Contents

Search

ranitidine (Zantac, Gastrosedol)

Tradename: Zantac. (ranitidine hydrochloride) Indications: - peptic ulcer disease - gastroesophageal reflux (GERD) - pyrosis - erosive esophagitis - part of a multidrug regimen for treatment of H. pylori - prevention of upper GI bleed due to hypersecretory conditions - Zollinger-Ellison syndrome - systemic mastocytosis - multiple endocrine neoplasia - prophylaxis for stress ulceration Dosage: 1) peptic ulcer disease: a) short term: 150 mg PO BID or 300 mg PO QHS b) maintenance: 150 mg PO QHS 2) erosive esophagitis: 150 mg PO QID or 300 mg PO BID 3) stress ulcer prophylaxis: a) 150 mg PO BID b) 50 mg IV every 8 hours 4) IV administration: a) 50 mg IV every 6-8 hours b) continuous infusion @ 6.25 mg/hr (150 mg/day) Tabs: 150, 300 mg. Syrup: 75 mg/5 mL. Injection: 25 mg/mL (2 mL, 10 mL) Dosage adjustment in renal failure: - creatinine clearance < 50 mg/min a) oral: use QD dosing b) IV: use every 18-24 hours dosing Pharmacokinetics: 1) oral bioavailability is about 55% 2) 15% of the drug is protein-bound 3) elimination 1/2life is 2 hours; increases to 7 hours in patients with renal failure 4) major metabolite is N-oxide Adverse effects: 1) not common (1-10%) - rash, nausea/vomiting, headache, drowsiness, dizziness, diarrhea, constipation 2) uncommon (< 1%) - thrombocytopenia, tachycardia, neutropenia, fever, confusion, bronchospasm, bradycardia, agranulocytosis 3) other - increases serum transaminases (rare) - anticholinergic activity 22% that of atropine Drug interactions: 1) ranitidine inhibits metabolism of a) warfarin b) phenytoin c) theophylline d) metoprolol e) fentanyl 2) ranitidine increases bioavailability of midazolam 3) ramitidine decreases renal clearance of procainamide 4) lidocaine 5) carbamazepine 6) benzodiazepines 7) alcohol 8) ketoconazole 9) antacids reduce ranitidine absorption Laboratory: 1) specimen: serum, plasma (heparin, EDTA), urine 2) methods: HPLC, RIA 3) interferences: RIA: some cross-reactivity with N-oxide metabolite Mechanism of action: 1) H2 receptor antagonist 2) some cyt P450 inhibition , but less than cimetidine Notes: - N-nitrosodimethylamine (NDMA) found in some ranitidine products including Zantac [6] - levels of NDMA in ranitidine products similar to those in grilled or smoked meats [7] - FDA recommends removal of all ranitidine drugs from the market due to concerns that NDMA content increases over time 7 when stored above room temperature [8] - paper alleging that rantidine increases urinary NMMA retracted [9] - rantidine does not increase urinary NMMA in normal healthy adults [10]

Interactions

drug interactions drug adverse effects of H2-receptor antagonists

General

antiulcer agent H2 receptor antagonist

Properties

MISC-INFO: elimination route KIDNEY LIVER 1/2life 0.9-2.3 HOURS therapeutic-range 100-200 NG/ML protein-binding 12-18% elimination by hemodialysis + pregnancy-category B safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  4. Clinical Guide to Laboratory Tests, NW Tietz (ed) 3rd ed, WB Saunders, Philadelpha 1995
  5. Journal Watch 25(3):26-27, 2005 Carnahan RM, Lund BC, Perry PJ, Chrischilles EA. The concurrent use of anticholinergics and cholinesterase inhibitors: rare event or common practice? J Am Geriatr Soc. 2004 Dec;52(12):2082-7. PMID: 15571547
  6. FDA Safety Alert. Sept 13, 2019 Zantac (ranitidine): Safety Information - NDMA Found in Samples of Some Ranitidine Medicines. https://www.fda.gov/safety/medwatch-safety-alerts-human-medical-products/zantac-ranitidine-safety-information-ndma-found-samples-some-ranitidine-medicines - FDA Safety Alert. Sept 23, 2019 Sandoz Inc. Issues Voluntary Recall of Ranitidine Hydrochloride Capsules 150mg and 300mg Due to An Elevated Amount of Unexpected Impurity, N-Nitrosodimethylamine (NDMA), in the Product https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/sandoz-inc-issues-voluntary-recall-ranitidine-hydrochloride-capsules-150mg-and-300mg-due-elevated
  7. Woodcock J. Director - Center for Drug Evaluation and Research FDA News Release. Nov 1, 2019 Statement on new testing results, including low levels of impurities in ranitidine drugs. https://www.fda.gov/news-events/press-announcements/statement-new-testing-results-including-low-levels-impurities-ranitidine-drugs
  8. FDA News Release. April 1, 2020 FDA Requests Removal of All Ranitidine Products (Zantac) from the Market. https://www.fda.gov/news-events/press-announcements/fda-requests-removal-all-ranitidine-products-zantac-market
  9. Retraction Watch Staff Widely Covered Paper on Ranitidine-Cancer Link Retracted. Medscape 2021. June 15 https://www.medscape.com/viewarticle/953118 - Zeng T, Mitch WA Retracted: Oral intake of ranitidine increases urinary excretion of N-nitrosodimethylamine. Carcinogenesis, Volume 37, Issue 6, June 2016, Pages 625-634 https://academic.oup.com/carcin/article/37/6/625/1744630
  10. Florian J, Matta MK, DePalma R et al Effect of Oral Ranitidine on Urinary Excretion of N-Nitrosodimethylamine (NDMA). A Randomized Clinical Trial. JAMA. Published online June 28, 2021 PMID: 34180947 https://jamanetwork.com/journals/jama/fullarticle/2781670 - White CM, Hernandez AV. Ranitidine and Risk of N-Nitrosodimethylamine (NDMA) Formation. JAMA. Published online June 28, 2021 PMID: 34180953 https://jamanetwork.com/journals/jama/fullarticle/2781671

Component-of

bismuth citrate/ranitidine (Tritec) intravenous anti-emetic combination