Famotidine
1. Drug Name
Generic Name: Famotidine
Brand Names: Pepcid, Pepcid AC, and others.
2. Drug Classification
Class: Histamine H2 Receptor Antagonist (H2 Blocker)
Subclass: Antacid, Gastrointestinal agent
Other Classifications: Anti-ulcerant
3. Mechanism of Action
Histamine H2 Receptor Blockade: Famotidine works by selectively inhibiting the histamine H2 receptors found on the parietal cells in the stomach lining. These receptors are normally activated by histamine, leading to the stimulation of gastric acid secretion. By blocking this receptor, famotidine effectively reduces the amount of gastric acid produced.
Gastric Acid Secretion: This inhibition reduces basal and stimulated gastric acid secretion, which helps prevent conditions related to excess stomach acid, such as gastroesophageal reflux disease (GERD), peptic ulcers, and Zollinger-Ellison syndrome.
Gastric pH Increase: The reduction in acid production increases gastric pH, which assists in the healing of acid-induced damage to the stomach lining and esophagus.
4. Pharmacokinetics
Absorption:
Famotidine is well absorbed after oral administration, with peak plasma concentrations occurring within 1-3 hours.
Bioavailability is approximately 40-45% after oral administration.
Food does not significantly affect the absorption of famotidine.
Distribution:
The volume of distribution (Vd) of famotidine is approximately 1.0 L/kg, and it is weakly protein-bound (15-20%).
Metabolism:
Famotidine is primarily excreted unchanged in the urine, with minimal metabolism occurring in the liver.
It undergoes negligible hepatic metabolism, making it a preferred option in patients with liver dysfunction.
Excretion:
Half-life (t½): The elimination half-life of famotidine is about 2.5 to 3.5 hours.
The drug is excreted primarily unchanged through the kidneys.
In patients with renal impairment, the half-life may be prolonged, and dose adjustments are recommended.
Special Considerations: In patients with renal impairment, the dosage should be reduced due to slower clearance.
5. Indications
Primary Indications:
Gastroesophageal Reflux Disease (GERD): Famotidine is used to relieve heartburn and acid reflux symptoms associated with GERD.
Peptic Ulcers: Treatment of gastric and duodenal ulcers, both for healing and for prophylaxis.
Zollinger-Ellison Syndrome: A condition characterized by excessive gastric acid production, often due to tumors in the pancreas or duodenum.
Erosive Esophagitis: Management of esophagitis caused by acid reflux.
Off-label Uses:
Stress Ulcer Prophylaxis: Famotidine may be used for preventing stress-related mucosal damage in critically ill patients.
Gastroparesis: In some cases, famotidine is used off-label to manage delayed gastric emptying, particularly in diabetic patients.
6. Dosage and Administration
Adult Dosing:
GERD: 20-40 mg once or twice daily.
Peptic Ulcer Disease:
Duodenal ulcers: 40 mg once daily at bedtime for 4 to 8 weeks.
Gastric ulcers: 40 mg once daily at bedtime for 6 to 8 weeks.
Zollinger-Ellison Syndrome: 20 mg twice daily, which may be increased based on clinical response.
Erosive Esophagitis: 20 mg twice daily for 6-12 weeks.
Pediatric Dosing:
GERD and Peptic Ulcer Disease: 0.5 mg/kg (up to 40 mg) once or twice daily, depending on age and condition.
Renal and Hepatic Adjustments:
Renal Impairment: Dose reduction is recommended in patients with creatinine clearance <50 mL/min. Typical adjustments are 20 mg once daily or every other day depending on severity.
Hepatic Impairment: No dosage adjustment is generally required, but caution is advised in patients with moderate to severe hepatic disease.
7. Contraindications
Absolute Contraindications:
Hypersensitivity: Known hypersensitivity to famotidine or any of its components.
Relative Contraindications:
Pregnancy: Famotidine is categorized as a Category B drug in pregnancy. It is generally considered safe for use during pregnancy when the potential benefit outweighs the risk to the fetus.
Lactation: Famotidine is excreted in breast milk, but it is considered safe for short-term use in breastfeeding women.
Severe Renal Impairment: In patients with severe renal dysfunction, dosing adjustments are necessary to prevent accumulation and adverse effects.
8. Warnings and Precautions
Renal Impairment: Dose reduction or adjustment may be necessary in patients with renal insufficiency to avoid accumulation and toxicity.
B12 Deficiency: Long-term use of H2 blockers may lead to vitamin B12 deficiency, as reduced stomach acid can impair B12 absorption. This should be monitored during prolonged treatment.
Gastric Cancer: Chronic use of H2 blockers can mask symptoms of gastric cancer, particularly in patients with early-stage gastric malignancy.
QT Prolongation: Caution is advised when administering famotidine to patients with a history of QT prolongation or those on other medications that can prolong the QT interval.
Acid Rebound: Abrupt discontinuation of famotidine can lead to a rebound increase in gastric acid secretion, potentially worsening symptoms of acid reflux or peptic ulcers.
9. Adverse Effects
Common Adverse Effects:
Headache: One of the most frequently reported side effects.
Dizziness: Lightheadedness or dizziness can occur, particularly with higher doses.
Gastrointestinal: Nausea, constipation, or diarrhea may occur.
Fatigue: Some patients report feeling unusually tired or fatigued.
Less Common but Clinically Significant:
Elevated Liver Enzymes: Mild increases in liver enzymes (AST, ALT) may occur.
Rash: Some individuals may experience skin rashes or pruritus.
Rare/Serious Adverse Reactions:
Hematological Disorders: Rare cases of agranulocytosis, thrombocytopenia, or pancytopenia.
Severe Allergic Reactions: Anaphylaxis, angioedema, and severe hypersensitivity reactions have been reported, though rare.
QT Prolongation: As with other H2 blockers, famotidine may be associated with QT interval prolongation, particularly in those with underlying cardiac conditions.
10. Drug Interactions
CYP450 Enzyme Interactions: Famotidine does not significantly interact with cytochrome P450 enzymes, making it a safer choice for patients on multiple medications.
Antacids: Antacids can reduce the absorption of famotidine, so it is advisable to space out the administration of famotidine and antacids.
Ketoconazole and Itraconazole: Reduced gastric acid may impair the absorption of drugs that require an acidic environment for optimal absorption (e.g., ketoconazole).
Warfarin: Caution should be taken when using famotidine with warfarin, as there may be an increased risk of bleeding due to potential alteration in warfarin metabolism.
11. Clinical Pharmacology
Pharmacodynamics: Famotidine reduces gastric acid secretion by blocking the histamine H2 receptors on parietal cells, thereby decreasing gastric acid production. Its effect is dose-dependent, with the greatest reduction in gastric acid occurring at higher doses.
Additional Effects: Famotidine has minimal effect on the secretion of pepsin or intrinsic factor, and it does not alter the pH of the duodenum or jejunum.
12. Special Populations
Pregnancy: Category B. Famotidine is generally considered safe for use during pregnancy, particularly in short-term treatments.
Lactation: Excreted in breast milk in small amounts, and considered safe for use during breastfeeding.
Geriatrics: Older patients may be more susceptible to adverse effects such as confusion, dizziness, and renal dysfunction. Monitoring is advised.
Renal and Hepatic Dysfunction: Dosage adjustments are recommended in patients with moderate to severe renal impairment.
13. Therapeutic Uses
First-line Therapy for conditions like GERD, peptic ulcer disease, and esophagitis.
Zollinger-Ellison Syndrome: Effective in managing hypersecretion of gastric acid.
Adjunct to Antibiotics for Helicobacter pylori eradication in peptic ulcer disease.
14. Monitoring and Follow-Up
Renal Function: Regular monitoring of kidney function in patients with renal disease or those on long-term famotidine therapy.
Liver Enzymes: Liver function tests are advised during prolonged use.
Vitamin B12 Levels: Long-term use of famotidine 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. Treatment is supportive, including intravenous fluids and monitoring.
16. Patient Counseling Information
Administration: Take famotidine as directed, usually once or twice a day. Take it 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.