Usage
Lafutidine is prescribed for the treatment of gastric ulcer, duodenal ulcer, anastomotic ulcer, reflux esophagitis (GERD), and gastric mucosal lesions (such as erosions and bleeding) in acute gastritis or acute exacerbation of chronic gastritis. It is also used as a pre-anesthetic medication. It belongs to the pharmacological class of histamine H₂-receptor antagonists. Lafutidine works by blocking histamine H₂-receptors in the stomach, which reduces the production of gastric acid. It also increases the production of gastric mucus, providing additional gastroprotective action.
Alternate Names
Lafutidine is also known as Lafutidine hydrochloride. Brand names include Lafumac, Stogar, Protecadin, Lafaxid, and Lafter among others.
How It Works
Pharmacodynamics: Lafutidine competitively inhibits histamine at H₂ receptors of the gastric parietal cells, thereby suppressing basal and nocturnal gastric acid secretion stimulated by histamine, gastrin and pentagastrin. This inhibition reduces gastric volume and increases gastric pH. Lafutidine also enhances mucosal defense mechanisms by stimulating gastric mucus secretion, thus protecting the gastric mucosa against harmful agents like acid and pepsin.
Pharmacokinetics: Lafutidine is rapidly absorbed after oral administration, reaching peak plasma concentrations in about 1–2 hours. It has a protein binding of approximately 88%. Lafutidine is primarily metabolized by CYP3A4 and, to a lesser extent, CYP2D6 enzymes in the liver. It is mainly excreted in the urine as unchanged drug and metabolites. The elimination half-life is approximately 2 hours in healthy adults. It is important to note that the elimination half-life might be prolonged in patients with severe renal impairment.
Mode of Action: Lafutidine acts by competitively and reversibly binding to histamine H₂ receptors on the basolateral membrane of parietal cells in the stomach. This binding prevents histamine from stimulating these receptors, thus reducing the activation of adenylate cyclase and decreasing the intracellular concentration of cyclic adenosine monophosphate (cAMP). Consequently, this leads to the inhibition of proton pump activity and reduced secretion of gastric acid into the stomach lumen.
Elimination Pathways: Lafutidine is primarily eliminated through renal excretion (approximately 60-70% as unchanged drug) with the remaining portion eliminated via hepatic metabolism involving primarily CYP3A4 and, to a lesser extent, CYP2D6.
Dosage
Standard Dosage
Adults:
- Gastric/Duodenal/Anastomotic Ulcer and Reflux Esophagitis: 10 mg twice daily (after breakfast and after the evening meal or before bed).
- Gastric Mucosal Lesions (Acute Gastritis/Acute Exacerbation of Chronic Gastritis): 10 mg once daily (after the evening meal or before bed).
- Pre-anesthetic Medication: 10 mg twice (once before bedtime on the day before surgery and once 2 hours before anesthesia induction on the day of surgery).
Children:
The safety and efficacy of Lafutidine in children have not been established. Therefore, it is generally not recommended for pediatric use.
Special Cases:
- Elderly Patients: Dose reduction or increased dosing intervals may be necessary due to age-related decline in renal and hepatic function. Start with a lower dose and titrate cautiously based on patient response and tolerability. Close monitoring is recommended.
- Patients with Renal Impairment: Dose reduction or increased dosing intervals may be needed.
- Patients with Hepatic Dysfunction: Dose reduction or increased dosing intervals may be needed.
- Patients with Comorbid Conditions: Dosage adjustments should be considered on a case-by-case basis.
Clinical Use Cases
The standard dosage recommendations apply to the clinical use cases mentioned (intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations). However, dose adjustments may be required in these settings based on patient-specific factors, organ function, and concurrent medications.
Dosage Adjustments
Dosage modifications are essential for patients with renal or hepatic impairment. Close monitoring of renal function and liver enzymes is recommended, especially during long-term therapy.
Side Effects
Common Side Effects:
Constipation, fatigue, headache, diarrhea, increased liver enzymes (transaminases), hyperuricemia.
Rare but Serious Side Effects:
Anaphylactic reactions, blood dyscrasias (e.g., agranulocytosis, thrombocytopenia), hallucinations, gynecomastia, anorexia.
Long-Term Effects:
Long-term effects are not well established, but regular monitoring of liver function and blood counts is advised during prolonged therapy.
Adverse Drug Reactions (ADR):
Severe allergic reactions, significant changes in liver function tests, hematological abnormalities require immediate medical attention.
Contraindications
- Hypersensitivity to Lafutidine or other H₂-receptor antagonists.
- Lactation (breastfeeding).
Drug Interactions
Lafutidine is primarily metabolized by CYP3A4 and to a lesser extent, CYP2D6. Consequently, drugs that inhibit or induce these enzymes can affect Lafutidine levels. Caution is advised when using Lafutidine concomitantly with:
- CYP3A4 Inhibitors: (e.g., ketoconazole, itraconazole, erythromycin, clarithromycin) may increase Lafutidine concentrations.
- CYP3A4 Inducers: (e.g., rifampicin, phenytoin, carbamazepine) may decrease Lafutidine concentrations.
Interactions with other medications, OTC drugs, or supplements should be considered.
Pregnancy and Breastfeeding
Lafutidine’s pregnancy safety category has not been formally assigned. Use during pregnancy only if clearly needed and the potential benefits outweigh the potential risks to the fetus. Lafutidine is excreted in breast milk. It’s contraindicated during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Histamine H₂-receptor antagonist, reducing gastric acid secretion and increasing gastric mucus.
- Side Effects: Constipation, headache, diarrhea, increased liver enzymes, hyperuricemia. Rarely: anaphylaxis, blood dyscrasias, hallucinations.
- Contraindications: Hypersensitivity, lactation.
- Drug Interactions: CYP3A4 inhibitors and inducers.
- Pregnancy & Breastfeeding: Not assigned pregnancy category. Contraindicated in breastfeeding.
- Dosage: Adults: 10mg once or twice daily, depending on the indication. Dose adjustments in renal/hepatic impairment and elderly.
- Monitoring Parameters: Liver function tests, complete blood count during long-term use.
Popular Combinations
Lafutidine is sometimes combined with Domperidone (a prokinetic agent) for the treatment of GERD and other conditions where improving gastric motility is beneficial. However, this combination should be used with caution due to the potential for Domperidone-induced cardiac adverse effects.
Precautions
- General Precautions: Assess renal and hepatic function before starting treatment.
- Specific Populations: Use cautiously in pregnant women, elderly, and those with hepatic or renal impairment. Contraindicated during breastfeeding.
- Lifestyle Considerations: Alcohol may exacerbate gastric irritation.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Lafutidine?
A: The recommended dose is 10 mg twice daily for ulcers and GERD, and 10 mg once daily for gastric mucosal lesions. For pre-anesthetic medication, it is 10 mg the night before surgery and 10 mg 2 hours before the induction of anesthesia. Dosage adjustments are needed in patients with renal/hepatic impairment and in the elderly.
Q2: How does Lafutidine differ from other H₂ blockers?
A: Lafutidine has higher H2-receptor selectivity and potentially a longer duration of action than some older H₂ blockers. Additionally, it might have stronger mucoprotective effects.
Q3: Can Lafutidine be used in patients with kidney problems?
A: Yes, but the dose needs to be reduced or the dosage interval should be increased based on the severity of renal impairment. Close monitoring of renal function is necessary.
A: Anaphylactic reactions (difficulty breathing, swelling, rash), severe changes in liver function tests, and signs of blood dyscrasias (e.g., unusual bleeding, bruising, fatigue, infections) require immediate medical intervention.
Q5: Can Lafutidine be crushed or chewed?
A: It depends on the formulation. Standard tablets should be swallowed whole. However, dispersible tablets can be dissolved in water before administration. Always check the specific product information.
Q6: Are there any dietary restrictions while taking Lafutidine?
A: While no specific dietary restrictions are mandatory, it’s generally advisable to avoid foods and beverages that might irritate the stomach, such as spicy foods, excessive caffeine, and alcohol.
Q7: Can Lafutidine be used with proton pump inhibitors (PPIs)?
A: While sometimes used concurrently, combining Lafutidine with a PPI might not offer substantial additional benefit and might increase the risk of side effects. Such combination should be reserved for specific cases resistant to monotherapy and under careful monitoring.
Q8: Does Lafutidine interact with any commonly used drugs?
A: Yes, it can interact with drugs metabolized by CYP3A4 and CYP2D6, like some antifungals (ketoconazole, itraconazole), antibiotics (erythromycin, clarithromycin), and antiepileptics (phenytoin, carbamazepine).
Q9: Can Lafutidine be used for the long-term management of GERD?
A: Yes, Lafutidine can be used for long-term GERD management, but patients should undergo regular monitoring of liver function and blood parameters. Lifestyle modifications, including dietary changes and weight management, are also important.
