OMECLAMOX-PAK
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OMECLAMOX-PAK (OMECLAMOX-PAK).
Omeprazole 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. Clarithromycin is a macrolide antibiotic that binds to the 50S ribosomal subunit of susceptible bacteria, inhibiting protein synthesis. Amoxicillin is a semisynthetic penicillin that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs).
| Metabolism | Omeprazole: extensively metabolized in the liver primarily by CYP2C19 and CYP3A4. Clarithromycin: metabolized in the liver primarily by CYP3A4. Amoxicillin: partially metabolized by hydrolysis to penicilloic acid. |
| Excretion | Amoxicillin: 60-70% renal (glomerular filtration and tubular secretion), remainder fecal via bile; Omeprazole: ~80% renal (metabolites), ~20% fecal; Clarithromycin: 20-30% renal (unchanged), ~40% fecal (metabolites). |
| Half-life | Amoxicillin: 1-1.5 h (prolonged in renal impairment); Omeprazole: 0.5-1 h (single dose), 1-1.5 h (repeated dosing); Clarithromycin: 3-4 h (single dose), 5-7 h (steady-state). |
| Protein binding | Amoxicillin: 17-20% (albumin); Omeprazole: 95-97% (albumin and alpha1-acid glycoprotein); Clarithromycin: 70-75% (albumin). |
| Volume of Distribution | Amoxicillin: 0.3-0.5 L/kg; Omeprazole: 0.3-0.4 L/kg; Clarithromycin: 200-300 L (not L/kg, approx 3-4 L/kg in 70 kg adult; actual Vd ~3-4 L/kg). |
| Bioavailability | Amoxicillin: 74-92% oral (fasting); Omeprazole: 30-40% oral (first-pass metabolism); Clarithromycin: 50-55% oral (food delays absorption, no significant effect on extent). |
| Onset of Action | Oral: Amoxicillin 1-2 h; Omeprazole 1-3 h (max effect at 2-6 h); Clarithromycin 1-2 h. |
| Duration of Action | Amoxicillin: 6-8 h (in utero); Omeprazole: 24 h (acid suppression); Clarithromycin: 8-12 h. |
OMECLAMOX-PAK (omeprazole 20 mg + clarithromycin 500 mg + amoxicillin 500 mg) combination pack: one tablet of omeprazole 20 mg and one tablet of clarithromycin 500 mg and one capsule of amoxicillin 500 mg orally twice daily for 10 days.
| Dosage form | CAPSULE, TABLET, CAPSULE, DELAYED RELEASE |
| Renal impairment | For CrCl 30-89 mL/min: no dose adjustment. For CrCl <30 mL/min: use with caution; not recommended. For hemodialysis: not recommended. |
| Liver impairment | Child-Pugh Class A and B: no adjustment. Child-Pugh Class C: avoid use (clarithromycin contraindicated in severe hepatic failure). |
| Pediatric use | Not approved for use in pediatric patients (safety and efficacy not established). |
| Geriatric use | No specific dose adjustment; use with monitoring for renal function and potential increased risk of adverse effects (e.g., QT prolongation, Clostridium difficile infection). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for OMECLAMOX-PAK (OMECLAMOX-PAK).
| Breastfeeding | Amoxicillin and clarithromycin are excreted into breast milk in small amounts (amoxicillin M/P ratio ~0.01–0.05; clarithromycin M/P ratio ~0.25–1.0). Omeprazole is poorly excreted (M/P ratio <0.01). Theoretical risks include infant sensitization, diarrhea, alteration of gut flora, and potential for antibiotic resistance. Safety data are limited; weigh benefits against risks. Use alternative therapy if possible. Monitor infant for gastrointestinal disturbances. |
| Teratogenic Risk | OMECLAMOX-PAK (amoxicillin, clarithromycin, omeprazole) assigns amoxicillin to FDA pregnancy category B and clarithromycin to category C, with omeprazole having conflicting data. First trimester: Clarithromycin is associated with a small increased risk of spontaneous abortion and cardiovascular malformations; omeprazole has mixed evidence for a possible increase in major malformations, though recent studies suggest no major teratogenic risk. Second and third trimester: Amoxicillin is considered safe; clarithromycin and omeprazole should be avoided unless essential, as data on fetal effects are limited. Overall, the combination is contraindicated in pregnancy unless no safer alternative exists. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to omeprazole, clarithromycin, amoxicillin, or any component of the formulation.","History of hypersensitivity reactions to penicillins, cephalosporins, or other beta-lactam antibiotics.","Concurrent use with ticagrelor (clarithromycin increases ticagrelor exposure).","Concurrent use with colchicine (clarithromycin increases colchicine exposure, especially in renal or hepatic impairment).","Concurrent use with ergotamine or dihydroergotamine (clarithromycin may cause acute ergot toxicity).","Concurrent use with HMG-CoA reductase inhibitors (statins) metabolized by CYP3A4 (e.g., lovastatin, simvastatin) due to increased risk of myopathy/rhabdomyolysis.","Concurrent use with pimozide (clarithromycin increases pimozide levels, risk of QT prolongation and arrhythmias).","Patients with known QT prolongation or history of Torsades de Pointes.","Patients with severe renal impairment (CrCl <30 mL/min) for clarithromycin-containing regimens.","Hepatic impairment (severe) for clarithromycin.","Use in pregnant women unless clearly needed (pregnancy category C for clarithromycin)."]
| Precautions | ["Clarithromycin: increased risk of cardiac arrhythmias (QT prolongation, ventricular tachycardia, torsades de pointes) in patients with existing QT prolongation, electrolyte disturbances, or concurrent use with other QT-prolonging drugs.","Clarithromycin: hepatotoxicity, including hepatic failure and jaundice.","Clarithromycin: exacerbation of myasthenia gravis.","Omeprazole: long-term use associated with increased risk of Clostridium difficile-associated diarrhea, osteoporosis-related fractures, vitamin B12 deficiency, and hypomagnesemia.","Amoxicillin: serious hypersensitivity reactions (anaphylaxis, serum sickness) and severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis).","Amoxicillin: development of drug-resistant bacteria.","Antibiotic-associated pseudomembranous colitis due to Clostridium difficile."] |
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| Fetal Monitoring | Monitor maternal liver function tests (LFTs) and renal function periodically due to omeprazole and clarithromycin metabolism. Assess for Clostridioides difficile infection if diarrhea develops. For fetus: Ultrasound to assess for cardiovascular malformations if clarithromycin exposure in first trimester. No specific fetal monitoring required for amoxicillin or omeprazole, but growth and development should be followed clinically. |
| Fertility Effects | No specific effects on fertility reported for this combination. Clarithromycin and amoxicillin may transiently alter vaginal flora, but no evidence of impaired fertility. Omeprazole has no known effects on fertility. |