Version April 2023
Note: All neonatal dosing recommendations based on immediate-release product formulations (ie, oral suspension).
General dosing: Limited data available; optimal dose not established:
High-dose regimen (Ref):
Preterm and term neonates:
1.5 to <2 kg: 75 mg/kg/day in divided doses every 12 hours.
≥2 kg: 100 mg/kg/day in divided doses every 12 hours.
Traditional-dose regimen: Preterm and term neonates: Oral: 30 mg/kg/day in divided doses every 12 hours (Ref).
Otitis media, acute (AOM), Group A or B streptococcus: Neonates: Oral stepdown therapy following parenteral treatment: Oral: 30 to 40 mg/kg/day in divided doses every 8 hours for 10 days (Ref).
Pneumococcal infection prophylaxis for anatomic or functional asplenia: Neonates: Oral: 20 mg/kg/day in divided doses twice daily (Ref).
Urinary tract infection, prophylaxis (hydronephrosis, vesicoureteral reflux): Neonates: Oral: 10 to 15 mg/kg/day once daily (Ref).
Note: Unless otherwise specified, all pediatric dosing recommendations are based on immediate-release product formulations (oral suspension, chewable tablet, tablet, and capsule).
General dosing:
Infants, Children, and Adolescents:
Standard-dose regimen: Oral: 40 to 45 mg/kg/day in divided doses every 8 hours; maximum dose: 500 mg/dose (Ref).
High-dose regimen: 80 to 90 mg/kg/day divided every 12 hours; a maximum dose has not been established; however, some experts suggest a maximum daily dose of 4,000 mg/day (Ref).
Anthrax:
Infants, Children, and Adolescents (Ref):
Postexposure prophylaxis, exposure to aerosolized spores: Oral: 75 mg/kg/day in divided doses every 8 hours for 60 days after exposure; maximum dose: 1,000 mg/dose.
Cutaneous, without systemic involvement: Oral: 75 mg/kg/day in divided doses every 8 hours; maximum dose: 1,000 mg/dose. Duration of therapy: 7 to 10 days for naturally acquired infection, up to 60 days for biological weapon-related exposure.
Systemic, oral step-down therapy: Oral: 75 mg/kg/day in divided doses every 8 hours as part of appropriate combination therapy to complete 60-day course; maximum dose: 1,000 mg/dose.
Catheter (peritoneal dialysis), exit-site or tunnel infection: Infants, Children, and Adolescents: Oral: 10 to 20 mg/kg/dose every 24 hours; maximum dose: 1,000 mg/dose (Ref).
Endocarditis, prophylaxis before invasive dental or respiratory tract procedures: Note: Recommended only in patients who are at highest risk for infective endocarditis (IE) or adverse outcomes (eg, history of IE, prosthetic heart valves or prosthetic material used to repair valves, unrepaired cyanotic congenital heart disease, repaired congenital heart disease with prosthetic material or device during first 6 months after procedure, repaired congenital heart disease with residual defects at the site or adjacent to site of prosthetic patch or device, heart transplant recipients with cardiac valvulopathy) (Ref).
Infants, Children, and Adolescents: Oral: 50 mg/kg administered 30 to 60 minutes prior to procedure; maximum dose: 2,000 mg/dose (Ref).
Helicobacter pylori eradication: Limited data available: Note: Use as part of an appropriate combination regimen; usual duration of therapy is 14 days (Ref).
Standard-dose regimen:
Weight-directed dosing: Children and Adolescents: Oral: 50 mg/kg/day in divided doses every 12 hours; maximum dose: 1,000 mg/dose (Ref).
Fixed dosing (Ref): Children and Adolescents:
15 to <25 kg: Oral: 500 mg twice daily.
25 to <35 kg: Oral: 750 mg twice daily.
≥35 kg: Oral: 1,000 mg twice daily.
High-dose regimen:
Note: For use in combination with a proton pump inhibitor and metronidazole when susceptibility is unknown or when H. pylori isolate is resistant to clarithromycin AND metronidazole. Fixed (weight-band) dosing based on a target dose of ~75 mg/kg/day divided twice daily; maximum dose reported: 100 mg/kg/day divided twice daily (Ref).
Children and Adolescents (Ref).
15 to <25 kg: Oral: 750 mg twice daily.
25 to <35 kg: Oral: 1,000 mg twice daily.
≥35 kg: Oral: 1,500 mg twice daily.
Lyme disease ( Borrelia spp. infection): Infants, Children, and Adolescents: Oral: 50 mg/kg/day in divided doses every 8 hours; maximum dose: 500 mg/dose. Duration of therapy depends on clinical syndrome; treat erythema migrans and borrelial lymphocytoma for 14 days, carditis for 14 to 21 days, arthritis (initial, recurrent, or refractory) for 28 days, and acrodermatitis chronica atrophicans for 21 to 28 days (Ref).
Osteoarticular infection, acute (eg, septic [bacterial] arthritis, osteomyelitis): Step-down therapy following parenteral treatment (targeted therapy for susceptible pathogen): Limited data available:
Infants, Children, and Adolescents: Oral: 80 to 120 mg/kg/day in divided doses every 6 to 8 hours; maximum daily dose: 4,000 mg/day (Ref). Minimum total duration (IV plus oral therapy) is 2 to 3 weeks for septic arthritis and 3 to 4 weeks for osteomyelitis; however, duration should be individualized based on several factors including causative pathogen, response to therapy, and normalization of inflammatory markers (Ref).
Otitis media, acute (AOM):
High-dose regimen: Note: Preferred in the United States and when activity against penicillin nonsusceptible Streptococcus pneumoniae is desired (Ref).
Infants ≥3 months and Children: Oral: 80 to 90 mg/kg/day in divided doses every 12 hours. Maximum dose has not been established for AOM; however, 4,000 mg/day has been suggested (Ref).
Standard-dose regimen: Note: Only for use in areas where rates of penicillin nonsusceptible S. pneumoniae are known to be low or if an isolated pathogen is penicillin-susceptible (Ref).
Infants ≥3 months and Children: Oral: 40 to 50 mg/kg/day in divided doses every 8 to 12 hours. Maximum daily dose: 1,500 mg/day (Ref).
Duration of therapy: For patients with severe or recurrent AOM, tympanic membrane perforation, or who are <2 years of age, treat for 10 days; for patients ≥2 years of age with mild to moderate, nonrecurrent disease without tympanic membrane perforation, shorter durations of 5 to 7 days may be sufficient (Ref).
Peritonitis, prophylaxis for peritoneal dialysis patients requiring invasive dental procedures: Infants, Children, and Adolescents: Oral: 50 mg/kg as a single dose administered 30 to 60 minutes before dental procedure; maximum dose: 2,000 mg/dose (Ref).
Pneumonia, community-acquired:
Infants ≥3 months, Children, and Adolescents:
Empiric therapy for presumed bacterial pneumonia: Oral: 90 mg/kg/day in divided doses every 12 hours; maximum daily dose: 4,000 mg/day (Ref).
Group A Streptococcus, mild infection or step-down therapy: Oral: 50 to 75 mg/kg/day in divided doses every 12 hours; maximum daily dose: 4,000 mg/day (Ref).
Haemophilus influenzae, mild infection or step-down therapy: Oral: 75 to 100 mg/kg/day in divided doses every 8 hours; maximum daily dose: 4,000 mg/day (Ref).
Streptococcus pneumoniae, mild infection or step-down therapy (penicillin minimal inhibitory concentration [MIC] ≤2 mcg/mL): Oral: 90 mg/kg/day in divided doses every 12 hours or 45 mg/kg/day in divided doses every 8 hours; maximum daily dose: 4,000 mg/day (Ref).
S. pneumoniae, elevated penicillin MIC (penicillin MIC = 2 mcg/mL): Oral: 90 to 100 mg/kg/day in divided doses every 8 hours; dosing based on pharmacokinetic modeling to optimize pharmacodynamic target attainment (time over MIC) (Ref).
Duration of therapy: For outpatient treatment of uncomplicated disease in patients who respond to therapy, 5 days of therapy is likely adequate (Ref). Longer duration (eg, total course of 7 to 10 days) may be necessary in patients with complicated disease or who do not respond quickly to therapy (Ref).
Pneumococcal infection prophylaxis for anatomic or functional asplenia (eg, sickle cell disease [SCD]): Note: The decision to discontinue antibiotic prophylaxis after 5 years of age in children with SCD who have not experienced invasive pneumococcal infection and have received recommended pneumococcal immunizations should be individualized (Ref).
Infants (as soon as SCD diagnosed or asplenic) and Children <6 years: Oral: 20 mg/kg/day in divided doses every 12 hours; maximum dose: 250 mg/dose (Ref).
Children ≥6 years and Adolescents: Oral: 250 mg every 12 hours (Ref).
Rhinosinusitis, acute bacterial; uncomplicated: Note: While IDSA guidelines consider amoxicillin/clavulanate as the preferred therapy, AAP guidelines allow amoxicillin for uncomplicated, mild to moderate infections in patients who do not attend daycare and who have not received antibiotics within the last month (Ref).
Standard-dose regimen: Note: Recommended in areas where <10% of Streptococcus pneumoniae are penicillin-nonsusceptible.
Children ≥2 years and Adolescents: Oral: 45 mg/kg/day in divided doses every 12 hours.
High-dose regimen: Note: Recommended in areas where ≥10% of S. pneumoniae are penicillin-nonsusceptible.
Children ≥2 years and Adolescents: Oral: 80 to 90 mg/kg/day in divided doses every 12 hours; maximum dose: 2,000 mg/dose.
Streptococcus, group A; pharyngitis/tonsillitis: Children and Adolescents: Oral: 50 mg/kg/day once daily or in divided doses every 12 hours for 10 days; maximum daily dose: 1,000 mg/day (Ref).
Urinary tract infection, prophylaxis (hydronephrosis, vesicoureteral reflux): Infants ≤2 months: Oral: 10 to 15 mg/kg once daily; some suggest administration in the evening (drug resides in bladder longer); Note: Due to resistance, amoxicillin should not be used for prophylaxis after 2 months of age (Ref).
Urinary tract infection, treatment: Note: Recommended only when pathogen has been proven susceptible (Ref). Duration of therapy should be individualized based on patient age, severity/extent of infection, and clinical response; typical duration is 7 to 14 days, though it may be as short as 3 to 5 days (eg, for uncomplicated cystitis in patients ≥2 years of age) (Ref).
Infants: Oral: 50 to 100 mg/kg/day in divided doses every 12 hours (Ref).
Children and Adolescents: Oral: 50 to 100 mg/kg/day in divided doses every 8 hours; maximum dose: 500 mg/dose (Ref); for uncomplicated cystitis, may consider 30 mg/kg/day in divided doses every 8 hours (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, the following guidelines have been used by some clinicians (Ref): Oral:
Immediate release: Infants, Children, and Adolescents:
Mild to moderate infection: Dosing based on 25 to 50 mg/kg/day divided every 8 hours:
GFR >30 mL/minute/1.73 m2: No adjustment required.
GFR 10 to 29 mL/minute/1.73 m2: 8 to 20 mg/kg/dose every 12 hours.
GFR <10 mL/minute/1.73 m2: 8 to 20 mg/kg/dose every 24 hours.
Hemodialysis: Moderately dialyzable (20% to 50%); ~30% removed by 3-hour hemodialysis: 8 to 20 mg/kg/dose every 24 hours; give after dialysis.
Peritoneal dialysis: 8 to 20 mg/kg/dose every 24 hours.
Severe infection (high dose): Dosing based on 80 to 90 mg/kg/day divided every 12 hours:
GFR >30 mL/minute/1.73 m2: No adjustment required.
GFR 10 to 29 mL/minute/1.73 m2: 20 mg/kg/dose every 12 hours; do not use the 875 mg tablet.
GFR <10 mL/minute/1.73 m2: 20 mg/kg/dose every 24 hours; do not use the 875 mg tablet.
Hemodialysis: Moderately dialyzable (20% to 50%); ~30% removed by 3-hour hemodialysis: 20 mg/kg/dose every 24 hours; give after dialysis.
Peritoneal dialysis: 20 mg/kg/dose every 24 hours.
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Amoxicillin: Drug information")
Note: Amoxicillin 775 mg ER tablets (brand and generic) have been discontinued in the United States for >1 year.
Note: Unless otherwise specified, all dosing recommendations are based on IR product formulations.
Usual dosage range:
Immediate release: Oral: 500 mg to 1 g every 8 to 12 hours.
Extended release: Oral: 775 mg once daily.
Actinomycosis (off-label use):
Note: For initial therapy of mild infection or step-down therapy following parenteral treatment of severe infection.
Oral: 500 mg 3 to 4 times daily or 1 g 3 times daily (Ref); higher doses of 4 to 6 g/day in divided doses have been utilized in case reports (Ref). Optimal duration is uncertain; some experts suggest total durations of 2 to 6 months for mild infection and 6 to 12 months for severe or extensive infection (Ref).
Anthrax (alternative agent [susceptible strains only]) (off-label use):
Note: Consult public health officials for event-specific recommendations. A high index of suspicion for emergent beta-lactam resistance during therapy is warranted (Ref).
Inhalational exposure postexposure prophylaxis (PEP): Oral: 1 g every 8 hours (Ref); duration depends on anthrax vaccine status and series completion, age, immune status, and pregnancy/breastfeeding status. For those who have not previously received anthrax vaccine, duration ranges from 42 to 60 days (Ref).
Note: Anthrax vaccine should also be administered to exposed individuals (Ref)
Cutaneous, without systemic involvement, treatment: Oral: 1 g every 8 hours; duration is 7 to 10 days after naturally acquired infection and 60 days following biological weapon-related event. Note: Patients with extensive edema or cutaneous lesions of the head or neck should be treated with a parenteral regimen recommended for systemic involvement (Ref).
Asplenia, prophylaxis against bacterial infection in select high-risk patients (off-label use): Oral: Based on expert opinion: 500 mg twice daily. Duration varies based on patient-specific factors (Ref).
Bronchiectasis (off-label use):
Treatment of pulmonary exacerbations in patients without beta-lactamase-positive H. influenzae or Pseudomonas aeruginosa: Oral: 500 mg 3 times daily (Ref) or 1 g 3 times daily (Ref) for up to 14 days (Ref).
Prevention of pulmonary exacerbations: Oral: 500 mg twice daily; dosing based on expert opinion (Ref). Note: Recommended for patients with ≥3 exacerbations per year who are not colonized with P. aeruginosa and not candidates for long-term macrolide therapy (Ref).
Endocarditis, prophylaxis (dental or invasive respiratory tract procedures) (off-label use): Oral: 2 g 30 to 60 minutes before procedure; if inadvertently not given prior to the procedure, may be administered up to 2 hours after the procedure. Note: Reserve for select situations (cardiac condition with the highest risk of adverse endocarditis outcomes and procedure likely to result in bacteremia with an organism that can cause endocarditis) (Ref).
Helicobacter pylori eradication: Oral:
Clarithromycin triple regimen: Amoxicillin 1 g twice daily in combination with clarithromycin 500 mg twice daily, plus a standard-dose or double-dose proton pump inhibitor; continue regimen for 14 days. Note: Avoid use in patients with risk factors for macrolide resistance (eg, prior macrolide exposure or local clarithromycin resistance rates ≥15%, which is assumed in the United States) (Ref).
Concomitant regimen: Amoxicillin 1 g twice daily in combination with clarithromycin 500 mg twice daily, either metronidazole or tinidazole 500 mg twice daily, plus a standard-dose proton pump inhibitor twice daily; continue regimen for 10 to 14 days (Ref).
Sequential regimen (alternative regimen): Amoxicillin 1 g twice daily plus a standard-dose proton pump inhibitor twice daily for 5 to 7 days; followed by clarithromycin 500 mg twice daily, either metronidazole or tinidazole 500 mg twice daily, plus a standard-dose proton pump inhibitor twice daily for 5 to 7 days; some experts prefer the 10-day regimen due to the lack of data showing superiority of the 14-day sequential regimen in North America (Ref)
Hybrid regimen (alternative regimen): Amoxicillin 1 g twice daily, plus a standard-dose proton pump inhibitor twice daily for 7 days; followed by amoxicillin 1 g twice daily, clarithromycin 500 mg twice daily, either metronidazole or tinidazole 500 mg twice daily, plus a standard-dose proton pump inhibitor twice daily for 7 days (Ref).
Levofloxacin triple regimen (salvage regimen): Amoxicillin 750 mg 3 times daily in combination with a double-dose proton pump inhibitor twice daily plus levofloxacin 500 mg once daily; continue regimen for 14 days (Ref).
High-dose dual therapy (alternative salvage regimen): Amoxicillin 750 mg 4 times daily or 1 g 3 times daily; in combination with a double-dose proton pump inhibitor twice daily for 14 days (Ref).
Lyme disease (Borrelia spp. infection) (off-label use):
Erythema migrans: Oral: 500 mg 3 times daily for 14 days (Ref).
Carditis (initial therapy for mild disease [first-degree atrioventricular block with PR interval <300 msec] or step-down therapy after initial parenteral treatment for more severe disease once PR interval <300 msec): Oral: 500 mg 3 times daily for 14 to 21 days (Ref).
Arthritis without neurologic involvement: Oral: 500 mg 3 times daily for 28 days (Ref).
Otitis media, acute (alternative agent):
Note: Some experts recommend amoxicillin/clavulanate over amoxicillin alone due to the frequency of otopathogens that produce beta-lactamases (eg, H. influenzae, Moraxella catarrhalis) (Ref).
Oral: 500 mg every 8 hours or 875 mg every 12 hours (Ref). Some experts use 1 g every 8 hours for patients at high risk of severe infection or resistant Streptococcus pneumoniae. Duration is 5 to 7 days for mild to moderate infection and 10 days for severe infection (Ref).
Periodontitis, severe, plaque-associated (off-label use): Oral: 500 mg every 8 hours in combination with metronidazole for 14 days or until clinical resolution, whichever is longer; use in addition to periodontal debridement (Ref).
Pneumonia, community acquired:
Note: For empiric therapy in outpatients without comorbidities or risk factors for antibiotic-resistant pathogens or oral step-down therapy following initial parenteral therapy (Ref).
Oral: 1 g 3 times daily (Ref); for initial empiric therapy, some experts prefer use of amoxicillin in combination with an antibiotic that targets atypical pathogens (Ref). Duration is for a minimum of 5 days; patients should be clinically stable with normal vital signs before therapy is discontinued (Ref).
Prosthetic joint infection, chronic suppression (off-label use):
Note: For infection caused by beta-hemolytic streptococci, penicillin-susceptible Enterococcus spp., or Cutibacterium spp. (following pathogen-specific IV therapy in patients undergoing 1-stage exchange or debridement with retention of prosthesis).
Oral: 500 mg 3 times daily (Ref); duration depends on patient-specific factors (Ref).
Rhinosinusitis, acute bacterial:
Note: In uncomplicated acute bacterial rhinosinusitis, initial observation and symptom management without antibiotic therapy is appropriate in most patients. Reserve antibiotic therapy for poor follow-up or lack of improvement over the observation period (Ref). For initial therapy of nonsevere infection in patients without risk factors for pneumococcal resistance or poor outcome (eg, ≥65 years of age, recent hospitalization or antibiotic use, multiple comorbidities, high endemic resistance) (Ref).
Oral: 500 mg every 8 hours or 875 mg every 12 hours for 5 to 7 days (Ref).
Skin and soft tissue infection:
Erysipelas, treatment of mild infection or step-down therapy after initial parenteral therapy:
Oral: 500 mg 3 times daily or 875 mg twice daily; total duration is 5 days, with extension to 14 days for slow response, severe infection, or immunosuppression (Ref).
Erysipeloid (localized cutaneous Erysipelothrix rhusiopathiae infection):
Oral: 500 mg 3 times daily for 5 to 10 days (Ref).
Streptococcal pharyngitis (group A): Oral: 500 mg twice daily or 1 g once daily for 10 days (Ref).
Extended release: 775 mg once daily for 10 days.
Urinary tract infection:
Note: Not recommended for empiric therapy given decreased efficacy compared to first-line agents and high prevalence of resistance (Ref).
Asymptomatic bacteriuria (≥105 CFU per mL) in pregnancy (eg, group B Streptococcus): Oral: 500 mg every 8 hours or 875 mg every 12 hours for 4 to 7 days (Ref).
Cystitis, acute uncomplicated or acute simple cystitis (infection limited to the bladder without signs/symptoms of upper tract, prostate, or systemic infection) due to Enterococcus spp.: Oral: 500 mg every 8 hours or 875 mg every 12 hours for 5 days (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function:
Oral: Immediate release:
|
GFR (mL/minute) |
If the normal recommended dose is 250 to 500 mg every 8 hoursa |
If the normal recommended dose is 875 mg to 1 g every 12 hoursb |
If the normal recommended dose is 1 g every 8 hoursb,c |
|---|---|---|---|
|
aGolightly 2013; Szeto 2017; manufacturer's labeling; expert opinion | |||
|
bExpert opinion | |||
|
cKeller 2015 | |||
|
dDialyzable (30% to 47% with low flux filters [Davies 1988; Francke 1979]). If utilizing a 24-hour dosing interval, administer dose after dialysis or give an additional dose after dialysis on dialysis days. | |||
|
≥30 |
No dosage adjustment necessary |
No dosage adjustment necessary |
No dosage adjustment necessary |
|
10 to 30 |
250 to 500 mg every 12 hours |
500 mg every 12 hours |
1 g every 12 hours |
|
<10 |
250 to 500 mg every 12 to 24 hours |
500 mg every 12 to 24 hours |
500 mg every 12 hours |
|
Hemodialysis, intermittent (thrice weekly)d |
250 to 500 mg every 12 to 24 hours |
500 mg every 12 to 24 hours |
500 mg every 12 hours |
|
Peritoneal dialysis |
250 to 500 mg every 12 hours |
500 mg every 12 hours |
500 mg every 12 hours |
Oral: Extended release:
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
CrCl <30 mL/minute: Not recommended.
Hemodialysis, intermittent (thrice weekly): Not recommended.
There are no dosage adjustments provided in the manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Generic: 250 mg, 500 mg
Suspension Reconstituted, Oral:
Generic: 125 mg/5 mL (80 mL, 100 mL, 150 mL); 200 mg/5 mL (50 mL, 75 mL, 100 mL); 250 mg/5 mL (80 mL, 100 mL, 150 mL); 400 mg/5 mL (50 mL, 75 mL, 100 mL)
Tablet, Oral:
Generic: 500 mg, 875 mg
Tablet Chewable, Oral:
Generic: 125 mg, 250 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Polymox: 250 mg, 500 mg
Generic: 250 mg, 500 mg
Suspension Reconstituted, Oral:
Polymox: 125 mg/5 mL (150 mL); 250 mg/5 mL (150 mL)
Generic: 125 mg/5 mL (100 mL, 150 mL); 250 mg/5 mL (75 mL, 100 mL, 150 mL)
Tablet Chewable, Oral:
Generic: 125 mg [DSC], 250 mg
Amoxicillin 775 mg ER tablets (brand and generic) have been discontinued in the United States for >1 year.
Oral: May be administered on an empty or full stomach; may be mixed with small amount of formula, milk, cold drink, or juice; administer dose immediately after mixing; shake suspension well before use.
Oral: Administer around-the-clock to promote less variation in peak and trough serum levels.
Extended release: Administer within 1 hour of finishing a meal; do not chew or crush tablet.
Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Switch to IR formulation.
Suspension: Shake well before use; may be mixed with formula, milk, fruit juice, water, ginger ale, or cold drinks; administer dose immediately after mixing.
Store at room temperature. Reconstituted oral suspension remains stable for 14 days at room temperature or refrigerated (refrigeration preferred). Unit-dose antibiotic oral syringes are stable at room temperature for at least 72 hours (Tu 1988).
Treatment of infections of skin and soft tissue, GU tract, or upper or lower respiratory tract due to susceptible organisms (FDA approved in all ages); combination therapy of Helicobacter pylori (FDA approved in adults); has also been used for the treatment of Lyme disease and acute osteoarticular infection; prophylaxis of bacterial endocarditis, prophylaxis of pneumococcal infection in patients with sickle cell disease or asplenia, prophylaxis of peritonitis in patients undergoing dental treatment or treatment of exit-site or tunnel infections in patients with peritoneal dialysis catheters, urinary tract infection prophylaxis, and postexposure prophylaxis and treatment of anthrax.
Amoxicillin may be confused with amoxapine, Augmentin
Amoxil may be confused with amoxapine
Fisamox [Australia] may be confused with Fosamax brand name for alendronate [US, Canada, and multiple international markets] and Vigamox brand name for moxifloxacin [US, Canada, and multiple international markets]
Limoxin [Mexico] may be confused with Lanoxin brand name for digoxin [US, Canada, and multiple international markets]; Lincocin brand name for lincomycin [US, Canada, and multiple international markets]
Zimox: Brand name for amoxicillin [Italy], but also the brand name for carbidopa/levodopa [Greece]
Zimox [Italy] may be confused with Diamox which is the brand name for acetazolamide [Canada and multiple international markets]
GI effects range from antibiotic-associated [non–Clostridioides difficile] diarrhea (AAD), nausea, and vomiting. Most cases of AAD are mild and self-limiting. However, Clostridioides difficile may account for as many as >20% of cases in children, adolescents, and adults (discussed separately) (Ref). Diarrhea is less common with amoxicillin or ampicillin alone than with amoxicillin/clavulanic acid (Ref).
Mechanism: Dose- and time-related; antibiotic disruption of indigenous gut microbiota (Ref).
Onset: Varied; mean time to onset of AAD is 3 to 18 days for adult patients and 2 to 6 days for pediatric patients. The majority of AAD cases occur during (versus after) antibiotic therapy in pediatric patients (Ref).
Risk factors:
• High-dose amoxicillin regimens
• Longer duration of therapy (Ref)
• Longer length of hospitalization or ICU stay (Ref)
• Age (younger pediatric patients <2 years and older adults) (Ref)
• Longer duration of proton pump inhibitor use (Ref)
• Parenteral nutrition (Ref)
• Combined administration of antibiotics (Ref)
Clostridioides difficile infection (CDI) has occurred, including Clostridioides difficile associated diarrhea (CDAD) and Clostridioides difficile colitis.
Mechanism: Dose- and time-related; related to cumulative antibiotic exposure. Amoxicillin may cause disruption of the intestinal microbiota resulting in the overgrowth of pathogens, such as C. difficile (Ref).
Onset: Varied; may start on the first day of antibiotic therapy or up to 3 months postantibiotic (Ref).
Risk factors:
• Antibiotic exposure (highest risk factor), especially prolonged use (Ref)
• Type of antibiotic (Ref)
• Long durations in a hospital or other health care setting (recent or current) (Ref)
• Older adults (Ref)
• Immunocompromised conditions (Ref)
• A serious underlying condition (Ref)
• GI surgery/manipulation (Ref)
• Antiulcer medications (eg, proton pump inhibitors, H2 blockers) (Ref)
• Chemotherapy (Ref)
Hypersensitivity and immunologic reactions (immediate and delayed) range from skin rash to rare cases of anaphylaxis in adult and pediatric patients (Ref). Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome and toxic epidermal necrolysis (Ref), drug rash with eosinophilia and systemic symptoms (DRESS) (Ref), and acute generalized exanthematous pustulosis (Ref) have been reported. Aseptic meningitis has also been documented (Ref).
Mechanism: Non–dose-related; immunologic. Immediate hypersensitivity reactions (eg, anaphylaxis, urticaria) are IgE-mediated. Delayed hypersensitivity reactions, such as maculopapular rash and SCARs, are T-cell-mediated (Ref). Amoxicillin may trigger a flare of DRESS caused by other drugs, such as carbamazepine and allopurinol (Ref), possibly through reactivation of HHV-6 (Ref).
Onset: Immediate hypersensitivity reactions: Rapid; occur within 1 hour of administration but may occur up to 6 hours after exposure (Ref). Delayed hypersensitivity reactions: Maculopapular rash reactions: Intermediate; occur 7 to 10 days after initiation (Ref). Other reactions (including SCARs): Varied; occur after days to 8 weeks after initiation (Ref).
Risk factors:
• Cross-reactivity between penicillins and cephalosporins and among cephalosporins is mostly related to side chain similarity (Ref). For cephalexin, ampicillin and amoxicillin share identical or similar side chains, respectively, and cross-reactions have been reported (Ref). Additionally, cross-reactivity between benzylpenicillin and aminopenicillins (eg, amoxicillin, ampicillin) may occur (Ref).
• Viral infections (eg, Epstein-Barr virus [infectious mononucleosis], cytomegalovirus, HHV 6 and 7) (Ref)
• Epstein-Barr virus (EBV): Reported incidence of skin rash is higher in patients with an acute EBV infection concomitantly treated with amoxicillin (Ref), although not all studies have shown similar results (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%: Gastrointestinal: Diarrhea, nausea, vomiting
Postmarketing:
Dermatologic: Acute generalized exanthematous pustulosis (Choon 2018), erythema multiforme, erythematous maculopapular rash (Koosakulchai 2021), exfoliative dermatitis, pruritus, skin rash (Katoh 2021), Stevens-Johnson syndrome (Yang 2020), toxic epidermal necrolysis (Yang 2020), urticaria (Koosakulchai 2021)
Gastrointestinal: Clostridioides difficile colitis, Clostridioides difficile-associated diarrhea, hemorrhagic colitis, melanoglossia, mucocutaneous candidiasis, staining of tooth
Genitourinary: Crystalluria
Hematologic & oncologic: Agranulocytosis, anemia, eosinophilia, hemolytic anemia (Rossi 2010), immune thrombocytopenia, leukopenia, neutropenia (Curtis 2017), thrombocytopenia
Hepatic: Cholestatic hepatitis (Kim 2011), cholestatic jaundice, hepatitis (acute cytolytic), increased serum alanine aminotransferase (Kim 2011), increased serum aspartate aminotransferase (Kim 2011)
Hypersensitivity: Anaphylactic shock, anaphylaxis (Piotin 2021), angioedema (Koosakulchai 2021), drug reaction with eosinophilia and systemic symptoms (De La Cruz 2021), hypersensitivity angiitis (Garcia-Porrua 1999), nonimmune anaphylaxis, serum sickness-like reaction (Mohsenzadeh 2020)
Nervous system: Agitation, anxiety, aseptic meningitis, behavioral changes, confusion, dizziness, hyperactive behavior (reversible), insomnia, seizure
Serious hypersensitivity to amoxicillin (eg, anaphylaxis, Stevens-Johnson syndrome) or to other beta-lactams, or any component of the formulation
Canadian labeling: Additional contraindications (not in US labeling): Infectious mononucleosis (suspected or confirmed)
Concerns related to adverse effects:
• Superinfection: Prolonged use may result in fungal or bacterial superinfection.
Disease-related concerns:
• Infectious mononucleosis: A high percentage of patients with infectious mononucleosis develop an erythematous rash during amoxicillin therapy; avoid use in these patients.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
• Chewable tablets: May contain phenylalanine; see manufacturer's labeling.
Substrate of OAT1/3
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acemetacin: May increase the serum concentration of Penicillins. Risk C: Monitor therapy
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Amoxicillin. Risk C: Monitor therapy
Aminoglycosides: Penicillins may decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Risk C: Monitor therapy
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Dichlorphenamide: Penicillins may enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy
Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Khat: May decrease the serum concentration of Amoxicillin. Management: Consider administering amoxicillin before, or 2 hours after, khat chewing to avoid reductions in amoxicillin bioavailability. Risk D: Consider therapy modification
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Methotrexate: Penicillins may increase the serum concentration of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Penicillins. Risk C: Monitor therapy
Sodium Benzoate: Penicillins may diminish the therapeutic effect of Sodium Benzoate. Risk C: Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Tetracyclines: May diminish the therapeutic effect of Penicillins. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Some products may contain phenylalanine.
Amoxicillin crosses the placenta (Muller 2009; Zareba-Szczudlik 2017). Maternal serum concentrations are significantly greater than the umbilical cord, placenta, and amniotic fluid concentrations when amoxicillin is administered orally prior to delivery (Buckingham 1975; Zareba-Szczudlik 2017).
Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of oral amoxicillin may be altered. Renal clearance is increased in the second and third trimester compared to postpartum values. In addition, oral absorption is decreased during labor. Maternal adipose tissue and the presence of anemia may influence maternal serum and amniotic fluid concentrations. Although minimum inhibitory concentrations can be reached, higher oral doses (or a parenteral antibiotic) may be needed based on the specific maternal infection or if treating an infection of the fetus and/or placenta (Andrew 2007; Buckingham 1975; Zareba-Szczudlik 2017).
As a class, penicillin antibiotics are widely used in pregnant patients. Based on available data, penicillin antibiotics are generally considered compatible for use during pregnancy (Ailes 2016; Bookstaver 2015; Crider 2009; Damkier 2019; Lamont 2014; Muanda 2017a; Muanda 2017b).
Amoxicillin may be used for the management of Bacillus anthracis in pregnant patients when penicillin susceptibility is documented. Maternal infection with B. anthracis may cause preterm labor, fetal infection, fetal distress, or fetal loss. Maternal death may also occur. Amoxicillin is an alternative agent for the treatment of cutaneous anthrax without systemic involvement and for the postexposure prophylaxis of B. anthracis during pregnancy. The dose and duration of amoxicillin therapy in pregnant and postpartum patients is the same as in nonpregnant adults. Adjustments in dose for pregnancy are not recommended until additional pharmacokinetic data become available (Meaney-Delman 2014).
Untreated chlamydial disease can cause pelvic inflammatory disease, ectopic pregnancy, and infertility. In addition, treatment of maternal disease usually prevents transmission to the neonate during birth. Due to concerns of chlamydia persistence following exposure to penicillin class antibiotics, amoxicillin is an alternative antibiotic for the treatment of chlamydial infections in pregnancy (CDC [Workowski 2021]).
Amoxicillin is used for the treatment of Lyme disease. Vertical transmission from mother to fetus is not well documented; it is unclear if infection increases the risk of adverse pregnancy outcomes. When treatment for Lyme disease in pregnancy is needed, the indications and dosing of amoxicillin are the same as in nonpregnant patients (IDSA/AAN/ACR [Lantos 2021]; Lambert 2020; SOGC [Smith 2020]).
Untreated urinary tract infections (UTIs) during pregnancy are associated with an increased risk of developing pyelonephritis, low birth weight, and preterm labor. Amoxicillin may be an option for the treatment of UTI during pregnancy (de Rossi 2020; IDSA [Nicolle 2019]).
Amoxicillin is used in the management of H. pylori eradication. H. pylori is associated with hyperemesis gravidarum and may be linked to other adverse maternal and fetal outcomes. Treatment in patients with mild or no symptoms is generally delayed until after delivery; however, amoxicillin may be considered as part of a treatment regimen when otherwise appropriate (Cardaropoli 2014; Nguyen 2019; Zhan 2019).
Amoxicillin can also be used in the management of preterm prelabor rupture of membranes (PROM); treatment with antibiotics is used to prolong pregnancy and decrease maternal and newborn infections (ACOG 217 2020). Amoxicillin may also be used in certain situations prior to vaginal delivery in patients at high risk for endocarditis (ACOG 199 2018).
Amoxicillin is considered compatible for the treatment airway diseases in pregnant patients (ERS/TSANZ [Middleton 2020]).
With prolonged therapy, monitor renal, hepatic, and hematologic function; observe for change in bowel frequency; monitor for signs and symptoms of hypersensitivity, including anaphylaxis.
Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
Absorption: Oral:
Immediate release: Rapid with or without food; delayed absorption may be seen in some neonates and infants <60 days of age (Mir 2020).
Extended release: Rate of absorption is slower compared to immediate-release formulations; food decreases the rate but not extent of absorption.
Distribution: Readily into liver, lungs, prostate, muscle, middle ear effusions, maxillary sinus secretions, bone, gallbladder, bile, and ascitic and synovial fluids; poor cerebrospinal fluid penetration (except when meninges are inflamed).
Vd:
Neonates, including preterm (GA: 25 to 42 weeks; PNA: ≤9 days): 0.65 ± 0.13 L/kg (Pullen 2006).
Infants ≥3 months of age and children ≤5 years of age: 1.44 ± 0.37 L/kg (Canafax 1998).
Protein binding: ~20%.
Bioavailability: Oral suspension: Neonates (GA: 37 to 43 weeks; PNA: 6 to 12 days): 75% (range: 60% to 101%) (Lönnerholm 1982).
Half-life elimination:
Preterm and term neonates (GA: 25 to 42 weeks; PNA: ≤9 days): Immediate release: 5.2 ± 1.9 hours (Pullen 2006).
Adults: Immediate release: 61.3 minutes; extended release: 90 minutes.
Time to peak:
Preterm and term neonates (PNA: <5 days): Oral suspension: ~4 hours (Cohen 1975; Weingartner 1977); reported mean range: 2 to 6 hours (Keij 2019).
Adults: Capsule, oral suspension: 1 to 2 hours; chewable tablet: 1 hour; extended release: 3.1 hours.
Excretion: Urine (60% as unchanged drug); lower in neonates (Cohen 1975; Weingartner 1977).
Anti-infective considerations:
Parameters associated with efficacy:
Time dependent; associated with time free drug concentration (fT) > minimum inhibitory concentration, goal: ≥40% to 50% (bactericidal) (Andes 1998; Craig 1996; Craig 1998; Gustafsson 2001).
Expected drug exposure in normal renal function:
Infants ≥3 months of age and children ≤4 years of age, Cmax (peak):
15 mg/kg/dose 3 times daily, steady state: 7.9 ± 3.5 mg/L (Fonseca 2003).
25 mg/kg/dose twice daily, steady state: 10.6 ± 5.1 mg/L (Fonseca 2003).
Adults, Cmax (peak):
125 mg, single dose (125 mg per 5 mL suspension): 1.5 to 3 mg/L.
250 mg, single dose (capsule or 250 mg per 5 mL suspension): 3.5 to 5 mg/L.
400 mg, single dose (chewable tablet): 5.18 ± 1.64 mg/L.
400 mg, single dose (400 mg per 5 mL suspension): 5.92 ± 1.62 mg/L.
500 mg, single dose: 5.5 to 7.5 mg/L.
875 mg, single dose: 13.8 ± 4.1 mg/L.
Postantibiotic effect:
H. influenzae: <1 hour; S. pneumoniae: 0.3 to 5.8 hours; viridans streptococci: 0.7 to 2 hours (Davies 2000; Dubois 2000; Lee 2000).
Note: Due to ongoing shortages of commercially available liquid preparations, the FDA has provided guidance regarding extemporaneous preparation using tablets or capsules for individual patients (FDA 2022).
50 mg/mL Oral Suspension:
Note: Use dedicated or disposable equipment, follow appropriate cleaning procedures, and avoid dust (ie, by wetting with vehicle and mixing carefully) to avoid contamination of compounding area since product is beta-lactam.
A 50 mg/mL oral suspension may be made with capsules or tablets and Ora-Blend or other oral suspension vehicle of choice. To prepare 100 mL, calculate the number of tablets or capsules needed to equal amoxicillin 5,000 mg; if using tablets, crush required number of tablets in a mortar and reduce to a fine powder; if using capsules, empty the contents of required number of capsules into a mortar. Add ~10 mL of vehicle (Ora-Blend, Ora-Blend SF, or other oral suspension of choice) and mix carefully to form a smooth paste. Add incremental amounts of vehicle to final volume of 100 mL, mixing thoroughly after each addition. Package in a tight, light-resistant container and label "shake well" and "refrigerate." Suspension may be stored for up to 14 days refrigerated.
Capsules (Amoxicillin Oral)
250 mg (per each): $0.13 - $0.25
500 mg (per each): $0.19 - $0.39
Chewable (Amoxicillin Oral)
125 mg (per each): $0.37
250 mg (per each): $0.74
Suspension (reconstituted) (Amoxicillin Oral)
125 mg/5 mL (per mL): $0.04
200 mg/5 mL (per mL): $0.09
250 mg/5 mL (per mL): $0.06
400 mg/5 mL (per mL): $0.10
Tablets (Amoxicillin Oral)
500 mg (per each): $0.50
875 mg (per each): $0.87
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