Amoxycillin (750mg) + Clarithromycin (500mg) + Esomeprazole (40mg)

Clinical Pharmacologist's Monograph

⚠️ Prescription Only: This medicine is Schedule H/H1. Do not self-medicate.

1. Clinical Overview

This is a triple-drug combination therapy primarily indicated for the eradication of Helicobacter pylori (H. pylori) in patients with peptic ulcer disease (PUD) and gastritis. Amoxycillin is a broad-spectrum beta-lactam antibiotic, Clarithromycin is a macrolide antibiotic, and Esomeprazole is a proton pump inhibitor (PPI). The combination synergistically targets H. pylori while reducing gastric acidity to promote ulcer healing and prevent recurrence. It is a cornerstone of first-line H. pylori eradication therapy in India, often used in a 10-14 day regimen.

OnsetDurationBioavailability
Esomeprazole: Gastric acid suppression begins within 1 hour; maximal effect after 5 days of repeated dosing. Amoxycillin/Clarithromycin: Antibacterial action begins immediately upon reaching effective concentrations.Esomeprazole: Acid suppression lasts >24 hours. Amoxycillin: 6-8 hours (dose-dependent). Clarithromycin: 12 hours (dose-dependent).Amoxycillin: ~80% (oral, unaffected by food). Clarithromycin: ~50% (oral). Esomeprazole: ~64% (oral, delayed-release formulation).

2. Mechanism of Action

This combination works synergistically for H. pylori eradication. Esomeprazole irreversibly inhibits the H+/K+ ATPase (proton pump) in gastric parietal cells, profoundly suppressing gastric acid secretion. This elevates gastric pH, which enhances the stability and antimicrobial activity of Amoxycillin and Clarithromycin against H. pylori. Amoxycillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs). Clarithromycin inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit.

3. Indications & Uses

  • Eradication of Helicobacter pylori in patients with: Active Peptic Ulcer Disease (Gastric & Duodenal Ulcer)
  • Eradication of Helicobacter pylori in patients with: Histologically confirmed Gastritis
  • Prevention of recurrence of Peptic Ulcer Disease in H. pylori positive patients

4. Dosage & Administration

Adult Dosage: One kit (containing Amoxycillin 750mg + Clarithromycin 500mg + Esomeprazole 40mg) twice daily, for 10 to 14 days. Typically administered before meals (breakfast and dinner).

Administration: Take on an empty stomach, 30-60 minutes before breakfast and dinner. Swallow the tablets whole with a glass of water; do not crush, chew, or break the delayed-release components. If a dose is missed, take it as soon as remembered unless it's almost time for the next dose. Do not double the dose.

5. Side Effects

Common side effects may include:

  • Diarrhea (can be antibiotic-associated)
  • Nausea
  • Abdominal pain
  • Headache
  • Taste perversion (metallic taste - Clarithromycin)
  • Flatulence
  • Constipation (Esomeprazole)

6. Drug Interactions

DrugEffectSeverity
Warfarin/AcenoocumarolIncreased anticoagulant effect & risk of bleeding (Esomeprazole inhibits CYP2C19; Clarithromycin inhibits warfarin metabolism).Major
DigoxinIncreased Digoxin serum levels (Clarithromycin reduces intestinal metabolism of Digoxin).Major
Statins (Atorvastatin, Simvastatin, Lovastatin)Increased risk of Myopathy/Rhabdomyolysis (Clarithromycin inhibits CYP3A4).Major
CarbamazepineIncreased Carbamazepine levels and toxicity (Clarithromycin inhibits metabolism).Major
Midazolam, TriazolamIncreased sedation and prolonged effect (Clarithromycin inhibits CYP3A4).Major
ColchicineIncreased Colchicine toxicity (myelosuppression, myopathy) in renal impaired patients (Clarithromycin inhibits CYP3A4 & P-gp).Contraindicated
MethotrexateIncreased Methotrexate levels and toxicity (Esomeprazole may reduce renal clearance).Major
ClopidogrelReduced antiplatelet efficacy (Esomeprazole, a CYP2C19 inhibitor, may interfere with Clopidogrel's activation).Moderate
Ketoconazole, ItraconazoleReduced absorption of these antifungals due to increased gastric pH (Esomeprazole).Moderate
HIV Protease Inhibitors (Ritonavir, Saquinavir)Complex interactions; both increased and decreased levels possible. Contraindicated or requires close monitoring.Major
Oral ContraceptivesPotential reduced efficacy (antibiotics may alter gut flora). Use additional barrier method.Moderate

7. Patient Counselling

  • DO complete the full prescribed course (10-14 days), even if you feel better.
  • DO take the medication 30-60 minutes BEFORE breakfast and dinner.
  • DO swallow the tablets whole with a full glass of water; do not crush or chew.
  • DO inform your doctor if you have a history of liver, kidney, or heart disease.
  • DO use additional contraceptive methods (e.g., condoms) if on oral pills, during and for 7 days after the course.
  • DON'T take antacids, H2 blockers (like Ranitidine), or sucralfate within 2 hours of this medicine.
  • DON'T consume grapefruit or grapefruit juice during therapy.
  • DON'T share this medication with others, even if they have similar symptoms.
  • DON'T stop the medication abruptly without consulting your doctor.

8. Toxicology & Storage

Overdose: Amoxycillin: Crystalluria, renal impairment, seizures (high doses in renal failure). Clarithromycin: Nausea, vomiting, diarrhea, severe abdominal pain, reversible hearing loss, QT prolongation. Esomeprazole: Blurred vision, confusion, drowsiness, dry mouth, flushing, headache, nausea, tachycardia.

Storage: Store below 25°C, in a cool, dry place. Protect from light and moisture. Keep in the original blister pack until use. Keep out of reach of children. Do not use after the expiry date printed on the pack.