Drug Interactions
Specific Drugs and Laboratory Tests
| Drug |
Interaction |
Comments |
| Allopurinol |
Possible increased incidence of rash; reported with ampicillin but no data regarding amoxicillin |
Unclear whether potentiation of rash is caused by allopurinol or hyperuricemia present in these patients |
| Chloramphenicol |
In vitro evidence of antagonism |
Clinical importance unclear |
| Clavulanic acid |
In vitro and in vivo synergistic bactericidal effect |
Used to therapeutic advantage in infections caused by β-lactamase-producing bacteria; commercially available in fixed combination with clavulanate potassium |
| Macrolides |
In vitro evidence of antagonism |
Clinical importance unclear |
| Methotrexate |
Possible decreased renal clearance of methotrexate; possible increased methotrexate concentrations and hematologic and GI toxicity |
Monitor closely if used concomitantly |
| Probenecid |
Decreased renal tubular secretion of amoxicillin; increased and prolonged amoxicillin concentrations may occur |
|
| Sulfonamides |
In vitro evidence of antagonism |
Clinical importance unclear |
| Tests for glucose |
Possible false-positive reactions in urine glucose tests using Clinitest®, Benedict’s solution, or Fehling’s solution; reported with ampicillin but no data regarding amoxicillin |
Use glucose tests based on enzymatic glucose oxidase reactions (e.g., Clinistix®, Tes-Tape®) |
| Tetracyclines |
In vitro evidence of antagonism |
Clinical importance unclear |
Pharmacokinetics
Absorption
Bioavailability
74–92% of an oral dose absorbed from GI tract.
Peak serum concentrations usually attained within 1–2 hours.
A 400-mg chewable tablet is bioequivalent to 5 mL of the oral suspension containing 400 mg/5 mL.
Food
Food has minimal or no effect on bioavailability of oral amoxicillin.
Special Populations
Oral absorption delayed in neonates compared with older children and adults; peak concentrations attained within 3–4.5 hours in neonates.
Distribution
Extent
Readily distributed into most tissues and fluids following oral administration, including lungs, bronchial secretions, maxillary sinus secretions, bile, pleural fluid, sputum, and middle ear fluid.
Only low concentrations attained in CSF.
Crosses the placenta and is distributed into human milk.
Plasma Protein Binding
17–20%.
Elimination
Metabolism
Probably metabolized to some extent in the liver.
Elimination Route
Eliminated principally in urine by both glomerular filtration and tubular secretion.
Approximately 50–80% of amoxicillin dose excreted unchanged in urine.
Half-life
1–1.4 hours.
Special Populations
Serum concentrations increased and half-life prolonged in patients with renal impairment.
Renal clearance may be delayed in neonates and young infants because of incompletely developed renal function.
Stability
Storage
Oral
Capsules
≤20°C.
For Suspension
250 mg/5 mL: ≤20°C. Following reconstitution, refrigerate (preferable but not required) and discard after 14 days.
200 or 400 mg/5 mL: ≤25°C. Following reconstitution, refrigerate (preferable but not required) and discard after 14 days.
Tablets
200- and 400-mg chewable tablets and 500- or 875-mg film-coated tablets: ≤25°C.
Actions
- A β-lactam antibacterial classified as an aminopenicillin. The p-hydroxyl analog of ampicillin.
- Usually bactericidal.
- Gram-positive aerobes: Active in vitro and in clinical infections against Staphylococcus (β-lactamase-negative strains only), Streptococcus pneumoniae, other Streptococcus (α- and β-hemolytic strains only), and Enterococcus faecalis.
- Gram-negative aerobes: Active in vitro and in clinical infections against H. influenzae, N. gonorrhoeae, E. coli, Corynebacterium diphtheriae, Listeria monocytogenes, Proteus mirabilis, Salmonella, and Shigella.
- Other organisms: Active in vitro and in clinical infections caused by H. pylori. Also active against Borrelia burgdorferi.
- Generally has same spectrum and level of activity as ampicillin, but more active than ampicillin against enterococci and Salmonella and less active against Shigella and Enterobacter.
- Resistance reported in gram-positive and gram-negative bacteria that produce β-lactamases, including β-lactamase-producing S. aureus and E. faecalis.
- Complete cross-resistance generally occurs between amoxicillin and ampicillin.
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