1 INDICATIONS AND USAGE Amoxicillin and clavulanate potassium for oral suspension 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) ] .

Limitations of Use Amoxicillin and clavulanate potassium for oral suspension is not indicated for the treatment of acute otitis media due to S.

pneumoniae with penicillin MIC greater than or equal to 4 mcg/mL.

Acute otitis media due to S.

pneumoniae alone can be treated with amoxicillin.

Therapy may be instituted prior to obtaining the results from bacteriological studies when there is reason to believe the infection may involve both S.

pneumoniae (penicillin MIC less than or equal to 2 mcg/mL) and the beta-lactamase-producing organisms listed above.

Usage 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.

Amoxicillin and clavulanate potassium for oral suspension is a combination of amoxicillin, a penicillin-class antibacterial and clavulanate potassium, a beta-lactamase inhibitor, 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 ( 1 ) : Antibacterial exposure for acute otitis media within the preceding 3 months, and either of the following: 1) age 2 years, or younger or 2) daycare attendance.

Limitations of Use Amoxicillin and clavulanate potassium for oral suspension is not indicated for the treatment of acute otitis media due to S.

pneumoniae with penicillin MIC greater than or equal to 4 mcg/mL.

Acute otitis media due to S.

pneumoniae alone can be treated with amoxicillin.

Therapy may be instituted prior to obtaining the results from bacteriological studies when there is reason to believe the infection may involve both S.

pneumoniae (penicillin MIC less than or equal to 2 mcg/mL) and the beta-lactamase-producing organisms listed above.

( 1 ) Usage 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 bacteria.

( 1 )

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in labeling: Anaphylactic reactions [see Warnings and Precautions (5.1) ] Severe Cutaneous Adverse Reactions (SCAR) [see Warnings and Precautions (5.2) ] Drug-Induced Enterocolitis Syndrome (DIES) [see Warnings and Precautions (5.3) ] Hepatic Dysfunction [see Warnings and Precautions (5.4) ] Clostridioides difficile- Associated Diarrhea (CDAD) [see Warnings and Precautions (5.5) ] Skin Rash in Patients with Mononucleosis [see Warnings and Precautions (5.6) ] The most frequently reported adverse reactions (incidence rate > 4 %) were coughing, vomiting, contact dermatitis (i.e., diaper rash), fever, upper respiratory tract infection, and diarrhea.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc.

at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Two clinical trials evaluated the safety of a 10-day treatment course of amoxicillin and clavulanate potassium for oral suspension 90/6.4 mg/kg/day, divided every 12 hours, in pediatric patients with acute otitis media [see Clinical Studies (14) ] .

The first trial involved 521 pediatric patients (3 months to 50 months) and the second trial involved 450 pediatric patients (3 months to 12 years).

In the intent-to-treat population of the first trial of 521 patients, the most frequently reported adverse events were vomiting (7%), fever (6%), contact dermatitis (i.e., diaper rash) (6%), upper respiratory tract infection (4%), and diarrhea (4%).

Protocol-defined diarrhea (i.e., 3 or more watery stools in one day or 2 watery stools per day for 2 consecutive days as recorded on diary cards) occurred in 13% of patients.

The primary objective of the second study was to compare the safety of amoxicillin and clavulanate potassium for oral suspension (90/6.4 mg/kg/day, divided every 12 hours) to amoxicillin and clavulanate potassium (45/6.4 mg/kg/day, divided every 12 hours) for ten days.

There was no statistically significant difference between treatments in the proportion of patients with 1 or more adverse events.

The most frequently reported adverse reactions for amoxicillin and clavulanate potassium for oral suspension and the comparator of amoxicillin and clavulanate potassium were coughing (12% versus 7%), vomiting (7% versus 8%), contact dermatitis (i.e., diaper rash, 6% versus 5%), fever (6% versus 4%), and upper respiratory infection (3% versus 9%), respectively.

The frequencies of protocol-defined diarrhea with amoxicillin and clavulanate potassium for oral suspension (11%) and amoxicillin and clavulanate potassium (9%) were not statistically different.

Two patients in the group treated with amoxicillin and clavulanate potassium for oral suspension and one patient in the group treated with amoxicillin and clavulanate potassium were withdrawn due to diarrhea.

6.2 Postmarketing Experience The following adverse reactions have been identified during postmarketing use of amoxicillin and clavulanate potassium products, including amoxicillin and clavulanate potassium for oral suspension.

Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Gastrointestinal : Drug-induced enterocolitis syndrome (DIES), diarrhea, nausea, vomiting, indigestion, gastritis, stomatitis, glossitis, black “hairy” tongue, mucocutaneous candidiasis, enterocolitis, and hemorrhagic/pseudomembranous colitis.

Onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment [see Warnings and Precautions (5.3 , 5.5) ].

Immune: Hypersensitivity reactions, anaphylactic/anaphylactoid reactions (including shock), angioedema, serum sickness-like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, and frequently fever), hypersensitivity vasculitis [see Warnings and Precautions (5.1) ].

Skin and Appendages: Rashes, pruritus, urticaria, erythema multiforme, SJS, TEN, DRESS, AGEP, exfoliative dermatitis, and linear IgA bullous dermatosis [see Warnings and Precautions (5.1 , 5.2 , 5.6) ].

Liver: A moderate rise in AST (SGOT) and/or ALT (SGPT) has been noted in patients treated with ampicillin-class antibacterials.

Hepatic dysfunction, including increases in serum transaminases (AST and/or ALT), serum bilirubin, and/or alkaline phosphatase, has been infrequently reported with amoxicillin and clavulanate potassium or amoxicillin and clavulanate potassium for oral suspension.

It has been reported more commonly in the elderly, in males, or in patients on prolonged treatment.

The histologic findings on liver biopsy have consisted of cholestatic, hepatocellular, or mixed cholestatic-hepatocellular changes.

The onset of signs/symptoms of hepatic dysfunction may occur during or several weeks after therapy has been discontinued.

The hepatic dysfunction, which may be severe, is usually reversible.

Deaths have been reported [see Contraindications (4.2) , Warnings and Precautions (5.4) ].

Renal: Interstitial nephritis and hematuria have been reported.

Crystalluria has also been reported [see Overdosage (10) ] .

Hemic and Lymphatic Systems: Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis have been reported during therapy with penicillins.

These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena.

There have been reports of increased prothrombin time in patients receiving amoxicillin and clavulanate potassium and anticoagulant therapy concomitantly.

Central Nervous System: Agitation, anxiety, behavioral changes, aseptic meningitis, confusion, convulsions, dizziness, insomnia, and reversible hyperactivity have been reported.

Miscellaneous: Tooth discoloration (brown, yellow, or gray staining) has been reported.

Most reports occurred in pediatric patients.

Discoloration was reduced or eliminated with brushing or dental cleaning in most cases.