Augmentin®

Amoxicillin / Clavulanate · oral tablet

Antibiotic

Approved uses

Infections due to beta-lactamase producing isolates: lower respiratory tract, acute bacterial otitis media, sinusitis, skin and skin structure, urinary tract

Adults and patients over 40 kg: 500 mg/125 mg every 12 hours or 250 mg/125 mg every 8 hours, or 875 mg/125 mg every 12 hours or 500 mg/125 mg every 8 hours for more severe and respiratory infection. Pediatric patients 12 weeks and older, on the amoxicillin component: 45 mg/kg/day divided every 12 hours or 40 mg/kg/day divided every 8 hours, or 25 mg/kg/day divided every 12 hours or 20 mg/kg/day divided every 8 hours for less severe infection.

OFF-LABELNot in the FDA label for this product

Acute dacryocystitis

Label regimen for more severe infection: adults and patients over 40 kg 875 mg/125 mg every 12 hours or 500 mg/125 mg every 8 hours; pediatric patients 12 weeks and older 45 mg/kg/day of the amoxicillin component divided every 12 hours.

Retrospective · in vitro only

Single-center retrospective chart review of 137 patients with acute or chronic dacryocystitis, 205 samples and 156 isolates: S. aureus was the most common at 46 of 156 (30%), then Pseudomonas species 19 of 156 (12%) and Propionibacterium acnes 15 of 156 (10%). On in vitro susceptibility the two most effective oral antibiotics in this population were levofloxacin and amoxicillin/clavulanate, but the latter would still have met at least one resistant organism in 32% of patients and potentially another 8% (levofloxacin 16% and 15%). The authors conclude that routine treatment with any single antibiotic may fail in up to a third of patients and recommend culturing at the time empiric therapy is started. Susceptibility data only, no clinical outcome and no dosing data.

Chung SY, Rafailov L, Turbin RE, Langer PD. The microbiologic profile of dacryocystitis. Orbit. 2018;38(1):72-78 (retrospective chart review). PMID 29750587. Dose: FDA label, Dosage and Administration (2.1, 2.2).

Preseptal (periorbital) cellulitis

Label regimen for more severe infection: adults and patients over 40 kg 875 mg/125 mg every 12 hours or 500 mg/125 mg every 8 hours; pediatric patients 12 weeks and older 45 mg/kg/day of the amoxicillin component divided every 12 hours.

Narrative review · no trials

A narrative review of pediatric preseptal and orbital cellulitis lists amoxicillin-clavulanate among the antibacterials often used, notes significant variation in agent selection, supports transition from IV to oral therapy once clinical and laboratory improvement is clear, and reports total durations trending toward about 2 weeks. That is expert review, not comparative trial evidence. The nearest treatment data are postseptal, not preseptal: in a retrospective series of 48 children with subperiosteal orbital abscess complicating acute ethmoiditis, oral amoxicillin-clavulanate was the step-down for about 8.5 days after a mean of four days of IV third-generation cephalosporin plus metronidazole, given to 94% of the children, and all were cured without sequelae. The practical argument for this product over plain amoxicillin is spectrum, since the label lists S. aureus, H. influenzae and M. catarrhalis among covered organisms.

Stimes GT, Girotto JE. Applying Pharmacodynamics and Antimicrobial Stewardship to Pediatric Preseptal and Orbital Cellulitis. Paediatr Drugs. 2019;21(6):427-438 (review). PMID 31608423. Coudert A, Ayari-Khalfallah S, Suy P, Truy E. Microbiology and antibiotic therapy of subperiosteal orbital abscess in children with acute ethmoiditis. Int J Pediatr Otorhinolaryngol. 2018;106:91-95 (retrospective series). PMID 29447900. Dose and spectrum: FDA label, Dosage and Administration (2.1, 2.2) and Clinical Pharmacology 12.4.

Contraindications

History of a serious hypersensitivity reaction such as anaphylaxis or Stevens-Johnson syndrome to amoxicillin, clavulanate, or other beta-lactams including penicillins and cephalosporins.
Previous cholestatic jaundice or hepatic dysfunction associated with this combination.

Available Forms

Tablets 250 mg/125 mg, 500 mg/125 mg and 875 mg/125 mg; chewable tablets 125 mg/31.25 mg, 250 mg/62.5 mg, 200 mg/28.5 mg and 400 mg/57 mg; powder for oral suspension 125 mg/31.25 mg and 250 mg/62.5 mg per 5 mL in 75, 100 and 150 mL bottles, 200 mg/28.5 mg and 400 mg/57 mg per 5 mL in 50, 75 and 100 mL bottles

Mechanism of Action

Aminopenicillin paired with a beta-lactamase inhibitor. Clavulanic acid inactivates many beta-lactamases, including the plasmid-mediated enzymes behind transferred resistance, protecting amoxicillin from degradation and extending its spectrum to S. aureus, H. influenzae, M. catarrhalis, Klebsiella, Enterobacter and E. coli.

Warnings & Precautions

Hypersensitivity reactions: Serious and occasionally fatal anaphylactic reactions have been reported with beta-lactam antibacterials; risk is higher with a history of penicillin hypersensitivity or sensitivity to multiple allergens, and therapy should be stopped and treated if a reaction occurs.
Hepatic dysfunction: Hepatitis and cholestatic jaundice have been associated with use; toxicity is usually reversible but deaths have been reported, and hepatic function should be monitored at regular intervals in patients with hepatic impairment.
Clostridium difficile associated diarrhea: Ranges from mild diarrhea to fatal colitis, may be refractory and require colectomy, and has been reported over 2 months after antibacterial administration.
Skin rash in mononucleosis: A high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous rash; do not administer in mononucleosis.
Microbial overgrowth: Superinfection with fungal or bacterial pathogens should be considered during therapy; if it occurs, stop treatment and institute appropriate therapy.
Phenylketonuria: Chewable tablets and oral suspension contain aspartame, 2.1 mg phenylalanine per 200 mg chewable tablet, 4.2 mg per 400 mg chewable tablet, and 7 mg per 5 mL of the 200 mg/5 mL or 400 mg/5 mL suspension; the other formulations contain no phenylalanine.
Tablet substitution error: Two 250 mg tablets are not equivalent to one 500 mg tablet because both strengths contain 125 mg clavulanic acid; the 250 mg tablet and the 250 mg chewable tablet are not interchangeable (125 mg versus 62.5 mg clavulanic acid); the 250 mg tablet should not be used until the child weighs at least 40 kg.
Allopurinol interaction: Concurrent administration increases the incidence of rashes in patients receiving both drugs.
Oral anticoagulant interaction: Abnormal prolongation of prothrombin time with increased INR has been reported; monitor and adjust anticoagulant dosing.

Common Side Effects

Systemic, clinical trials: Diarrhea or loose stools 9%, nausea 3%, skin rash and urticaria 3%, vomiting 1%, vaginitis 1%; overall incidence, and diarrhea in particular, rises with the higher recommended dose, and fewer than 3% of patients discontinued for a drug-related reaction.
Systemic, under 1%: Abdominal discomfort, flatulence, headache.
Hepatic: Hepatitis and cholestatic jaundice with rises in AST, ALT, bilirubin or alkaline phosphatase, reported more commonly in the elderly, in males, and on prolonged treatment; onset may follow several weeks after therapy stops, is usually reversible, and deaths have been reported.
Hypersensitivity: Pruritus, angioedema, serum sickness-like reactions, erythema multiforme, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, hypersensitivity vasculitis, exfoliative dermatitis including toxic epidermal necrolysis.
Gastrointestinal: Indigestion, gastritis, stomatitis, glossitis, black hairy tongue, mucocutaneous candidiasis, enterocolitis, hemorrhagic or pseudomembranous colitis; colitis onset may occur during or after treatment.
Hematologic: Anemia including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, agranulocytosis, usually reversible on discontinuation; thrombocytosis in under 1%; increased prothrombin time reported with concomitant anticoagulants.
Renal: Interstitial nephritis, hematuria, crystalluria.
Central nervous system: Agitation, anxiety, behavioral changes, confusion, convulsions, dizziness, insomnia, reversible hyperactivity.
Dental: Tooth discoloration, brown, yellow or gray, mostly in pediatric patients and in most cases reduced or eliminated by brushing or dental cleaning.

Oral contraceptive interaction: Efficacy of combined estrogen and progesterone contraceptives may fall through reduced estrogen reabsorption.

Pregnancy & Lactation

Pregnancy: Category B. Reproduction studies in pregnant rats and mice at oral doses up to 1200 mg/kg/day of the 2 to 1 amoxicillin to clavulanate formulation showed no evidence of fetal harm, roughly 4 and 2 times the maximum recommended adult human dose by body surface area for the amoxicillin component (875 mg every 12 hours) and 9 and 4 times for clavulanate (125 mg every 8 hours); there are no adequate and well-controlled studies in pregnant women, so use only if clearly needed.

Lactation: Excreted in human milk and use by a nursing mother may sensitize the infant; exercise caution.

Pediatric Use

Effectiveness established for the oral suspension and chewable tablets.