Introduction
Zantac (ranitidine hydrochloride) is a histamine H2-receptor antagonist that was widely prescribed for the management of gastric acid-related disorders. First approved by the FDA in 1983, it became one of the most commonly used medications worldwide for treating conditions such as gastroesophageal reflux disease (GERD) and peptic ulcer disease. In April 2020, the FDA requested the removal of all ranitidine products from the market due to concerns about N-nitrosodimethylamine (NDMA) contamination, a probable human carcinogen.
Mechanism of Action
Ranitidine competitively inhibits histamine at H2 receptors of parietal cells in the stomach. This action reduces basal and nocturnal gastric acid secretion, as well as acid secretion stimulated by food, histamine, pentagastrin, caffeine, and insulin. Unlike proton pump inhibitors, ranitidine does not completely suppress acid production but reduces it by approximately 70% for up to 12 hours.
Indications
Zantac was FDA-approved for:
- Treatment and maintenance of duodenal ulcers
- Treatment of benign gastric ulcers
- Management of GERD
- Treatment of pathological hypersecretory conditions (Zollinger-Ellison syndrome)
- Erosive esophagitis
- Prevention of stress ulcers in critically ill patients
- Relief of heartburn, acid indigestion, and sour stomach
Dosage and Administration
Adults:- Active duodenal ulcer: 150 mg twice daily or 300 mg once daily
- Maintenance: 150 mg once daily
- GERD: 150 mg twice daily
- Hypersecretory conditions: 150 mg twice daily (may increase up to 6 g/day)
- Erosive esophagitis: 150 mg four times daily
- CrCl <50 mL/min: Reduce dose to 150 mg every 24 hours
- Oral tablets: May be taken with or without food
- Should be stored at room temperature, protected from moisture
Pharmacokinetics
Absorption: Rapidly absorbed from GI tract; bioavailability is approximately 50% due to first-pass metabolism Distribution: Volume of distribution: 1.2-1.8 L/kg; protein binding: 10-19% Metabolism: Hepatic metabolism via cytochrome P450 system; forms N-oxide, S-oxide, and desmethyl metabolites Elimination: Half-life: 2-3 hours; primarily renal excretion (30% unchanged drug); clearance decreases with renal impairmentContraindications
- Hypersensitivity to ranitidine or any component of formulation
- History of acute porphyria
- Concomitant use with drugs that rely on gastric pH for absorption (delavirdine, atazanavir)
Warnings and Precautions
- NDMA contamination: All ranitidine products withdrawn from market due to carcinogen concerns
- QT prolongation: May cause dose-dependent QT interval prolongation
- Liver dysfunction: Use with caution in patients with hepatic impairment
- Renal impairment: Requires dose adjustment
- Vitamin B12 deficiency: Long-term use may reduce vitamin B12 absorption
- Pneumonia risk: May increase risk of hospital-acquired pneumonia
- C. difficile infection: Potential increased risk
Drug Interactions
- Atazanavir, delavirdine: Reduced absorption due to increased gastric pH
- Warfarin: Potential increased anticoagulant effect
- Ketoconazole, itraconazole: Reduced absorption
- Midazolam: May increase serum concentrations
- Procainamide: May increase levels due to renal tubular secretion competition
- Sulfonylureas: Potential enhanced hypoglycemic effect
Adverse Effects
Common (≥1%):- Headache
- Constipation
- Diarrhea
- Nausea/vomiting
- Abdominal discomfort
- Hepatotoxicity (elevated LFTs, hepatitis)
- Blood dyscrasias (thrombocytopenia, leukopenia)
- Bradycardia
- QT prolongation
- Stevens-Johnson syndrome
- Anaphylaxis
- Acute interstitial nephritis
- Gynecomastia (with long-term use)
Monitoring Parameters
- Symptom improvement and resolution
- Renal function (BUN, creatinine)
- Liver function tests (periodically)
- Complete blood count (with long-term use)
- Vitamin B12 levels (with prolonged therapy)
- ECG monitoring in patients at risk for QT prolongation
- Signs of infection (particularly pneumonia)
Patient Education
- Take as directed, with or without food
- Complete full course of therapy for ulcer treatment
- Avoid alcohol and smoking, which can aggravate conditions
- Report any signs of allergic reaction immediately
- Be aware of potential interactions with other medications
- Understand that all ranitidine products have been removed from market due to safety concerns
- Discuss alternative treatment options with healthcare provider
References
1. FDA Drug Safety Communication: NDMA found in ranitidine medications. FDA.gov. 2020 2. Ranitidine hydrochloride monograph. Lexicomp Online. Wolters Kluwer Clinical Drug Information 3. Wolfe MM, Sachs G. Acid suppression: optimizing therapy for gastroduodenal ulcer healing, gastroesophageal reflux disease, and stress-related erosive syndrome. Gastroenterology. 2000;118(2 Suppl 1):S9-S31 4. Shin JM, Sachs G. Pharmacology of proton pump inhibitors. Curr Gastroenterol Rep. 2008;10(6):528-534 5. Thomson AB, Sauve MD, Kassam N, et al. Safety of the long-term use of proton pump inhibitors. World J Gastroenterol. 2010;16(19):2323-2330 6. Maton PN. Profile and assessment of the safety of proton pump inhibitors. Am J Gastroenterol. 2003;98(3 Suppl):S27-S30