No

Antibiotic, Penicillin

Dental: Treatment of orofacial infections when beta-lactamase-producing staphylococci and beta-lactamase-producing Bacteroides are present

Medical: Treatment of otitis media, sinusitis, and infections caused by susceptible organisms involving the lower respiratory tract, skin and skin structure, and urinary tract; spectrum same as amoxicillin with additional coverage of beta-lactamase producing B. catarrhalis, H. influenzae, N. gonorrhoeae, and S. aureus (not MRSA). The expanded coverage of this combination makes it a useful alternative when amoxicillin resistance is present and patients cannot tolerate alternative treatments.

B

Known hypersensitivity to amoxicillin, clavulanic acid, or penicillin; concomitant use of disulfiram

In patients with renal impairment, doses and/or frequency of administration should be modified in response to the degree of renal impairment; high percentage of patients with infectious mononucleosis have developed rash during therapy; a low incidence of cross-allergy with cephalosporins exists; incidence of diarrhea is higher than with amoxicillin alone. Hepatic dysfunction, although rare, is more common in elderly and/or males, and occurs more frequently with prolonged treatment.

1% to 10%:

Dermatologic: Rash, urticaria

Gastrointestinal: Nausea, vomiting, diarrhea

Genitourinary: Vaginitis

<1%: Headache, abdominal discomfort, flatulence

Symptoms of penicillin overdose include neuromuscular hypersensitivity (agitation, hallucinations, asterixis, encephalopathy, confusion, and seizures) and electrolyte imbalance with potassium or sodium salts, especially in renal failure

Hemodialysis may be helpful to aid in the removal of the drug from the blood, otherwise most treatment is supportive or symptom directed

Decreased effect: Efficacy of oral contraceptives may be reduced

Increased effect: Disulfiram, probenecid may increase amoxicillin levels, increased effect of anticoagulants

Increased toxicity: Allopurinol theoretically has an additive potential for amoxicillin rash

Discard unused suspension after 10 days; reconstituted oral suspension should be kept in refrigerator; unit dose antibiotic oral syringes are stable for 48 hours

Clavulanic acid binds and inhibits beta-lactamases that inactivate amoxicillin resulting in amoxicillin having an expanded spectrum of activity. Amoxicillin inhibits bacterial cell wall synthesis by binding to one or more of the penicillin binding proteins (PBPs); which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.

Amoxicillin pharmacokinetics are not affected by clavulanic acid

Distribution: Both distribute into pleural fluids, lungs, and peritoneal fluid; high urine concentrations are attained; also into synovial fluid, liver, prostate, muscle, and gallbladder; penetrates into middle ear effusions, maxillary sinus secretions, tonsils, sputum, and bronchial secretions; crosses the placenta; low concentrations occur in breast milk

Protein binding: 17% to 20%

Metabolism: Partial (Clavulanic acid is hepatically metabolized)

Half-life:

Neonates, full-term: 3.7 hours

Infants and Children: 1-2 hours

Adults with normal renal function: ~1 hour for both agents

Patients with Cl_cr <10 mL/minute: 7-21 hours

Time to peak: 2 hours (capsule) and 1 hour (suspension)

Elimination: Amoxicillin excreted primarily (80%) unchanged and clavulanic acid is excreted 30% to 40% unchanged in the urine (lower in neonates)

Oral:

Children >40 kg and Adults: 250-500 mg every 8 hours or 875 mg every 12 hours

Note: Augmentin® 200 suspension or chewable tablets 200 mg dosed every 12 hours is considered equivalent to Augmentin®"125" dosed every 8 hours; Augmentin® 400 suspension and chewable tablets may be similarly dosed every 12 hours and are equivalent to Augmentin®"250" every 8 hours

Dosing interval in renal impairment:

Cl_cr 10-30 mL/minute: Administer every 12 hours

Cl_cr <10 mL/minute: Administer every 24 hours

Hemodialysis: Moderately dialyzable (20% to 50%)

Amoxicillin/clavulanic acid: Administer dose after dialysis

Peritoneal dialysis: Moderately dialyzable (20% to 50%)

Amoxicillin: Administer 250 mg every 12 hours

Clavulanic acid: Dose for Cl_cr <10 mL/minute

Continuous arteriovenous or venovenous hemofiltration (CAVH) effects:

Amoxicillin: ~50 mg of amoxicillin/L of filtrate is removed

Clavulanic acid: Dose for Cl_cr <10 mL/minute

May be taken with meals or on an empty stomach; may mix with milk, formula, or juice

Assess patient at beginning and throughout therapy for infection; with prolonged therapy, monitor renal, hepatic, and hematologic function periodically; monitor for signs of anaphylaxis during first dose

May interfere with urinary glucose tests using cupric sulfate (Benedict's solution, Clinitest®); may inactivate aminoglycosides in vitro

Penicillins have been reported to cause apprehension, illusions, agitation, insomnia, depersonalization, and encephalopathy

Disulfiram may increase amoxicillin levels

No information available to require special precautions

Prolonged use of penicillins may lead to development of oral candidiasis

Take entire prescription, even if you are feeling better. Take at equal intervals around-the-clock; may be taken with milk, juice, or food. You may experience nausea or vomiting (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help). If using oral contraceptives, use additional contraceptive measures; amoxicillin may reduce effectiveness of your oral contraceptive. Report rash; unusual diarrhea; vaginal itching, burning, or pain; unresolved vomiting or constipation; fever or chills; unusual bruising or bleeding; or if condition being treated worsens or does not improve by the time prescription is completed.

Two 250 mg tablets are not equivalent to a 500 mg tablet (both tablet sizes contain equivalent clavulanate); potassium content: 0.16 mEq of potassium per 31.25 mg of clavulanic acid

Suspension, oral:

125 (banana flavor): Amoxicillin trihydrate 125 mg and clavulanate potassium 31.25 mg per 5 mL (75 mL, 150 mL)

200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL (50 mL, 75 mL, 100 mL)

250 (orange flavor): Amoxicillin trihydrate 250 mg and clavulanate potassium 62.5 mg per 5 mL (75 mL, 150 mL)

400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL (50 mL, 75 mL, 100 mL)

Tablet:

250: Amoxicillin trihydrate 250 mg and clavulanate potassium 125 mg

500: Amoxicillin trihydrate 500 mg and clavulanate potassium 125 mg

875: Amoxicillin trihydrate 875 mg and clavulanate potassium 125 mg

Tablet, chewable:

125: Amoxicillin trihydrate 125 mg and clavulanate potassium 31.25 mg

200: Amoxicillin trihydrate 200 mg and clavulanate potassium 28.5 mg

250: Amoxicillin trihydrate 250 mg and clavulanate potassium 62.5 mg

400: Amoxicillin trihydrate 400 mg and clavulanate potassium 57 mg

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Ancill RJ, Ballard JH, and Capewell MA, "Urinary Tract Infections in Geriatric Inpatients: A Comparative Study of Amoxicillin-Clavulanic Acid and Co-trimoxazole," Curr Ther Res, 1987, 41(4):444-8.

Donowitz GR and Mandell GL, "Beta-Lactam Antibiotics," N Engl J Med, 1988, 318(7):419-26 and 318(8):490-500.

Gan VN, Kusmiesz H, Shelton S, et al, "Comparative Evaluation of Loracarbef and Amoxicillin-Clavulanate for Acute Otitis Media," Antimicrob Agents Chemother, 1991, 35(5):967-71.

Hoberman A, Paradise JL, Burch DJ, et al, "Equivalent Efficiency and Reduced Occurrence of Diarrhea From a New Formulation of Amoxicillin/Clavulanate Potassium (Augmentin®) for Treatment of Acute Otitis Media in Children," Pediatr Infect Dis J, 1997, 16(5):463-70.

Reed MD, "Clinical Pharmacokinetics of Amoxicillin and Clavulanate," Pediatr Infect Dis J, 1996, 15(10):949-54.

Thoene DE and Johnson CE, "Pharmacotherapy of Otitis Media," Pharmacotherapy, 1991, 11(3):212-21.

Todd PA and Benfield P, "Amoxicillin/Clavulanic Acid. An Update of Its Antibacterial Activity, Pharmacokinetic Properties, and Therapeutic Use," Drugs, 1990, 39(2):264-307.

Wright AJ, "The Penicillins," Mayo Clin Proc, 1999, 74(3):290-307.

Wynn RL and Bergman SA, "Antibiotics and Their Use in the Treatment of Orofacial Infections, Part I and Part II," Gen Dent, 1994, 42(5):398-402, 498-502.