ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following are discussed in more detail in other sections of the labeling:Anaphylactic reactions [see Warnings and Precautions (5.1)]CDAD [see Warnings and Precautions (5.2)]. Anaphylactic reactions [see Warnings and Precautions (5.1)]. CDAD [see Warnings and Precautions (5.2)]. The most common adverse reactions (> 1%) observed in clinical trials of amoxicillin capsules, tablets (chewable) or oral suspension were diarrhea, rash, vomiting, and nausea. (6.1)To report SUSPECTED ADVERSE REACTIONS, contact Teva Pharmaceuticals USA, Inc. at 1-888-838-2872 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 drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.The most common adverse reactions (> 1%) observed in clinical trials of amoxicillin capsules, tablets or oral suspension were diarrhea, rash, vomiting, and nausea.Triple Therapy: The most frequently reported adverse events for patients who received triple therapy (amoxicillin/clarithromycin/lansoprazole) were diarrhea (7%), headache (6%), and taste perversion (5%).Dual Therapy: The most frequently reported adverse events for patients who received double therapy amoxicillin/lansoprazole were diarrhea (8%) and headache (7%). For more information on adverse reactions with clarithromycin or lansoprazole, refer to the Adverse Reactions section of their package inserts.. 6.2 Postmarketing or Other Experience. In addition to adverse events reported from clinical trials, the following events have been identified during postmarketing use of penicillins. Because they are reported voluntarily from population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to combination of their seriousness, frequency of reporting, or potential causal connection to amoxicillin.Infections and Infestations: Mucocutaneous candidiasis.Gastrointestinal: Black hairy tongue and hemorrhagic/pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment [see Warnings and Precautions (5.2)].Hypersensitivity Reactions: Anaphylaxis [see Warnings and Precautions (5.1)]. 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.Liver: moderate rise in AST and/or ALT 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 been reported [see Overdosage (10)].Hemic and Lymphatic Systems: Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis have been reported. 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.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.. Infections and Infestations: Mucocutaneous candidiasis.. Gastrointestinal: Black hairy tongue and hemorrhagic/pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment [see Warnings and Precautions (5.2)].. Hypersensitivity Reactions: Anaphylaxis [see Warnings and Precautions (5.1)]. 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.. Liver: moderate rise in AST and/or ALT 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 been reported [see Overdosage (10)].. Hemic and Lymphatic Systems: Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis have been reported. 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.. 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.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 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 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 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 times the g human dose based on body surface area).

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Amoxicillin is an antibacterial drug [see Microbiology (12.4)].. 12.3 Pharmacokinetics. Absorption Amoxicillin is stable in the presence of gastric acid and is rapidly absorbed after oral administration. The effect of food on the absorption of amoxicillin from the tablets and suspension of amoxicillin has been partially investigated; 400 mg and 875 mg formulations have been studied only when administered at the start of light meal.Orally administered doses of 250 mg and 500 mg amoxicillin capsules result in average peak blood levels to hours after administration in the range of 3.5 mcg/mL to mcg/mL and 5.5 mcg/mL to 7.5 mcg/mL, respectively.Mean amoxicillin pharmacokinetic parameters from an open, two-part, single-dose crossover bioequivalence study in 27 adults comparing 875 mg of amoxicillin with 875 mg of amoxicillin/clavulanate potassium showed that the 875 mg of amoxicillin tablet produces an AUC0 to of 35.4 +- 8.1 mcgohr/mL and Cmax of 13.8 +- 4.1 mcg/mL. Dosing was at the start of light meal following an overnight fast. Orally administered doses of amoxicillin suspension, 125 mg/5 mL and 250 mg/5 mL, result in average peak blood levels to hours after administration in the range of 1.5 mcg/mL to mcg/mL and 3.5 mcg/mL to mcg/mL, respectively.Oral administration of single doses of 400 mg chewable tablets and 400 mg/5 mL suspension of amoxicillin to 24 adult volunteers yielded comparable pharmacokinetic data:Table 3: Mean Pharmacokinetic Parameters of Amoxicillin (400 mg chewable tablets and 400 mg/5 mL suspension) in Healthy AdultsDoseaAUC0 to (mcgohr/mL) Cmax (mcg/mL)bAmoxicillinAmoxicillin (+- S.D.)Amoxicillin (+- S.D.)400 mg (5 mL of suspension)17.1 (3.1)5.92 (1.62)400 mg (1 chewable tablet)17.9 (2.4)5.18 (1.64)a. Administered at the start of light meal.b. Mean values of 24 normal volunteers. Peak concentrations occurred approximately hour after the dose.Distribution Amoxicillin diffuses readily into most body tissues and fluids, with the exception of brain and spinal fluid, except when meninges are inflamed. In blood serum, amoxicillin is approximately 20% protein-bound. Following 1 gram dose and utilizing special skin window technique to determine levels of the antibiotic, it was noted that therapeutic levels were found in the interstitial fluid.Metabolism and Excretion The half-life of amoxicillin is 61.3 minutes. Approximately 60% of an orally administered dose of amoxicillin is excreted in the urine within to hours. Detectable serum levels are observed up to hours after an orally administered dose of amoxicillin. Since most of the amoxicillin is excreted unchanged in the urine, its excretion can be delayed by concurrent administration of probenecid [see DRUG INTERACTIONS (7.1)].. 12.4 Microbiology. Mechanism of ActionAmoxicillin is similar to penicillin in its bactericidal action against susceptible bacteria during the stage of active multiplication. It acts through the inhibition of cell wall biosynthesis that leads to the death of the bacteria.Mechanism of ResistanceResistance to amoxicillin is mediated primarily through enzymes called beta-lactamases that cleave the beta-lactam ring of amoxicillin, rendering it inactive.Amoxicillin has been shown to be active against most isolates of the bacteria listed below, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.Gram-Positive BacteriaEnterococcus faecalisStaphylococcus spp.Streptococcus pneumoniaeStreptococcus spp. (alpha and beta-hemolytic)Gram-Negative BacteriaEscherichia coli Haemophilus influenzae Helicobacter pylori Proteus mirabilisSusceptibility Testing For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. 14.1 H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence. Randomized, double-blind clinical studies performed in the United States in patients with H. pylori and duodenal ulcer disease (defined as an active ulcer or history of an ulcer within year) evaluated the efficacy of lansoprazole in combination with amoxicillin capsules and clarithromycin tablets as triple 14 day therapy, or in combination with amoxicillin capsules as dual 14 day therapy, for the eradication of H. pylori. Based on the results of these studies, the safety and efficacy of different eradication regimens were established: Triple Therapy: Amoxicillin gram twice daily/clarithromycin 500 mg twice daily/lansoprazole 30 mg twice daily (see Table 6). Dual Therapy: Amoxicillin gram three times daily/lansoprazole 30 mg three times daily (see Table 7). All treatments were for 14 days. H. pylori eradication was defined as negative tests (culture and histology) at to weeks following the end of treatment. Triple therapy was shown to be more effective than all possible dual therapy combinations. Dual therapy was shown to be more effective than both monotherapies. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence.Table 6. H. pylori Eradication Rates When Amoxicillin is Administered as Part of Triple Therapy RegimenStudy Triple TherapyTriple TherapyEvaluable Analysisa[95% Confidence Interval](Number of Patients)Intent-to-Treat Analysisb[95% Confidence Interval](Number of Patients)Study 192[80 to 97.7](n 48)86[73.3 to 93.5](n 55)Study 286[75.7 to 93.6](n 66)83[72 to 90.8](n 70)a. This analysis was based on evaluable patients with confirmed duodenal ulcer (active or within year) and H. pylori infection at baseline defined as at least of positive endoscopic tests from CLOtest(R), histology, and/or culture. Patients were included in the analysis if they completed the study. Additionally, if patients dropped out of the study due to an adverse event related to the study drug, they were included in the analysis as failures of therapy.b. Patients were included in the analysis if they had documented H. pylori infection at baseline as defined above and had confirmed duodenal ulcer (active or within year). All dropouts were included as failures of therapy.Table 7. H. pylori Eradication Rates When Amoxicillin is Administered as Part of Dual Therapy Regimen StudyDual TherapyDual TherapyEvaluable Analysisa[95% Confidence Interval](Number of Patients)Intent-to-Treat Analysisb[95% Confidence Interval](Number of Patients)Study 177[62.5 to 87.2](n 51)70[56.8 to 81.2](n 60)Study 266[51.9 to 77.5](n 58)61[48.5 to 72.9](n 67)a. This analysis was based on evaluable patients with confirmed duodenal ulcer (active or within year) and H. pylori infection at baseline defined as at least of positive endoscopic tests from CLOtest(R), histology, and/or culture. Patients were included in the analysis if they completed the study. Additionally, if patients dropped out of the study due to an adverse event related to the study drug, they were included in the analysis as failures of therapy. b. Patients were included in the analysis if they had documented H. pylori infection at baseline as defined above and had confirmed duodenal ulcer (active or within year). All dropouts were included as failures of therapy.

DESCRIPTION SECTION.

11 DESCRIPTION. Amoxicillin, USP is semisynthetic antibiotic, an analog of ampicillin, with broad spectrum of bactericidal activity against many gram-positive and gram-negative microorganisms. Chemically, it is (2S,5R,6R)-6-[(R)-(-)-2-amino-2-(p-hydroxyphenyl)acetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid trihydrate. The structural formula is:C16H19N3O5So3H2O M.W. 419.45Amoxicillin Capsules USPEach capsule, for oral administration, contains 250 mg or 500 mg amoxicillin, USP as the trihydrate.Inactive Ingredients: CAPSULES-DRUG PRODUCT: magnesium stearate, talc.CAPSULE SHELL AND PRINT CONSTITUENTS: black iron oxide, D&C Yellow 10, D&C Yellow 10 Aluminum Lake, FD&C Blue Aluminum Lake, FD&C Blue Aluminum Lake, FD&C Red 40, FD&C Red 40 Aluminum Lake, gelatin, propylene glycol, shellac, titanium dioxide. In addition, the 500 mg capsule shell may also contain methylparaben, potassium hydroxide, propylparaben, and sodium lauryl sulfate; and the 250 mg capsule shell contains D&C Red 28 and FD&C Blue 1.Amoxicillin for Oral Suspension USPEach mL of reconstituted suspension contains 125 mg or 250 mg of amoxicillin, USP as the trihydrate.Inactive Ingredients: SUSPENSION: FD&C Red 40, mixed berry flavoring, silicon dioxide, sodium benzoate, sodium citrate, sucrose, and xanthan gum.Amoxicillin Tablets USP (Chewable)Each chewable tablet, for oral administration, contains 125 mg or 250 mg of amoxicillin, USP as the trihydrate.Inactive Ingredients: CHEWABLE TABLETS: cherry flavor, lactose anhydrous, magnesium stearate, mannitol, microcrystalline cellulose, sodium citrate, and sucrose.. Chemical Structure.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. In adults, 750 to 1750 mg/day in divided doses every to 12 hours. In Pediatric Patients 3 Months of Age, 20 to 45 mg/kg/day in divided doses every to 12 hours. Refer to full prescribing information for specific dosing regimens. (2.1, 2.2, 2.3)The upper dose for neonates and infants <= months is 30 mg/kg/day divided every 12 hours. (2.2)Dosing for H. pylori Infection: Triple therapy: gram amoxicillin, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily (every 12 hours) for 14 days. Dual therapy: gram amoxicillin and 30 mg lansoprazole, each given three times daily (every hours) for 14 days. (2.3)Reduce the dose in patients with severe renal impairment (GFR 30 mL/min). (2.4). In adults, 750 to 1750 mg/day in divided doses every to 12 hours. In Pediatric Patients 3 Months of Age, 20 to 45 mg/kg/day in divided doses every to 12 hours. Refer to full prescribing information for specific dosing regimens. (2.1, 2.2, 2.3). The upper dose for neonates and infants <= months is 30 mg/kg/day divided every 12 hours. (2.2). Dosing for H. pylori Infection: Triple therapy: gram amoxicillin, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily (every 12 hours) for 14 days. Dual therapy: gram amoxicillin and 30 mg lansoprazole, each given three times daily (every hours) for 14 days. (2.3). Reduce the dose in patients with severe renal impairment (GFR 30 mL/min). (2.4). 2.1 Dosing for Adult and Pediatric Patients 3 Months of Age. Treatment should be continued for minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. It is recommended that there be at least 10 days treatment for any infection caused by Streptococcus pyogenes to prevent the occurrence of acute rheumatic fever. In some infections, therapy may be required for several weeks. It may be necessary to continue clinical and/or bacteriological follow-up for several months after cessation of therapy.Table 1. Dosing Recommendations for Adult and Pediatric Patients 3 Months of Age InfectionSeverityaUsual Adult DoseUsual Dose for Children 3 MonthsbEar/Nose/ThroatSkin/Skin StructureGenitourinary TractMild/Moderate500 mg every 12 hours or250 mg every hours25 mg/kg/day in divided doses every 12 hoursor20 mg/kg/day in divided dosesevery hoursSevere875 mg every 12 hours or500 mg every hours45 mg/kg/day in divided doses every 12 hoursor40 mg/kg/day in divided dosesevery hoursLower RespiratoryTractMild/Moderate orSevere875 mg every 12 hours or500 mg every hours45 mg/kg/day in divided dosesevery 12 hoursor40 mg/kg/day in divided dosesevery hoursa. Dosing for infections caused by bacteria that are intermediate in their susceptibility to amoxicillin should follow the recommendations for severe infections.b. The childrens dosage is intended for individuals whose weight is less than 40 kg. Children weighing 40 kg or more should be dosed according to the adult recommendations.. 2.2 Dosing in Neonates and Infants Aged <= 12 Weeks (<= Months). Treatment should be continued for minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. It is recommended that there be at least 10 days treatment for any infection caused by Streptococcus pyogenes to prevent the occurrence of acute rheumatic fever. Due to incompletely developed renal function affecting elimination of amoxicillin in this age group, the recommended upper dose of amoxicillin is 30 mg/kg/day divided every 12 hours. There are currently no dosing recommendations for pediatric patients with impaired renal function.. 2.3 Dosing for H. pylori Infection. Triple Therapy: The recommended adult oral dose is gram amoxicillin, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily (every 12 hours) for 14 days.Dual Therapy: The recommended adult oral dose is gram amoxicillin and 30 mg lansoprazole, each given three times daily (every hours) for 14 days.Please refer to clarithromycin and lansoprazole full prescribing information.. 2.4 Dosing in Renal Impairment. Patients with impaired renal function do not generally require reduction in dose unless the impairment is severe.Severely impaired patients with glomerular filtration rate of 30 mL/min should not receive 875 mg dose.Patients with glomerular filtration rate of 10 to 30 mL/min should receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection.Patients with glomerular filtration rate less than 10 mL/min should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection.Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.. Patients with impaired renal function do not generally require reduction in dose unless the impairment is severe.. Severely impaired patients with glomerular filtration rate of 30 mL/min should not receive 875 mg dose.. Patients with glomerular filtration rate of 10 to 30 mL/min should receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection.. Patients with glomerular filtration rate less than 10 mL/min should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection.. Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.. 2.5 Directions for Mixing Oral Suspension. Tap bottle until all powder flows freely. Add approximately 1/3 of the total amount of water for reconstitution (see Table 2) and shake vigorously to wet powder. Add remainder of the water and again shake vigorously.Table 2. Amount of Water for Mixing Oral Suspension StrengthBottle SizeAmount of WaterRequired for ReconstitutionOral Suspension 125 mg/5 mL80 mL62 mL100 mL77 mL150 mL113 mLOral Suspension 250 mg/5 mL80 mL47 mL100 mL60 mL150 mL90 mLAfter reconstitution, the required amount of suspension should be placed directly on the childs tongue for swallowing. Alternate means of administration are to add the required amount of suspension to formula, milk, fruit juice, water, ginger ale, or cold drinks. These preparations should then be taken immediately.NOTE: SHAKE ORAL SUSPENSION WELL BEFORE USING. Keep bottle tightly closed. Any unused portion of the reconstituted suspension must be discarded after 14 days. Refrigeration is preferable, but not required.

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. Amoxicillin Capsules USP250 mg: Opaque caramel cap and opaque buff body, hard gelatin capsule. Printed black TEVA on cap and 3107 on body portions of the capsule and contain 250 mg amoxicillin as the trihydrate. 500 mg: Opaque buff cap and opaque buff body, hard gelatin capsules. Printed black TEVA on cap and 3109 on body portions of the capsules and contain 500 mg amoxicillin as the trihydrate.Amoxicillin for Oral Suspension USP125 mg/5 mL: Each mL of reconstituted mixed berry flavored suspension contains 125 mg amoxicillin as the trihydrate. 250 mg/5 mL: Each mL of reconstituted mixed berry flavored suspension contains 250 mg amoxicillin as the trihydrate. Amoxicillin Tablets USP (Chewable)125 mg: White to off-white, capsule-shaped tablet, unscored, debossed 93 on one side and 2267 on the other side and contain 125 mg amoxicillin as the trihydrate. 250 mg: White to off-white, capsule-shaped tablet, debossed 93 (partial bisect between and 3) on one side and 2268 on the other side and contain 250 mg amoxicillin as the trihydrate.. Capsules: 250 mg, 500 mg (3)Powder for Oral Suspension: 125 mg/5 mL, 250 mg/5 mL (3)Tablets (Chewable): 125 mg, 250 mg (3). Capsules: 250 mg, 500 mg (3). Powder for Oral Suspension: 125 mg/5 mL, 250 mg/5 mL (3). Tablets (Chewable): 125 mg, 250 mg (3).

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS. Probenicid decreases renal tubular secretion of amoxicillin which may result in increased blood levels of amoxicillin. (7.1)Concomitant use of amoxicillin and oral anticoagulants may increase the prolongation of prothrombin time. (7.2)Coadministration with allopurinol increases the risk of rash. (7.3)Amoxicillin may reduce the efficacy of oral contraceptives. (7.4). Probenicid decreases renal tubular secretion of amoxicillin which may result in increased blood levels of amoxicillin. (7.1). Concomitant use of amoxicillin and oral anticoagulants may increase the prolongation of prothrombin time. (7.2). Coadministration with allopurinol increases the risk of rash. (7.3). Amoxicillin may reduce the efficacy of oral contraceptives. (7.4). 7.1 Probenecid. Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use of amoxicillin and probenecid may result in increased and prolonged blood levels of amoxicillin.. 7.2 Oral Anticoagulants. Abnormal prolongation of prothrombin time (increased international normalized ratio [INR]) has been reported in patients receiving amoxicillin and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation.. 7.3 Allopurinol. The concurrent administration of allopurinol and amoxicillin increases the incidence of rashes in patients receiving both drugs as compared to patients receiving amoxicillin alone. It is not known whether this potentiation of amoxicillin rashes is due to allopurinol or the hyperuricemia present in these patients.. 7.4 Oral Contraceptives. Amoxicillin may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.. 7.5 Other Antibacterials. 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.. 7.6 Effects on Laboratory Tests. High urine concentrations of ampicillin may result in false-positive reactions when testing for the presence of glucose in urine using CLINITEST(R), Benedicts Solution, or Fehlings Solution. Since this effect may also occur with amoxicillin, it is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as CLINISTIX(R)) be used.Following administration of ampicillin or amoxicillin to pregnant women, transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol has been noted.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. Amoxicillin Capsules USP are supplied as follows:250 mg: Opaque caramel cap and opaque buff body, hard gelatin capsule. Printed black TEVA on cap and 3107 on body portions of the capsule and contain 250 mg amoxicillin as the trihydrate. They are available in bottles of 100 (NDC 0093-3107-01) and 500 (NDC 0093-3107-05) capsules.500 mg: Opaque buff cap and opaque buff body, hard gelatin capsules. Printed black TEVA on cap and 3109 on body portions of the capsules and contain 500 mg amoxicillin as the trihydrate. They are available in bottles of 50 (NDC 0093-3109-53) and 500 (NDC 0093-3109-05) capsules.Amoxicillin for Oral Suspension USP is supplied as follows:125 mg/5 mL: Each mL of reconstituted mixed berry flavored suspension contains 125 mg amoxicillin as the trihydrate. It is available in bottles of 80 mL (NDC 0093-4150-79), and 150 mL (NDC 0093-4150-80).250 mg/5 mL: Each mL of reconstituted mixed berry flavored suspension contains 250 mg amoxicillin as the trihydrate. It is available in bottles of 80 mL (NDC 0093-4155-79), 100 mL (NDC 0093-4155-73), and 150 mL (NDC 0093-4155-80).Amoxicillin Tablets USP (Chewable) are supplied as follows: 125 mg: White to off-white, capsule-shaped tablet, unscored, debossed 93 on one side and 2267 on the other side and contain 125 mg amoxicillin as the trihydrate. They are available in bottles of 100 tablets (NDC 0093-2267-01).250 mg: White to off-white, capsule-shaped tablet, debossed 93 (partial bisect between and 3) on one side and 2268 on the other side and contain 250 mg amoxicillin as the trihydrate. They are available in bottles of 100 tablets (NDC 0093-2268-01).Store at 20 to 25C (68 to 77F) [See USP Controlled Room Temperature].Dispense in tight, light-resistant container as defined in the USP, with child-resistant closure (as required).KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. Amoxicillin is penicillin-class antibacterial indicated for treatment of infections due to susceptible strains of designated microorganisms.Infections of the ear, nose, throat, genitourinary tract, skin and skin structure, and lower respiratory tract. (1.1 to 1.4)In combination for treatment of H. pylori infection and duodenal ulcer disease. (1.5)To reduce the development of drug-resistant bacteria and maintain the effectiveness of amoxicillin capsules, amoxicillin for oral suspension, amoxicillin tablets (chewable) and other antibacterial drugs, amoxicillin capsules, amoxicillin for oral suspension, and amoxicillin tablets (chewable) should be used only to treat infections that are proven or strongly suspected to be caused by bacteria. (1.6). Infections of the ear, nose, throat, genitourinary tract, skin and skin structure, and lower respiratory tract. (1.1 to 1.4). In combination for treatment of H. pylori infection and duodenal ulcer disease. (1.5). 1.1 Infections of the Ear, Nose, and Throat. Amoxicillin capsules, amoxicillin for oral suspension, amoxicillin tablets (chewable) are indicated in the treatment of infections due to susceptible (ONLY -lactamase-negative) isolates of Streptococcus species (- and -hemolytic isolates only), Streptococcus pneumoniae, Staphylococcus spp., or Haemophilus influenzae.. 1.2 Infections of the Genitourinary Tract. Amoxicillin capsules, amoxicillin for oral suspension, amoxicillin tablets (chewable) are indicated in the treatment of infections due to susceptible (ONLY -lactamase-negative) isolates of Escherichia coli, Proteus mirabilis, or Enterococcus faecalis.. 1.3 Infections of the Skin and Skin Structure. Amoxicillin capsules, amoxicillin for oral suspension, amoxicillin tablets (chewable) are indicated in the treatment of infections due to susceptible (ONLY -lactamase-negative) isolates of Streptococcus spp. (- and -hemolytic isolates only), Staphylococcus spp., or E. coli.. 1.4 Infections of the Lower Respiratory Tract. Amoxicillin capsules, amoxicillin for oral suspension, amoxicillin tablets (chewable) are indicated in the treatment of infections due to susceptible (ONLY -lactamase-negative) isolates of Streptococcus spp. (- and -hemolytic isolates only), S. pneumoniae, Staphylococcus spp., or H. influenzae.. 1.5 Helicobacter pylori Infection. Triple therapy for Helicobacter pylori with clarithromycin and lansoprazole:Amoxicillin, in combination with clarithromycin plus lansoprazole as triple therapy, is indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or year history of duodenal ulcer) to eradicate H. pylori. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence.Dual therapy for H. pylori with lansoprazole:Amoxicillin, in combination with lansoprazole delayed-release capsules as dual therapy, is indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or year history of duodenal ulcer) who are either allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected. (See the clarithromycin package insert, MICROBIOLOGY.) Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence.. 1.6 Usage. To reduce the development of drug-resistant bacteria and maintain the effectiveness of amoxicillin and other antibacterial drugs, amoxicillin should be used only to treat infections that are proven or strongly suspected to be caused by 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.

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Information for PatientsPatients should be advised that amoxicillin may be taken every hours or every 12 hours, depending on the dose prescribed.Patients should be counseled that antibacterial drugs, including amoxicillin, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When amoxicillin is prescribed to treat bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may: (1) decrease the effectiveness of the immediate treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by amoxicillin or other antibacterial drugs in the future.Patients should be counseled that diarrhea is common problem caused by antibiotics, and it usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as or more months after having taken their last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.Patients should be aware that amoxicillin contains penicillin class drug product that can cause allergic reactions in some individuals.All brand names listed are the registered trademarks of their respective owners and are not trademarks of Teva Pharmaceuticals USA.Manufactured In Canada By:Teva Canada LimitedToronto, Canada M1B 2K9Manufactured For:Teva Pharmaceuticals USA, Inc.North Wales, PA 19454Rev. 8/2018. Patients should be advised that amoxicillin may be taken every hours or every 12 hours, depending on the dose prescribed.. Patients should be counseled that antibacterial drugs, including amoxicillin, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When amoxicillin is prescribed to treat bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may: (1) decrease the effectiveness of the immediate treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by amoxicillin or other antibacterial drugs in the future.. Patients should be counseled that diarrhea is common problem caused by antibiotics, and it usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as or more months after having taken their last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.. Patients should be aware that amoxicillin contains penicillin class drug product that can cause allergic reactions in some individuals.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 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 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 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 times the g human dose based on body surface area).

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. Absorption Amoxicillin is stable in the presence of gastric acid and is rapidly absorbed after oral administration. The effect of food on the absorption of amoxicillin from the tablets and suspension of amoxicillin has been partially investigated; 400 mg and 875 mg formulations have been studied only when administered at the start of light meal.Orally administered doses of 250 mg and 500 mg amoxicillin capsules result in average peak blood levels to hours after administration in the range of 3.5 mcg/mL to mcg/mL and 5.5 mcg/mL to 7.5 mcg/mL, respectively.Mean amoxicillin pharmacokinetic parameters from an open, two-part, single-dose crossover bioequivalence study in 27 adults comparing 875 mg of amoxicillin with 875 mg of amoxicillin/clavulanate potassium showed that the 875 mg of amoxicillin tablet produces an AUC0 to of 35.4 +- 8.1 mcgohr/mL and Cmax of 13.8 +- 4.1 mcg/mL. Dosing was at the start of light meal following an overnight fast. Orally administered doses of amoxicillin suspension, 125 mg/5 mL and 250 mg/5 mL, result in average peak blood levels to hours after administration in the range of 1.5 mcg/mL to mcg/mL and 3.5 mcg/mL to mcg/mL, respectively.Oral administration of single doses of 400 mg chewable tablets and 400 mg/5 mL suspension of amoxicillin to 24 adult volunteers yielded comparable pharmacokinetic data:Table 3: Mean Pharmacokinetic Parameters of Amoxicillin (400 mg chewable tablets and 400 mg/5 mL suspension) in Healthy AdultsDoseaAUC0 to (mcgohr/mL) Cmax (mcg/mL)bAmoxicillinAmoxicillin (+- S.D.)Amoxicillin (+- S.D.)400 mg (5 mL of suspension)17.1 (3.1)5.92 (1.62)400 mg (1 chewable tablet)17.9 (2.4)5.18 (1.64)a. Administered at the start of light meal.b. Mean values of 24 normal volunteers. Peak concentrations occurred approximately hour after the dose.Distribution Amoxicillin diffuses readily into most body tissues and fluids, with the exception of brain and spinal fluid, except when meninges are inflamed. In blood serum, amoxicillin is approximately 20% protein-bound. Following 1 gram dose and utilizing special skin window technique to determine levels of the antibiotic, it was noted that therapeutic levels were found in the interstitial fluid.Metabolism and Excretion The half-life of amoxicillin is 61.3 minutes. Approximately 60% of an orally administered dose of amoxicillin is excreted in the urine within to hours. Detectable serum levels are observed up to hours after an orally administered dose of amoxicillin. Since most of the amoxicillin is excreted unchanged in the urine, its excretion can be delayed by concurrent administration of probenecid [see DRUG INTERACTIONS (7.1)].

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. Pediatric: Modify dose in patients 12 weeks or younger (<= months). (8.4). Pediatric: Modify dose in patients 12 weeks or younger (<= months). (8.4). 8.1 Pregnancy. Teratogenic Effects. Pregnancy Category BReproduction studies have been performed in mice and rats at doses up to 2000 mg/kg (3 and times the g human dose, based on body surface area). There was no evidence of harm to the fetus due to amoxicillin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, amoxicillin should be used during pregnancy only if clearly needed.. 8.2 Labor and Delivery. Oral ampicillin is poorly absorbed during labor. It is not known whether use of amoxicillin in humans during labor or delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor, or increases the likelihood of the necessity for an obstetrical intervention.. 8.3 Nursing Mothers. Penicillins have been shown to be excreted in human milk. Amoxicillin use by nursing mothers may lead to sensitization of infants. Caution should be exercised when amoxicillin is administered to nursing woman.. 8.4 Pediatric Use. Because of incompletely developed renal function in neonates and young infants, the elimination of amoxicillin may be delayed. Dosing of amoxicillin should be modified in pediatric patients 12 weeks or younger (<= months) [see Dosage and Administration (2.2)].. 8.5 Geriatric Use. An analysis of clinical studies of amoxicillin was conducted to determine whether subjects aged 65 and over respond differently from younger subjects. These analyses have not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.. 8.6 Dosing in Renal Impairment. Amoxicillin is primarily eliminated by the kidney and dosage adjustment is usually required in patients with severe renal impairment (GFR 30 mL/min). See Dosing in Renal Impairment (2.4) for specific recommendations in patients with renal impairment.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Anaphylactic Reactions: Serious and occasionally fatal anaphylactic reactions have been reported in patients on penicillin therapy. Serious anaphylactic reactions require immediate emergency treatment with supportive measures. (5.1)Clostridium difficile Associated Diarrhea (ranging from mild diarrhea to fatal colitis): Evaluate if diarrhea occurs. (5.2). Anaphylactic Reactions: Serious and occasionally fatal anaphylactic reactions have been reported in patients on penicillin therapy. Serious anaphylactic reactions require immediate emergency treatment with supportive measures. (5.1). Clostridium difficile Associated Diarrhea (ranging from mild diarrhea to fatal colitis): Evaluate if diarrhea occurs. (5.2). 5.1 Anaphylactic Reactions. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy including amoxicillin. 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 history of penicillin hypersensitivity and/or history of sensitivity to multiple allergens. There have been reports of individuals with history of penicillin hypersensitivity who have experienced severe reactions when treated with cephalosporins. Before initiating therapy with amoxicillin, careful inquiry should be made regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, amoxicillin should be discontinued and appropriate therapy instituted.. 5.2 Clostridium difficile Associated Diarrhea. 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 and 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 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.. 5.3 Development of Drug-Resistant Bacteria. Prescribing amoxicillin in the absence of proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.. 5.4 Use in Patients With Mononucleosis. high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash. Thus amoxicillin should not be administered to patients with mononucleosis.