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). |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
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 |
| Breastfeeding | Lansoprazole: excreted into breast milk in low amounts, M/P ratio unknown, considered compatible; amoxicillin: excreted into breast milk in low amounts, M/P ratio ~0.02, compatible; clarithromycin: excreted into breast milk, M/P ratio not well defined, caution due to potential GI effects in infant. Weigh benefits vs risks. |
| Teratogenic Risk |
■ FDA Black Box Warning
None
| Common Effects | Nausea Headache Flatulence Diarrhea |
| Serious Effects |
Known hypersensitivity to any component (lansoprazole, amoxicillin, clarithromycin, or other macrolides); history of cholestatic jaundice or hepatic dysfunction with clarithromycin; concomitant use with pimozide, ergot alkaloids (ergotamine, dihydroergotamine), ticagrelor, ranolazine, lovastatin, simvastatin, or colchicine (clarithromycin); patients with severe renal impairment (CrCl <30 mL/min) for the triple therapy regimen (dose adjustment needed for clarithromycin); elderly patients with moderate to severe renal impairment; caution with concomitant use of warfarin and other anticoagulants; history of allergic reaction to penicillins or cephalosporins (amoxicillin); caution in patients with phenylketonuria (product may contain phenylalanine).
| 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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| 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. |