FDA label 47686d15-2e23-bdca-e063-6394a90aef43

WARNINGS AND PRECAUTIONS WARNINGS SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC) REACTIONS HAVE BEEN REPORTED IN PATIENTS ON PENICILLIN THERAPY. ALTHOUGH ANAPHYLAXIS IS MORE FREQUENT FOLLOWING PARENTERAL THERAPY, IT HAS OCCURRED IN PATIENTS ON ORAL PENICILLINS. THESE REACTIONS ARE MORE LIKELY TO OCCUR IN INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY AND/OR A HISTORY OF SENSITIVITY TO MULTIPLE ALLERGENS. THERE HAVE BEEN REPORTS OF INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVERE REACTIONS WHEN TREATED WITH CEPHALOSPORINS. BEFORE INITIATING THERAPY WITH AMOXICILLIN, CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS, CEPHALOSPORINS, OR OTHER ALLERGENS. IF AN ALLERGIC REACTION OCCURS, AMOXICILLIN SHOULD BE DISCONTINUED AND APPROPRIATE THERAPY INSTITUTED. SERIOUS ANAPHYLACTIC REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including amoxicillin, 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 antibiotic 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 antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated. PRECAUTIONS General The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur, amoxicillin should be discontinued and appropriate therapy instituted. A high percentage of patients with mononucleosis who receive ampicillin develop an erythematous skin rash. Thus, ampicillin-class antibiotics should not be administered to patients with mononucleosis. Prescribing amoxicillin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Laboratory Tests As with any potent drug, periodic assessment of renal, hepatic, and hematopoietic function should be made during prolonged therapy. All patients with gonorrhea should have a serologic test for syphilis at the time of diagnosis. Patients treated with amoxicillin should have a follow-up serologic test for syphilis after 3 months. Drug Interactions Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use of amoxicillin and probenecid may result in increased and prolonged blood levels of amoxicillin. Chloramphenicol, macrolides, sulfonamides, and tetracyclines may interfere with the bactericidal effects of penicillin. This has been demonstrated in vitro; however, the clinical significance of this interaction is not well documented. In common with other antibiotics, amoxicillin may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives. Drug/Laboratory Test Interactions High urine concentrations of ampicillin may result in false-positive reactions when testing for the presence of glucose in urine using CLINITEST®, Benedict’s Solution, or Fehling’s Solution. Since this effect may also occur with amoxicillin, it is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as CLINISTIX®) be used. Following administration of ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol has been noted. This effect may also occur with amoxicillin. Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals have not been performed to evaluate carcinogenic potential. Studies to detect mutagenic potential of amoxicillin alone have not been conducted; however, the following information is available from tests on a 4:1 mixture of amoxicillin and potassium clavulanate. Amoxicillin and potassium clavulanate was non-mutagenic in the Ames bacterial mutation assay, and the yeast gene conversion assay. Amoxicillin and potassium clavulanate was weakly positive in the mouse lymphoma assay, but the trend toward increased mutation frequencies in this assay occurred at doses that were also associated with decreased cell survival. Amoxicillin and potassium clavulanate was negative in the mouse micronucleus test, and in the dominant lethal assay in mice. Potassium clavulanate alone was tested in the Ames bacterial mutation assay and in the mouse micronucleus test, and was negative in each of these assays. In a multi-generation reproduction study in rats, no impairment of fertility or other adverse reproductive effects were seen at doses up to 500 mg/kg (approximately 3 times the human dose in mg/m2).

ADVERSE REACTIONS As with other penicillins, it may be expected that untoward reactions will be essentially limited to sensitivity phenomena. They are more likely to occur in individuals who have previously demonstrated hypersensitivity to penicillins and in those with a history of allergy, asthma, hay fever, or urticaria. The following adverse reactions have been reported as associated with the use of penicillins: Infections and Infestations: Mucocutaneous candidiasis. Gastrointestinal: Nausea, vomiting, diarrhea, black hairy tongue, and hemorrhagic/ pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment. (See WARNINGS section.) Hypersensitivity Reactions: Anaphylaxis (See WARNINGS section) Serum sickness-like reactions, erythematous maculopapular rashes, erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, hypersensitivity vasculitis and urticaria have been reported. NOTE: These hypersensitivity reactions may be controlled with antihistamines and, if necessary, systemic corticosteroids. Whenever such reactions occur, amoxicillin should be discontinued unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to amoxicillin therapy. Liver: A moderate rise in AST (SGOT) and/or ALT (SGPT) has been noted, but the significance of this finding is unknown. Hepatic dysfunction including cholestatic jaundice, hepatic cholestasis and acute cytolytic hepatitis have been reported. Renal: Crystalluria has also been reported (see OVERDOSAGE section). 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. Central Nervous System: Reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioral changes, and/or dizziness have been reported rarely. Miscellaneous: Tooth discoloration (brown, yellow, or gray staining) has been rarely reported. Most reports occurred in pediatric patients. Discoloration was reduced or eliminated with brushing or dental cleaning in most cases. Combination Therapy with Clarithromycin and Lansoprazole In clinical trials using combination therapy with amoxicillin plus clarithromycin and lansoprazole, and amoxicillin plus lansoprazole, no adverse reactions peculiar to these drug combinations were observed. Adverse reactions that have occurred have been limited to those that had been previously reported with amoxicillin, clarithromycin, or lansoprazole. Triple Therapy Amoxicillin/Clarithromycin/Lansoprazole The most frequently reported adverse events for patients who received triple therapy were diarrhea (7%), headache (6%), and taste perversion (5%). No treatment-emergent adverse events were observed at significantly higher rates with triple therapy than with any dual therapy regimen. Dual Therapy Amoxicillin/Lansoprazole The most frequently reported adverse events for patients who received amoxicillin three times daily plus lansoprazole three times daily dual therapy were diarrhea (8%) and headache (7%). No treatment-emergent adverse events were observed at significantly higher rates with amoxicillin three times daily plus lansoprazole three times daily dual therapy than with lansoprazole alone. For more information on adverse reactions with clarithromycin or lansoprazole, refer to their package inserts, ADVERSE REACTIONS section.