AMOXICILLIN tablet, chewable

Amoxicillin by

Drug Labeling and Warnings

Amoxicillin by is a Prescription medication manufactured, distributed, or labeled by Northwind Pharmaceuticals, LLC, EPM Packaging. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

  • 1 INDICATIONS AND USAGE

    Adults and Pediatric Patients

    • Upper Respiratory Tract Infections of the Ear, Nose, and Throat:Amoxicillin tablets, amoxicillin for oral suspension, amoxicillin tablets (chewable), and amoxicillin capsules are indicated in the treatment of infections due to susceptible (ONLY β-lactamase-negative) isolates of Streptococcusspecies. (α- and β-hemolytic isolates only), Streptococcus pneumoniae, Staphylococcusspp., or Haemophilus influenzae.
    • Infections of the Genitourinary Tract:Amoxicillin tablets, amoxicillin for oral suspension, amoxicillin tablets (chewable), and amoxicillin capsules are indicated in the treatment of infections due to susceptible (ONLY β-lactamase-negative) isolates of Escherichia coli, Proteus mirabilis, or Enterococcus faecalis.
    • Infections of the Skin and Skin Structure:Amoxicillin tablets, amoxicillin for oral suspension, amoxicillin tablets (chewable), and amoxicillin capsules are indicated in the treatment of infections due to susceptible (ONLY β-lactamase-negative) isolates of Streptococcusspp. (α- and β-hemolytic isolates only), Staphylococcusspp., or E. coli.
    • Infections of the Lower Respiratory Tract:Amoxicillin tablets, amoxicillin for oral suspension, amoxicillin tablets (chewable), and amoxicillin capsules are indicated in the treatment of infections due to susceptible (ONLY β-lactamase-negative) isolates of Streptococcusspp. (α- and β-hemolytic isolates only), S. pneumoniae, Staphylococcusspp., or H. influenzae.

    Adult Patients only

    • Helicobacter pyloriInfection and Duodenal Ulcer Disease:

      Triple therapy for Helicobacter pylori (H. pylori)with clarithromycin and lansoprazole:
      Amoxicillin, in combination with clarithromycin plus lansoprazole as triple therapy, is indicated for the treatment of patients with H. pyloriinfection and duodenal ulcer disease (active or 1-year history of a duodenal ulcer) to eradicate H. pylori. Eradication of H. pylorihas been shown to reduce the risk of duodenal ulcer recurrence.

      Dual therapy for H. pyloriwith lansoprazole:
      Amoxicillin, in combination with lansoprazole delayed-release capsules as dual therapy, is indicated for the treatment of patients with H. pyloriinfection and duodenal ulcer disease (active or 1-year history of a 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. pylorihas been shown to reduce the risk of duodenal ulcer recurrence.

    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.

  • 2 DOSAGE AND ADMINISTRATION

    2.1 Important Administration Instructions

    To minimize the potential for gastrointestinal intolerance, amoxicillin should be taken at the start of a meal.

    2.2 Dosage for Adults and Pediatric Patients Aged 3 Months (12 weeks) and Older

    • Treatment should be continued for a 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 pyogenesto 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. Dosage Recommendations for Adult and Pediatric Patients Aged 3 Months (12 weeks) and Older

    Infection

    Severity a

    Recommended Dosage for Adults and Pediatric Patients Aged 3 Months and Older and Weight Greater than 40 kg

    Recommended Dosage for Pediatric Patients Aged 3 Months and Older and Weight Less than 40 kg

    Ear/Nose/Throat Skin/Skin Structure Genitourinary Tract

    Mild/Moderate

    500 mg every 12 hours or

    250 mg every 8 hours

    25 mg/kg/day in divided doses every 12 hours

    or

    20 mg/kg/day in divided doses every 8 hours

    Severe

    875 mg every 12 hours or

    500 mg every 8 hours

    45 mg/kg/day in divided doses every 12 hours

    or

    40 mg/kg/day in divided doses every 8 hours

    Lower Respiratory Tract

    Mild/Moderate or Severe

    875 mg every 12 hours or

    500 mg every 8 hours

    45 mg/kg/day in divided doses every 12 hours

    or

    40 mg/kg/day in divided doses every 8 hours

    aDosage for infections caused by bacteria that are intermediate in their susceptibility to amoxicillin should follow the recommendations for severe infections.


    2.3 Dosage in Pediatric Patients Aged Less than 12 Weeks (3 months)

    • It is recommended that there be at least 10 days’ treatment for any infection caused by Streptococcus pyogenesto 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.
    • Treatment should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic, or evidence of bacterial eradication has been obtained.

    2.4 Dosage for H. pyloriInfection in Adults

    Triple therapy:The recommended adult oral dose is 1 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 1 gram amoxicillin and 30 mg lansoprazole, each given three times daily (every 8 hours) for 14 days.

    Please refer to clarithromycin and lansoprazole full prescribing information.

    2.5 Dosage in Renal Impairment for Adults and Pediatric Patients Aged 3 Months and Older and Weight Greater than 40 kg

    • Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Renal impairment patients with a glomerular filtration rate of less than 30 mL/min should NOTreceive the 875 mg dose. See dosage regimens in patients with severe renal impairment provided in Table 2.
    Table 2. Dosing in Patients with Severe Renal Impairment

    Patients with Renal Impairment

    Dosage Regimen

    GFR 10 to 30 mL/min

    500 mg or 250 mg every 12 hours, depending on the severity of the infection

    GFR less than 10 mL/min

    500 mg or 250 mg every 24 hours, depending on severity of the infection

    Hemodialysis

    500 mg or 250 mg every 24 hours, depending on severity of the infection

    Administer an additional dose both during and at the end of dialysis

    2.6 Directions for Mixing Oral Suspension

    Prepare a suspension at time of dispensing as follows: Tap bottle until all powder flows freely. Measure the total amount of water (see Table 3). Add approximately 1/3 of the water to powder. Replace cap and shake vigorouslyto wet powder. Add remaining water. Replace cap and shake vigorously.

    Table 3. Amount of Water for Mixing For Oral Suspension

    Strength

    Bottle Size

    Total Amount of Water
    Required for Reconstitution

    For Oral Suspension 200 mg/5 mL

    50 mL

    39 mL

    75 mL

    57 mL

    100 mL

    75 mL

    For Oral Suspension 250 mg/5 mL

    80 mL

    47 mL

    100 mL

    60 mL

    150 mL

    90 mL

    For Oral Suspension 400 mg/5 mL

    50 mL

    35 mL

    75 mL

    51 mL

    100 mL

    67 mL

    After reconstitution, the required amount of suspension should be placed directly on the child’s 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.

    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.

  • 3 DOSAGE FORMS AND STRENGTHS

    Amoxicillin:

    • Tablets:

      500 mg: Each tablet contains 500 mg of amoxicillin, USP as the trihydrate. Each film-coated, capsule-shaped, off-white, tablet is debossed with “93” on one side and “2263” on the other side.

      875 mg: Each tablet contains 875 mg of amoxicillin, USP as the trihydrate. Each film-coated, capsule-shaped, off-white tablet is scored on one side, debossed with “93” on one side of the score and “2264” on the other side of the score.

       

    • For Oral Suspension:

      200 mg/5 mL: Each 5 mL of reconstituted pink, fruit gum flavored suspension contains 200 mg amoxicillin, USP as the trihydrate.

      250 mg/5 mL: Each 5 mL of reconstituted mixed berry flavored suspension contains 250 mg amoxicillin, USP as the trihydrate.

      400 mg/5 mL: Each 5 mL of reconstituted pink, fruit gum flavored suspension contains 400 mg amoxicillin, USP as the trihydrate.

    • Tablets (Chewable):

      125 mg: Each white to off-white, capsule-shaped tablet, debossed 93 on one side and 2267 on the other side and contains 125 mg of amoxicillin, USP as the trihydrate.

      250 mg: Each white to off-white, capsule-shaped tablet, debossed 93 (partial bisect between 9 and 3) on one side and 2268 on the other side and contains 250 mg of amoxicillin, USP as the trihydrate.

    • Capsules:
      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, USP 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, USP as the trihydrate.
  • 4 CONTRAINDICATIONS

    Amoxicillin is contraindicated in patients who have experienced a serious hypersensitivity reaction (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin or to other β-lactam antibacterial drugs (e.g., penicillins and cephalosporins).

  • 5 WARNINGS AND PRECAUTIONS

    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 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 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 Severe Cutaneous Adverse Reactions

    Amoxicillin may cause severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). If patients develop skin rash they should be monitored closely, and amoxicillin discontinued if lesions progress.

    5.3 Drug-Induced Enterocolitis Syndrome (DIES)

    Drug-induced enterocolitis syndrome (DIES) has been reported with amoxicillin use [see Adverse Reactions ( 6.2)] , with most cases occurring in pediatric patients ≤18 years of age. DIES is a non-IgE mediated hypersensitivity reaction characterized by protracted vomiting occurring 1 to 4 hours after drug ingestion in the absence of skin or respiratory symptoms. DIES may be associated with pallor, lethargy, hypotension, shock, diarrhea within 24 hours after ingesting amoxicillin, and leukocytosis with neutrophilia. If DIES occurs, discontinue amoxicillin and institute appropriate therapy.

    5.4  Clostridioides difficile-Associated Diarrhea (CDAD)

    Clostridioides 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. difficileproduces toxins A and B which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficilecause 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 2 months after the administration of antibacterial agents.

    If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficilemay need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

    5.5 Development of Drug-Resistant Bacteria

    Prescribing amoxicillin in the absence of a proven or strongly suspected bacterial infection or prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

    5.6 Skin Rash in Patients with Mononucleosis

    A high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash. Thus, amoxicillin should not be administered to patients with mononucleosis.

  • 6 ADVERSE REACTIONS

    The following are discussed in more detail in other sections of the labeling:

    • Anaphylactic reactions [see Warnings and Precautions ( 5.1)]
    • Severe Cutaneous Adverse Reactions [see Warnings and Precautions ( 5.2)]
    • Drug-Induced Enterocolitis Syndrome (DIES) [see Warnings and Precautions ( 5.3)]
    • Clostridioides difficile-Associated Diarrhea (CDAD) [see Warnings and Precautions ( 5.4)]

    6.1 Clinical Trials Experience

    Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a 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 (greater than 1%) observed in clinical trials of amoxicillin capsules, amoxicillin tablets or for 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 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 a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to amoxicillin.

    • Infections and Infestations:Mucocutaneous candidiasis.
    • Gastrointestinal:Drug-induced enterocolitis syndrome (DIES), black hairy tongue, and hemorrhagic/pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment [see Warnings and Precautions ( 5.4)] .
    • Immune:Hypersensitivity reactions, anaphylactic/anaphylactoid reactions (including shock), angioedema, serum sickness-like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, and frequently fever), hypersensitivity vasculitis [see Warnings and Precautions ( 5.1)] .
    • Skin and Appendages:Rashes, pruritus, urticaria, erythema multiforme, SJS, TEN, DRESS, AGEP, exfoliative dermatitis, and linear IgA bullous dermatosis.
    • 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, aseptic meningitis, 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

    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 rashes is due to allopurinol or the hyperuricemia present in these patients.

    7.4 Oral Contraceptives

    Amoxicillin may affect the intestinal 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 ®, 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 or amoxicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol has been noted.

  • 8 USE IN SPECIFIC POPULATIONS

    8.1 Pregnancy

    Teratogenic Effects: Pregnancy Category B.

    Reproduction studies have been performed in mice and rats at doses up to 2000 mg/kg (3 and 6 times the 3 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 a nursing woman.

    8.4 Pediatric Use

    The safety and effectiveness of amoxicillin for the treatment of upper respiratory tract infections, and infections of the genitourinary tract, skin and skin structure and lower respiratory tract have been established in pediatric patients.

    The safety and effectiveness of amoxicillin for the treatment of H. Pyloriinfection have not been established in pediatric patients.

    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 (3 months or younger) [see Dosage and Administration ( 2.3)] .

    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 a 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 less than 30 mL/min). See Dosing in Renal Impairment ( 2.5) for specific recommendations in patients with renal impairment.

  • 10 OVERDOSAGE

    In case of overdosage, discontinue amoxicillin, treat symptomatically, and institute supportive measures as required. 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.

    Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients after overdosage with amoxicillin 1.

    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.

  • 11 DESCRIPTION

    Amoxicillin, USP is a semisynthetic antibacterial (amoxicillin), an analog of ampicillin, with a broad spectrum of bactericidal activity against many Gram-positive and Gram-negative microorganisms. Chemically, it is (2 S,5 R,6 R)-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:

    1

    The amoxicillin, USP molecular formula is C 16H 19N 3O 5S3H 2O, and the molecular weight is 419.45.

    Tablets:Each tablet contains 500 mg or 875 mg of amoxicillin, USP as the trihydrate. Each film-coated tablet contains: colloidal silicon dioxide, crospovidone, D&C Yellow No. 10 aluminum lake, hypromellose, magnesium stearate, microcrystalline cellulose, lactose monohydrate, sodium starch glycolate, titanium dioxide and triacetin.

    For Oral Suspension:Each 5 mL of reconstituted suspension contains 200 mg, 250 mg or 400 mg of amoxicillin, USP as the trihydrate. Each 5 mL of the 200 mg reconstituted suspension contains 0.09 mEq (2.11 mg) of sodium. Each 5 mL of the 250 mg reconstituted suspension contains 0.14 mEq (3.24 mg) of sodium. Each 5 mL of the 400 mg reconstituted suspension contains 0.12 mEq (2.69 mg) of sodium.

    Inactive ingredients for 200 mg and 400 mg: Colloidal silicon dioxide, FD&C Red No. 40, natural and artificial fruit gum flavor, sodium benzoate, sodium citrate, spray dried mask flavor, sucrose, and xanthan gum.

    Inactive ingredients for 250 mg: FD&C Red No. 40, mixed berry flavoring, silicon dioxide, sodium benzoate, sodium citrate, sucrose, and xanthan gum.

    Tablets (Chewable):Each tablet contains 125 mg or 250 mg of amoxicillin, USP as the trihydrate. Inactive ingredients in each 125 mg or 250 mg chewable tablet: cherry flavor, lactose anhydrous, magnesium stearate, mannitol, microcrystalline cellulose, sodium citrate, and sucrose.

    Capsules:Each capsule, for oral administration, contains 250 mg or 500 mg amoxicillin, USP as the trihydrate. The capsules contain the following inactive ingredients: magnesium stearate and talc. The capsule shell contains D&C Yellow No. 10, FD&C Red No. 40, gelatin, and titanium dioxide. In addition, the 250 mg contains D&C Red No. 28 and FD&C Blue No. 1. The 500 mg may also contain methylparaben, propylparaben, and sodium lauryl sulfate. The printing ink contains black iron oxide, propylene glycol, shellac, and strong ammonia solution. In addition, the 250 mg may contain D&C Yellow No. 10 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake, FD&C Blue No. 2 Aluminum Lake, and FD&C Red No. 40 Aluminum Lake. The 500 mg may also contain potassium hydroxide.

  • 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 a light meal.

    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 5.0 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 bioequivalencestudy in 27 adults comparing 875 mg of amoxicillin with 875 mg of AUGMENTIN ® showed that the 875 mg tablet of amoxicillin produces an AUC 0-∞of 35.4 ± 8.1 mcghr/mL and a C maxof 13.8 ± 4.1 mcg/mL. Dosing was at the start of a 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 1 to 2 hours after administration in the range of 1.5 mcg/mL to 3.0 mcg/mL and 3.5 mcg/mL to 5.0 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 4: Mean Pharmacokinetic Parameters of Amoxicillin (400 mg chewable tablets and 400 mg/5 mL suspension) in Healthy Adults

    Dose *

    Amoxicillin

    AUC 0-∞(mcghr/mL)

    Amoxicillin (±S.D.)

    C max(mcg/mL) †

    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)

    *Administered at the start of a light meal.

    †Mean values of 24 normal volunteers. Peak concentrations occurred approximately 1 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 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.

    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 6 to 8 hours. Detectable serum levels are observed up to 8 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 Action

    Amoxicillin 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.

    Resistance

    Resistance to Amoxicillin is mediated primarily through enzymes called beta-lactamases that cleave the beta-lactam ring of amoxicillin, rendering it inactive.

    Antimicrobial Activity

    Amoxicillin has been shown to be active against most isolates of the following microorganisms, both in vitroand in clinical infections [see Indications and Usage ( 1)] .

    Gram-Positive Bacteria

    Enterococcus faecalis

    Staphylococcusspp.

    Streptococcus pneumoniae

    Streptococcusspp. (alpha and beta-hemolytic)

    Gram-Negative Bacteria

    Escherichia coli

    Haemophilus influenzae

    Helicobacter pylori

    Proteus mirabilis

    Susceptibility 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.

  • 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 a 4:1 mixture of AUGMENTIN ®. AUGMENTIN ®was non-mutagenic in the Ames bacterial mutation assay, and the yeast gene conversion assay. AUGMENTIN ®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. AUGMENTIN ®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 2 times the 3 g human dose based on body surface area).

  • 14 CLINICAL STUDIES

    14.1 H. pyloriEradication to Reduce the Risk of Duodenal Ulcer Recurrence

    Randomized, double-blind clinical studies performed in the United States in patients with H. pyloriand 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 H. pylori. Based on the results of these studies, the safety and efficacy of 2 different eradication regimens were established: Triple therapy:Amoxicillin 1 gram twice daily/clarithromycin 500 mg twice daily/lansoprazole 30 mg twice daily (see Table 5). Dual therapy:Amoxicillin 1 gram three times daily/lansoprazole 30 mg three times daily (see Table 6). All treatments were for 14 days. H. pylorieradication was defined as 2 negative tests (culture and histology) at 4 to 6 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. pylorihas been shown to reduce the risk of duodenal ulcer recurrence.

    Table 5. H. pylori Eradication Rates When Amoxicillin is Administered as Part of a Triple Therapy Regimen


    Study

    Triple Therapy

    Triple Therapy

    Evaluable Analysis a

    [95% Confidence Interval]

    (number of patients)

    Intent-to-Treat Analysis b

    [95% Confidence Interval]

    (number of patients)

    Study 1

    92

    [80.0 to 97.7]

    (n equals 48)

    86

    [73.3 to 93.5]

    (n equals 55)

    Study 2

    86

    [75.7 to 93.6]

    (n equals 66)

    83

    [72.0 to 90.8]

    (n equals 70)

    aThis analysis was based on evaluable patients with confirmed duodenal ulcer (active or within 1 year) and H. pyloriinfection 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.

    bPatients were included in the analysis if they had documented H. pyloriinfection at baseline as defined above and had a confirmed duodenal ulcer (active or within 1 year). All dropouts were included as failures of therapy.

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


    Study

    Dual Therapy

    Dual Therapy

    Evaluable Analysis a
    [95% Confidence Interval]

    (number of patients)

    Intent-to-Treat Analysis b
    [95% Confidence Interval]

    (number of patients)

    Study 1

    77

    [62.5 to 87.2]

    (n equals 51)

    70

    [56.8 to 81.2]

    (n equals 60)

    Study 2

    66

    [51.9 to 77.5]

    (n equals 58)

    61

    [48.5 to 72.9]

    (n equals 67)

    aThis analysis was based on evaluable patients with confirmed duodenal ulcer (active or within 1 year) and H. pyloriinfection 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.

    bPatients were included in the analysis if they had documented H. pyloriinfection at baseline as defined above and had a confirmed duodenal ulcer (active or within 1 year). All dropouts were included as failures of therapy.


  • 15 REFERENCES

    1. 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.
  • 16 HOW SUPPLIED/STORAGE AND HANDLING

    Amoxicillin Tablets (Chewable), USP:

    250 mg: Each white to off-white, capsule-shaped tablet, debossed 93 (partial bisect between 9 and 3) on one side and 2268 on the other side and contain 250 mg amoxicillin, USP as the trihydrate. They are available in bottles of 30 tablets (NDC: 82868-063-30).

    Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

    Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

    Keep this and all medications out of the reach of children.

  • 17 PATIENT COUNSELING INFORMATION

    Administration Instructions

    Advise patients that amoxicillin tablets, amoxicillin for oral suspension, amoxicillin tablets (chewable), and amoxicillin capsules may be taken every 8 hours or every 12 hours, depending on the dose prescribed.

    Allergic Reactions

    Counsel patients that amoxicillin contains a penicillin class drug product that can cause allergic reactions in some individuals.

    Severe Cutaneous Adverse Reactions (SCAR)

    Advise patients about the signs and symptoms of serious skin manifestations. Instruct patients to stop taking amoxicillin immediately and promptly report the first signs or symptoms of skin rash, mucosal lesions, or any other sign of hypersensitivity [see Warnings and Precautions ( 5.2)] .

    Diarrhea

    Counsel patients that diarrhea is a common problem caused by antibacterial drugs which usually ends when the antibacterial drug is discontinued. Sometimes after starting treatment with antibacterial drugs, 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 antibacterial drug. If this occurs, patients should contact their physician as soon as possible.

    Antibacterial Resistance

    Patients should be counseled that antibacterial drugs, including amoxicillin, should only be used to treat or prevent bacterial infections. Antibacterial drugs do not treat viral infections (e.g., the common cold). When amoxicillin tablets, amoxicillin for oral suspension, amoxicillin tablets (chewable), and amoxicillin capsules are 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.

    Storage and Special Handling Instructions

    It is preferable to refrigerate amoxicillin suspensions, but not required. Shake oral suspensions well before each use. Keep bottle tightly closed. When dosing a child with the suspension (liquid), use a calibrated oral syringe. Be sure to rinse the calibrated oral syringe after each use. Bottles of suspension of amoxicillin may contain more liquid than required. Follow your doctor’s instructions about the amount to use and the days of treatment your child requires. Discard any unused portion of the suspension after 14 days.

    Brands listed are the trademarks of their respective owners.

    Manufactured In Canada By:
    Teva Canada Limited
    Toronto, Canada M1B 2K9

    Manufactured For:
    Teva Pharmaceuticals
    Parsippany, NJ 07054

    Rev. 5/2024

  • Principal Display Panel

    NDC: 82868-063-30

    Label

  • INGREDIENTS AND APPEARANCE
    AMOXICILLIN 
    amoxicillin tablet, chewable
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 82868-063(NDC:0093-2268)
    Route of AdministrationORAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    AMOXICILLIN (UNII: 804826J2HU) (AMOXICILLIN ANHYDROUS - UNII:9EM05410Q9) AMOXICILLIN ANHYDROUS250 mg
    Inactive Ingredients
    Ingredient NameStrength
    ANHYDROUS LACTOSE (UNII: 3SY5LH9PMK)  
    MAGNESIUM STEARATE (UNII: 70097M6I30)  
    MANNITOL (UNII: 3OWL53L36A)  
    CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)  
    SODIUM CITRATE (UNII: 1Q73Q2JULR)  
    SUCROSE (UNII: C151H8M554)  
    Product Characteristics
    Colorwhite (white to off-white) Score2 pieces
    ShapeOVAL (capsule-shaped) Size19mm
    FlavorCHERRYImprint Code 9;3;2268
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 82868-063-3030 in 1 BOTTLE, PLASTIC; Type 0: Not a Combination Product07/18/2024
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA06401307/18/2024
    Labeler - Northwind Pharmaceuticals, LLC (036986393)
    Registrant - Northwind Pharmaceuticals, LLC (036986393)
    Establishment
    NameAddressID/FEIBusiness Operations
    EPM Packaging079124340repack(82868-063)
    • © 2024 FDA.report
    This site is not affiliated with or endorsed by the FDA.