LANSOPRAZOLE, AMOXICILLIN AND CLARITHROMYCIN (COPACKAGED)
Clinical safety rating: safe
Can reduce absorption of drugs requiring gastric pH for absorption (eg ketoconazole) May increase risk of Clostridium difficile-associated diarrhea and bone fractures with long-term use.
Lansoprazole is a proton pump inhibitor that irreversibly inhibits the H+/K+ ATPase enzyme system (proton pump) at the secretory surface of gastric parietal cells, suppressing basal and stimulated gastric acid secretion. Amoxicillin is a beta-lactam antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), leading to cell lysis. Clarithromycin is a macrolide antibiotic that binds to the 50S ribosomal subunit of susceptible bacteria, inhibiting protein synthesis.
| Metabolism | Lansoprazole is extensively metabolized in the liver primarily by CYP2C19 and CYP3A4 to hydroxylated and sulfone metabolites. Amoxicillin is partially metabolized to penicilloic acid, mainly renally excreted. Clarithromycin is metabolized by CYP3A4 to 14-hydroxyclarithromycin (active) and other metabolites. |
| Excretion | Lansoprazole: primarily hepatic metabolism, ~33% renal (metabolites), ~67% fecal; Amoxicillin: ~60-80% renal unchanged; Clarithromycin: ~20-30% renal unchanged, ~50% hepatic metabolism, ~30% fecal. |
| Half-life | Lansoprazole: ~1.5 h (prolonged in hepatic impairment); Amoxicillin: ~1-1.5 h (prolonged in renal impairment); Clarithromycin: ~3-4 h (6-9 h for 14-hydroxy metabolite). |
| Protein binding | Lansoprazole: ~97% (mainly albumin); Amoxicillin: ~17% (albumin); Clarithromycin: ~70% (mainly albumin). |
| Volume of Distribution | Lansoprazole: ~0.4 L/kg; Amoxicillin: ~0.3 L/kg; Clarithromycin: ~3-5 L/kg (extensive tissue penetration). |
| Bioavailability | Lansoprazole: oral ~80-91% (fasted), reduced with food; Amoxicillin: oral ~60-80%; Clarithromycin: oral ~50% (immediate-release), increased to ~80% with food. |
| Onset of Action | Lansoprazole: peak acid suppression ~2-4 h; Amoxicillin: bactericidal effect within 1-2 h; Clarithromycin: bacteriostatic effect begins within 2-4 h. |
| Duration of Action | Lansoprazole: acid suppression ~24 h (once daily dosing); Amoxicillin: serum levels above MIC for ~6-8 h; Clarithromycin: levels above MIC for ~12 h (with active metabolite). |
| Molecular Weight | Lansoprazole: 369.36 Da; Amoxicillin: 365.40 Da; Clarithromycin: 747.96 Da |
Each dose: Lansoprazole 30 mg, Amoxicillin 1000 mg, Clarithromycin 500 mg administered orally twice daily for 10-14 days.
| Dosage form | CAPSULE, TABLET, CAPSULE, DELAYED REL PELLETS |
| Renal impairment | CrCl 30-90 mL/min: No adjustment. CrCl 10-29 mL/min: Reduce clarithromycin to 250 mg twice daily; lansoprazole and amoxicillin no adjustment. CrCl <10 mL/min: Not recommended. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B or C: Avoid clarithromycin; consider alternative therapy. |
| Pediatric use | Not recommended for children; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; monitor renal function and potential for increased adverse effects. |
| 1st trimester | Amoxicillin and clarithromycin are generally considered safe in the first trimester, but lansoprazole has limited safety data; avoid unless necessary. |
| 2nd trimester | Amoxicillin and clarithromycin are generally safe; lansoprazole has limited data but is often used if indicated. |
| 3rd trimester | Amoxicillin and clarithromycin are safe; lansoprazole has limited data but is considered low risk. |
Clinical note
Can reduce absorption of drugs requiring gastric pH for absorption (eg ketoconazole) May increase risk of Clostridium difficile-associated diarrhea and bone fractures with long-term use.
| FDA category | Animal |
| Placental transfer | All three drugs cross the placenta: amoxicillin (moderate), clarithromycin (moderate), lansoprazole (limited data, likely minimal). |
■ FDA Black Box Warning
None
| Common Effects | Nausea Headache Flatulence Diarrhea |
| Serious Effects |
Hypersensitivity to any of the componentsConcomitant use with cisapride, pimozide, or ergot alkaloids (clarithromycin interaction)History of cholestatic jaundice or hepatic dysfunction with clarithromycinConcomitant use with ticagrelor or ranolazine (clarithromycin interaction)
| Precautions | Clostridium difficile associated diarrhea (CDAD); hypersensitivity reactions (anaphylaxis, Stevens-Johnson syndrome); severe cutaneous adverse reactions (SCAR); hepatic dysfunction; renal impairment; exacerbation of myasthenia gravis; QT prolongation (clarithromycin); interactions with warfarin, methotrexate, digoxin, benzodiazepines, statins; increased risk of fundic gland polyps with long-term PPI use; bone fracture risk with high-dose/long-term PPI; cyanocobalamin (Vitamin B12) deficiency with long-term PPI; acute interstitial nephritis; severe hypoglycemia with concomitant use of repaglinide or insulin secretagogues; hyponatremia; potential for magnesium depletion; increased INR with warfarin. |
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| Breastfeeding |
| Lansoprazole and amoxicillin are excreted in breast milk in low amounts; clarithromycin is excreted in significant amounts. Consider risk-benefit; monitor infant for gastrointestinal effects. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Lansoprazole: no increased risk of major malformations based on large cohort studies; amoxicillin: generally considered low risk, no consistent association with major defects; clarithromycin: epidemiological studies suggest a small increased risk of spontaneous abortion and major congenital malformations, particularly cardiac defects, when used in early pregnancy. Avoid in first trimester. All three cross the placenta. |
| Fetal Monitoring | Monitor maternal hepatic and renal function, complete blood count, and signs of Clostridioides difficile infection. Fetal monitoring as per routine prenatal care; consider fetal echocardiography if clarithromycin used in first trimester. |
| Fertility Effects | No known adverse effects on fertility for any of the three drugs; clarithromycin and amoxicillin may cause transient GI disturbances but no direct impact on reproductive function. |
| Food/Dietary | Take lansoprazole at least 30 minutes before food. Avoid alcohol. Clarithromycin may interact with certain foods; no specific restrictions but maintain consistent intake. No grapefruit interaction known for this combination. |
| Clinical Pearls | Use this triple therapy for H. pylori eradication. Amoxicillin dose adjustment needed in renal impairment (CrCl <30 mL/min). Clarithromycin may cause QT prolongation; avoid with other QT-prolonging drugs. Lansoprazole should be taken 30-60 minutes before meals. Warn patients about metallic taste from clarithromycin. |
| Patient Advice | Take all three medications exactly as prescribed, usually twice daily for 14 days. · Take lansoprazole on an empty stomach at least 30 minutes before a meal. · Amoxicillin and clarithromycin can be taken with or without food, but taking with food reduces stomach upset. · Complete the full course even if symptoms improve; skipping doses can cause treatment failure. · Common side effects include diarrhea, metallic taste, nausea, and headache. · Avoid alcohol while taking clarithromycin and amoxicillin. · Contact your healthcare provider if you experience severe diarrhea, rash, or jaundice. · Do not take this combination if you are allergic to any of the components. · Inform your doctor of all medications you take, especially blood thinners, seizure medications, and antacids. · Store at room temperature away from moisture and heat. |