Ranitidine
1. Drug Name
Generic Name: Ranitidine
Brand Names: Zantac, Zantac 75, Zantac 150, and others.
2. Drug Classification
Class: Histamine H2 Receptor Antagonist (H2 Blocker)
Subclass: Anti-ulcerant, Gastrointestinal agent
Other Classifications: Antacid
3. Mechanism of Action
Histamine H2 Receptor Blockade: Ranitidine works by competitively inhibiting histamine at the H2 receptors located on the parietal cells of the stomach lining. Normally, histamine binds to these receptors to stimulate gastric acid secretion. By blocking this action, ranitidine reduces the amount of gastric acid produced.
Reduction in Acid Secretion: This inhibition leads to decreased acid secretion in response to both basal and food-stimulated secretion, thereby reducing gastric acidity.
Healing of Acid-Induced Damage: Reduced acid secretion helps in the healing of ulcers in the stomach and duodenum and alleviates symptoms of gastroesophageal reflux disease (GERD).
4. Pharmacokinetics
Absorption:
Ranitidine is well absorbed from the gastrointestinal tract after oral administration, with peak plasma concentrations reached within 2-3 hours.
Bioavailability is approximately 50% after oral administration, which can be affected by food intake but not to a significant extent.
Distribution:
The volume of distribution (Vd) is around 1.4 L/kg, with about 15% of the drug being protein-bound in plasma.
Metabolism:
Ranitidine is primarily metabolized in the liver via the cytochrome P450 enzyme system (CYP1A2, CYP2C19, CYP3A4), although to a lesser extent than other drugs that undergo extensive hepatic metabolism.
Excretion:
Half-life (t½): The elimination half-life of ranitidine is approximately 2-3 hours in healthy individuals.
Excretion is mainly via the kidneys, with about 30-35% of the drug excreted unchanged in the urine.
In patients with renal impairment, the half-life may be prolonged, necessitating dose adjustment.
Special Considerations: In patients with renal dysfunction, the dose should be adjusted based on renal clearance to avoid drug accumulation.
5. Indications
Primary Indications:
Gastroesophageal Reflux Disease (GERD): Ranitidine is used for the short-term relief and management of GERD symptoms.
Peptic Ulcers: Treatment of duodenal and gastric ulcers, both for healing and prophylaxis.
Erosive Esophagitis: Healing of esophagitis caused by acid reflux.
Zollinger-Ellison Syndrome: Used in the management of excessive gastric acid secretion.
Off-label Uses:
Stress Ulcer Prophylaxis: Used for preventing gastric ulcer formation in critically ill patients or those undergoing major surgeries.
Gastroparesis: Occasionally used off-label to help manage symptoms of delayed gastric emptying in patients, particularly those with diabetes.
6. Dosage and Administration
Adult Dosing:
GERD: 150 mg twice daily or 300 mg once daily, depending on severity.
Peptic Ulcer Disease:
Duodenal ulcers: 150 mg twice daily or 300 mg once daily at bedtime for 4-6 weeks.
Gastric ulcers: 150 mg twice daily or 300 mg once daily at bedtime for 6-8 weeks.
Zollinger-Ellison Syndrome: Doses start at 150 mg twice daily, and may be increased based on clinical response.
Erosive Esophagitis: 150 mg twice daily for 6-12 weeks.
Pediatric Dosing:
For children ≥1 year of age: 2-5 mg/kg per day, divided into two doses, up to 150 mg/day, depending on the condition being treated.
Renal and Hepatic Adjustments:
Renal Impairment: Dose reduction is recommended in patients with impaired renal function (creatinine clearance <50 mL/min) to avoid accumulation. Dosage is typically halved or administered every other day.
Hepatic Impairment: No significant dosage adjustment is required for mild to moderate hepatic impairment, but caution is advised in severe hepatic disease.
7. Contraindications
Absolute Contraindications:
Hypersensitivity: Known hypersensitivity to ranitidine or any of its components.
Relative Contraindications:
Pregnancy: Category B. Generally considered safe during pregnancy for short-term use, but should only be used if the potential benefit outweighs the risk to the fetus.
Lactation: Ranitidine is excreted in breast milk in small amounts, but it is considered safe for short-term use while breastfeeding.
Severe Renal Impairment: In patients with severe renal impairment, dose adjustment is essential to prevent drug accumulation.
8. Warnings and Precautions
Renal Impairment: In patients with impaired renal function, the drug should be dosed carefully, as accumulation may lead to adverse effects.
Gastric Cancer: Long-term use of H2 blockers like ranitidine can mask the symptoms of gastric cancer, delaying diagnosis in some cases.
QT Prolongation: Caution is advised in patients with a history of QT prolongation or those using medications that can prolong the QT interval.
B12 Deficiency: Prolonged use of ranitidine can impair vitamin B12 absorption, and patients on long-term therapy should have B12 levels monitored.
9. Adverse Effects
Common Adverse Effects:
Headache: A common side effect, often mild and transient.
Dizziness: Some patients may experience dizziness, especially at higher doses.
Gastrointestinal: Constipation, diarrhea, or nausea.
Fatigue: Fatigue or feeling of tiredness may occur.
Less Common but Clinically Significant:
Elevated Liver Enzymes: Mild increases in liver function tests (ALT, AST) have been observed.
Rash: Skin rashes or pruritus can occur in some individuals.
Rare/Serious Adverse Effects:
Hematological Disorders: Rare cases of agranulocytosis, thrombocytopenia, and pancytopenia have been reported.
Severe Allergic Reactions: Hypersensitivity reactions such as anaphylaxis, angioedema, and severe rashes are rare but serious.
QT Prolongation: Although uncommon, ranitidine may cause QT interval prolongation, particularly in patients with underlying heart disease or when used with other QT-prolonging drugs.
10. Drug Interactions
CYP450 Enzyme Interactions: Ranitidine does not significantly interact with cytochrome P450 enzymes, making it safer for use in patients taking medications that undergo extensive hepatic metabolism.
Antacids: Concurrent use with antacids may decrease the absorption of ranitidine. It is advisable to space out the administration of ranitidine and antacids by at least 1 hour.
Warfarin: Ranitidine may slightly enhance the effects of warfarin, increasing the risk of bleeding. Monitoring of INR is advised when used together.
Ketoconazole and Itraconazole: Reduced gastric acidity may impair the absorption of drugs that require an acidic environment for optimal absorption (e.g., ketoconazole).
Theophylline: Ranitidine may increase plasma concentrations of theophylline, necessitating close monitoring of theophylline levels.
11. Clinical Pharmacology
Pharmacodynamics: Ranitidine reduces gastric acid secretion by blocking histamine H2 receptors on the parietal cells. This leads to a decrease in both basal and stimulated acid production, providing relief for conditions like GERD and ulcers.
Additional Effects: Ranitidine has a long duration of action and is effective in preventing nocturnal acid secretion when taken before bedtime.
12. Special Populations
Pregnancy: Category B. Generally safe when used during pregnancy but should be used with caution, especially in the first trimester.
Lactation: Excreted in breast milk in small amounts, but no significant effects have been reported in breastfeeding infants. It is considered safe for short-term use.
Geriatrics: Elderly patients may be more susceptible to side effects such as confusion, dizziness, or renal dysfunction. Monitoring is recommended.
Renal and Hepatic Dysfunction: Dosage adjustments are required for patients with renal impairment. Caution is advised in hepatic impairment.
13. Therapeutic Uses
First-line Therapy for GERD, erosive esophagitis, and peptic ulcers.
Prophylactic Therapy for stress ulcers, particularly in critically ill patients.
Adjunct in H. pylori Eradication: As part of a multi-drug regimen for treating H. pylori infection, in combination with antibiotics and proton pump inhibitors.
14. Monitoring and Follow-Up
Renal Function: Regular monitoring of kidney function in patients with renal disease or those on long-term ranitidine therapy.
Liver Enzymes: Liver function tests are advised during prolonged use.
Vitamin B12 Levels: Long-term use of ranitidine may affect vitamin B12 absorption, necessitating periodic monitoring.
15. Overdose Management
Symptoms of Overdose: Symptoms include confusion, agitation, dizziness, and tachycardia.
Management: There is no specific antidote for ranitidine overdose. Treatment is symptomatic and supportive, including intravenous fluids and monitoring.
16. Patient Counseling Information
Administration: Take ranitidine as directed, usually once or twice a day. It should be taken before meals for optimal effect.
Lifestyle Modifications: Advise patients to avoid food or drink that may irritate the stomach (spicy food, alcohol, caffeine).
Side Effects: Inform patients to report any unusual side effects, particularly persistent abdominal pain, difficulty swallowing, or signs of allergic reactions such as swelling or rash.