Ranitidine
Ranitidine
Generic Name
Ranitidine
Brand Names
Zantac®) is a competitive antagonist of histamine‑2 (H₂) receptors on gastric parietal cells. It was widely used for acid‑related disorders until the 2020‑2023 recall due to NDMA contamination, yet it remains a reference drug for understanding H₂ blockade pharmacology.
Mechanism
- Competitive H₂ receptor blockade: Ranitidine binds reversibly to H₂ receptors, preventing histamine‑mediated activation of adenylate cyclase and subsequent cAMP production.
- Decreased chloride ion transport: By inhibiting the H⁺/K⁺‑ATPase pathway indirectly, gastric acid secretion is reduced.
- Effect on other mediators: It also modestly antagonizes acetylcholine, histamine‑4, and VIP‑induced acid secretion, contributing to its overall hypochlorhydric effect.
Result – suppression of basal and stimulated gastric acid output, allowing ulcers to heal and reflux symptoms to diminish.
Pharmacokinetics
| Parameter | Ranitidine |
| Formulation | Oral tablets/SL, IV, IM, rectal powder |
| Bioavailability | 80–90 % (oral) |
| Peak plasma (Tmax) | 1–4 h (oral) |
| Half‑life | 2–3 h (oral); 3–4 h (IV) |
| Metabolism | CYP1A2, CYP2D6, and CYP3A4 (minor) |
| Excretion | Renal (60–70 % unchanged) |
| Steady‑state | Achieved after 2–3 days with twice‑daily dosing |
| Drug interactions | ↑*Cimetidine* use may increase ranitidine levels; *ketoconazole* slows metabolism; *trimethoprim* may modestly increase serum ranitidine. |
> Note: The drug is not significantly protein‑bound, allowing free drug for receptor binding.
Indications
- Peptic ulcer disease (active or healing)
- Gastro‑oesophageal reflux disease (GERD) – symptomatic relief and mucosal protection
- Zollinger‑Ellison syndrome – adjunctive therapy to reduce acid hypersecretion
- Antibiotic‑associated diarrhoea – prophylaxis in some regimens (historical)
- Pre‑operative prophylaxis against stress‑induced gastric ulceration in high‑risk patients
> Historical note: Ranitidine was also used off‑label as a pre‑medication for endoscopic procedures to maintain a higher gastric pH.
Contraindications
- Hypersensitivity to ranitidine or any of its excipients
- Pregnancy and lactation: limited data; generally avoided unless benefits outweigh risks
- Children under 12 y: insufficient data for safety/efficacy
- Severe renal impairment: dose adjustment required
- NDMA contamination: all current formulations have been recalled by regulatory agencies; consider alternatives (e.g., famotidine, domperidone)
> Warning: Abrupt discontinuation can cause rebound acid hypersecretion (up to 2–3× baseline), leading to haematemesis or ulcer recurrence.
Dosing
| Condition | Oral Dose (tablet/SL) | IV Dose (IV) | Frequency | Notes |
| Adults | 150 mg BID (or 300 mg daily) | 150 mg IV q12 h | Re: ulcers | ↓ Dose by 25 % if CrCl 30–50 mL/min |
| Elderly | 150 mg BID | 150 mg IV q12 h | ↑ risk of adverse effects; monitor for renal function | |
| Renal impairment | 75 mg BID | 75 mg IV q12 h | Adjust per CrCl | |
| Acute ulcer bleeding | 300 mg BID | 300 mg IV q12 h | Start in hospital, transition to oral |
• Oral: Take with a full glass of water, 30 min before meals.
• IV: Use 5 % dextrose or saline; avoid propylene glycol‑rich solutions.
Adverse Effects
Common
• Headache
• Dizziness
• Diarrhea or constipation
• Nausea, vomiting
• Flatulence
• Rare photosensitivity
Serious
• Rebound acid hypersecretion (after abrupt cessation)
• Hypotension (rare, associated with fast IV infusion)
• Sexual dysfunction in some men (↓ejaculation)
• Allergic reactions: rash, pruritus, urticaria, angioedema
• Hypokalemia/Hypomagnesemia (with chronic high‑dose use)
> Monitoring: Routine labs not required for short courses; consider electrolytes or renal panel if chronic therapy >8 weeks.
Monitoring
- Renal function: CrCl or eGFR before initiating therapy and every 3–6 months during long‑term use.
- Serum electrolytes: especially in patients with diarrhea or long‑term therapy.
- Clinical response: symptom relief, healing of ulcers (via endoscopy if indicated).
- Recording adverse events: particularly rebound acid symptoms when tapering.
Clinical Pearls
- Prophylactic pre‑operative dosing: A single 150 mg IV dose 1 h before surgery reduces the risk of stress‑related mucosal damage in major procedures.
- NDMA recall logic: Ranitidine can degrade into NDMA when stored >48 h at room temperature; always verify product expiry and storage conditions.
- Pediatric use: While off‑label, lower‑dose regimens (e.g., 50 mg in children 2–12 y) have shown symptom control for GERD; monitor growth and GI symptoms closely.
- Drug‑drug interaction awareness: Cimetidine competition can double ranitidine serum concentration; likewise, ranitidine inhibits Cimetidine's metabolism, increasing cimetidine exposure.
- Polarity matters: Being a relatively hydrophilic drug, ranitidine does not readily cross the blood–brain barrier, reducing central adverse effects compared to other antihistamines.
- Infusion safety checklist: Slow IV infusion (≤30 min) prevents hypotension; avoid rapid bolus >10 mL/min.
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• *Note: Due to the widespread recall of ranitidine for NDMA contamination, healthcare providers are strongly encouraged to substitute approved alternatives such as famotidine, lansoprazole, or omeprazole for acid‑related indications.*