1. Dosage

Histamine H2-receptor antagonists (H2RAs) are FDA-approved for use in gastric ulcer, duodenal ulcer, gastroesophageal reflux disease (GERD), esophagitis, hypersecretory conditions, and non-ulcer indigestion/heartburn.

In April 2020, the Food and Drug Administration requested that manufacturers remove all prescription and over-the-counter (OTC) formulations of ranitidine from the market. The request for removal was precipitated by the discovery of N-nitrosodimethylamine (NDMA), a probable human carcinogen, in various ranitidine products. Zantac® is one of several trade names for ranitidine, and in June 2021, Sanofi Pharmaceuticals released Zantac 360°® as an OTC product. However, this new formulation contains famotidine rather than ranitidine.

1.1. Adults

The maximum adult H2RA daily doses when prescribed for acute and maintenance FDA-approved conditions are summarized in Table 1 and Table 2. Dosage regimens exceeding these maximum recommended values will be reviewed.

Table 1. Adult Maximum Daily Acute Doses for Histamine H2-Receptor Antagonists: Monotherapy1-10
Drug Name Dosage Form/Strength Treatment Indication Maximum Recommended Dosage 
cimetidine (generics) 200 mg, 300 mg, 400 mg, 800 mg tablets; 300 mg/5 mL oral solution duodenal ulcer 1200 mg/day ^
    gastric ulcer 1200 mg/day
    gastroesophageal reflux disease (GERD) - nonerosive 1600 mg/day
    heartburn 400 mg/day
    hypersecretory conditions 2400 mg/day
famotidine (Pepcid, Zantac 360°, generics) 10 mg, 20 mg, 40 mg tablets; 40 mg/5 mL oral suspension duodenal ulcer 40 mg/day
    erosive esophagitis (EE) 80 mg/day
    gastric ulcer 40 mg/day
    GERD - nonerosive 40 mg/day
    heartburn 40 mg/day
    hypersecretory conditions 640 mg/day
nizatidine (generics) 150 mg, 300 mg capsules; 15 mg/mL oral solution  duodenal ulcer 300 mg/day in single or divided doses
    gastric ulcer 300 mg/day in single or divided doses
    GERD - nonerosive 300 mg/day in single or divided doses

Legend:

  • ^ Patients who are heavy smokers with duodenal ulcers greater than 1 cm may benefit from cimetidine 1600 mg at bedtime.
Table 2. Adult Maximum Daily Maintenance Dose for Histamine H2-Receptor Antagonists: Monotherapy1-10
Drug Name Dosage Form/Strength Treatment Indication Maximum Recommended Dosage 
cimetidine (generics) 200 mg, 300 mg, 400 mg, 800 mg tablets; 300 mg/5 mL oral solution duodenal ulcer 400 mg/day
    hypersecretory conditions 2400 mg/day
famotidine (Pepcid®, generics) 10 mg, 20 mg, 40 mg tablets; 40 mg/5 mL oral suspension duodenal ulcer 20 mg/day
    hypersecretory conditions 640 mg/day
nizatidine (generics) 150 mg, 300 mg capsules; 15 mg/mL oral solution  duodenal ulcer 150 mg/day at bedtime

Current American College of Gastroenterology guidelines recommend the use of a proton pump inhibitor over H2RAs for Helicobacter pylori treatment regimens13.

Currently, famotidine is available as a combination product with ibuprofen, and it is marketed under the trade name Duexis®. Duexis® is FDA approved for the prophylaxis against upper gastrointestinal ulcers in adult patients with osteoarthritis or rheumatoid arthritis.14 Dosing for this agent is provided in Table 3.

Table 3. Adult Maximum Daily Dose for Histamine H2-Receptor Antagonists: Combination Therapy1,2,14
Drug Name Dosage Form/Strength Treatment Indication Maximum Recommended Dosage
famotidine/ ibuprofen (Duexis®, generics) 26.6 mg/ 800 mg oral tablets gastric ulcer prophylaxis in osteoarthritis or rheumatoid arthritis 79.8 mg / 2400 mg/day in three divided doses

1.2. Pediatrics

Maximum recommended pediatric H2RA daily doses for acute and maintenance therapy are summarized in Table 4. Dosages exceeding these recommendations will be reviewed.

Table 4. Pediatric Maximum Daily Acute Doses for Histamine H2-Receptor Antagonists: Monotherapy1-10
Drug Name Patient Characteristics Treatment Indication Maximum Recommended Dosage
cimetidine (generics) Greater than or equal to 16 years of age duodenal ulcer 1200 mg/day ^
  Greater than or equal to 16 years of age gastric ulcer 1200 mg/day
  Greater than or equal to 16 years of age gastroesophageal reflux disease (GERD) - nonerosive 1600 mg/day
  Greater than or equal to 12 years of age heartburn 400 mg/day
  Greater than or equal to 16 years of age hypersecretory conditions 2400 mg/day
famotidine (Pepcid®, generics) 1 to 17 years of age duodenal ulcer tablet: 40 mg/day*
suspension: 40 mg/day
  1 to 17 years of age erosive esophagitis (EE) tablet: 80 mg/day*
suspension: 80 mg/day
  1 to 17 years of age gastric ulcer tablet: 40 mg/ day*
suspension: 40 mg/day
  1 to 16 years of age GERD - nonerosive tablet: 40 mg/day*
suspension: 80 mg/day 
  3 months to 1 year of age GERD - nonerosive suspension: 1 mg/kg twice daily (maximum of 40 mg daily)
  Less than 3 months of age GERD - nonerosive suspension: 1 mg/kg once daily
famotidine (Pepcid®, Zantac 360°,  generics) Greater than or equal to 12 years of age heartburn 40 mg/day
nizatidine (generics) Greater than or equal to 12 years of age EE 300 mg/day in single or divided doses
  Greater than or equal to 12 years of age GERD - nonerosive 300 mg/day in single or divided doses

Legend:

  • ^ Patients who are heavy smokers with duodenal ulcers greater than 1 cm may benefit from cimetidine 1600 mg at bedtime
  • * dosing for pediatric patients weighing greater than or equal to 40 kg
Table 5. Pediatric Maximum Daily Maintenance Doses for Histamine H2-Receptor Antagonists1-4
Drug Name Patient Characteristics Treatment Indication Maximum Recommended Dosage
cimetidine (generics) Greater than or equal to 16 years of age duodenal ulcer 400 mg at bedtime
  Greater than or equal to 16 years of age hypersecretory conditions 2400 mg/day

1.3. Dosage in Renal Impairment

H2RAs are primarily renally excreted. Dosage modifications for H2RA use in renal impairment are summarized in Table 6.

Table 6. H2RA Dosage Modifications in Renal Impairment1-10
Drug Name Dosage Adjustments in Renal Impairment
cimetidine
  • CrCl greater than or equal to 30 mL/min: No dose adjustment recommendations
  • CrCl less than 30 ml/min: 300 mg orally every 12 hours; may increase to every 8 hours cautiously based on patient response
famotidine
  • CrCl 30-60 mL/min
    • active duodenal ulcer, active gastric ulcer, and erosive esophagitis diagnosed by endoscopy: 20 mg orally daily; or 40 mg orally every other day 
    • symptomatic non-erosive GERD: 20 mg orally daily
    • risk reduction of duodenal ulcer recurrence: 20 mg orally every other day
    • pathological hypersecretory conditions: avoid use
  • CrCl less than 30 mL/min
    • active duodenal ulcer, active gastric ulcer, erosive esophagitis diagnosed by endoscopy, and symptomatic non-erosive GERD: 10 mg orally daily; or 20 mg orally every other day 
    • risk reduction of duodenal ulcer recurrence: 10 mg orally every other day
    • pathological hypersecretory conditions: avoid usenizatidine
nizatidine

active treatment:

  • CrCl 20-50 ml/min: 150 mg/day orally 
  • CrCl less than 20 ml/min: 150 mg orally every other day

maintenance therapy:

  • CrCl 20-50 ml/min: 150 mg every other day orally
  • CrCl less than 20 ml/min: 150 mg every 3 days orally