AMOXICILLIN

STAT Rx USA LLC
PSS World Medical Inc.

HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use amoxicillin capsules safely and effectively. See full prescribing information for amoxicillin capsules, USP. Amoxicillin Capsules, USPInitial U.S. Approval: 1974 MicrobiologyTo reduce the development of drug-resistant bacteria and maintain the effectiveness of amoxicillin capsules, USP and other antibacterial drugs, amoxicillin capsules, USP should be used only to treat infections that are proven or strongly suspected to be caused by bacteria.INDICATIONS AND USAGE Infections of the ear, nose, throat, genitourinary tract, skin and skin structure, and lower respiratory tract. (1.1, 1.2, 1.3, 1.4, 1.5) In combination for treatment of H. pylori infection and duodenal ulcer disease. (1.6, 1.7) DOSAGE AND ADMINISTRATION In adults, 750 to 1750 mg/day in divided doses every 8 to 12 hours. In Pediatric Patients > 3 Months of Age, 20 to 45 mg/kg/day in divided doses every 8 to 12 hours. Refer to full prescribing information for specific dosing regimens. (2.1, 2.2, 2.3) Treatment of gonorrhea is 3 grams as a single oral dose. (2.1) The upper dose for neonates and infants ≤ 3 months is 30 mg/kg/day divided every 12 hours. (2.2) Dosing for H. pylori Infection: Triple Therapy: 1 gram amoxicillin, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily (every 12 hours) for 14 days. Dual Therapy: 1 gram amoxicillin and 30 mg lansoprazole, each given three times daily (every 8 hours) for 14 days. (2.3) Reduce the dose in patients with severe renal impairment (GFR

FULL PRESCRIBING INFORMATION: CONTENTS*

• 1 AMOXICILLIN INDICATIONS AND USAGE
  • 1.1 Infections of the Ear, Nose, and Throat
  • 1.2 Infections of the Genitourinary Tract
  • 1.3 Infections of the Skin and Skin Structure
  • 1.4 Infections of the Lower Respiratory Tract
  • 1.5 Gonorrhea, Acute Uncomplicated (ano-genital and urethral infections in males and females)
  • 1.6 Triple Therapy for Helicobacter pylori with Clarithromycin and Lansoprazole
  • 1.7 Dual Therapy for H. pylori with Lansoprazole
• 2 AMOXICILLIN DOSAGE AND ADMINISTRATION
  • 2.1 Dosing for Adult and Pediatric Patients > 3 Months of Age
  • 2.2 Dosing in Neonates and Infants Aged ≤ 12 Weeks (≤ 3 Months)
  • 2.3 Dosing for H. pylori Infection
  • 2.4 Dosing in Renal Impairment
• 3 DOSAGE FORMS AND STRENGTHS
• 4 AMOXICILLIN CONTRAINDICATIONS
• 5 WARNINGS AND PRECAUTIONS
  • 5.1 Anaphylactic Reactions
  • 5.2 Clostridium difficile Associated Diarrhea
  • 5.3 Potential for Microbial Overgrowth or Bacterial Resistance
  • 5.4 Use in Patients With Mononucleosis
• 6 AMOXICILLIN ADVERSE REACTIONS
  • 6.1 Clinical Trials Experience
  • 6.2 Postmarketing or Other Experience
• 7 DRUG INTERACTIONS
  • 7.1 Probenecid
  • 7.2 Oral Anticoagulants
  • 7.3 Allopurinol
  • 7.4 Oral Contraceptives
  • 7.5 Other Antibacterials
  • 7.6 Effects on Laboratory Tests
• 8 USE IN SPECIFIC POPULATIONS
  • 8.1 Pregnancy
  • 8.2 Labor and Delivery
  • 8.3 Nursing Mothers
  • 8.4 Pediatric Use
  • 8.5 Geriatric Use
  • 8.6 Dosing in Renal Impairment
• 10 OVERDOSAGE
• 11 AMOXICILLIN DESCRIPTION
• 12 CLINICAL PHARMACOLOGY
  • 12.1 Mechanism of Action
  • 12.3 Pharmacokinetics
  • 12.4 Microbiology
• 13 NONCLINICAL TOXICOLOGY
  • 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
• 14 CLINICAL STUDIES
  • 14.1 H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence
• 15 REFERENCES
• 16 HOW SUPPLIED/STORAGE AND HANDLING
• 17 PATIENT COUNSELING INFORMATION
  • 17.1 Information for Patients
• PACKAGE LABEL - AMOXICILLIN - 250 mg CAPSULES
• PACKAGE LABEL - AMOXICILLIN - 500 mg CAPSULES

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

1.1 Infections of the Ear, Nose, and Throat

1.2 Infections of the Genitourinary Tract

1.3 Infections of the Skin and Skin Structure

1.4 Infections of the Lower Respiratory Tract

1.5 Gonorrhea, Acute Uncomplicated (ano-genital and urethral infections in males and females)

1.6 Triple Therapy for Helicobacter pylori with Clarithromycin and Lansoprazole

1.7 Dual Therapy for H. pylori with Lansoprazole

2 DOSAGE AND ADMINISTRATION

2.1 Dosing for Adult and Pediatric Patients > 3 Months of Age

2.2 Dosing in Neonates and Infants Aged ≤ 12 Weeks (≤ 3 Months)

2.3 Dosing for H. pylori Infection

2.4 Dosing in Renal Impairment

• Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe.
• Severely impaired patients with a glomerular filtration rate of < 30 mL/min should not receive a 875 mg dose.
• Patients with a 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 a 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.

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Anaphylactic Reactions

5.2 Clostridium difficile Associated Diarrhea

Clostridium difficile C. difficile. C. difficile C. difficile

C. difficileC. difficile

5.3 Potential for Microbial Overgrowth or Bacterial Resistance

5.4 Use in Patients With Mononucleosis

6 ADVERSE REACTIONS

• Anaphylactic reactions [see Warnings and Precautions (5.1)]
• CDAD [see Warnings and Precautions (5.2)]

6.1 Clinical Trials Experience

Triple Therapy:

Dual Therapy:

6.2 Postmarketing or Other Experience

• 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: A 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.

7 DRUG INTERACTIONS

7.1 Probenecid

7.2 Oral Anticoagulants

7.3 Allopurinol

7.4 Oral Contraceptives

7.5 Other Antibacterials

in vitro

7.6 Effects on Laboratory Tests

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8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Teratogenic Effects:

8.2 Labor and Delivery

8.3 Nursing Mothers

8.4 Pediatric Use

[See Dosage and Administration (2.2).]

8.5 Geriatric Use

8.6 Dosing in Renal Impairment

See Dosage and Administration (2.4)

10 OVERDOSAGE

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11 DESCRIPTION

SRRRp

_1619352

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

[see Clinical Pharmacology (12.4)].

12.3 Pharmacokinetics

Absorption:



_{0-∞ max}

Table 3. Mean Pharmacokinetic Parameters of Amoxicillin (400 mg chewable tablets and 400 mg/5 mL suspension) in Healthy Adults

Dose *	AUC0-∞ (mcg●hr/mL)	Cmax (mcg/mL)†
* Administered at the start of a light meal. † Mean values of 24 normal volunteers. Peak concentrations occurred approximately 1 hour after the dose.
Amoxicillin	Amoxicillin (±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)

Distribution:

Metabolism and Excretion:[see Drug Interactions (7.1)]

12.4 Microbiology

Mechanism of Action



Method of Resistance



in vitro INDICATIONS AND USAGE

Gram-Positive Bacteria	Gram-Negative Bacteria
Enterococcus faecalis  Staphylococcus spp.  Streptococcus pneumoniae  Alpha and β-hemolytic streptococci.	Escherichia coli  Haemophilus influenzae  Neisseria gonorrhoeae  Proteus mirabilis  Helicobacter pylori

Susceptibility Test Methods:

in vitro

Dilution Techniques: ^2,3

Diffusion Techniques: ³

Table 4. Susceptibility Test Interpretive Criteria for Amoxicillin

	Minimum Inhibitory Concentration (mcg/mL)			Disk Diffusion (zone diameter in mm)
	Susceptible	Intermediate	Resistant	Susceptible	Intermediate	Resistant
* S. pneumoniae should be tested using a 1 mcg oxacillin disk. Isolates with oxacillin zone sizes of ≥ 20 mm are susceptible to amoxicillin. An amoxicillin MIC should be determined on isolates of S. pneumoniae with oxacillin zone sizes of ≤ 19 mm. **A positive beta lactamase test indicates resistance to amoxicillin. Isolates that are resistant to penicillin by MIC testing are also expected to be resistant to amoxicillin.
Enterococcus spp.	≤ 8	-	≥ 16	≥ 17	-	≤ 16
Staphylococcus spp.	≤ 0.25		≥ 0.5	≥ 29		≤ 28
Streptococci, viridians group  (alpha-hemolytic streptococci)	≤ 0.25	0.5 to 4	≥ 8	-	-	-
β-hemolytic streptococci	≤ 0.25	-	-	≥ 24	-	-
Streptococcus pneumoniae  (non-meningitis isolates)*	≤ 2	4	≥ 8	-	-	-
Enterobacteriaceae	≤ 8	16	≥ 32	≥ 17	14 to 16	≤ 13
Haemophilus influenzae	≤ 1	2	≥ 4	≥ 22	19 to 21	≤ 18
Neisseria gonorrhoeae**	-	-	-	-	-	-

Quality Control
 
^2,3,4

Table 5. Acceptable Quality Control Ranges for Amoxicillin

Bacteria	ATCC#	MIC Range (mcg/mL)	Disk Diffusion Zone Range (mm)
# ATCC = American Type Culture Collection
Escherichia coli	25922	2 to 8	16 to 22
Enterococcus faecalis	29212	0.5 to 2
Haemophilus influenzae	49247	2 to 8	13 to 21
Staphylococcus aureus	29213	0.5 to 2
	25923		27 to 35
Streptococcus pneumoniae	49619	0.06 to 0.25

Susceptibility Testing for Helicobacter pylori: Amoxicillin in vitro susceptibility testing methods for determining minimum inhibitory concentrations (MICs) and zone sizes have not been standardized, validated, or approved for testing H. pylori. Specimens for H. pylori and clarithromycin susceptibility test results should be obtained on isolates from patients who fail triple therapy. If clarithromycin resistance is found, a non-clarithromycin-containing regimen should be used.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

14.1 H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence

H. pyloriH. pylori

Triple Therapy:

Dual Therapy:H. pyloriH. pylori

Table 6. H. pylori Eradication Rates When Amoxicillin is Administered as Part of a Triple Therapy Regimen

Study	Triple Therapy	Triple Therapy
	Evaluable Analysisa [95% Confidence Interval] (number of patients)	Intent-to-Treat Analysisb [95% Confidence Interval] (number of patients)
a This analysis was based on evaluable patients with confirmed duodenal ulcer (active or within 1 year) and H. pylori infection at baseline defined as at least 2 of 3 positive endoscopic tests from CLOtest®, 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 a confirmed duodenal ulcer (active or within 1 year). All dropouts were included as failures of therapy.
Study 1	92 [80 - 97.7] (n = 48)	86 [73.3 - 93.5] (n = 55)
Study 2	86 [75.7 - 93.6] (n = 66)	83 [72 - 90.8] (n = 70)

Table 7. H. pylori Eradication Rates When Amoxicillin is Administered as Part of a Dual Therapy Regimen

Study	Dual Therapy	Dual Therapy
	Evaluable Analysisa [95% Confidence Interval] (number of patients)	Intent-to-Treat Analysisb [95% Confidence Interval] (number of patients)
a This analysis was based on evaluable patients with confirmed duodenal ulcer (active or within 1 year) and H. pylori infection at baseline defined as at least 2 of 3 positive endoscopic tests from CLOtest®, 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 a confirmed duodenal ulcer (active or within 1 year). All dropouts were included as failures of therapy.
Study 1	77 [62.5 - 87.2] (n = 51)	70 [56.8 - 81.2] (n = 60)
Study 2	66 [51.9 - 77.5] (n = 58)	61 [48.5 - 72.9] (n = 67)

15 REFERENCES

• Swanson-Biearman B, Dean BS, Lopez G, Krenzelok EP. The effects of penicillin and cephalosporin ingestions in children less than six years of age. Vet Hum Toxicol. 1988; 30: 66-67.
• Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard – 8^th ed. CLSI Document M7-A8, Vol. 29, No.2. CLSI, Wayne, PA, Jan. 2009.
• Clinical and Laboratory Standards Institute (CLSI). Performance Standard for Antimicrobial Disk Susceptibility Tests; Approved Standard – 10^th ed. CLSI Document M2-A10, Vol. 29, No. 1. CLSI, Wayne, PA, 2009.
• Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing: 21^st Informational Supplement. Approved Standard CLSI Document M100-S21 CLSI, Wayne, PA, January 2011.

16 HOW SUPPLIED/STORAGE AND HANDLING

Amoxicillin Capsules, USP

250 mg Capsule







500 mg Capsule









Store at


Relabeling and Repackaging by

17 PATIENT COUNSELING INFORMATION

17.1 Information for Patients

• Patients should be advised that amoxicillin may be taken every 8 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 a 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 a 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 2 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 a penicillin class drug product that can cause allergic reactions in some individuals.

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Aurobindo Pharma USA, Inc.




Aurobindo Pharma Limited

PACKAGE LABEL - AMOXICILLIN - 250 mg CAPSULES

Amoxicillin Capsules, USP 250 mg

Rx only  
          

PACKAGE LABEL - AMOXICILLIN - 500 mg CAPSULES

Amoxicillin Capsules, USP 500 mg

Rx only
            

AMOXICILLIN AMOXICILLIN CAPSULE Product Information Product Type Human prescription drug label Item Code (Source) NDC:16590-014(NDC:65862-016) Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength AMOXICILLIN amoxicillin anhydrous 250 mg Inactive Ingredients Ingredient Name Strength cellulose, microcrystalline D&C RED NO. 28 FD&C BLUE NO. 1 FD&C RED NO. 40 GELATIN MAGNESIUM STEARATE titanium dioxide SODIUM LAURYL SULFATE Product Characteristics Color Size Imprint Code Shape pink 19 mm A44 CAPSULE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:16590-014-30 30 in 1 BOTTLE 2 NDC:16590-014-71 100 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA065271 2005-09-11

AMOXICILLIN AMOXICILLIN CAPSULE Product Information Product Type Human prescription drug label Item Code (Source) NDC:16590-016(NDC:65862-017) Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength AMOXICILLIN amoxicillin anhydrous 500 mg Inactive Ingredients Ingredient Name Strength cellulose, microcrystalline D&C RED NO. 28 FD&C BLUE NO. 1 FD&C RED NO. 40 GELATIN MAGNESIUM STEARATE titanium dioxide SODIUM LAURYL SULFATE Product Characteristics Color Size Imprint Code Shape pink 23 mm A45 CAPSULE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:16590-016-20 20 in 1 BOTTLE 2 NDC:16590-016-21 21 in 1 BOTTLE 3 NDC:16590-016-30 30 in 1 BOTTLE 4 NDC:16590-016-40 40 in 1 BOTTLE 5 NDC:16590-016-60 60 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA065271 2005-09-11