Amoxicillin and Clavulanate Potassium

Pronunciation (a moks i SIL in & klav yoo LAN ate poe TASS ee um)

Related Information

U.S. Brand Names Augmentin®; Augmentin ES-600TM

Synonyms Amoxicillin and Clavulanic Acid

Generic Available No

Canadian Brand Names Augmentin®; Clavulin®

Pharmacologic Category Antibiotic, Penicillin

Use 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.

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

Pregnancy Risk Factor B

Lactation Enters breast milk/compatible

Contraindications Hypersensitivity to amoxicillin, clavulanic acid, penicillin, or any component of the formulation; concomitant use of disulfiram; history of cholestatic jaundice or hepatic dysfunction with amoxicillin/clavulanate potassium therapy

Warnings/Precautions Prolonged use may result in superinfection; 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. Use caution in patients with hepatic dysfunction. Hepatic dysfunction, although rare, is more common in elderly and/or males, and occurs more frequently with prolonged treatment, and may occur after therapy is complete. Due to differing content of clavulanic acid, not all formulations are interchangeable. Some products contain phenylalanine.

Adverse Reactions

>10%: Gastrointestinal: Diarrhea (3% to 34% incidence varies upon dose and regimen used)

1% to 10%:

Dermatologic: Diaper rash, skin rash, urticaria

Gastrointestinal: Loose stools, nausea, vomiting

Genitourinary: Vaginitis

Miscellaneous: Moniliasis

<1%: Abdominal discomfort, cholestatic jaundice, flatulence, headache, hepatic dysfunction, prothrombin time increased, thrombocytosis

Additional adverse reactions seen with ampicillin-class antibiotics: Agitation, agranulocytosis, ALT elevated, anaphylaxis, anemia, angioedema, anxiety, AST elevated, behavioral changes, black "hairy" tongue, confusion, convulsions, dizziness, enterocolitis, eosinophilia, erythema multiforme, exanthematous pustulosis, exfoliative dermatitis, gastritis, glossitis, hematuria, hemolytic anemia, hemorrhagic colitis, indigestion, insomnia, hyperactivity, interstitial nephritis, leukopenia, mucocutaneous candidiasis, pruritus, pseudomembranous colitis, serum sickness-like reaction, Stevens-Johnson syndrome, stomatitis, thrombocytopenia, thrombocytopenic purpura, tooth discoloration, toxic epidermal necrolysis

Overdosage/Toxicology Symptoms of overdose may include abdominal pain, diarrhea, drowsiness, rash, hyperactivity, stomach pain, and vomiting. Electrolyte imbalance may occur, especially in renal failure. Hemodialysis may be helpful to aid in removal of the drug from blood; otherwise, treatment is supportive or symptom-directed.

Drug Interactions

Allopurinol: Additive potential for amoxicillin rash

Aminoglycosides: May be synergistic against selected organisms

Oral contraceptives: Anecdotal reports suggesting decreased contraceptive efficacy with penicillins have been refuted by more rigorous scientific and clinical data.

Probenecid: May increase levels of penicillins (amoxicillin)

Warfarin: Effects of warfarin may be increased

Stability Store dry powder at room temperature of 25°C (77°F). Reconstitute powder for oral suspension with appropriate amount of water as specified on the bottle. Shake vigorously until suspended. Reconstituted oral suspension should be kept in refrigerator. Discard unused suspension after 10 days. Unit-dose antibiotic oral syringes are stable for 48 hours.

Mechanism of Action 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.

Pharmacodynamics/Kinetics Amoxicillin pharmacokinetics are not affected by clavulanic acid.

Amoxicillin: See Amoxicillin monograph.

Clavulanic acid:

Metabolism: Hepatic

Excretion: Urine (30% to 40% as unchanged drug)

Dosage Note: Dose is based on the amoxicillin component; see "Augmentin® Product-Specific Considerations table".

Infants <3 months: 30 mg/kg/day divided every 12 hours using the 125 mg/5 mL suspension

Children 3 months and <40 kg:

Otitis media: 90 mg/kg/day divided every 12 hours for 10 days

Lower respiratory tract infections, severe infections, sinusitis: 45 mg/kg/day divided every 12 hoursor 40 mg/kg/day divided every 8 hours

Less severe infections: 25 mg/kg/day divided every 12 hours or 20 mg/kg/day divided every 8 hours

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

Dosing interval in renal impairment:

Clcr<30 mL/minute: Do not use 875 mg tablet

Clcr 10-30 mL/minute: 250-500 mg every 12 hours

Clcr<10 mL/minute: 250-500 every 24 hours

Hemodialysis: Moderately dialyzable (20% to 50%)

250-500 mg every 24 hours; administer dose during and after dialysis

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

Amoxicillin: Administer 250 mg every 12 hours

Clavulanic acid: Dose for Clcr<10 mL/minute

Continuous arteriovenous or venovenous hemofiltration effects:

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

Clavulanic acid: Dose for Clcr<10 mL/minute

Augmentin® Product-Specific Considerations

Strength

Form

Consideration

125 mg

CT, S

q8h dosing

S

For adults having difficulty swallowing tablets, 125 mg/5 mL suspension may be substituted for 500 mg tablet.

200 mg

CT, S

q12h dosing

CT

Contains phenylalanine

S

For adults having difficulty swallowing tablets, 200 mg/5 mL suspension may be substituted for 875 mg tablet.

250 mg

CT, S, T

q8h dosing

CT

Contains phenylalanine

T

Not for use in patients <40 kg

CT, T

Tablet and chewable tablet are not interchangeable due to differences in clavulanic acid.

S

For adults having difficulty swallowing tablets, 250 mg/5 mL suspension may be substituted for 500 mg tablet.

400 mg

CT, S

q12h dosing

CT

Contains phenylalanine

S

For adults having difficulty swallowing tablets, 400 mg/5 mL suspension may be substituted for 875 mg tablet.

500 mg

T

q8h or q12h dosing

600 mg

S

q12 h dosing

Contains phenylalanine

Not for use in adults or children 40 kg

600 mg/5 mL suspension is not equivalent to or interchangeable with 200 mg/5 mL or 400 mg/5 mL due to differences in clavulanic acid.

875 mg

T

Not for use in Clcr<30 mL/minute

Legend: CT = chewable tablet, S = suspension, T = tablet

Administration Administer around-the-clock to promote less variation in peak and trough serum levels. Administer with food to decrease stomach upset; shake suspension well before use.

Monitoring Parameters 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

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

Dietary Considerations May be taken with meals or on an empty stomach; take with meals to increase absorption and decrease GI intolerance; may mix with milk, formula, or juice. Some products contain phenylalanine; avoid use in phenylketonurics. All dosage forms contain potassium.

Patient Information Take entire prescription, even if you are feeling better. (For small children, bottles may contain more suspension than needed, take for number of days prescribed.) Take at equal intervals around-the-clock; may be taken with milk, juice, or food. Take with meals to decrease possible stomach upset. You may experience nausea or vomiting (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help). Some products contain phenylalanine. Avoid use in phenylketonurics. 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.

Nursing Implications Two 250 mg tablets are not equivalent to a 500 mg tablet (both tablet sizes contain equivalent clavulanate)

Dental Health: Effects on Dental Treatment Prolonged use of penicillins may lead to development of oral candidiasis.

Dental Health: Vasoconstrictor/Local Anesthetic Precautions No information available to require special precautions

Dental Comment In maxillary sinus, anterior nasal cavity, and deep neck infections, beta-lactamase-producing staphylococci and beta-lactamase-producing Bacteroides usually are present. In these situations, antibiotics that resist the beta-lactamase enzyme are indicated. Amoxicillin and clavulanic acid is administered orally for moderate infections. Ampicillin sodium and sulbactam sodium (Unasyn®) is administered parenterally for more severe infections.

Mental Health: Effects on Mental Status Penicillins have been reported to cause apprehension, illusions, agitation, insomnia, depersonalization, and encephalopathy

Mental Health: Effects on Psychiatric Treatment Disulfiram may increase amoxicillin levels

Dosage Forms

Powder for oral suspension:

125: Amoxicillin trihydrate 125 mg and clavulanate potassium 31.25 mg per 5 mL (75 mL, 100 mL, 150 mL) [banana flavor]

200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine 7 mg/5 mL; orange-raspberry flavor]

250: Amoxicillin trihydrate 250 mg and clavulanate potassium 62.5 mg per 5 mL (75 mL, 100 mL, 150 mL) [orange flavor]

400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine 7 mg/5 mL; orange-raspberry flavor]

600 (ES-600TM): Amoxicillin 600 mg and clavulanic potassium 42.9 mg per 5 mL (50 mL, 75 mL, 100 mL, 150 mL) [contains phenylalanine 7 mg/5 mL; orange-raspberry flavor]

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 [lemon-lime flavor]

200: Amoxicillin trihydrate 200 mg and clavulanate potassium 28.5 mg [contains phenylalanine 2.1 mg/tablet; cherry-banana flavor]

250: Amoxicillin trihydrate 250 mg and clavulanate potassium 62.5 mg [lemon-lime flavor]

400: Amoxicillin trihydrate 400 mg and clavulanate potassium 57 mg [contains phenylalanine 4.2 mg/tablet; cherry-banana flavor]

References

American Thoracic Society, "Guidelines for the Initial Management of Adults With Community-Acquired Pneumonia: Diagnosis, Assessment of Severity, and Initial Antimicrobial Therapy,"Am Rev Respir Dis, 1993, 148(5):1418-26.

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.

International Brand Names Amoclan (AT); Amoclav (DE); Amoclavam (PT); Amoclave (ES); Amoxi-Clavulan (DE); Amoxidura (DE); Amoxillat-Clav (DE); Amoxyplus (ES); Augmentin (AU, BR, CA); Ausclav (AU); Aziclav (CH); Betamox (PT); Bigpen (ES); Bremide (NO); Burmicin (ES); Ciblor (FR); Clamoxyl (AU); Clavamel (IE); Clavamox (PT); Clavepen (PT, ES); Clavius (ES); Clavucid (BE, ES); Clavulin (AU, BR, CA, IT, MX); Clavumox (ES); Duonasa (ES); Eumetinex (MX); Eupeclanic (ES); Germentin (IE); Inmupen (ES); Kelsopen (ES); Naxina (ES); Neoduplamox (IT); Novamox (BR); Pangamox (ES); Penilan (PT); Spektramox (DK, SE); Stacillin (IT); Ultramoxil (ES)