Amoxicillinside effects

The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Allergic Reactions, including Anaphylaxis Severe Cutaneous Adverse Reactions Drug-Induced Enterocolitis Syndrome (DIES) Hepatic Dysfunction Clostridioides difficile -associated diarrhea (CDAD) Skin Rash in Patients with Mononucleosis The most frequently reported adverse reactions with amoxicillin and clavulanate potassium for oral suspension were (incidence ≥3%) diarrhea/loose stools, nausea, skin rash, and urticaria. 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. Amoxicillin and Clavulanate Potassium for Oral Suspension The most frequently reported adverse reactions in clinical trials were diarrhea/loose stools (9%), nausea (3%), skin rash and urticaria (3%), vomiting (1%) and vaginitis (1%). Less than 3% of patients discontinued therapy due to adverse reactions. The overall incidence of adverse reactions, particularly diarrhea, increased with higher recommended doses. Other less frequently reported adverse reactions (<1%) included abdominal discomfort, flatulence, and headache. In two pivotal trials in adults with lower respiratory tract or urinary tract infections, the overall incidence of adverse reactions was similar between AUGMENTIN 875 mg/125 mg Tablets every 12 hours and AUGMENTIN 500 mg/125 mg Tablets every 8 hours. The most common adverse reaction was diarrhea, reported in 15% of patients receiving AUGMENTIN 875 mg/125 mg every 12 hours and 14% of patients receiving AUGMENTIN 500 mg/125 mg every 8 hours. The rate of severe diarrhea or discontinuation due to diarrhea was 1% versus 2%, respectively. In a controlled clinical trial of pediatric patients aged 2 months to 12 years with acute otitis media, diarrhea was defined in the protocol as ≥3 watery stools or ≥4 loose/watery stools in 1 day, or ≥2 watery stools or ≥3 loose/watery stools per day for 2 consecutive days, as recorded on diary cards. The incidence of diarrhea was significantly lower in patients treated with amoxicillin and clavulanate potassium for oral suspension 45 mg/kg/day divided every 12 hours (14%) compared to patients treated with amoxicillin and clavulanate potassium for oral suspension 40 mg/kg/day divided every 8 hours (34%). It is not known whether the statistically significant reduction in diarrhea with the oral suspension dosed every 12 hours, versus suspensions dosed every 8 hours, can be extrapolated to the chewable tablets, all of which contain mannitol. The presence of mannitol in the chewable tablets may contribute to a different diarrhea profile. Severe diarrhea or discontinuation due to diarrhea occurred in 3% and 8% of patients, respectively. Allergic reactions leading to discontinuation occurred in 1% and <1% of patients, and candidal infection of the diaper area was reported in 4% and 6% of patients, respectively.

6.2 Postmarketing

Experience The following adverse reactions have been identified during postmarketing use of amoxicillin and clavulanate potassium product. Because these reactions are reported voluntarily from a population of uncertain 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.

Immune: Hypersensitivity reactions, anaphylactic reactions (including shock), angioedema, serum sickness-like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, and frequently fever), hypersensitivity vasculitis.

Skin and Appendages: Rashes, pruritus, urticaria, erythema multiforme, SJS, TEN, DRESS, AGEP, exfoliative dermatitis, and linear IgA bullous dermatosis.

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 reported with amoxicillin and clavulanate potassium. 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.

Renal: Interstitial nephritis and hematuria have been reported. Crystalluria has also been reported.

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.