Amoxicillin And Clavulanate Potassium

Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL is indicated for the treatment of pediatric patients aged 3 months to 12 years weighing less than or equal to 40 kg with:

• Recurrent or persistent acute otitis media due to
  S. pneumoniae
  (penicillin MICs less than or equal to 2 mcg/mL),
  H. influenzae
  (including beta-lactamase-producing strains), or
  M. catarrhalis
  (including beta-lactamase-producing strains) characterized by the following risk factors:
  • Antibacterial drug exposure for acute otitis media within the preceding 3 months, and either of the following: 1) age 2 years, or younger or 2) day care attendance [
    see Microbiology
    (
    12.4 Microbiology

    Amoxicillin is a semisynthetic antibacterial with a broad spectrum of bactericidal activity against many gram-positive and gram-negative microorganisms. Amoxicillin is, however, susceptible to degradation by beta-lactamases, and therefore, its spectrum of activity does not include organisms which produce these enzymes. Clavulanic acid is a beta-lactam, structurally related to penicillin, which possesses the ability to inactivate a wide range of beta-lactamase enzymes commonly found in microorganisms resistant to penicillins and cephalosporins. In particular, it has good activity against the clinically important plasmid-mediated beta-lactamases frequently found responsible for transferred drug resistance.

    The clavulanic acid component of Amoxicillin and clavulanate potassium for oral suspension protects amoxicillin from degradation by beta-lactamase enzymes and effectively extends the antibacterial spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin and other beta-lactam antibacterials. Thus, Amoxicillin and clavulanate potassium for oral suspension possesses the distinctive properties of a broad spectrum antibacterial and a beta-lactamase inhibitor.

    Antimicrobial Activity

    Amoxicillin/clavulanic acid has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections

    [see Indications and Usage

    ( 1

    )]

    .

    Gram-positive bacteria:

    Streptococcus pneumoniae

    (including isolates with penicillin MICs less than or equal 2 mcg/mL)

    Gram-negative bacteria:

    Haemophilus influenzae

    (including beta-lactamase–producing isolates)

    Moraxella catarrhalis

    (including beta-lactamase–producing isolates)

    The following

    in vitro

    data are available, but their clinical significance is unknown. At least 90% of the following microorganisms exhibit in vitro minimum inhibitory concentrations (MICs) less than or equal to the susceptible breakpoint for amoxicillin/clavulanic acid. However, the safety and efficacy of amoxicillin/clavulanic acid in treating infections due to these microorganisms have not been established in adequate and well-controlled trials.

    Gram-positive bacteria:

    Staphylococcus aureus

    (including bata-lactamase–producing isolates)

    Staphylococci which are resistant to methicillin/oxacillin must be considered resistant to amoxicillin/clavulanic
    
    acid.

    Streptococcus pyogenes

    S. pyogenes

    do not produce beta-lactamase, and therefore, are susceptible to amoxicillin alone. Adequate and well-controlled clinical trials have established the effectiveness of amoxicillin alone in treating certain clinical infections due to

    S. pyogenes.

    Susceptibility Test Methods:

    
    
    For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.
    )].

Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL is not indicated for the treatment of acute otitis media due to

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL and other antibacterial drugs, Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Amoxicillin and Clavulanate Potassium Powder for Oral Suspension, USP:

• 600 mg/42.9 mg per 5 mL:
  Vanilla and tutti frutti-flavored for oral suspension (each 5 mL of reconstituted suspension contains 600 mg of amoxicillin as the Trihydrate, and 42.9 mg of clavulanic acid as the potassium salt).

Available data from published epidemiologic studies and pharmacovigilance case reports over several decades of use with amoxicillin and clavulanate during pregnancy have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal outcomes. A study in women with preterm prelabor rupture of membranes (PPROM) reported that prophylactic treatment with amoxicillin and clavulanate may be associated with an increased risk of necrotizing enterocolitis in neonates

One randomized, controlled trial included 4,826 pregnant women with premature rupture of fetal membranes who were randomly assigned to 250 mg erythromycin (n=1,197), 250 mg amoxicillin and 125 mg clavulanic acid (amoxicillin and clavulanate, n=1,212), amoxicillin and clavulanate and erythromycin (n=1,192), or placebo (n=1,225) four times daily for 10 days or until delivery. Amoxicillin and clavulanate was associated with a significantly increased rate of proven neonatal necrotizing enterocolitis: 1.9% (n = 24) in the amoxicillin and clavulanate only group versus 0.5% (n = 6) in the placebo group (p = 0.001), and 1.8% (n = 44) in the any amoxicillin and clavulanate group versus 0.7% (n =17) in the no amoxicillin and clavulanate group (p = 0.0005).

Reproduction studies performed in pregnant rats and mice given amoxicillin and clavulanate (2:1 ratio formulation of amoxicillin:clavulanate) at oral doses up to 1200 mg/kg/day revealed no evidence of harm to the fetus due to amoxicillin and clavulanate. The amoxicillin doses in rodents (based on body surface area and assuming a 20 kg child) were approximately 2 times (rats) or equal to (mice) the recommended clinical Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL dose of 90/6.4 mg/kg/day. For clavulanate, these dose multiples were approximately 15 times and 7.5 times the recommended daily dose of Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL.

• Serious (including fatal) hypersensitivity reactions: Discontinue amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL if a reaction occurs and institute appropriate therapy. (
  5.1 Serious Allergic Reactions, Including Anaphylaxis

  Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterials, including amoxicillin and clavulanate potassium. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens.

  Before initiating therapy with amoxicillin and clavulanate potassium, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, discontinue amoxicillin and clavulanate potassium and institute appropriate therapy.
  )
• Severe cutaneous adverse reactions (SCAR): Monitor closely. Discontinue if rash progresses. (
  5.2 Severe Cutaneous Adverse Reactions

  Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL may cause severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). If patients develop a skin rash, they should be monitored closely, and amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL discontinued if lesions progress.
  )
• Drug-induced enterocolitis syndrome (DIES) has been reported with the use of amoxicillin, a component of Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL. If this occurs, discontinue Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL and institute appropriate therapy. (
  5.5

  Clostridium difficile

  -Associated Diarrhea (CDAD)

  Clostridium difficile

  associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including amoxicillin and clavulanate potassium and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of

  C. difficile

  .

  C. difficile

  produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of

  C. difficile

  cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

  If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against

  C. difficile

  may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of

  C. difficile

  , and surgical evaluation should be instituted as clinically indicated.
  )
• Hepatic dysfunction and cholestatic jaundice: Discontinue if signs/symptoms of hepatitis occur. Monitor liver function tests in patients with hepatic impairment. (
  5.2 Severe Cutaneous Adverse Reactions

  Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL may cause severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). If patients develop a skin rash, they should be monitored closely, and amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL discontinued if lesions progress.
  )
• Clostridium difficile
  -associated diarrhea (CDAD): Evaluate patients if diarrhea occurs. (
  5.5

  Clostridium difficile

  -Associated Diarrhea (CDAD)

  Clostridium difficile

  associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including amoxicillin and clavulanate potassium and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of

  C. difficile

  .

  C. difficile

  produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of

  C. difficile

  cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

  If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against

  C. difficile

  may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of

  C. difficile

  , and surgical evaluation should be instituted as clinically indicated.
  )
• Patients with mononucleosis who receive amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL develop skin rash. Avoid amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL use in these patients. (
  5.6 Skin Rash in Patients with Mononucleosis

  A high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash. Avoid amoxicillin and clavulanate potassium use in patients with mononucleosis.

The following clinically significant adverse reactions are described elsewhere in labeling:

• Anaphylactic reactions
  [see Warnings and Precautions (

  5.1 Serious Allergic Reactions, Including Anaphylaxis

  Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterials, including amoxicillin and clavulanate potassium. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens.

  Before initiating therapy with amoxicillin and clavulanate potassium, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, discontinue amoxicillin and clavulanate potassium and institute appropriate therapy.

  )]
• Severe Cutaneous Adverse Reactions (SCAR)
  [see Warnings and Precautions (

  5.2 Severe Cutaneous Adverse Reactions

  Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL may cause severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). If patients develop a skin rash, they should be monitored closely, and amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL discontinued if lesions progress.

  )]
• Drug-Induced Enterocolitis Syndrome (DIES)
  [see Warnings and Precautions ]
• Hepatic Dysfunction
  [see Warnings and Precautions (

  5.4 Hepatic Dysfunction

  Use amoxicillin and clavulanate potassium with caution in patients with evidence of hepatic dysfunction. Hepatic toxicity associated with the use of amoxicillin and clavulanate potassium is usually reversible. Deaths have been reported (fewer than one death reported per estimated four million prescriptions worldwide). These have generally been cases associated with serious underlying diseases or concomitant medications

  [see Contraindications (

  4.2) and Adverse Reactions ].

  ]
• Clostridioides difficile
  Associated Diarrhea (CDAD)
  [see Warnings and Precautions ]
• Skin Rash in Patients with Mononucleosis
  [see Warnings and Precautions (

  5.6 Skin Rash in Patients with Mononucleosis

  A high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash. Avoid amoxicillin and clavulanate potassium use in patients with mononucleosis.

  )]