Pronunciation
a-mox-i-SILL-in/klav-yoo-LAN -ate [Pronunciation]

Trade Name(s)

• Augmentin

• Augmentin ES

• Augmentin XR

• Clavulin [Canada]

Pregnancy Category
Category B

Ther. class.
anti-infectives

Pharm. class.
aminopenicillins beta lactamase inhibitors

Treatment of a variety of infections including:

» Skin and skin structure infections,

» Otitis media,

» Sinusitis,

» Respiratory tract infections,

» Genitourinary tract infections.

Binds to bacterial cell wall, causing cell death; spectrum of amoxicillin is broader than penicillin. Clavulanate resists action of beta-lactamase, an enzyme produced by bacteria that is capable of inactivating some penicillins.

Therapeutic Effect(s):
Bactericidal action against susceptible bacteria.

Spectrum:
Active against:

» Streptococci,

» Pneumococci,

» Enterococci,

» Haemophilus influenzae ,

» Escherichia coli ,

» Proteus mirabilis ,

» Neisseria meningitidis ,

» N. gonorrhoeae ,

» Staphylococcus aureus ,

» Klebsiella pneumoniae ,

» Shigella ,

» Salmonella ,

» Moraxella catarrhalis .

Absorption: Well absorbed from the duodenum (75–90%). More resistant to acid inactivation than other penicillins.

Distribution: Diffuses readily into most body tissues and fluids. Does not readily enter brain/CSF; CSF penetration is ↑ in the presence of inflamed meninges. Crosses the placenta and enters breast milk in small amounts.

Metabolism and Excretion: 70% excreted unchanged in the urine; 30% metabolized by the liver.

Half-life: 1–1.3 hr.

TIME/ACTION PROFILE (peak blood levels)

ROUTE	ONSET	PEAK	DURATION
PO	30 min	1–2 hr	8–12 hrhr

Contraindicated in:

• Hypersensitivity to penicillins or clavulanate;

• Suspension and chewable tablets contain aspartame and should be avoided in phenylketonurics;

• History of amoxicillin/clavulanate-associated cholestatic jaundice.

Use Cautiously in:

• Severe renal insufficiency (dose ↓ necessary);

• Infectious mononucleosis (↑ risk of rash);

• Hepatic impairment (dose cautiously, monitor liver function).

CNS: SEIZURES (HIGH DOSES) .

GI: PSEUDOMEMBRANOUS COLITIS, diarrhea, hepatic dysfunction, nausea, vomiting.

GU: vaginal candidiasis.

Derm: rash, urticaria.

Hemat: blood dyscrasias.

Misc: ALLERGIC REACTIONS INCLUDING ANAPHYLAXIS AND SERUM SICKNESS , superinfection.

*CAPITALS indicates life-threatening.
*italic indicates most frequent.

Drug-Drug

• Probenecid ↓ renal excretion and ↑ blood levels of amoxicillin—therapy may be combined for this purpose.

• May ↑ the effect of warfarin .

• Concurrent allopurinol therapy ↑ risk of rash.

• May ↓ the effectiveness of hormonal contraceptives .

Drug-Food
Clavulanate absorption is ↓ by a high fat meal.

Most Infections (Dosing based on amoxicillin component)

• PO (Adults and Children >40 kg): 250 mg q 8 hr or 500 mg q 12 hr..

Serious Infections and Respiratory Tract Infections

• PO (Adults and Children >40 kg): 875 mg q 12 hr or 500 mg q 8 hr; Acute bacterial sinusitis—2000 mg q 12 hr for 10 days as extended release (XR) product; Community-acquired pneumonia—2000 mg every 12 hr for 7–10 days as extended release (XR) product..

Recurrent/persistent acute otitis media due to Multidrug-resistant Streptococcus pneumonia,H. influenzae, or M. catarrhalis

• PO (Children <40 kg): 80–90 mg/kg/day in divided doses q 12 hr for 10 days (as ES formulation only)..

Renal Impairment

• PO (Adults): CCr 10–30 mL/min—250–500 mg q 12 hr (do not use 875 mg tablet); CCr <10 mL/min—250–500 mg q 24 hr..

Otitis Media, Sinusitis, Lower Respiratory Tract Infections, Serious Infections

• PO (Children ≥3 mo): 200 mg/5 mL or 400 mg/5 mL suspension—45 mg/kg/day divided q 12 hr; 125 mg/5 mL or 250 mg/5 mL suspension—40 mg/kg/day divided q 8 hr..

Less Serious Infections

• PO (Children ≥3 mo): 200 mg/5 mL or 400 mg/5 mL suspension—25 mg/kg/day divided q 12 hr or 20 mg/kg/day divided q 8 hr (as 125 mg/5 mL or 250 mg/5 mL suspension)..

• PO (Children <3 mo): 15 mg/kg q 12 hr (125 mg/mL suspension recommended)..

• Tablets: 250 mg amoxicillin with 125 mg clavulanate, 500 mg amoxicillin with 125 mg clavulanate, 875 mg amoxicillin with 125 mg clavulanate

» Cost:
Generic: 250 mg $149.99/30, 500 mg $68.98/30, 875 mg $47.98/30.

• Chewable tablets (cherry-banana flavor): 200 mg amoxicillin with 28.5 mg clavulanate, 400 mg amoxicillin with 57 mg clavulanate

» Cost:
Generic: 400 mg $60.99/20.

• Extended-release tablets (scored): 1000 mg amoxicillin with 62.5 mg clavulanate

» Cost: 1000 mg $116.69/28.

• Powder for oral suspension (125 mg/5 mL is banana flavor; 200 mg/5ml is fruit flavor; 250 mg/5 mL is orange flavor; 400 mg/5 mL is fruit flavor; 600 mg/5 mL is orange or strawberry-creme flavor): 125 mg amoxicillin with 31.25 mg clavulanate/5 mL, 200 mg amoxicillin with 28.5 mg clavulanate/5 mL, 250 mg amoxicillin with 62.5 mg clavulanate/5 mL, 400 mg amoxicillin with 57 mg clavulanate/5 mL, 600 mg amoxicillin with 42.9 mg clavulanate/5 mL (ES formulation)

» Cost:
Generic: 250 mg $85.99/100 mL, 600 mg $35.99/75 mL.

• Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and throughout therapy.

• Obtain a history before initiating therapy to determine previous use of and reactions to penicillins or cephalosporins. Persons with a negative history of penicillin sensitivity may still have an allergic response.

• Observe for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Notify health care professional immediately if these occur.

• Obtain specimens for culture and sensitivity prior to therapy. First dose may be given before receiving results.

• Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of pseudomembranous colitis. May begin up to several weeks following cessation of therapy.

Lab Test Considerations

• May cause ↑ serum alkaline phosphatase, LDH, AST, and ALT concentrations. Elderly men and patients receiving prolonged treatment are at ↑ risk for hepatic dysfunction.

» May cause false-positive direct Coombs' test result.

• Risk for infection (Indications)(Side Effects)

• Noncompliance (Patient/Family Teaching)

PO: Administer around the clock. Administer at the start of a meal to enhance absorption and to decrease GI side effects. Do not administer with high fat meals; clavulanate absorption is decreased. XR tablet is scored and can be broken for ease of administration. Capsule contents may be emptied and swallowed with liquids. Chewable tablets should be crushed or chewed before swallowing with liquids. Shake oral suspension before administering. Refrigerated reconstituted suspension should be discarded after 10 days.

» Two 250-mg tablets are not bioequivalent to one 500-mg tablet; 250-mg tablets and 250-mg chewable tablets are also not interchangeable. Two 500-mg tablets are not interchangeable with one 1000-mg XR tablet; amounts of clavulanic acid and durations of action are different. Augmentin ES 600 (600 mg/5 mL) does not contain the same amount of clavulanic acid as any of the other Augmentin suspensions. Suspensions are not interchangeable.

» Pedi: Do not administer 250-mg chewable tablets to children <40 kg due to clavulanate content. Children <3 mo should receive the 125-mg/5 mL oral solution.

• Instruct patients to take medication around the clock and to finish the drug completely as directed, even if feeling better. Advise patients that sharing of this medication may be dangerous.

• Pedi: Teach parents or caregivers to calculate and measure doses accurately. Reinforce importance of using measuring device supplied by pharmacy or with product, not household items.

• Advise patient to report the signs of superinfection (furry overgrowth on the tongue, vaginal itching or discharge, loose or foul-smelling stools) and allergy.

• Instruct patient to notify health care professional immediately if diarrhea, abdominal cramping, fever, or bloody stools occur and not to treat with antidiarrheals without consulting health care professionals.

• Instruct the patient to notify health care professional if symptoms do not improve or if nausea or diarrhea persists when drug is administered with food.

• Instruct female patients taking oral contraceptives to use an alternate or additional method of contraception during therapy and until next menstrual period.

Resolution of the signs and symptoms of infection. Length of time for complete resolution depends on the organism and site of infection.