Amoxicillin for Oral Suspension, USP

DESCRIPTION

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displayName: Description Section
FDA Article Code: 34089-3

Formulations of amoxicillin for oral suspension, USP 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 (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. It may be represented structurally as:
 

The amoxicillin molecular formula is C₁₆H₁₉N₃O₅S•3H₂O, and the molecular weight is 419.45.
 
Amoxicillin for oral suspension is intended for oral administration.
 
Each 5 mL of reconstituted suspension contains amoxicillin trihydrate equivalent to 200 mg or 400 mg anhydrous amoxicillin. Each 5 mL of the 200 mg and 400 mg reconstituted suspension contains 0.16 mEq (3.61 mg) of sodium.
 
Amoxicillin trihydrate for oral suspension 200 mg/5 mL and 400 mg/5 mL (reconstituted) are bubble-gum flavored pink suspensions. Inactive ingredients: Sucrose, sodium citrate, sodium benzoate, edetate disodium, FD&C Red No. 3, xanthan gum, bubble-gum flavor, and colloidal silicon dioxide.

CLINICAL PHARMACOLOGY

id: a0045a93-1552-43d2-8d97-3f80cea911ab
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. The effect of food on the absorption of amoxicillin from the suspension of amoxicillin has been partially investigated. The 400 mg formulation has been studied only when administered at the start of a light meal. 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 amoxicillin suspension, 125 mg/5 mL and 250 mg/5 mL, result in average peak blood levels 1 to 2 hours after administration in the range of 1.5 mcg/mL to 3 mcg/mL and 3.5 mcg/mL to 5 mcg/mL, respectively.
 
Detectable serum levels are observed up to 8 hours after an orally administered dose of amoxicillin. Following a 1 gram dose and utilizing a special skin window technique to determine levels of the antibiotic, it was noted that therapeutic levels were found in the interstitial fluid. Approximately 60%  of an orally administered dose of amoxicillin is excreted in the urine within 6 to 8 hours.

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:

Infections of the ear, nose, and throat – due to Streptococcus spp. (α- and β-hemolytic strains only), S. pneumoniae, Staphylococcus spp., or H. influenzae.

Infections of the genitourinary tract – due to E. coli, P. mirabilis, or E. faecalis.

Infections of the skin and skin structure – due to Streptococcus spp. (α- and β-hemolytic strains only), Staphylococcus spp., or E. coli.

Infections of the lower respiratory tract – due to Streptococcus spp. (α- and β-hemolytic strains only), S. pneumoniae, Staphylococcus spp., or H. influenzae.

Gonorrhea, acute uncomplicated (ano-genital and urethral infections) – due to N. gonorrhoeae (males and females).

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.

 
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.

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:

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 .)

Hypersensitivity Reactions

Anaphylaxis (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.

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 ).

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.

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 overdosage 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

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displayName: Dosage & Administration Section
FDA Article Code: 34068-7

Oral suspensions of amoxicillin may be given without regard to meals. The 400 mg suspension has been studied only when administered at the start of a light meal.

HOW SUPPLIED

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displayName: How Supplied Section
FDA Article Code: 34069-5

Amoxicillin for Oral Suspension, USP: Each 5 mL of reconstituted bubble-gum-flavored pink suspension contains 200 or 400 mg amoxicillin as the trihydrate.

                                             200 mg/5 mL

 
                  50 mL bottle                                               NDC 65862-070-50
                  75 mL bottle                                               NDC 65862-070-75
                100 mL bottle                                               NDC 65862-070-01

                                             400 mg/5 mL

 
                  50 mL bottle                                               NDC 65862-071-50
                  75 mL bottle                                               NDC 65862-071-75
                100 mL bottle                                               NDC 65862-071-01

Store dry powder at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

REFERENCES

id: 5ebdbc0f-8c5e-42a0-bcf4-facb1b86f884
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.      CLINITEST is a registered trademark of Miles, Inc.
CLINISTIX is a registered trademark of Bayer Corporation.
CLOtest is a registered trademark of Kimberly-Clark Corporation.
 
Manufactured for:
Aurobindo Pharma USA, Inc.

2400 Route 130 North
Dayton, NJ 08810
 
Manufactured by:
Aurobindo Pharma Limited

Hyderabad-500 072, India

Repacked by:
H.J. Harkins Company, Inc.
Nipomo, CA 93444
 
Revised: 10/2011

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL – 400 mg/5 mL (50 mL Bottle)

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displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

NDC 65862-071-50

Amoxicillin for Oral Suspension, USP

400 mg/5 mL

50 mL when reconstituted

Rx only       

AUROBINDO