Amoxicillin and clavulanate potassium

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Augmentin® may be confused with Azulfidine®

U.S. BRAND NAMES — Amoclan; Augmentin ES-600®; Augmentin XR®; Augmentin®

PHARMACOLOGIC CATEGORY
Antibiotic, Penicillin

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

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

Augmentin® Product-Specific Considerations

125 mg: Chewable tablet: q8h dosing Suspension:

" q8h dosing
" For adults having difficulty swallowing tablets, 125 mg/5 mL suspension may be substituted for 500 mg tablet.

200 mg: Chewable tablet:

" q12h dosing
" Contains phenylalanine Suspension:

" q12h dosing
" For adults having difficulty swallowing tablets, 200 mg/5 mL suspension may be substituted for 875 mg tablet.

250 mg: Chewable tablet:

" q8h dosing
" Contains phenylalanine
" Tablet and chewable tablet are not interchangeable due to differences in clavulanic acid. Suspension:

" q8h dosing
" For adults having difficulty swallowing tablets, 250 mg/5 mL suspension may be substituted for 500 mg tablet. Tablet:

" q8h dosing
" Not for use in patients <40 kg
" Tablet and chewable tablet are not interchangeable due to differences in clavulanic acid.

400 mg: Chewable tablet:

" q12h dosing
" Contains phenylalanine Suspension:

" q12h dosing
" For adults having difficulty swallowing tablets, 400 mg/5 mL suspension may be substituted for 875 mg tablet.

500 mg: Tablet: q8h or q12h dosing

600 mg: Suspension:

" q12h dosing
" 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: Tablet:

" q12h dosing
" Not for use in Clcr <30 mL/minute

1000 mg: Extended release tablet:

" q12h dosing
" Not for use in children <16 years of age
" Not interchangeable with two 500 mg tablets
" Not for use if Clcr <30 mL/minute or hemodialysis

Acute bacterial sinusitis: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 10 days

Bite wounds (animal/human): Oral: 875 mg every 12 hours or 500 mg every 8 hours

Chronic obstructive pulmonary disease: Oral: 875 mg every 12 hours or 500 mg every 8 hours

Diabetic foot: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 7-14 days

Diverticulitis, perirectal abscess: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 7-10 days

Erysipelas: Oral: 875 mg every 12 hours or 500 mg every 8 hours

Febrile neutropenia: Oral: 875 mg every 12 hours

Pneumonia:
Aspiration: Oral: 875 mg every 12 hours
Community-acquired: Oral: Extended release tablet: Two 1000 mg tablets every 12 hours for 7-10 days

Pyelonephritis (acute, uncomplicated): Oral: 875 mg every 12 hours or 500 mg every 8 hours

Skin abscess: Oral: 875 mg every 12 hours

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

(For additional information see "Amoxicillin and clavulanate potassium: Pediatric drug information")

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

Lower respiratory tract infections, severe infections, sinusitis: Children ≥ 3 months and <40 kg: Oral: 45 mg/kg/day divided every 12 hours or 40 mg/kg/day divided every 8 hours

Mild-to-moderate infections: Children ≥ 3 months and <40 kg: Oral: 25 mg/kg/day divided every 12 hours or 20 mg/kg/day divided every 8 hours

Otitis media (Augmentin ES-600®): Children ≥ 3 months and <40 kg: Oral: 90 mg/kg/day divided every 12 hours for 10 days in children with severe illness and when coverage for ß-lactamase positive H. influenzae and M. catarrhalis is needed.

Children >40 kg: Refer to adult dosing.

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT
Clcr <30 mL/minute: Do not use 875 mg tablet or extended release tablets.

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. Do not use extended release tablets.

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

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Powder for oral suspension: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine]; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL (50 mL, 75 mL, 100 mL) [contains phenylalanine]; 600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL (75 mL, 125 mL, 200 mL)
Amoclan:
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 and potassium 0.14 mEq/5 mL; fruit 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 and potassium 0.29 mEq/5 mL; fruit flavor]
600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL (75 mL, 125 mL) [contains phenylalanine 7 mg/5 mL, potassium 0.248 mEq/5 mL; orange flavor]
Augmentin®:
125: Amoxicillin 125 mg and clavulanate potassium 31.25 mg per 5 mL (75 mL, 100 mL, 150 mL) [contains potassium 0.16 mEq/5 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 and potassium 0.14 mEq/5 mL; orange flavor] [DSC]
250: Amoxicillin 250 mg and clavulanate potassium 62.5 mg per 5 mL (75 mL, 100 mL, 150 mL) [contains potassium 0.32 mEq/5 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 and potassium 0.29 mEq/5 mL; orange flavor] [DSC]
Augmentin ES-600®: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL (75 mL, 125 mL, 200 mL) [contains phenylalanine 7 mg/5 mL and potassium 0.23 mEq/5 mL; strawberry cream flavor]

Tablet: 250: Amoxicillin 250 mg and clavulanate potassium 125 mg; 500: Amoxicillin 500 mg and clavulanate potassium 125 mg; 875: Amoxicillin 875 mg and clavulanate potassium 125 mg
Augmentin®:
250: Amoxicillin 250 mg and clavulanate potassium 125 mg [contains potassium 0.63 mEq/tablet]
500: Amoxicillin 500 mg and clavulanate potassium 125 mg [contains potassium 0.63 mEq/tablet]
875: Amoxicillin 875 mg and clavulanate potassium 125 mg [contains potassium 0.63 mEq/tablet]

Tablet, chewable: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg [contains phenylalanine]; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg [contains phenylalanine]

Tablet, extended release:
Augmentin XR®: 1000: Amoxicillin 1000 mg and clavulanate acid 62.5 mg [contains potassium 12.6 mg (0.32 mEq) and sodium 29.3 mg (1.27 mEq) per tablet; packaged in either a 7-day or 10-day package]

DOSAGE FORMS: CONCISE
Powder for oral suspension: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL; 600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL
Amoclan:
200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL
400: Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL
600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL
Augmentin®:
125: Amoxicillin 125 mg and clavulanate potassium 31.25 mg per 5 mL
250: Amoxicillin 250 mg and clavulanate potassium 62.5 mg per 5 mL
Augmentin ES-600®: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL

Tablet: 500: Amoxicillin 500 mg and clavulanate potassium 125 mg; 875: Amoxicillin 875 mg and clavulanate potassium 125 mg
Augmentin®:
250: Amoxicillin 250 mg and clavulanate potassium 125 mg
500: Amoxicillin 500 mg and clavulanate potassium 125 mg
875: Amoxicillin 875 mg and clavulanate potassium 125 mg

Tablet, chewable: 200: Amoxicillin 200 mg and clavulanate potassium 28.5 mg; 400: Amoxicillin 400 mg and clavulanate potassium 57 mg

Tablet, extended release:
Augmentin XR®: 1000: Amoxicillin 1000 mg and clavulanate acid 62.5 mg

GENERIC EQUIVALENT AVAILABLE — Yes: Excludes extended release

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. Extended release tablets should be administered with food.

Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.

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.

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

1% to 10%:
Dermatologic: Diaper rash, skin rash, urticaria
Gastrointestinal: Abdominal discomfort, loose stools, nausea, vomiting
Genitourinary: Vaginitis, vaginal mycosis
Miscellaneous: Moniliasis

<1% (Limited to important or life-threatening): Alkaline phosphatase increased, cholestatic jaundice, flatulence, headache, hepatic dysfunction, hepatitis, liver function tests increased, prothrombin time increased, thrombocytosis, vasculitis (hypersensitivity)

Additional adverse reactions seen with ampicillin-class antibiotics: Agitation, agranulocytosis, alkaline phosphatase increased, anaphylaxis, anemia, angioedema, anxiety, behavioral changes, bilirubin increased, black "hairy" tongue, confusion, convulsions, crystalluria, 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, transaminases increased, thrombocytopenia, thrombocytopenic purpura, tooth discoloration, toxic epidermal necrolysis

CONTRAINDICATIONS — Hypersensitivity to amoxicillin, clavulanic acid, penicillin, or any component of the formulation; history of cholestatic jaundice or hepatic dysfunction with amoxicillin/clavulanate potassium therapy; Augmentin XR™ : severe renal impairment (Clcr <30 mL/minute) and hemodialysis patients

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients. Low incidence of cross-allergy with cephalosporins exists. Diarrhea: Incidence of diarrhea is higher than with amoxicillin alone. Hepatic effects: Although rare, hepatic dysfunction is more common in elderly and/or males, and occurs more frequently with prolonged treatment, and may occur after therapy is complete. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns: Hepatic impairment: Use with caution in patients with hepatic impairment. Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients. Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.

Dosage form specific issues: Clavulanic acid content: Due to differing content of clavulanic acid, not all formulations are interchangeable. Phenylalanine: Some products contain phenylalanine.

DRUG INTERACTIONS
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Amoxicillin. Risk C: Monitor therapy

Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification

Methotrexate: Penicillins may decrease the excretion of Methotrexate. Risk C: Monitor therapy

Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy

Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification

Uricosuric Agents: May decrease the excretion of Penicillins. Risk C: Monitor therapy

PREGNANCY RISK FACTOR — B (show table)

PREGNANCY IMPLICATIONS — Adverse events have not been observed in animal studies; therefore, amoxicillin/clavulanate is classified as pregnancy category B. Both amoxicillin and clavulanic acid cross the placenta. There is no documented increased risk of teratogenic effects caused by amoxicillin/clavulanate. A potential increased risk of necrotizing enterocolitis in the newborn has been noted after maternal use of amoxicillin/clavulanate for preterm labor or premature prolonged rupture of membranes. When used during pregnancy, pharmacokinetic changes have been observed with amoxicillin alone (refer to the Amoxicillin monograph for details).

LACTATION — Enters breast milk/use caution

BREAST-FEEDING CONSIDERATIONS — Amoxicillin is found in breast milk. The manufacturer recommends that caution be used if administered to breast-feeding women. The use of amoxicillin/clavulanate may be safe while breast-feeding; however, the risk of adverse events in the infant may be increased when compared to the use of amoxicillin alone. The risk of adverse events may be related to maternal dose. Nondose-related effects could include modification of bowel flora and allergic sensitization of the infant.

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. Extended release tablets should be taken with food. Some products contain phenylalanine. If you have phenylketonuria or PKU, avoid use. All dosage forms contain potassium.

PRICING — (data from drugstore.com)
Chewable (Amoxicillin-Pot Clavulanate)
400-57 mg (20): $63.79

Suspension (reconstituted) (Amoxicillin-Pot Clavulanate)
600-42.9 mg/5 mL (75): $35.99

Tablet, 12-hour (Augmentin XR)
1000-62.5 mg (28): $116.70

Tablets (Amoxicillin-Pot Clavulanate)
250-125 mg (30): $116.54
500-125 mg (20): $45.99
875-125 mg (20): $31.99

Tablets (Augmentin)
250-125 mg (30): $118.99
500-125 mg (30): $166.71
875-125 mg (20): $145.99

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

CANADIAN BRAND NAMES — Alti-Amoxi-Clav; Apo-Amoxi-Clav®; Augmentin®; Clavulin®; Novo-Clavamoxin; ratio-Aclavulanate

INTERNATIONAL BRAND NAMES — Acarbixin (MX); Aclam (ID); Ambilan (PE); AMK (TH); Amobay Cl (MX); Amocla (KP); Amocla Duo (KP); Amoclan (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Amoclav (DE); Amoksiclav (TH); Amoksiklav (CL, PL); Amolanic (KP); Amolanic Duo (KP); Amoxa (KP); Amoxi Plus (PY); Amoxiclav (MX); Amoxiclav-BID (MX); Amoxiclav-Teva (IL); Amoxsiklav Forte (TH); Amoxxlin (KP); Amoxyclav (IL); Augamox (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); AugMaxcil (ZA); Augmentan (DE); Augmentin (AE, AT, AU, BB, BE, BF, BG, BH, BJ, BM, BS, BZ, CH, CI, CR, CY, CZ, DE, DK, DO, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, IE, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KP, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, NO, OM, PA, PE, PK, PL, PT, QA, RU, SA, SC, SD, SE, SL, SN, SR, SV, SY, TH, TN, TR, TT, TZ, UG, UY, VE, YE, ZA, ZM, ZW); Augmentine (ES); Augmex (PH); Augpen (TH); Augurcin (PH); Bactiv (PH); Bactoclav (PH); Bioclavid (AE, BH, CY, DE, DK, EG, IL, IQ, IR, JO, KW, LB, LY, OM, PH, QA, SA, SE, SY, YE); Bioclavid Forte (PH); Cavumox (MY, TH); Cax (PH); Clacillin Duo Dry Syrup (KP); Clamax (KP); Clamentin (ZA); Clamohexal (AU); Clamohexal Duo (AU); Clamovid (HK, MY, SG); Clamoxin (MX); Clamoxyl (AU); Clamoxyl Duo 400 (AU); Clamoxyl DuoForte (AU); Clavamox (DE, ID, IN); Clavant (MX); Clavar (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Claventin (IL); Clavinex (CN, EC); Clavipen (MX); Clavmex (PH); Clavodar (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Clavoxil (BR); Clavoxine (EC); Clavucyd (MX); Clavulin (BF, BJ, CI, CO, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, MX, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Clavulin Duo Forte (AU); Clavulox Duo (AR, PY); Clavumox (DE, PE, ZA); Clavuser (MX); Cramon Duo (KP); Curam (AU, CO, CR, DO, GT, HK, MY, NI, PA, PE, PL, SG, SV, TH, TW); Danoclav (ID); Darzitil Plus (AR); E-Moxclav (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Enhancin (SG); Exten (PH); Fleming (HK); Forcid (PL); Fugentin (SG); Fullicilina Plus (AR); Gimaclav (MX); Hibiotic (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Klamonex (KP); Klavic (PH); Klavocin (PL); Kmoxilin (KP); Lansiclav (ID); Moxiclav (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SG, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM, ZW); Moxicle (KP, TH); Moxlin (MX); Natravox (PH); Novamox (BR); Nufaclav (ID); Penhance (PH); Quali-Mentin (HK); Ramoclav (PL); Ranclav (TH, ZA); Riclasip (MX); Servamox (MX); Sinufin (MX); Spektramox (SE); Sullivan (PH); Suplentin (PH); Synermox (NZ); Taromentin (PL); Velamox CL (PE); Vestaclav (MY); Viaclav (ID); Vulamox (CO, ID)

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:
Protein binding: ~25%
Metabolism: Hepatic
Half-life elimination: 1 hour
Time to peak: 1 hour
Excretion: Urine (30% to 40% as unchanged drug)

PATIENT INFORMATION — Take entire course of medication. Take extended release tablets with food. Report diarrhea promptly. Females should report onset of symptoms of candidal vaginitis