Triokit

Approved Indication:

• Eradication of Helicobacter pylori infection in patients with duodenal ulcer disease:
• Indicated for the eradication of H. pylori to reduce the risk of duodenal ulcer recurrence.
• This triple therapy is used in adults as part of a combination regimen containing a proton pump inhibitor (Lansoprazole), a beta-lactam antibiotic (Amoxicillin), and a macrolide antibiotic (Clarithromycin).

Clinically Accepted (Off-Label) Uses:

• H. pylori eradication in gastric ulcers.
• Treatment of H. pylori-associated chronic gastritis.

Route of Administration: Oral

Adults (Triple Therapy Regimen):

• Lansoprazole: 30 mg orally twice daily
• Amoxicillin: 1000 mg orally twice daily
• Clarithromycin: 500 mg orally twice daily
• Duration: 10 to 14 consecutive days (commonly 14 days for higher eradication success)

Administration Advice:

• All three drugs should be taken at the same time, preferably before meals.
• Complete the full course of therapy even if symptoms improve before completion.

Pediatric Use:

• Safety and efficacy of this fixed-dose triple regimen in children have not been established; not routinely recommended.

Elderly:

• Use the same adult dosing. Monitor closely for gastrointestinal intolerance, hepatic function, and QT interval.

Renal Impairment:

• Amoxicillin: Use with caution in severe renal impairment (CrCl <30 mL/min); dose adjustment may be required.
• Clarithromycin: Reduce dose or avoid if CrCl <30 mL/min.
• Lansoprazole: No dose adjustment necessary.

Hepatic Impairment:

• Clarithromycin: Use with caution in moderate to severe hepatic impairment.
• Amoxicillin and Lansoprazole: Generally safe; monitor for adverse effects in severe cases.

This combination works synergistically to eradicate Helicobacter pylori through acid suppression and direct antimicrobial action:

• Lansoprazole irreversibly inhibits the gastric H⁺/K⁺-ATPase (proton pump) in parietal cells, reducing gastric acid secretion. This creates an optimal environment for the antibiotics to act more effectively.
• Amoxicillin is a beta-lactam antibiotic that disrupts bacterial cell wall synthesis by binding to penicillin-binding proteins, causing bacterial lysis.
• Clarithromycin is a macrolide antibiotic that binds to the 50S subunit of bacterial ribosomes, inhibiting protein synthesis and leading to bacteriostatic or bactericidal effects, depending on concentration.
• Together, these agents reduce gastric acidity and directly eliminate H. pylori bacteria

Lansoprazole:

• Absorption: Rapid; peak plasma levels in 1.5–2 hours.
• Bioavailability: ~85%; delayed by food but not clinically significant.
• Metabolism: Hepatic via CYP2C19 and CYP3A4.
• Half-Life: ~1.5 hours; acid suppression lasts up to 24 hours.
• Excretion: Mainly feces and urine as inactive metabolites.

Amoxicillin:

• Absorption: Rapid and nearly complete; unaffected by food.
• Bioavailability: >90%.
• Metabolism: Minimal.
• Half-Life: 1–1.5 hours.
• Excretion: Primarily via renal route (unchanged).

Clarithromycin:

• Absorption: Rapid; enhanced with food.
• Bioavailability: ~55%.
• Metabolism: Liver via CYP3A4; active metabolite (14-hydroxy clarithromycin).
• Half-Life: 3–7 hours (parent); 5–9 hours (metabolite).
• Excretion: 40% via urine, 40% via feces.

Pregnancy:

• Lansoprazole: Category B – No evidence of fetal harm in animal studies; limited human data.
• Amoxicillin: Category B – Widely used in pregnancy with no known teratogenic effects.
• Clarithromycin: Category C – Animal studies show potential fetal risk; use only if benefits outweigh risks.

Lactation:

• Amoxicillin: Present in breast milk; generally considered safe.
• Clarithromycin: Excreted in breast milk; caution advised due to potential infant exposure.
• Lansoprazole: Human data limited; use with caution during breastfeeding.

Overall: Avoid use during pregnancy or lactation unless clearly indicated.

• Primary Class: Anti-H. pylori Combination Therapy
• Subclasses:
• Lansoprazole: Proton Pump Inhibitor (PPI)
• Amoxicillin: Penicillin-Class Beta-Lactam Antibiotic
• Clarithromycin: Macrolide Antibiotic

• Hypersensitivity to lansoprazole, amoxicillin, clarithromycin, other beta-lactams, or macrolides.
• History of cholestatic jaundice or hepatic dysfunction with clarithromycin.
• Concomitant use with drugs that prolong QT interval (e.g., cisapride, pimozide, ergot alkaloids).
• Severe hepatic impairment (especially with clarithromycin).
• Known infectious mononucleosis (due to rash with amoxicillin).

• QT Prolongation and Arrhythmias: Clarithromycin may prolong QT interval; avoid in patients with cardiac history.
• Clostridioides difficile–associated diarrhea: Risk with amoxicillin or clarithromycin.
• Hepatotoxicity: Especially with clarithromycin; monitor liver enzymes.
• Allergic Reactions: Serious reactions including anaphylaxis with beta-lactams or macrolides.
• Renal Impairment: Clarithromycin and amoxicillin require dosage adjustments in severe renal dysfunction.
• Superinfection Risk: Including fungal or resistant bacterial overgrowth.
• Drug Interactions: Clarithromycin is a strong CYP3A4 inhibitor.

Common (≥1%):

• Gastrointestinal: Nausea, diarrhea, abdominal pain, vomiting, taste disturbance
• Neurologic: Headache, dizziness
• Skin: Rash, pruritus

Serious or Rare:

• Anaphylaxis
• Stevens-Johnson syndrome, toxic epidermal necrolysis
• Hepatotoxicity (elevated liver enzymes, hepatitis)
• QT prolongation, torsades de pointes
• Pseudomembranous colitis
• Acute interstitial nephritis
• Blood dyscrasias (rare)

• Clarithromycin: Potent CYP3A4 inhibitor – increases serum levels of warfarin, digoxin, statins, benzodiazepines, calcium channel blockers.
• Amoxicillin: May reduce efficacy of oral contraceptives; avoid concurrent use with bacteriostatic antibiotics (e.g., tetracycline).
• Lansoprazole: Decreases absorption of pH-dependent drugs (e.g., ketoconazole, atazanavir).
• Methotrexate: Risk of increased toxicity when used with PPIs.
• Warfarin: Potentiation of anticoagulant effect; monitor INR closely.

• Maastricht VI/ACG H. pylori Guidelines: Recommend triple therapy in areas with low clarithromycin resistance. In regions with high resistance, consider bismuth-based quadruple therapy.
• Preferred Treatment Duration: 14-day regimens now recommended over shorter courses for better eradication rates.
• Post-Treatment Testing: Confirm eradication 4 weeks after therapy using urea breath test or stool antigen test.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F to 86°F).
• Humidity & Light: Store in a dry place, protected from moisture and direct light.
• Handling:
• Keep in original packaging until use.
• Do not refrigerate or freeze.
• Orally disintegrating tablets (if used) should be used immediately after opening.