Amoxicillin And Clavulanate Potassium

Amoxicillin and clavulanate potassium for oral suspension is indicated for the treatment of infections in adults and pediatric patients, due to susceptible isolates of the designated bacteria in the conditions listed below:

• Lower Respiratory Tract Infections
  -
  caused by beta-lactamase–producing isolates of
  Haemophilus influenzae and Moraxella catarrhalis
  .

• Acute Bacterial Otitis Media
  -
  caused by beta-lactamase–producing isolates of
  H. influenzae and M. catarrhalis
  .

• Sinusitis
  -
  caused by beta-lactamase–producing isolates of
  H. influenzae and M. catarrhalis
  .

• Skin and Skin Structure Infections
  -
  caused by beta-lactamase–producing isolates of
  Staphylococcus aureus, Escherichia coli,
  and
  Klebsiella
  species
  .

• Urinary Tract Infections
  -
  caused by beta-lactamase–producing isolates of
  E. coli, Klebsiella
  species
  ,
  and
  Enterobacter
  species.

When susceptibility test results show susceptibility to amoxicillin, indicating no beta-lactamase production, amoxicillin and clavulanate potassium for oral suspension should not be used.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of amoxicillin and clavulanate potassium for oral suspension and other antibacterial drugs, amoxicillin and clavulanate potassium for oral suspension 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.

• Adults and Pediatric Patients greater than 40 kg: 500 or 875 mg every 12 hours or 250 or 500 mg every 8 hours, based on amoxicillin component. (
  2.2 Adult Patients

  See dosing regimens of amoxicillin and clavulanate potassium (based on the amoxicillin component) provided in Table 1below.

  Table 1. Dosing Regimens of Amoxicillin and Clavulanate Potassium in Adult Patients

  TYPE OF INFECTION	DOSING REGIMEN OF AMOXICILLIN AND CLAVULANATE POTASSIUM
  Severe infections and infections of the respiratory tract	one 875 mg tabletaof amoxicillin and clavulanate potassium every 12 hours or one 500 mg tabletb,cof amoxicillin and clavulanate potassium every 8 hours
  Less severe infections	one 500 mg tabletb,cof amoxicillin and clavulanate potassium every 12 hours or one 250 mg tabletdof amoxicillin and clavulanate potassium every 8 hours

  ^aAdults who have difficulty swallowing may be given the amoxicillin and clavulanate potassium 200 mg/28.5 mg per 5 mL suspension or the amoxicillin and clavulanate potassium 400 mg/57 mg per 5 mL suspension may be used in place of the 875 mg/125 mg tablet.

  ^bAdults who have difficulty swallowing may be given the amoxicillin and clavulanate potassium 125 mg/31.25 mg per 5 mL or amoxicillin and clavulanate potassium 250 mg/62.5 mg per 5 mL suspension in place of the 500 mg/125 mg tablet.

  ^cTwo amoxicillin and clavulanate potassium 250 mg/125 mg tablets are

  NOT

  substitutable with one 500 mg/125 mg amoxicillin and clavulanate potassium tablet

  [see Dosage and Administration ]

  .

  ^damoxicillin and clavulanate potassium 250 mg/125 mg tablet is

  NOT

  substitutable with amoxicillin and clavulanate potassium 250 mg/62.5 mg chewable tablet

  [see Dosage and Administration ]

  .
  ,
  2.3 Pediatric Patients

  Based on the amoxicillin component, amoxicillin and clavulanate potassium for oral suspension should be dosed as follows:

  Neonates and Infants Aged less than 12 weeks (less than 3 months):

  See dosing regimens of amoxicillin and clavulanate potassium for oral suspension provided in Table 2below.

  Table 2: Dosing Regimens of Amoxicillin and Clavulanate Potassium for Oral Suspension in Neonates and Infants Aged Less than 12 Weeks (Less than 3 Months)

  PATIENT POPULATION	DOSING REGIMEN
  	Amoxicillin and clavulanate potassium 125 mg/31.25 mg per 5 mL for oral suspension a
  Neonates and Infants aged less than 12 weeks (less than 3 months)	30 mg/kg/day every 12 hours

  ^aExperience with the amoxicillin and clavulanate potassium for oral suspension 200 mg/28.5 mg per 5 mL formulation in this age group is limited, and thus, use of the amoxicillin and clavulanate potassium 125 mg/31.25 mg per 5 mL for oral suspension is recommended.

  Patients Aged 12 weeks (3 months) and Older and Weighing Less than 40 kg:

  See dosing regimens provided in Table 3below.

  • The every 12 hour regimen is recommended as it is associated with significantly less diarrhea
    [see Clinical Studies ]
    .
  • The amoxicillin and clavulanate potassium 200 mg/28.5 mg per 5 mL and amoxicillin and clavulanate potassium 400 mg/57 mg per 5 mL for oral suspension and amoxicillin and clavulanate potassium 200 mg/28.5 mg and amoxicillin and clavulanate potassium 400 mg/57 mg chewable tablets contain aspartame and should not be used by phenylketonurics
    [see Warnings and Precautions ]
    .

  Table 3: Dosing in Patients Aged 12 Weeks (3 Months) and Older and Weighing Less than 40 kg

  INFECTION	DOSING REGIMEN
  	Every 12 hours	Every 8 hours
  	Amoxicillin and clavulanate potassium 200 mg/28.5 mg per 5 mL or Amoxicillin and clavulanate potassium 400 mg/57 mg per 5 mL for oral suspensiona	Amoxicillin and clavulanate potassium 125 mg/31.25 mg per 5 mL or Amoxicillin and clavulanate potassium 250 mg/62.5 mg per 5 mL for oral suspensiona
  Otitis mediab, sinusitis, lower respiratory tract infections, and more severe infections	45 mg/kg/day every 12 hours	40 mg/kg/day every 8 hours
  Less severe infections	25 mg/kg/day every 12 hours	20 mg/kg/day every 8 hours

  ^aEach strength of amoxicillin and clavulanate potassium for oral suspension is available as a chewable tablet for use by older children.

  ^bDuration of therapy studied and recommended for acute otitis media is 10 days.

  Patients Weighing 40 kg or More:

  Pediatric patients weighing 40 kg or more should be dosed according to adult recommendations.

  • The 250 mg/125 mg tablet of amoxicillin and clavulanate potassium should
    NOT
    be used until the child weighs at least 40 kg, due to the different amoxicillin to clavulanic acid ratios in the 250 mg/125 mg tablet of amoxicillin and clavulanate potassium versus the 250 mg/62.5 mg chewable tablet of amoxicillin and clavulanate potassium.
  )
• Pediatric patients aged 12 weeks (3 months) and older: 25 to 45 mg/kg/day every 12 hours or 20 to 40 mg/kg/day every 8 hours, up to the adult dose. (
  2.3 Pediatric Patients

  Based on the amoxicillin component, amoxicillin and clavulanate potassium for oral suspension should be dosed as follows:

  Neonates and Infants Aged less than 12 weeks (less than 3 months):

  See dosing regimens of amoxicillin and clavulanate potassium for oral suspension provided in Table 2below.

  Table 2: Dosing Regimens of Amoxicillin and Clavulanate Potassium for Oral Suspension in Neonates and Infants Aged Less than 12 Weeks (Less than 3 Months)

  PATIENT POPULATION	DOSING REGIMEN
  	Amoxicillin and clavulanate potassium 125 mg/31.25 mg per 5 mL for oral suspension a
  Neonates and Infants aged less than 12 weeks (less than 3 months)	30 mg/kg/day every 12 hours

  ^aExperience with the amoxicillin and clavulanate potassium for oral suspension 200 mg/28.5 mg per 5 mL formulation in this age group is limited, and thus, use of the amoxicillin and clavulanate potassium 125 mg/31.25 mg per 5 mL for oral suspension is recommended.

  Patients Aged 12 weeks (3 months) and Older and Weighing Less than 40 kg:

  See dosing regimens provided in Table 3below.

  • The every 12 hour regimen is recommended as it is associated with significantly less diarrhea
    [see Clinical Studies ]
    .
  • The amoxicillin and clavulanate potassium 200 mg/28.5 mg per 5 mL and amoxicillin and clavulanate potassium 400 mg/57 mg per 5 mL for oral suspension and amoxicillin and clavulanate potassium 200 mg/28.5 mg and amoxicillin and clavulanate potassium 400 mg/57 mg chewable tablets contain aspartame and should not be used by phenylketonurics
    [see Warnings and Precautions ]
    .

  Table 3: Dosing in Patients Aged 12 Weeks (3 Months) and Older and Weighing Less than 40 kg

  INFECTION	DOSING REGIMEN
  	Every 12 hours	Every 8 hours
  	Amoxicillin and clavulanate potassium 200 mg/28.5 mg per 5 mL or Amoxicillin and clavulanate potassium 400 mg/57 mg per 5 mL for oral suspensiona	Amoxicillin and clavulanate potassium 125 mg/31.25 mg per 5 mL or Amoxicillin and clavulanate potassium 250 mg/62.5 mg per 5 mL for oral suspensiona
  Otitis mediab, sinusitis, lower respiratory tract infections, and more severe infections	45 mg/kg/day every 12 hours	40 mg/kg/day every 8 hours
  Less severe infections	25 mg/kg/day every 12 hours	20 mg/kg/day every 8 hours

  ^aEach strength of amoxicillin and clavulanate potassium for oral suspension is available as a chewable tablet for use by older children.

  ^bDuration of therapy studied and recommended for acute otitis media is 10 days.

  Patients Weighing 40 kg or More:

  Pediatric patients weighing 40 kg or more should be dosed according to adult recommendations.

  • The 250 mg/125 mg tablet of amoxicillin and clavulanate potassium should
    NOT
    be used until the child weighs at least 40 kg, due to the different amoxicillin to clavulanic acid ratios in the 250 mg/125 mg tablet of amoxicillin and clavulanate potassium versus the 250 mg/62.5 mg chewable tablet of amoxicillin and clavulanate potassium.
  )
• Neonates and infants less than 12 weeks of age: 30 mg/kg/day divided every 12 hours, based on the amoxicillin component. Use of the 125 mg/5 mL oral suspension is recommended. (
  2.3 Pediatric Patients

  Based on the amoxicillin component, amoxicillin and clavulanate potassium for oral suspension should be dosed as follows:

  Neonates and Infants Aged less than 12 weeks (less than 3 months):

  See dosing regimens of amoxicillin and clavulanate potassium for oral suspension provided in Table 2below.

  Table 2: Dosing Regimens of Amoxicillin and Clavulanate Potassium for Oral Suspension in Neonates and Infants Aged Less than 12 Weeks (Less than 3 Months)

  PATIENT POPULATION	DOSING REGIMEN
  	Amoxicillin and clavulanate potassium 125 mg/31.25 mg per 5 mL for oral suspension a
  Neonates and Infants aged less than 12 weeks (less than 3 months)	30 mg/kg/day every 12 hours

  ^aExperience with the amoxicillin and clavulanate potassium for oral suspension 200 mg/28.5 mg per 5 mL formulation in this age group is limited, and thus, use of the amoxicillin and clavulanate potassium 125 mg/31.25 mg per 5 mL for oral suspension is recommended.

  Patients Aged 12 weeks (3 months) and Older and Weighing Less than 40 kg:

  See dosing regimens provided in Table 3below.

  • The every 12 hour regimen is recommended as it is associated with significantly less diarrhea
    [see Clinical Studies ]
    .
  • The amoxicillin and clavulanate potassium 200 mg/28.5 mg per 5 mL and amoxicillin and clavulanate potassium 400 mg/57 mg per 5 mL for oral suspension and amoxicillin and clavulanate potassium 200 mg/28.5 mg and amoxicillin and clavulanate potassium 400 mg/57 mg chewable tablets contain aspartame and should not be used by phenylketonurics
    [see Warnings and Precautions ]
    .

  Table 3: Dosing in Patients Aged 12 Weeks (3 Months) and Older and Weighing Less than 40 kg

  INFECTION	DOSING REGIMEN
  	Every 12 hours	Every 8 hours
  	Amoxicillin and clavulanate potassium 200 mg/28.5 mg per 5 mL or Amoxicillin and clavulanate potassium 400 mg/57 mg per 5 mL for oral suspensiona	Amoxicillin and clavulanate potassium 125 mg/31.25 mg per 5 mL or Amoxicillin and clavulanate potassium 250 mg/62.5 mg per 5 mL for oral suspensiona
  Otitis mediab, sinusitis, lower respiratory tract infections, and more severe infections	45 mg/kg/day every 12 hours	40 mg/kg/day every 8 hours
  Less severe infections	25 mg/kg/day every 12 hours	20 mg/kg/day every 8 hours

  ^aEach strength of amoxicillin and clavulanate potassium for oral suspension is available as a chewable tablet for use by older children.

  ^bDuration of therapy studied and recommended for acute otitis media is 10 days.

  Patients Weighing 40 kg or More:

  Pediatric patients weighing 40 kg or more should be dosed according to adult recommendations.

  • The 250 mg/125 mg tablet of amoxicillin and clavulanate potassium should
    NOT
    be used until the child weighs at least 40 kg, due to the different amoxicillin to clavulanic acid ratios in the 250 mg/125 mg tablet of amoxicillin and clavulanate potassium versus the 250 mg/62.5 mg chewable tablet of amoxicillin and clavulanate potassium.
  )

• Pediatric Use: Modify dose in patients 12 weeks or younger. (
  8.4 Pediatric Use

  The safety and effectiveness of Amoxicillin and Clavulanate Potassium Powder for Oral Suspension and Chewable Tablets have been established in pediatric patients. Use of Amoxicillin and Clavulanate Potassium powder for oral suspension in pediatric patients is supported by evidence from studies of Amoxicillin and Clavulanate Potassium Tablets in adults with additional data from a study of Amoxicillin and Clavulanate Potassium Powder for Oral Suspension in pediatric patients aged 2 months to 12 years with acute otitis media

  [see Clinical Studies ].

  Because of incompletely developed renal function in neonates and young infants, the elimination of amoxicillin may be delayed; clavulanate elimination is unaltered in this age group. Dosing of Amoxicillin and Clavulanate Potassium for oral suspension should be modified in pediatric patients aged less than 12 weeks (less than 3 months)

  [see Dosage and Administration ]

  for specific recommendations in patients with renal impairment.
  )

• Serious (including fatal) hypersensitivity reactions: Discontinue Amoxicillin and Clavulanate Potassium for Oral Suspension if a reaction occurs. (
  5.1 Hypersensitivity Reactions

  Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterials, including Amoxicillin and Clavulanate Potassium for Oral Suspension 250 mg/62.5 mg per 5 mL. 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 for Oral Suspension, careful inquiry should be made regarding
  
  previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, Amoxicillin and Clavulanate Potassium for Oral Suspension should be discontinued, and appropriate therapy instituted.
  )
• Severe Cutaneous Adverse Reactions (SCAR): Monitor closely. Discontinue if rash progresses. (
  5.2 Severe Cutaneous Adverse Reactions

  Amoxicillin and clavulanate potassium 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 discontinued if lesions progress.
  )
• Drug-induced enterocolitis syndrome (DIES) has been reported with use of amoxicillin, a component of Amoxicillin and Clavulanate Potassium for Oral Suspension. If this occurs, discontinue Amoxicillin and Clavulanate Potassium for Oral Suspension and institute appropriate therapy. (
  5.3 Drug-Induced Enterocolitis Syndrome (DIES)

  Drug-induced enterocolitis syndrome (DIES) has been reported with use of amoxicillin, a component of Amoxicillin and clavulanate potassium for Oral Suspension [see Adverse Reactions (6.2)], with most cases occurring in pediatric patients ≤ 18 years of age. DIES is a non-IgE mediated hypersensitivity reaction characterized by protracted vomiting occurring 1 to 4 hours after drug ingestion in the absence of skin or respiratory symptoms. DIES may be associated with pallor, lethargy, hypotension, shock, diarrhea within 24 hours of ingesting amoxicillin, and leukocytosis with neutrophilia. If DIES occurs, discontinue Amoxicillin and clavulanate potassium for Oral Suspension and institute appropriate therapy.
  )
• Hepatic dysfunction and cholestatic jaundice: Discontinue if signs/symptoms of hepatitis occur. Monitor liver function tests in patients with hepatic impairment. (
  5.4 Hepatic Dysfunction

  Hepatic dysfunction, including hepatitis and cholestatic jaundice has been associated with the use of Amoxicillin and Clavulanate Potassium for Oral Suspension. Hepatic toxicity is usually reversible; however, deaths have been reported. Hepatic function should be monitored at regular intervals in patients with hepatic impairment.
  )
• Clostridioides
  difficile
  -associated diarrhea (CDAD): Evaluate patients if diarrhea occurs. (
  5.5

  Clostridioides difficile

  Associated Diarrhea (CDAD)

  Clostridioides difficile

  associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Amoxicillin and Clavulanate Potassium for Oral Suspension, 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 use. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents.

  If CDAD is suspected or confirmed, ongoing antibacterial 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 develop skin rash. Avoid Amoxicillin and Clavulanate Potassium for Oral Suspension 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. Thus, Amoxicillin and Clavulanate Potassium for Oral Suspension should not be administered to patients with mononucleosis.
• Overgrowth: The possibility of superinfections with fungal or bacterial pathogens should be considered during therapy. (
  5.7 Potential for Microbial Overgrowth

  The possibility of superinfections with fungal or bacterial pathogens should be considered during therapy. If superinfection occurs, amoxicillin/clavulanate potassium should be discontinued and appropriate therapy instituted.
  )