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.

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

  The safety and effectiveness of amoxicillin and clavulanate potassium for oral suspension and chewable tablets have been established in pediatric patients. Use of amoxicillin and clavulanate potassium 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 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 should be modified in pediatric patients aged less than 12 weeks (less than 3 months). [

  see Dosage and Administration

  ]
  )
• Renal Impairment: Dosage adjustment is recommended for severe renal impairment (GFR less than 30mL/min). (
  2.4 Patients With Renal Impairment

  Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Renal impairment patients with a glomerular filtration rate (GFR) of less than 30 mL/min should NOT receive the 875 mg dose (based on the amoxicillin component) of amoxicillin and clavulanate potassium. See dosing regimens in patients with severe renal impairment provided in Table 4.

  Table 4. Dosing Regimens of Amoxicillin and clavulanate potassium in Patients with Severe Renal Impairment

  Patients with Renal Impairment	Dosing Regimen
  GFR 10 mL/min to 30 mL/min	500 mg or 250 mg every 12 hours, depending on the severity of the infection
  GFR less than 10 mL/min	500 mg or 250 mg every 24 hours, depending on the severity of the infection
  Hemodialysis	500 mg or 250 mg every 24 hours, depending on the severity of the infection Administer an additional dose both during and at the end of dialysis
  ,
  8.6 Renal Impairment

  Amoxicillin is primarily eliminated by the kidney and dosage adjustment is usually required in patients with severe renal impairment (GFR less than 30 mL/min). See Patients with Renal Impairment

  [see Dosage and Administration ]

  for specific recommendations in patients with renal impairment.
  )

• Serious (including fatal) hypersensitivity reactions: Discontinue amoxicillin and clavulanate potassium 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. 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 regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, amoxicillin and clavulanate potassium 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. If this occurs, discontinue amoxicillin and clavulanate potassium 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 develop skin rash. Avoid amoxicillin and clavulanate potassium 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 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.
  )

The following are discussed in more detail in other sections of the labeling:

• Anaphylactic reactions
  [see Warnings and Precautions (

  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. 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 regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, amoxicillin and clavulanate potassium should be discontinued and appropriate therapy instituted.

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

  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)
  [see Warnings and Precautions (

  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
  [see Warnings and Precautions (

  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)
  [see Warnings and Precautions ]