AMOXICILLIN

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Oral Administration
Oral Solid Formulations
-Chewable tablets only: Should be chewed before swallowing; do not swallow whole.
-Capsules, chewable tablets, and immediate-release tablets: May be given without regard to meals. The 400 mg chewable tablet and the 875 mg tablet have been studied only when administered at the start of a light meal.
-Extended-release tablets: Take within 1 hour of finishing a meal. Do not chew or crush.

Oral Liquid Formulations
-In general, amoxicillin oral suspension may be given without regard to meals. The 400 mg suspension has been studied only when administered at the start of a light meal.
-Shake well prior to each administration. Measure dosage with calibrated spoon, cup, or oral syringe.
-The measured dose of suspension may be added to formula, milk, fruit juice, water, ginger ale, or cold drinks for administration. These preparations should be administered immediately and consumed in their entirety to ensure all of the dose is received.

Reconstitution method for oral suspension:
-Review the reconstitution instructions for the particular product and package size, as the amount of water required for reconstitution varies from manufacturer to manufacturer.
-Prior to reconstitution, tap the bottle several times to loosen the powder. Add approximately 1/3 of the total amount of water as instructed by the manufacturer and shake well. Add the remainder of the water and shake well.
-Storage after reconstitution: Store under refrigeration (preferred) or at controlled room temperature for up to 14 days. Discard any unused portion after 14 days.

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). Monitor persons who develop skin rash closely and discontinue amoxicillin if lesions progress. Other hypersensitivity and dermatologic reactions reported with amoxicillin include anaphylactic/anaphylactoid reactions (including anaphylactic shock), angioedema, serum sickness-like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, and frequently fever), hypersensitivity vasculitis, erythema multiforme, hypersensitivity vasculitis, rash, pruritus, urticaria, and exfoliative dermatitis. If a hypersensitivity reaction occurs, discontinue amoxicillin and institute appropriate therapy.

Hematologic effects seen with penicillins, such as amoxicillin, include eosinophilia, anemia (including hemolytic anemia), thrombocytopenia, thrombotic thrombocytopenic purpura (TTP), agranulocytosis, and leukopenia. These adverse hematologic effects are generally reversible after discontinuation of the penicillin. Platelet dysfunction, prolonged bleeding time, and prolongation of APTT have been reported in patients receiving beta-lactams.

Nausea, vomiting, and diarrhea have been reported with penicillins, such as amoxicillin. In a tonsillitis and pharyngitis study, 302 adult and pediatric patients (12 years or older) were treated with the extended-release oral tablet. Reports of diarrhea (1.7%), nausea (1.3%), vomiting (0.7%), and abdominal pain (0.3%) were all similar to those reported with the comparator drug. Tongue discoloration (black hairy tongue) has also been reported with amoxicillin.

Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with amoxicillin. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate. Mucocutaneous candidiasis may occur as oral candidiasis (rare) or vaginal candidiasis. Vulvovaginal mycotic infections were reported in 2% of adult and pediatric (12 years or older) patients receiving the extended-release oral tablet during a tonsillitis and pharyngitis study (n = 302).

Headache is the most common CNS adverse effect associated with amoxicillin therapy. In a study of adult and pediatric patients (12 years and older) receiving extended-release amoxicillin tablets (n = 302), 1% of patients reported headache. Other adverse events such as agitation, reversible hyperactivity, anxiety, convulsions (seizures), confusion, aseptic meningitis, dizziness, insomnia, or other behavioral changes have been reported rarely. Seizures have been reported when large doses of penicillins were administered to patients with renal impairment. Appropriate dosage adjustments should be observed in these patients.

Hepatic dysfunction, including cholestatic jaundice, cholestasis, and acute cytolytic hepatitis, has been reported with amoxicillin therapy. Other reported side effects of amoxicillin include elevated hepatic enzymes (e.g., moderate rises in AST and/or ALT); however, the clinical significance is not known.

Tooth discoloration (brown, yellow, or gray staining) has been rarely reported with amoxicillin therapy. The majority of reports have been in children. In most cases, discoloration was reduced or eliminated by brushing or dental cleaning. A follow-up study accessing fluoride intake and amoxicillin use reported a possible link to amoxicillin-associated dental fluorosis affecting permanent teeth. After adjusting for fluoride intake and otitis media, the study noted a significant increase in the risk of fluorosis with amoxicillin therapy. The highest risk for fluorosis was noted with amoxicillin use in the first year of life, especially in early infancy (first 6 months).

Crystalluria has been reported in association with amoxicillin therapy.

The Jarisch-Herxheimer reaction is a self-limiting systemic reaction that has been reported in the setting of spirochete infections, such as Lyme disease, syphilis, relapsing fever, and leptospirosis, after the initiation of antimicrobial therapy. It is characterized by fever, chills, myalgias, headache, exacerbation of cutaneous lesions, tachycardia, hyperventilation, vasodilation with flushing, and mild hypotension. Less commonly, symptoms may include meningitis, pulmonary failure, hepatic and renal dysfunction, myocardial injury, premature uterine contractions in pregnant patients, and worsening cerebral function as well as strokes and seizures. The reaction has been noted in up to 30% of patients with early Lyme disease. The timing of the reaction varies by underlying infection but typically presents within a few hours after the initiation of antibiotics. For Lyme disease, the reaction usually begins within 1 to 2 hours after starting therapy and disappears within 12 to 24 hours. The reaction after treatment in syphilis usually starts at 4 hours, peaks at 8 hours, and subsides by 16 hours whereas it starts at about 1 to 2 hours, peaks at 4 hours, and subsides by 8 hours after treatment in relapsing fever. The pathogenesis of this reaction is unknown but may be due to the release of spirochetal heat-stable pyrogen. Fluids and antipyretics can be used to alleviate symptoms and duration of the reaction if severe.

Amoxicillin is contraindicated in patients with known serious hypersensitivity to amoxicillin or to other drugs in the same class (i.e., penicillin hypersensitivity) or patients who have demonstrated anaphylactic reactions to beta-lactams (i.e., cephalosporin hypersensitivity or carbapenem hypersensitivity). Patients with a history of sensitivity to multiple allergens may have a greater risk for hypersensitivity reactions to penicillins.

Use amoxicillin with caution in patients with renal impairment as the drug is substantially eliminated via renal mechanisms. Adjust dosage intervals in patients with CrCl of 30 mL/minute or less and in patients with renal failure. Dosage adjustments are also recommended for patients receiving dialysis. Do not use the extended-release tablet in patients with CrCl of 30 mL/minute or less or in patients receiving dialysis.

Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including amoxicillin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

Amoxicillin should not be used in patients with mononucleosis as a high incidence of skin rashes have been reported in these patients.

Administration of amoxicillin may result in laboratory test interference. A false-positive reaction for glucose in the urine has been observed in patients receiving penicillins and using glucose tests based on the Benedict's copper reduction reaction. Patients with diabetes mellitus who test their urine for glucose should use glucose tests based on enzymatic glucose oxidase reactions while on amoxicillin treatment. Antimicrobials are also known to suppress H. pylori; thus, ingestion of these agents within 4 weeks of performing diagnostic tests for H. pylori may lead to false negative results. At a minimum, instruct the patient to avoid the use of amoxicillin in the 4 weeks prior to the test.

Serious rash events, such as toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, exfoliative dermatitis, drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported in patients receiving treatment with amoxicillin. If a skin rash occurs, monitor patients closely and discontinue amoxicillin if lesions progress.

Some amoxicillin chewable tablets contain aspartame, which contains phenylalanine; counsel persons with phenylketonuria accordingly.

Description: Amoxicillin is an oral semisynthetic aminopenicillin similar to ampicillin. The aminopenicillins are not stable to beta-lactamases of either gram-positive or gram-negative bacteria. Amoxicillin is more stable to gastric acid than is penicillin and more bioavailable than oral ampicillin. Because of greater bioavailability, amoxicillin is associated with a lower incidence of diarrhea versus orally-administered ampicillin. Like ampicillin, amoxicillin has a broader spectrum of activity than penicillin, although the carboxy- and ureidopenicillins are much more active against gram-negative rods. Amoxicillin is first line therapy for acute otitis media in pediatric patients and is also commonly used to treat infections such as pneumonia, sinusitis, and skin infections caused by susceptible organisms. To increase the efficacy of amoxicillin against penicillin-resistant S. pneumoniae in otitis media or respiratory infections, higher dosage regimens (e.g., 80 to 90 mg/kg/day) are recommended for young children. Amoxicillin is routinely used for endocarditis prophylaxis and is also used in various regimens for the treatment of Helicobacter pylori infection. Amoxicillin immediate-release formulations are FDA approved for use in pediatric patients as young as neonates; an extended-release formulation is FDA approved for use in children 12 years of age and older.

Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Enterococcus faecalis, Escherichia coli, Haemophilus influenzae (beta-lactamase negative), Helicobacter pylori, Proteus mirabilis, Staphylococcus sp., Streptococcus agalactiae (group B streptococci), Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococci)
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.

This drug may also have activity against the following microorganisms: Bacillus anthracis, Borrelia burgdorferi, Chlamydia trachomatis, Salmonella enterica serotype Typhi
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.

For the treatment of acute otitis media:
NOTE: Guidelines do not recommend doses less than 80 mg/kg/day PO for the treatment of otitis media. Re-evaluate patients failing to respond within 48 to 72 hours. Amoxicillin; clavulanate is the preferred therapy for children who have received amoxicillin within the past 30 days, who have purulent conjunctivitis, or who have a history of recurrent acute otitis media unresponsive to amoxicillin.
Oral dosage (immediate-release):
Infants 1 to 3 months: 30 mg/kg/day PO divided every 12 hours.
Infants 4 to 5 months: 80 to 90 mg/kg/day PO divided every 12 hours for 10 days. The FDA-approved dosage is 20 mg/kg/day PO every 8 hours or 25 mg/kg/day PO divided every 12 hours for mild to moderate infections and 40 mg/kg/day PO divided every 8 hours or 45 mg/kg/day PO divided every 12 hours for severe infections.
Infants and Children 6 to 23 months: 80 to 90 mg/kg/day PO divided every 12 hours for 10 days as first-line therapy. The FDA-approved dosage is 20 mg/kg/day PO every 8 hours or 25 mg/kg/day PO divided every 12 hours for mild to moderate infections and 40 mg/kg/day PO divided every 8 hours or 45 mg/kg/day PO divided every 12 hours for severe infections.
Children 2 to 5 years: 80 to 90 mg/kg/day PO divided every 12 hours for 7 days for mild to moderate disease and 10 days for severe disease as first-line therapy. The FDA-approved dosage is 20 mg/kg/day (Max: 750 mg/day) PO every 8 hours or 25 mg/kg/day (Max: 1,000 mg/day) PO divided every 12 hours for mild to moderate infections and 40 mg/kg/day (Max: 1,500 mg/day) PO divided every 8 hours or 45 mg/kg/day (Max: 1,750 mg/day) PO divided every 12 hours for severe infections.
Children and Adolescents 6 to 17 years: 80 to 90 mg/kg/day (Usual Max: 4 g/day) PO divided every 12 hours for 5 to 7 days for mild to moderate disease and for 10 days for severe disease as first-line therapy. The FDA-approved dosage is 20 mg/kg/day (Max: 750 mg/day) PO every 8 hours or 25 mg/kg/day (Max: 1,000 mg/day) PO divided every 12 hours for mild to moderate infections and 40 mg/kg/day (Max: 1,500 mg/day) PO divided every 8 hours or 45 mg/kg/day (Max: 1,750 mg/day) PO divided every 12 hours for severe infections.

For the treatment of skin and skin structure infections, including cellulitis and erysipelas:
-for the treatment of mild to moderate, nonpurulent skin infections, such as cellulitis and erysipelas:
Oral dosage (immediate-release):
Neonates: 30 mg/kg/day PO divided every 12 hours for 5 to 14 days.
Infants 1 to 3 months: 30 mg/kg/day PO divided every 12 hours for 5 to 14 days.
Infants, Children, and Adolescents 4 months to 17 years: 20 mg/kg/day (Max: 750 mg/day) PO divided every 8 hours or 25 mg/kg/day (Max: 1,000 mg/day) PO divided every 12 hours for 5 to 14 days.
-for the treatment of severe, nonpurulent skin infections, such as cellulitis and erysipelas:
Oral dosage (immediate-release):
Neonates: 30 mg/kg/day PO divided every 12 hours for 5 to 14 days.
Infants 1 to 3 months: 30 mg/kg/day PO divided every 12 hours for 5 to 14 days.
Infants, Children, and Adolescents 4 months to 17 years: 40 mg/kg/day (Max: 1,500 mg/day) PO divided every 8 hours or 45 mg/kg/day (Max: 1,750 mg/day) PO divided every 12 hours for 5 to 14 days.

For the treatment of lower respiratory tract infections (LRTIs), including community-acquired pneumonia (CAP):
-for the treatment of nonspecific lower respiratory tract infections (LRTIs):
Oral dosage (immediate-release):
Neonates: 30 mg/kg/day PO divided every 12 hours.
Infants 1 to 3 months: 30 mg/kg/day PO divided every 12 hours.
Infants, Children, and Adolescents 4 months to 17 years: 45 mg/kg/day (Max: 1,750 mg/day) PO divided every 12 hours or 40 mg/kg/day (Max: 1,500 mg/day) PO divided every 8 hours.
-for the empiric treatment of community-acquired pneumonia (CAP):
Oral dosage (immediate-release):
Infants 1 to 3 months: 50 to 90 mg/kg/day PO divided every 8 to 12 hours for 5 to 7 days.
Infants and Children 4 months to 12 years: 90 mg/kg/day (Max: 4 g/day) PO divided every 12 hours for 5 to 7 days. Consider the addition of a macrolide for patients 5 years and older who do not have clinical, laboratory, or radiologic evidence to distinguish bacterial CAP from atypical CAP.
Adolescents: 90 mg/kg/day (Max: 4 g/day) PO divided every 12 hours for 5 to 7 days. Consider the addition of a macrolide for patients who do not have clinical, laboratory, or radiologic evidence to distinguish bacterial CAP from atypical CAP.
-for the treatment of CAP due to S. pneumoniae, mild infection or step-down therapy (penicillin MIC 2 mcg/mL or less):
Oral dosage (immediate-release):
Infants, Children, and Adolescents 4 months to 17 years: 90 mg/kg/day (Max: 4 g/day) PO divided every 12 hours or 45 mg/kg/day (Max: 4 g/day) PO divided every 8 hours for 5 to 7 days.
-for the treatment of CAP due to S. pneumoniae, relatively resistant (penicillin MIC = 2 mcg/mL):
Oral dosage (immediate-release):
Infants, Children, and Adolescents 4 months to 17 years: 90 mg/kg/day (Max: 4 g/day) PO divided every 8 hours for 5 to 7 days. Dividing 90 mg/kg/day into 3 doses/day vs. 2 doses/day increases the probability of reaching a clinical and microbiological cure to 90% compared to 65%, respectively, in patients with pneumococcal pneumonia (MIC = 2 mcg/mL).
-for the treatment of CAP due to Group A Streptococcus, mild infection or step-down therapy:
Oral dosage (immediate-release):
Infants, Children, and Adolescents 4 months to 17 years: 50 to 75 mg/kg/day (Max: 4 g/day) PO divided every 12 hours for 5 to 7 days.
-for the treatment of CAP due to H. influenzae (beta-lactamase negative), mild infection or step-down therapy:
Oral dosage (immediate-release):
Infants, Children, and Adolescents 4 months to 17 years: 75 to 100 mg/kg/day (Max: 4 g/day) PO divided every 8 hours for 5 to 7 days.

For the treatment of urinary tract infection (UTI), including cystitis and catheter-associated urinary tract infection:
-for the treatment of mild to moderate nonspecific UTI:
Oral dosage (immediate-release):
Neonates: 30 mg/kg/day PO divided every 12 hours.
Infants 1 to 3 months: 30 mg/kg/day PO divided every 12 hours.
Infants, Children, and Adolescents 4 months to 17 years: 20 mg/kg/day (Max: 750 mg/day) PO divided every 8 hours or 25 mg/kg/day (Max: 1,000 mg/day) PO divided every 12 hours.
-for the treatment severe nonspecific UTI or infections due less susceptible organisms:
Oral dosage (immediate-release):
Neonates: 30 mg/kg/day PO divided every 12 hours.
Infants 1 to 3 months: 30 mg/kg/day PO divided every 12 hours.
Infants, Children, and Adolescents 4 months to 17 years: 40 mg/kg/day (Max: 1,500 mg/day) PO divided every 8 hours or 45 mg/kg/day (Max: 1,750 mg/day) PO divided every 12 hours.
-for the treatment of acute uncomplicated lower UTI:
Oral dosage (immediate-release):
Infants 1 to 3 months: 40 mg/kg/day PO divided every 8 hours for 3 days.
Infants, Children, and Adolescents 4 months to 17 years: 40 mg/kg/day (Max: 1,500 mg/day) PO divided every 8 hours for 3 days.
-for the treatment of catheter-associated UTI:
Oral dosage (immediate-release):
Infants 1 to 3 months: 30 mg/kg/day PO divided every 12 hours for 7 to 14 days.
Infants, Children, and Adolescents 4 months to 17 years: 40 mg/kg/day (Max: 1,500 mg/day) PO divided every 8 hours or 45 mg/kg/day (Max: 1,750 mg/day) PO divided every 12 hours for 7 to 14 days.

For the treatment of Lyme disease*, including erythema migrans*, Lyme arthritis*, Lyme carditis*, borrelial lymphocytoma*, and acrodermatitis chronica atrophicans*:
-for the treatment of early Lyme disease* (erythema migrans*), including solitary and multiple erythema migrans*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 50 mg/kg/day PO in divided doses every 8 hours (Max: 500 mg/dose) for 14 days.
-for the initial treatment of Lyme arthritis*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 50 mg/kg/day PO in divided doses every 8 hours (Max: 500 mg/dose) for 28 days.
-for the treatment of recurrent or refractory Lyme arthritis*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 50 mg/kg/day PO in divided doses every 8 hours (Max: 500 mg/dose) for 28 days. A second course of oral antibiotics may be a reasonable alternative for patients in whom synovial proliferation is modest compared to joint swelling and for those who prefer repeating a course of oral antibiotics before considering IV therapy.
-for the treatment of Lyme carditis*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 50 mg/kg/day PO in divided doses every 8 hours (Max: 500 mg/dose) for 14 to 21 days for patients with mild disease not requiring hospitalization (i.e., first degree AV block with PR interval less than 300 milliseconds) or as appropriate oral stepdown treatment after IV therapy in hospitalized patients with severe disease (i.e., symptomatic, first degree AV block with PR interval 300 milliseconds or greater, second or third degree AV block).
-for the treatment of borrelial lymphocytoma*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 50 mg/kg/day PO in divided doses every 8 hours (Max: 500 mg/dose) for 14 days.
-for the treatment of acrodermatitis chronica atrophicans*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 50 mg/kg/day PO in divided doses every 8 hours (Max: 500 mg/dose) for 21 to 28 days.

For bacterial endocarditis prophylaxis*:
Oral dosage (immediate-release):
Children and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) PO as a single dose given 30 to 60 minutes before procedure. Prophylaxis is recommended for at-risk cardiac patients undergoing dental procedures that involve manipulation of gingival tissue, manipulation of the periapical region of teeth, or perforation of the oral mucosa.

For Helicobacter pylori (H. pylori) eradication*:
-for Helicobacter pylori (H. pylori) eradication* as part of clarithromycin-based triple therapy:
Oral dosage (immediate-release):
Children weighing 15 to 24 kg: 500 mg PO twice daily in combination with clarithromycin and a proton pump inhibitor (PPI) for 14 days.
Children and Adolescents weighing 25 to 34 kg: 750 mg PO twice daily in combination with clarithromycin and a proton pump inhibitor (PPI) for 14 days.
Children and Adolescents weighing 35 kg or more: 1,000 mg PO twice daily in combination with clarithromycin and a proton pump inhibitor (PPI) for 14 days.
-for Helicobacter pylori (H. pylori) eradication* as part of clarithromycin-based quadruple/concomitant therapy:
Oral dosage (immediate-release):
Children weighing 15 to 24 kg: 500 mg PO twice daily in combination with clarithromycin, metronidazole, and a proton pump inhibitor (PPI) for 14 days.
Children and Adolescents weighing 25 to 34 kg: 750 mg PO twice daily in combination with clarithromycin, metronidazole, and a proton pump inhibitor (PPI) for 14 days.
Children and Adolescents weighing 35 kg or more: 1,000 mg PO twice daily in combination with clarithromycin, metronidazole, and a proton pump inhibitor (PPI) for 14 days.
-for Helicobacter pylori (H. pylori) eradication* as part of clarithromycin-based sequential therapy:
Oral dosage (immediate-release):
Children weighing 15 to 24 kg: 500 mg PO twice daily in combination with a proton pump inhibitor (PPI) for 5 days, followed by clarithromycin, metronidazole, and a PPI for 5 days.
Children and Adolescents weighing 25 to 34 kg: 750 mg PO twice daily in combination with a proton pump inhibitor (PPI) for 5 days, followed by clarithromycin, metronidazole, and a PPI for 5 days.
Children and Adolescents weighing 35 kg or more: 1,000 mg PO twice daily in combination with a proton pump inhibitor (PPI) for 5 days, followed by clarithromycin, metronidazole, and a PPI for 5 days.
-for Helicobacter pylori (H. pylori) eradication* as part of metronidazole-based triple therapy in strains with known susceptibility to metronidazole and resistance to clarithromycin:
Oral dosage (immediate-release):
Children weighing 15 to 24 kg: 500 mg PO twice daily in combination with metronidazole and a proton pump inhibitor (PPI) for 14 days.
Children and Adolescents weighing 25 to 34 kg: 750 mg PO twice daily in combination with metronidazole and a proton pump inhibitor (PPI) for 14 days.
Children and Adolescents weighing 35 kg or more: 1,000 mg PO twice daily in combination with metronidazole and a proton pump inhibitor (PPI) for 14 days.
-for Helicobacter pylori (H. pylori) eradication* as part of metronidazole-based triple therapy in strains with dual resistance to clarithromycin and metronidazole or with unknown susceptibility:
Oral dosage (immediate-release):
Children weighing 15 to 24 kg: 750 mg PO twice daily in combination with metronidazole and a proton pump inhibitor (PPI) for 14 days.
Children and Adolescents weighing 25 to 34 kg: 1,000 mg PO twice daily in combination with metronidazole and a proton pump inhibitor (PPI) for 14 days.
Children and Adolescents weighing 35 kg or more: 1,500 mg PO twice daily in combination with metronidazole and a proton pump inhibitor (PPI) for 14 days.

For the treatment of adolescent aggressive periodontitis* in combination with metronidazole after scaling and root planing:
Oral dosage (immediate-release):
Adolescents 16 to 17 years: 250 to 375 mg PO 3 times daily with metronidazole (250 mg PO 3 times daily) for 7 to 10 days.

For the treatment of fully sensitive uncomplicated typhoid fever*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 50 to 100 mg/kg/day (Max: 3 g/day) PO divided every 6 to 8 hours for 14 days as an alternative.

For the treatment of anthrax*:
-for the treatment of cutaneous anthrax* without aerosol exposure and signs and symptoms of meningitis:
Oral dosage (immediate-release):
Neonates 32 to 33 weeks gestation and 0 to 6 days: 25 mg/kg/dose PO every 12 hours for 7 to 10 days or until clinical criteria for stability are met.
Neonates 32 to 33 weeks gestation and 7 days and older: 25 mg/kg/dose PO every 8 hours for 7 to 10 days or until clinical criteria for stability are met.
Neonates 34 weeks gestation and older: 25 mg/kg/dose PO every 8 hours for 7 to 10 days or until clinical criteria for stability are met.
Infants, Children, and Adolescents: 25 mg/kg/dose (Max: 1,000 mg/dose) PO every 8 hours for 7 to 10 days or until clinical criteria for stability are met.
-for the treatment of cutaneous anthrax* with aerosol exposure and without signs and symptoms of meningitis:
Oral dosage (immediate-release):
Neonates 32 to 33 weeks gestation and 0 to 6 days: 25 mg/kg/dose PO every 12 hours for 7 to 10 days or until clinical criteria for stability are met and then transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
Neonates 32 to 33 weeks gestation and 7 days and older: 25 mg/kg/dose PO every 8 hours for 7 to 10 days or until clinical criteria for stability are met and then transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
Neonates 34 weeks gestation and older: 25 mg/kg/dose PO every 8 hours for 7 to 10 days or until clinical criteria for stability are met and then transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
Infants, Children, and Adolescents: 25 mg/kg/dose (Max: 1,000 mg/dose) PO every 8 hours for 7 to 10 days or until clinical criteria for stability are met and then transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.

For postexposure anthrax prophylaxis*:
-for postexposure anthrax prophylaxis* after nonaerosol exposure (cutaneous or ingestion):
Oral dosage (immediate-release):
Neonates 32 to 33 weeks gestation and 0 to 6 days: 15 mg/kg/dose PO every 12 hours for 7 days after exposure.
Neonates 32 to 33 weeks gestation and 7 days and older: 15 mg/kg/dose PO every 8 hours for 7 days after exposure.
Neonates 34 weeks gestation and older: 15 mg/kg/dose PO every 8 hours for 7 days after exposure.
Infants, Children, and Adolescents: 25 mg/kg/dose (Max: 500 mg/dose) PO every 8 hours for 7 days after exposure.
-for postexposure anthrax prophylaxis* after aerosol exposure:
Oral dosage (immediate-release):
Neonates 32 to 33 weeks gestation and 0 to 6 days: 15 mg/kg/dose PO every 12 hours for 60 days after exposure.
Neonates 32 to 33 weeks gestation and 7 days and older: 15 mg/kg/dose PO every 8 hours for 60 days after exposure.
Neonates 34 weeks gestation and older: 15 mg/kg/dose PO every 8 hours for 60 days after exposure.
Infants, Children, and Adolescents: 25 mg/kg/dose (Max: 500 mg/dose) PO every 8 hours for 60 days after exposure.

For the treatment of group A beta-hemolytic streptococcal (GAS) pharyngitis (primary rheumatic fever prophylaxis) and tonsillitis:
Oral dosage (immediate-release):
Neonates: 50 mg/kg/dose PO once daily or 25 mg/kg/dose PO every 12 hours for 10 days. The FDA-approved dosage is 30 mg/kg/day PO divided every 12 hours.
Infants 1 to 3 months: 50 mg/kg/dose PO once daily or 25 mg/kg/dose PO every 12 hours for 10 days. The FDA-approved dosage is 30 mg/kg/day PO divided every 12 hours.
Infants, Children, and Adolescents 4 months to 17 years: 50 mg/kg/dose (Max: 1,000 mg/dose) PO once daily or 25 mg/kg/dose (Max: 500 mg/dose) PO every 12 hours for 10 days. The FDA-approved dosage is 20 mg/kg/day (Max: 750 mg/day) PO divided every 8 hours or 25 mg/kg/day (Max: 1,000 mg/day) PO divided every 12 hours for mild to moderate infections and 40 mg/kg/day (Max: 1,500 mg/day) PO divided every 8 hours or 45 mg/kg/day (Max: 1,750 mg/day) PO divided every 12 hours for severe infections.
Oral dosage (extended-release):
Children and Adolescents 12 to 17 years: 775 mg PO once daily for 10 days.

For the treatment of acute bacterial sinusitis:
Oral dosage (immediate-release, standard dose therapy):
Neonates: Not recommended by guidelines. The FDA-approved dosage is 30 mg/kg/day PO divided every 12 hours.
Infants 1 to 3 months: Not recommended by guidelines. The FDA-approved dosage is 30 mg/kg/day PO divided every 12 hours.
Infants and Children 4 months to 1 year: Not recommended by guidelines. The FDA-approved dosage is 20 mg/kg/day PO divided every 8 hours or 25 mg/kg/day PO divided every 12 hours for mild to moderate infections and 40 mg/kg/day PO divided every 8 hours or 45 mg/kg/day PO divided every 12 hours for severe infections.
Children and Adolescents 2 to 17 years: 45 mg/kg/day (Max: 1,750 mg/day) PO divided every 12 hours for 10 to 14 days for mild to moderate uncomplicated disease in children who do not attend daycare and who have not been treated with an antimicrobial agent in the previous 4 weeks. The FDA-approved dosage is 20 mg/kg/day (Max: 750 mg/day) PO divided every 8 hours or 25 mg/kg/day (Max: 1,000 mg/day) PO divided every 12 hours for mild to moderate infections and 40 mg/kg/day (Max: 1,500 mg/day) PO divided every 8 hours or 45 mg/kg/day (Max: 1,750 mg/day) PO divided every 12 hours for severe infections. Due to the high rates of H. influenzae and beta-lactamase-producing pathogens among upper respiratory tract infections in children, amoxicillin; clavulanic acid (and not amoxicillin alone) is recommended as first-line empiric therapy for acute bacterial sinusitis. However, amoxicillin is an option for children 2 years and older with uncomplicated disease in which antimicrobial resistance is not suspected. Children with moderate to severe disease, attending daycare, or who have recently been treated with antimicrobial therapy should receive high-dose amoxicillin; clavulanic acid.
Oral dosage (immediate-release, high-dose therapy*):
Children and Adolescents 2 to 17 years: 80 to 90 mg/kg/day (Max: 4 g/day) PO divided every 12 hours for 10 to 14 days for children in areas with high rates of S. pneumoniae resistance (more than 10%, including intermediate- and high-level resistance). Due to the high rates of H. influenzae and beta-lactamase-producing pathogens among upper respiratory tract infections in children, amoxicillin; clavulanic acid (and not amoxicillin alone) is recommended as first-line empiric therapy for acute bacterial sinusitis. However, amoxicillin is an option for children 2 years and older with uncomplicated disease in which antimicrobial resistance is not suspected. Children with moderate to severe disease, attending daycare, or who have recently been treated with antimicrobial therapy should receive high-dose amoxicillin; clavulanic acid.

For chronic typhoid carriage eradication*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 75 to 100 mg/kg/day (Max: 6 g/day) PO divided every 6 to 8 hours plus probenecid for 4 to 6 weeks.

For the treatment of peritoneal dialysis catheter-related infection*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 10 to 20 mg/kg/dose (Max: 1,000 mg/dose) PO every 24 hours for at least 14 to 28 days.

For the treatment of bone and joint infections*, including osteomyelitis*and infectious arthritis*:
-for step-down therapy for osteomyelitis* after initial IV therapy:
Oral dosage (immediate-release):
Neonates: 15 mg/kg/dose PO every 12 hours. Treat for a total duration of 4 to 6 weeks (parenteral plus oral). A longer course (several months) may be needed for severe or complicated infections.
Infants 1 to 2 months: 50 to 100 mg/kg/day PO divided every 8 hours. Treat for a total duration of 4 to 6 weeks (parenteral plus oral). A longer course (several months) may be needed for severe or complicated infections.
Infants, Children, and Adolescents 3 months to 17 years: 50 to 100 mg/kg/day (Max: 4 g/day) PO divided every 8 hours. Treat for a total duration of 3 to 4 weeks (parenteral plus oral) for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
-for step-down therapy for infectious arthritis* after initial IV therapy:
Oral dosage (immediate-release):
Neonates: 15 mg/kg/dose PO every 12 hours. Treat for a total duration of 4 to 6 weeks (parenteral plus oral). A longer course (several months) may be needed for severe or complicated infections.
Infants 1 to 2 months: 50 to 100 mg/kg/day PO divided every 8 hours. Treat for a total duration of 4 to 6 weeks (parenteral plus oral). A longer course (several months) may be needed for severe or complicated infections.
Infants, Children, and Adolescents 3 months to 17 years: 50 to 100 mg/kg/day (Max: 4 g/day) PO divided every 8 hours. Treat for a total duration of 2 to 3 weeks (parenteral plus oral) for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections. [67759

For the treatment of leptospirosis*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 30 to 40 mg/kg/day PO divided every 6 hours or 50 mg/kg/day PO divided every 12 hours (Max: 2 g/day) for 7 to 10 days as alternative therapy for mild or moderate disease.

For urinary tract infection (UTI) prophylaxis* in infants with hydronephrosis or vesicoureteral reflux:
NOTE: Routine antimicrobial prophylaxis for patients age 2 to 24 months with vesicoureteral reflux is not supported by currently available data; however, antimicrobial prophylaxis is still utilized and has biological plausibility.
Oral dosage (immediate-release):
Infants younger than 2 months: 10 to 15 mg/kg/dose PO once daily. Guidelines recommend antibiotic prophylaxis for all grades of vesicoureteral reflux in all children younger than 1 year.
Neonates: 10 to 15 mg/kg/dose PO once daily. Guidelines recommend antibiotic prophylaxis for all grades of vesicoureteral reflux in all children younger than 1 year.

For the treatment of acute exacerbations of bronchiectasis*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: 40 to 45 mg/kg/day (Max: 1,500 mg/day) PO divided every 8 hours for 14 days.

For pneumococcal prophylaxis* in persons with functional or anatomic asplenia:
Oral dosage (immediate-release):
Infants and Children 1 month to 5 years: 20 to 40 mg/kg/day (Max: 500 mg/day) PO divided once or twice daily until at least age 5 years. Lifelong prophylaxis may be warranted in certain populations.
Children and Adolescents 6 to 17 years: 20 to 40 mg/kg/day (Max: 500 mg/day) PO divided once or twice daily for at least 1 to 2 years post-splenectomy. Lifelong prophylaxis may be warranted in certain populations.

Maximum Dosage Limits:
-Neonates
30 mg/kg/day PO is FDA-approved maximum; however, doses up to 75 mg/kg/day PO have been used off-label.
-Infants
1 to 3 months: 30 mg/kg/day PO is FDA-approved maximum; however, doses up to 100 mg/kg/day PO have been used off-label.
4 to 11 months: 45 mg/kg/day PO is FDA-approved maximum; however, doses up to 100 mg/kg/day PO have been used off-label.
-Children
45 mg/kg/day (Max: 1,750 mg/day) PO is FDA-approved maximum; however, doses up to 100 mg/kg/day (Max: 4 g/day) PO have been used off-label.
-Adolescents
45 mg/kg/day (Max: 1,750 mg/day) PO is FDA-approved maximum; however, doses up to 100 mg/kg/day (Max: 4 g/day) PO have been used off-label.

Patients with Hepatic Impairment Dosing
No dosage adjustment needed; amoxicillin is not appreciably metabolized in the liver and does not undergo biliary secretion.

Patients with Renal Impairment Dosing
Pediatric patients (non-neonatal)*
The following renal dosage adjustments are based on a usual amoxicillin dose in pediatric patients of 25 to 50 mg/kg/day PO divided every 8 hours (standard-dose) or 80 to 90 mg/kg/day PO divided every 12 hours (high-dose):
CrCl 30 mL/minute/1.73 m2: no dosage adjustment needed.
CrCl 10 to 29 mL/minute/1.73 m2: 8 to 20 mg/kg/dose PO every 12 hours (standard-dose) or 20 mg/kg/dose PO every 12 hours (high-dose); Max: 500 mg/dose.
CrCl less than 10 mL/minute/1.73 m2: 8 to 20 mg/kg/dose PO every 24 hours (standard-dose) or 20 mg/kg/dose PO every 24 hours (high-dose); Max: 500 mg/dose.

Intermittent hemodialysis*
8 to 20 mg/kg/dose PO every 24 hours (standard-dose) or 20 mg/kg/dose PO every 24 hours (high-dose) after dialysis; Max: 500 mg/dose.

Peritoneal dialysis*
8 to 20 mg/kg/dose PO every 24 hours (standard-dose) or 20 mg/kg/dose PO every 24 hours (high-dose); Max: 500 mg/dose.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Beta-lactam antibiotics such as amoxicillin are mainly bactericidal. Like other penicillins, amoxicillin inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. Penicillin-binding proteins are responsible for several steps in the synthesis of the cell wall and are found in quantities of several hundred to several thousand molecules per bacterial cell. Penicillin-binding proteins vary among different bacterial species. Thus, the intrinsic activity of amoxicillin, as well as the other penicillins, against a particular organism depends on their ability to gain access to and bind with the necessary PBP. The aminopenicillins are able to penetrate gram-negative bacteria more readily than are the natural penicillins or penicillinase-resistant penicillins due to the presence of a free amino group within the structure. Like all beta-lactam antibiotics, amoxicillin's ability to interfere with PBP-mediated cell wall synthesis ultimately leads to cell lysis. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor. Prevention of the autolysin response to beta-lactam antibiotic exposure through loss of autolytic activity (mutation) or inactivation of autolysin (low-medium pH) by the microorganism can lead to tolerance to the beta-lactam antibiotic resulting in bacteriostatic activity.

The susceptibility interpretive criteria for amoxicillin are delineated by pathogen. For non-meningitis infections, the MICs are defined for S. pneumoniae as susceptible at 2 mcg/mL or less, intermediate at 4 mcg/mL, and resistant at 8 mcg/mL or more based on a dose of 500 mg PO every 8 hours or 875 mg PO every 12 hours. The MICs are defined for Pasteurella sp. as susceptible at 0.5 mcg/mL or less. The MICs are defined for B. anthracis as susceptible at 0.12 mcg/mL or less and resistant at 0.25 mcg/mL or more. For salmonellosis or uncomplicated UTIs due to E. coli, P. mirabilis, or Enterococcus sp. the results for ampicillin testing can be used to predict results for amoxicillin (based on an amoxicillin dosage of 250 mg PO every 8 hours or 500 mg PO every 12 hours). For anaerobes, H. influenzae, and H. parainfluenzae, the results of ampicillin susceptibility tests should be used to predict the activity of amoxicillin. For groups A, B, C, and G beta-hemolytic streptococci, penicillin is tested as a surrogate for amoxicillin. Oxacillin-susceptible staphylococci can be considered susceptible to amoxicillin. For Vibrio sp., ampicillin is considered a class representative for amoxicillin.

Pharmacokinetics: Amoxicillin is administered orally. Approximately 20% of the circulating drug is protein-bound. Amoxicillin is widely distributed into most body tissues and fluids, excluding the brain and spinal fluid except when meninges are inflamed. Amoxicillin does cross the placenta. A small percentage is excreted in breast milk. The unchanged drug and its metabolites are excreted into the urine primarily via tubular secretion and glomerular filtration. In adults, approximately 60% of an orally administered dose is excreted in the urine primarily via tubular secretion and glomerular filtration within 6 to 8 hours; concurrent administration of probenecid prolongs urinary excretion. In patients with normal renal function, the elimination half-life of amoxicillin is 1 to 1.5 hours.

Affected cytochrome P450 isoenzymes: none


-Route-Specific Pharmacokinetics
Oral Route
Amoxicillin is stable in the presence of gastric acid and is rapidly absorbed. Amoxicillin is more completely absorbed than ampicillin and, for this reason, is often the preferred oral aminopenicillin.

Immediate-release formulations
Peak concentrations are reached 1 to 2 hours after administration in adults.

Extended-release formulation
Administration of the extended-release formulation results in slower amoxicillin absorption compared to immediate-release products; peak concentrations are reached approximately 3 hours after administration. Amoxicillin exposure (AUC) achieved with the extended-release formulation is similar to that observed after oral administration of a comparable dose of immediate-release amoxicillin suspension. Food decreases the rate, but does not alter the extent of absorption.


-Special Populations
Pediatrics
Neonates and Young Infants
Because of incompletely developed renal function in neonates and young infants, the elimination of amoxicillin may be delayed. Dosing should be modified in pediatric patients 12 weeks of age or younger (3 months or age or less).

Renal Impairment
Pharmacokinetic data are unavailable in pediatric patients with renal impairment. However, amoxicillin is substantially eliminated by the kidneys and elimination half-life increases as renal function declines. Studies in adult patients have shown that the elimination half-life of amoxicillin is prolonged to approximately 10 to 13 hours in patients with end-stage renal disease. Dosage adjustments are recommended in patients with severe renal impairment.