapy and allergic reactions. Allergo J Int. 2015 Dec;24(8):303-311. [PMC free article: PMC5464390] [PubMed: 28603686]25.Kim JH, Min JH, Jo YW, Kwon JW, Her Y. Association Between Acid-Suppressive Drugs and Risk of Rosacea: Retrospective Study Using the Korean National Health Insurance Service-National Sample Cohort. J Korean Med Sci. 2023 Dec 04;38(47):e402. [PMC free article: PMC10695752] [PubMed: 38050914]26.Humphries TJ, Merritt GJ. Review article: drug interactions with agents used to treat acid-related diseases. Aliment Pharmacol Ther. 1999 Aug;13 Suppl 3:18-26. [PubMed: 10491725]27.Vinnakota RD, Brett AS. Iron Deficiency Anemia Associated With Acid-Modifying Medications: Two Cases and Literature Review. Am J Med Sci. 2019 Feb;357(2):160-163. [PubMed: 30528320]28.Oh DJ, Nam JH, Lee HS, Moon YR, Lim YJ. The combined use of anti-peptic agents is associated with an increased risk of osteoporotic fracture: a nationwide case-control study. Korean J Intern Med. 2024 Mar;39(2):228-237. [PMC free article: PMC10918386] [PubMed: 38321358]29.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]30.White CM. Ranitidine's N-nitrosodimethylamine Problem May be Tip of the Iceberg. JAMA Netw Open. 2021 Jan 04;4(1):e2035158. [PubMed: 33512513]31.Ben-Joseph R, Segal R, Russell WL. Risk for adverse events among patients receiving intravenous histamine2-receptor antagonists. Ann Pharmacother. 1993 Dec;27(12):1532-7. [PubMed: 8305790]32.Carroll C, Hassanin A. Polypharmacy in the Elderly-When Good Drugs Lead to Bad Outcomes: A Teachable Moment. JAMA Intern Med. 2017 Jun 01;177(6):871. [PubMed: 28437544]

Disclosure: Caitlin Nugent declares no relevant financial relationships with ineligible companies.

Disclosure: Samuel Falkson declares no relevant financial relationships with ineligible companies.

Disclosure: Jamie Terrell declares no relevant financial relationships with ineligible companies.

Copyright © 2025, StatPearls Publishing LLC.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

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• Cite this PageNugent CC, Falkson SR, Terrell JM. H2 Blockers. [Updated 2024 Aug 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-.

In this Page

• Continuing Education Activity
• Indications
• Mechanism of Action
• Administration
• Adverse Effects
• Contraindications
• Monitoring
• Toxicity
• Enhancing Healthcare Team Outcomes
• Review Questions
• References

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