Esotid HP

Approved Indications:

• Eradication of Helicobacter pylori infection in:
• Patients with active duodenal ulcer
• Patients with a history of duodenal ulcer disease
• Patients with gastric ulcer associated with H. pylori
• Patients with chronic gastritis due to H. pylori

Clinically Accepted Off-Label Uses:

• Prevention of recurrence of peptic ulcer disease in H. pylori-positive individuals
• Functional dyspepsia associated with H. pylori infection (select cases)
• Treatment of H. pylori-related MALT lymphoma (in localized stage I disease)

Adults:

Standard Triple Therapy Regimen:

• Esomeprazole 20 mg orally twice daily
• Amoxicillin 1000 mg orally twice daily
• Clarithromycin 500 mg orally twice daily
  Duration: 7–14 days (typically 10–14 days for better efficacy)

Alternative Regimen (based on local resistance patterns):

• Esomeprazole 40 mg once daily may be used in some variations

Pediatrics (children ≥12 years and ≥30 kg):

• Limited data; generally not recommended due to clarithromycin resistance concerns

Elderly:

• No dose adjustment required unless renal/hepatic impairment exists

Renal Impairment:

• Mild to moderate: No adjustment needed
• Severe (CrCl <30 mL/min): Use caution due to amoxicillin accumulation

Hepatic Impairment:

• Mild to moderate: No dosage adjustment
• Severe (Child-Pugh C): Use with caution; monitor liver function

Administration Instructions:

• Take all three medications simultaneously, with or without food
• Swallow tablets whole with water; do not crush or chew
• Maintain a consistent schedule for optimal efficacy

This triple combination targets H. pylori eradication through a synergistic mechanism:

• Esomeprazole is a proton pump inhibitor (PPI) that blocks the H+/K+-ATPase enzyme in gastric parietal cells, suppressing acid secretion. This increases gastric pH, creating a favorable environment for antibiotics to work and promoting mucosal healing.
• Amoxicillin is a beta-lactam antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), causing lysis of actively dividing H. pylori.
• Clarithromycin is a macrolide antibiotic that binds to the 50S ribosomal subunit of H. pylori, inhibiting protein synthesis and resulting in bacterial death.

Combined, these agents eradicate H. pylori and promote ulcer healing effectively.

Esomeprazole:

• Absorption: Rapid; peak plasma levels in 1.5 hours
• Bioavailability: 50–90% (dose-dependent)
• Metabolism: Hepatic (CYP2C19 and CYP3A4)
• Half-life: ~1.3 hours
• Excretion: Urine (80% as metabolites), feces (minor)

Amoxicillin:

• Absorption: Well absorbed orally; peak plasma in 1–2 hours
• Bioavailability: ~90%
• Metabolism: Minimal hepatic metabolism
• Half-life: 1–1.5 hours
• Excretion: Renal (via glomerular filtration and tubular secretion)

Clarithromycin:

• Absorption: Rapid; peak levels in ~2 hours
• Bioavailability: ~50% (enhanced by food)
• Metabolism: Hepatic (CYP3A4) into active metabolite 14-OH clarithromycin
• Half-life: 3–7 hours (dose-dependent)
• Excretion: Urine (40%), feces (via bile)

Pregnancy:

• Esomeprazole: Category C (risk cannot be ruled out); use only if clearly needed
• Amoxicillin: Category B (no evidence of risk in humans)
• Clarithromycin: Category C; not recommended due to potential teratogenic effects in animals

Lactation:

• Amoxicillin and esomeprazole are excreted into breast milk in low levels and are generally considered safe during breastfeeding
• Clarithromycin is also excreted in breast milk; caution advised due to potential adverse effects (e.g., diarrhea, fungal infections, and sensitization in infants)

• Primary Class: Antiulcer agent + Antibiotic combination
• Subclasses:
• Esomeprazole: Proton Pump Inhibitor (PPI)
• Amoxicillin: Beta-lactam Penicillin Antibiotic
• Clarithromycin: Macrolide Antibiotic

• Known hypersensitivity to esomeprazole, amoxicillin, clarithromycin, or any component of the formulation
• History of cholestatic jaundice or hepatic dysfunction associated with clarithromycin use
• Macrolide-resistant H. pylori infection (confirmed or suspected)
• Concomitant use with drugs metabolized by CYP3A4 that may cause QT prolongation (e.g., cisapride, pimozide, ergot alkaloids)
• Severe hepatic impairment (for clarithromycin use)

• Antibiotic-associated diarrhea, including Clostridioides difficile infection, may occur
• QT interval prolongation and cardiac arrhythmias (especially with clarithromycin)
• Risk of anaphylaxis or serious skin reactions from beta-lactam or macrolide components
• Hepatotoxicity, especially with clarithromycin
• Superinfection risk with prolonged use
• Renal or hepatic monitoring advised in long-term or high-risk patients
• May mask symptoms of gastric malignancy; rule out cancer before starting PPI
• Use caution in patients with myasthenia gravis

Common (≥1%):

• Gastrointestinal: Nausea, diarrhea, abdominal pain, taste disturbance, bloating
• Central Nervous System: Headache, dizziness
• Skin: Rash, itching

Less Common but Serious:

• Hepatic: Elevated liver enzymes, hepatitis, cholestatic jaundice
• Cardiac: QT prolongation, arrhythmias
• Allergic: Anaphylaxis, Stevens-Johnson syndrome, angioedema
• Hematologic: Leukopenia, thrombocytopenia (rare)

Onset & Severity:

• Most side effects appear within a few days of therapy initiation and are dose-dependent or related to clarithromycin

• CYP3A4 interactions (Clarithromycin):
• Inhibits CYP3A4, increasing levels of statins, benzodiazepines, carbamazepine, warfarin, etc.
• Risk of QT prolongation with other QT-prolonging agents (e.g., amiodarone, sotalol)
• Probenecid: Increases serum amoxicillin levels by reducing renal excretion
• PPIs (Esomeprazole):
• May reduce absorption of drugs requiring acidic pH (e.g., ketoconazole, atazanavir)
• May increase digoxin and methotrexate levels
• Warfarin: INR may increase; monitor closely
• Alcohol: Increases risk of GI irritation and hepatic stress; avoid concurrent use

• Recent guidelines (e.g., Maastricht VI, ACG): Recommend bismuth-containing quadruple therapy or concomitant therapy in areas with high clarithromycin resistance; however, clarithromycin-based triple therapy is still acceptable if local resistance <15%
• Updated FDA warnings: Clarithromycin use in patients with heart disease may increase long-term mortality risk; alternative antibiotics may be considered

• Esomeprazole: Store at 20°C to 25°C (68°F to 77°F); protect from moisture and light
• Amoxicillin (tablet/capsule): Store below 25°C; protect from moisture
• Clarithromycin: Store at 15°C to 30°C (59°F to 86°F); protect from heat, light, and moisture

Additional Notes:

• Do not freeze suspensions (if used)
• Use reconstituted suspensions within prescribed expiry window (usually 14 days) and store in the refrigerator (2°C–8°C)