Amoxicillin Capsules USP, 250 mg and Amoxicillin Capsules USP, 500 mg

DESCRIPTION

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displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Formulations of amoxicillin capsules contain amoxicillin, a semisynthetic antibiotic, an analog of ampicillin, with a broad spectrum of bactericidal activity against many gram-positive and gram-negative microorganisms. Chemically it is (2 , 5 , 6 )-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. It may be represented structurally as:
S
R
R

The amoxicillin molecular formula is C H N O S•3H O, and the molecular weight is 419.45.
_16
19
3
5
2 Each amoxicillin capsule USP, for oral administration, contains either 250 mg or 500 mg of amoxicillin as the trihydrate. In addition, the capsules also contain the following inactive ingredients: croscarmellose sodium, gelatin, magnesium stearate, titanium dioxide, and yellow iron oxide. Additionally, the 250 mg capsules contain black iron oxide and red iron oxide. The 250 mg capsule with caramel cap and ivory body is imprinted with West-ward 938, while the 500 mg capsule with ivory cap and ivory body is imprinted with West-ward 939.

CLINICAL PHARMACOLOGY

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displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1

Amoxicillin is stable in the presence of gastric acid and is rapidly absorbed after oral administration. Amoxicillin diffuses readily into most body tissues and fluids, with the exception of brain and spinal fluid, except when meninges are inflamed. The half-life of amoxicillin is 61.3 minutes. Most of the amoxicillin is excreted unchanged in the urine; its excretion can be delayed by concurrent administration of probenecid. In blood serum, amoxicillin is approximately 20% protein-bound. Orally administered doses of 250 mg and 500 mg amoxicillin capsules result in average peak blood levels 1 to 2 hours after administration in the range of 3.5 mcg/mL to 5 mcg/mL and 5.5 mcg/mL to 7.5 mcg/mL, respectively.

INDICATIONS AND USAGE

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displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

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 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 is indicated in the treatment of infections due to susceptible (ONLY β-lactamase–negative) strains of the designated microorganisms in the conditions listed below: –due to spp. (α- and β-hemolytic strains only), or – due to or – due to spp. (α- and β-hemolytic strains only), spp., or due to Streptococcus spp. (α- and β-hemolytic strains only), spp., or

Infections of the ear, nose, and throat
Streptococcus
Streptococcus pneumoniae, Staphylococcus spp.,
H. influenzae.

Infections of the genitourinary tract
E. coli, P. mirabilis,
E. faecalis.

Infections of the skin and skin structure
Streptococcus
Staphylococcus
E. coli.

Infections of the lower respiratory tract
S. pneumoniae, Staphylococcus
H. influenzae. Gonorrhea, acute uncomplicated (ano-genital and urethral infections) due to (males and females).
N. gonorrhoeae eradication to reduce the risk of duodenal ulcer recurrence
H. pylori Triple therapy: Amoxicillin /clarithromycin/lansoprazole Amoxicillin, in combination with clarithromycin plus lansoprazole as triple therapy, is indicated for the treatment of patients with infection and duodenal ulcer disease (active or 1-year history of a duodenal ulcer) to eradicate Eradication of has been shown to reduce the risk of duodenal ulcer recurrence. (See and )

H. pylori
H. pylori.
H. pylori
CLINICAL STUDIES
. DOSAGE AND ADMINISTRATION Dual therapy: Amoxicillin/lansoprazole Amoxicillin, in combination with lansoprazole delayed-release capsules as dual therapy, is indicated for the treatment of patients with infection and duodenal ulcer disease (active or 1-year history of a duodenal ulcer) (See the clarithromycin package insert, MICROBIOLOGY.) Eradication of has been shown to reduce the risk of duodenal ulcer recurrence. (See and )

H. pylori
who are either allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected.
H. pylori
CLINICAL STUDIES
. DOSAGE AND ADMINISTRATION Indicated surgical procedures should be performed.

CONTRAINDICATIONS

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displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

A history of allergic reaction to any of the penicillins is a contraindication.

WARNINGS

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displayName: WARNINGS SECTION
FDA Article Code: 34071-1

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. Pseudomembranous colitis has been reported with nearly all antibacterial agents, including amoxicillin, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by is a primary cause of “antibiotic-associated colitis.”
Clostridium difficile After the diagnosis of pseudomembranous colitis has been established, appropriate therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate-to-severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against colitis.
C. difficile

ADVERSE REACTIONS

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displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

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: Nausea, vomiting, diarrhea, and hemorrhagic / pseudomembranous colitis.

Gastrointestinal:
Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment. (See )
. WARNINGS 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.

Hypersensitivity Reactions:
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.
NOTE: 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.

Liver:
Crystalluria has also been reported (see )

Renal:

OVERDOSAGE 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.

Hemic and Lymphatic Systems:
Reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioral changes, and/or dizziness have been reported rarely.

Central Nervous System:
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.

Miscellaneous:
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.

Combination therapy with clarithromycin and lansoprazole:

OVERDOSAGE

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displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

In case of overdosage, discontinue medication, treat symptomatically, and institute supportive measures as required. If the overdosage is very recent and there is no contraindication, an attempt at emesis or other means of removal of drug from the stomach may be performed. A prospective study of 51 pediatric patients at a poison-control center suggested that overdosages of less than 250 mg/kg of amoxicillin are not associated with significant clinical symptoms and do not require gastric emptying.
³ Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients after over-dosage with amoxicillin. Crystalluria, in some cases leading to renal failure, has also been reported after amoxicillin overdosage in adult and pediatric patients. In case of overdosage, adequate fluid intake and diuresis should be maintained to reduce the risk of amoxicillin crystalluria. Renal impairment appears to be reversible with cessation of drug administration. High blood levels may occur more readily in patients with impaired renal function because of decreased renal clearance of amoxicillin. Amoxicillin may be removed from circulation by hemodialysis.

DOSAGE AND ADMINISTRATION

id: 51b7bfa4-0852-4533-81c3-7ec1f44dbf4a
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

Amoxicillin capsules may be given without regard to meals. However, food effect studies have not been performed with the 500 mg formulation.

CLINICAL STUDIES

id: 107f8319-1103-4180-ae0b-bbc9c820a50f
displayName: CLINICAL STUDIES SECTION
FDA Article Code: 34092-7

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 1 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 Based on the results of these studies, the safety and efficacy of 2 different eradication regimens were established:
H. pylori. Amoxicillin 1 gram twice daily/clarithromycin 500 mg twice daily/lansoprazole 30 mg twice daily.

Triple therapy:
Amoxicillin 1 gram three times daily/lansoprazole 30 mg 3 times daily.

Dual therapy:
All treatments were for 14 days. eradication was defined as 2 negative tests (culture and histology) at 4 to 6 weeks following the end of treatment.
H. pylori 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 has been shown to reduce the risk of duodenal ulcer recurrence.
H. pylori

REFERENCES

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displayName: REFERENCES SECTION
FDA Article Code: 34093-5

National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically – Fourth Edition; Approved Standard. NCCLS Document M7-A4, Vol. 17, No. 2. NCCLS, Wayne, PA, January 1997.
National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Disk Susceptibility Tests – Sixth Edition; Approved Standard. NCCLS Document M2-A6, Vol. 17, No. 1. NCCLS, Wayne, PA, January 1997.
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 Distributed by: Eatontown, NJ 07724 USA

West-ward Pharmaceutical Corp.

Manufactured by : P.O. Box 182400 Amman 11118 – Jordan

Hikma Pharmaceuticals

AMOXICILLIN CAPSULE

id: c9138d1d-d502-4931-897a-90c036ba98d9
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4