amoxicillin/clavulanate

General

amoxicillin/clavulanate

Pronunciation:
a-mox-i-sill-in/klav-yoo-lan-ate


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Trade Name(s)

  • Augmentin
  • Augmentin ES
  • Clavulin Canadian Trade name

Ther. Class.

anti-infectives

Pharm. Class.

aminopenicillins beta lactamase inhibitors

Indications

Treatment of a variety of infections, including:

  • Skin and skin structure infections,
  • Otitis media,
  • Sinusitis,
  • Respiratory tract infections,
  • Genitourinary tract infections.

Action

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,
  • Neisseria gonorrhoeae,
  • Staphylococcus aureus,
  • Klebsiella pneumoniae,
  • Shigella,
  • Salmonella,
  • Moraxella catarrhalis.

Pharmacokinetics

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.

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

Half-life: 1–1.3 hr.

TIME/ACTION PROFILE (plasma concentrations)

ROUTEONSETPEAKDURATION
PO30 min1–2 hr8–12 hr

Contraindication/Precautions

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 impairment;
  • Hepatic impairment;
  • Infectious mononucleosis (↑ risk of rash).

Adverse Reactions/Side Effects

Derm: rash, ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS, urticaria

GI: diarrhea, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), hepatic impairment, nausea, vomiting

GU: vaginal candidiasis

Hemat: blood dyscrasias

Neuro: SEIZURES (high doses)

Misc: ALLERGIC REACTIONS (including anaphylaxis and serum sickness), superinfection

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  •  Probenecid  ↓ renal excretion and ↑ levels; therapy may be combined for this purpose.
  • May ↑ risk of bleeding of  warfarin.
  • Concurrent  allopurinol  therapy ↑ risk of rash.
  • May ↓ effectiveness of  hormonal contraceptives.

Drug-Food:

Clavulanate absorption is ↓ by a high-fat meal.

Route/Dosage

Most Infections (Dosing based on amoxicillin component)

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

Serious Infections and Respiratory Tract Infections

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

Recurrent/Persistent Acute Otitis Media Due to Multidrug-Resistant Streptococcus pneumoniae, H. influenzae, or M. catarrhalis

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

Renal Impairment 
PO (Adults): CCr 10–30 mL/min:  250–500 mg every 12 hr;  CCr <10 mL/min:  250–500 mg every 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 every 12 hr;  125 mg/5 mL or 250 mg/5 mL suspension:  40 mg/kg/day divided every 8 hr.

Less Serious Infections

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

PO (Children  <3 mo): 125 mg/5 mL suspension: 15 mg/kg every 12 hr.

Availability (generic available)

Immediate-release tablets: 250 mg amoxicillin with 125 mg clavulanate, 500 mg amoxicillin with 125 mg clavulanate, 875 mg amoxicillin with 125 mg clavulanate

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

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

Powder for oral suspension (200 mg/5 mL 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): 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)

Assessment

  • Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and during 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, urticaria, pruritus, angioedema, hoarseness, dyspnea, wheezing). Notify health care professional immediately if these occur.
  • Assess for rash or signs and symptoms of SJS periodically during therapy (fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis). Discontinue therapy and provide supportive care.
  • 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 CDAD. May begin up to several wk 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 impairment.

  • Consider CBC to monitor for therapeutic response.
  • May cause false-positive direct Coombs test result.
  • May cause false positive readings on urine glucose tests.

Implementation

  • PO Administer around the clock. Administer at the start of a meal to enhance absorption and to ↓ GI side effects. Do not administer with high-fat meals; clavulanate absorption is ↓. Extended-release tablet is scored and can be broken for ease of administration DNC: however, do not crush extended-release tablet.  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 extended release 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.

Patient/Family Teaching

  • Educate patient on reason and side effects of amoxicillin/clavulanate. 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. Advise patient to read  Patient Information  before starting therapy.
  • 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.
  • Rep:  Instruct women of reproductive potential taking oral contraceptives to use an alternate or additional method of contraception during therapy and until next menstrual period; may ↓ effectiveness of hormonal contraceptives. Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

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

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