What medications interact with Augmentin (amoxicillin and clavulanic acid)?

Medication Interactions with Augmentin (Amoxicillin-Clavulanic Acid)

Augmentin has several important drug interactions that can affect medication efficacy and patient safety, with the most significant interactions occurring with probenecid, oral contraceptives, and medications that are substrates for P-glycoprotein. 1

Major Drug Interactions

P-glycoprotein Substrate Interactions

• Dabigatran: Augmentin contains clavulanic acid which may interact with dabigatran etexilate (a P-glycoprotein substrate). This interaction can potentially increase dabigatran exposure, increasing bleeding risk 2

Anticoagulants

• Warfarin: Clavulanic acid can interact with warfarin, potentially affecting anticoagulation control 2
• Phenytoin: May have reduced absorption when co-administered with bile acid sequestrants like cholestyramine 2

Antibiotics

• Tetracyclines: Reduced efficacy of both medications when co-administered 1
• Penicillin G: Potential interaction reducing effectiveness 1

Other Important Interactions

• Probenecid: Decreases renal tubular secretion of amoxicillin, resulting in increased and prolonged blood levels of amoxicillin. Co-administration is not recommended 1
• Allopurinol: Concurrent use with amoxicillin substantially increases the incidence of rashes 1
• Oral contraceptives: Augmentin may reduce the efficacy of oral contraceptives, potentially leading to contraceptive failure 1
• Digoxin: May have altered absorption when taken with Augmentin 1

Laboratory Test Interactions

• Glucose tests: High urine concentrations of amoxicillin may result in false-positive reactions when testing for glucose in urine using CLINITEST, Benedict's Solution, or Fehling's Solution. Glucose tests based on enzymatic glucose oxidase reactions (such as CLINISTIX) are recommended instead 1
• Estrogen tests: Following administration, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol may be noted 1

Special Considerations for Specific Patient Populations

Tuberculosis Treatment

• When using carbapenems for multidrug-resistant tuberculosis, Augmentin must be given to achieve a dose of 125mg clavulanate with each carbapenem dose 2, 3
• Clavulanic acid is only available as a co-formulation with amoxicillin 3

Timing of Administration

• For medications known to interact with Augmentin, separate administration times:
  • Take interacting drugs at least 1 hour before or 4-6 hours after Augmentin 2
  • Studies suggest a window of 3 hours between administration is adequate to avoid potential binding interactions 2

Monitoring Recommendations

• Renal function: Periodic assessment of renal function is advisable during prolonged therapy 1
• Hepatic function: Monitor liver enzymes, especially with prolonged use 1
• Hematopoietic function: Periodic assessment during prolonged therapy 1
• Superinfections: Monitor for signs of superinfections with mycotic or bacterial pathogens (usually involving Pseudomonas or Candida) 1

Common Pitfalls and Caveats

• Mononucleosis: Patients with mononucleosis have a high risk of developing an erythematous skin rash when given ampicillin-class antibiotics, including Augmentin 1
• Diarrhea: Gastrointestinal side effects can become problematic when the clavulanate dose exceeds approximately 10 mg/kg per day 3
• C. difficile: Monitor for Clostridioides difficile-associated diarrhea, which can occur up to two months after antibiotic treatment 1
• Resistance development: Complete the full prescribed course of Augmentin even if symptoms improve earlier, to prevent treatment failure and potential development of resistance 3

By understanding these interactions and implementing appropriate monitoring strategies, clinicians can maximize the therapeutic benefits of Augmentin while minimizing potential adverse effects from drug interactions.