AUGMENTIN '200'
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AUGMENTIN '200' (AUGMENTIN '200').
Amoxicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), while clavulanate irreversibly inhibits beta-lactamases, preventing degradation of amoxicillin.
| Metabolism | Amoxicillin is partially metabolized by hydrolysis and excreted renally unchanged; clavulanate is extensively metabolized and excreted renally and fecally. |
| Excretion | Amoxicillin: ~50-70% excreted unchanged in urine via glomerular filtration and tubular secretion, with the remainder hepatically metabolized and excreted in bile and feces. Clavulanate: ~30-50% excreted unchanged in urine, the rest metabolized and eliminated in bile and feces. |
| Half-life | Amoxicillin: ~1 hour in healthy adults, prolonged to 7-20 hours in renal impairment (CrCl <10 mL/min). Clavulanate: ~1 hour, similarly prolonged in renal impairment. The combination's half-life supports twice-daily dosing for most infections. |
| Protein binding | Amoxicillin: ~17-20% bound to serum proteins, primarily albumin. Clavulanate: ~25% bound to albumin. |
| Volume of Distribution | Amoxicillin: ~0.3-0.4 L/kg, indicating distribution into extracellular fluid and tissues. Clavulanate: ~0.3 L/kg. Both distribute well into middle ear, sinuses, respiratory secretions, and urine. |
| Bioavailability | Oral: Amoxicillin 75-90%, clavulanate ~60-75%. Absorption is not significantly affected by food, though clavulanate may be better tolerated with food. |
| Onset of Action | Oral: Clinical improvement typically within 24-48 hours for susceptible infections (e.g., acute otitis media, sinusitis). IV: Onset within minutes to hours for systemic infections. |
| Duration of Action | Dosing interval every 12 hours provides therapeutic levels throughout the interval. Bactericidal effect persists for most of the dosing period. For extended-release formulations, duration may be longer. |
| Molecular Weight | Amoxicillin: 365.4 Da; Clavulanate: 199.16 Da |
One 200 mg amoxicillin/28.5 mg clavulanate chewable tablet every 8 hours for mild to moderate infections; for severe infections, one 400 mg/57 mg tablet every 12 hours or one 200 mg/28.5 mg tablet every 8 hours.
| Dosage form | FOR SUSPENSION |
| Renal impairment | For GFR 10-30 mL/min: administer every 12 hours. For GFR <10 mL/min: administer every 24 hours. For hemodialysis: 200 mg/28.5 mg every 24 hours, plus a supplemental dose during dialysis. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50% or extend interval. Child-Pugh C: contraindicated due to risk of hepatotoxicity. |
| Pediatric use | For children 9 months to 40 kg: 20-40 mg/kg/day of amoxicillin component in divided doses every 8 hours, based on severity. For children >40 kg: use adult dosing. |
| Geriatric use | Assess renal function; use lower initial dose (e.g., 200 mg/28.5 mg every 8-12 hours) due to age-related decline in GFR. Adjust interval per renal function. |
| 1st trimester | Use caution; limited human data suggest low risk, but avoid routine use unless clearly needed. |
| 2nd trimester | Generally considered safe; no known teratogenic effects in second trimester. |
| 3rd trimester | Use with caution near term due to potential risk of kernicterus in neonates from amoxicillin component, though rare. |
Clinical note
Comprehensive clinical and safety monograph for AUGMENTIN '200' (AUGMENTIN '200').
| Placental transfer | Both amoxicillin and clavulanate cross the placenta; therapeutic levels achieved in fetal circulation. |
| Breastfeeding | Excreted into breast milk in low concentrations; considered compatible with breastfeeding. Monitor infant for potential diarrhea, rash, or candidiasis. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to amoxicillin, clavulanate, or any penicillinHistory of cholestatic jaundice or hepatic impairment associated with amoxicillin/clavulanate
| Precautions | Hypersensitivity reactions including anaphylaxis, Severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome, Hepatic dysfunction and cholestatic jaundice (more common in elderly and with prolonged use), Pseudomembranous colitis due to Clostridioides difficile, In patients with renal impairment, adjust dose based on creatinine clearance, Potential for superinfection with prolonged therapy |
| Food/Dietary | Take with food or milk to minimize GI upset and enhance absorption. No specific dietary restrictions; avoid excessive alcohol as it may increase risk of hepatotoxicity. |
Loading safety data…
| L1 (Safe) |
| Teratogenic Risk | FDA Pregnancy Category B. Animal studies do not indicate fetal harm. No adequate human studies in first trimester; use only if clearly needed. In second and third trimesters, no known teratogenic risk; however, premature infants and high-dose regimens may increase risk of kernicterus due to bilirubin displacement. |
| Fetal Monitoring | Monitor maternal renal function, hepatic function, and complete blood count (CBC) with differential during prolonged therapy. Fetal monitoring: standard prenatal care; no specific fetal monitoring required. In neonates, observe for jaundice if maternal high-dose therapy near term. |
| Fertility Effects | No known adverse effects on fertility in animal studies. No human data on fertility impairment. Antibiotic effects on gut flora do not impact reproductive function. |
| Clinical Pearls | AUGMENTIN '200' (amoxicillin/clavulanate 200mg/28.5mg per 5mL) is dosed based on amoxicillin component; use 45mg/kg/day divided q12h for pediatric infections. Clavulanate potassium content is 28.5mg per 5mL; note potential for diarrhea (especially high-dose). Check renal function: adjust dosing interval if CrCl <30mL/min. Not interchangeable with other Augmentin suspensions due to differing clavulanate ratios. |
| Patient Advice | Take exactly as prescribed; complete full course even if feeling better. · Shake suspension well before each use; measure with provided dosing device. · Take with food to reduce stomach upset and improve absorption. · Report any rash, severe diarrhea, or signs of allergic reaction immediately. · Store suspension in refrigerator; discard unused portion after 10 days. · May cause diarrhea; contact doctor if watery or bloody stools occur. · Do not share this medication with others. |