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Amoxicillin and Clavulanate

Medically reviewed by Drugs.com. Last updated on Aug 31, 2020.

Pronunciation

(a moks i SIL in & klav yoo LAN ate)

Index Terms

  • Amoxicillin and Clavulanate Potassium
  • Amoxicillin and Clavulanic Acid
  • Amoxicillin-Clavulanate
  • Amoxicillin/Clavulanate
  • Amoxicillin/Clavulanate K
  • Amoxicillin/Potassium Clav
  • Amoxycillin and Clavulanate Potassium
  • Amoxycillin and Clavulanic Acid
  • Clavulanic Acid and Amoxicillin
  • Clavulanic Acid and Amoxycillin
  • Co-Amoxiclav

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Suspension Reconstituted, Oral:

Augmentin: Amoxicillin 125 mg and clavulanate potassium 31.25 mg per 5 mL (75 mL [DSC], 100 mL [DSC], 150 mL [DSC]) [contains aspartame, saccharin sodium; banana flavor]

Augmentin: Amoxicillin 250 mg and clavulanate potassium 62.5 mg per 5 mL (75 mL [DSC], 100 mL [DSC], 150 mL [DSC]) [contains aspartame, saccharin sodium; orange flavor]

Augmentin: Amoxicillin 250 mg and clavulanate potassium 62.5 mg per 5 mL (75 mL, 100 mL, 150 mL); Amoxicillin 125 mg and clavulanate potassium 31.25 mg per 5 mL (75 mL, 100 mL, 150 mL) [contains saccharin sodium]

Augmentin ES-600: Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL (75 mL, 125 mL, 200 mL) [contains aspartame; strawberry cream flavor]

Generic: Amoxicillin 200 mg and clavulanate potassium 28.5 mg per 5 mL (50 mL, 75 mL, 100 mL); Amoxicillin 250 mg and clavulanate potassium 62.5 mg per 5 mL (75 mL, 100 mL, 150 mL); Amoxicillin 400 mg and clavulanate potassium 57 mg per 5 mL (50 mL, 75 mL, 100 mL); Amoxicillin 600 mg and clavulanate potassium 42.9 mg per 5 mL (75 mL, 125 mL, 200 mL)

Tablet, Oral:

Augmentin: Amoxicillin 500 mg and clavulanate potassium 125 mg

Augmentin: Amoxicillin 875 mg and clavulanate potassium 125 mg [DSC] [scored]

Generic: Amoxicillin 250 mg and clavulanate potassium 125 mg, Amoxicillin 500 mg and clavulanate potassium 125 mg, Amoxicillin 875 mg and clavulanate potassium 125 mg

Tablet Chewable, Oral:

Generic: Amoxicillin 200 mg and clavulanate potassium 28.5 mg, Amoxicillin 400 mg and clavulanate potassium 57 mg

Tablet Extended Release 12 Hour, Oral:

Augmentin XR: Amoxicillin 1000 mg and clavulanate potassium 62.5 mg [DSC] [scored]

Generic: Amoxicillin 1000 mg and clavulanate potassium 62.5 mg

Brand Names: U.S.

  • Augmentin
  • Augmentin ES-600
  • Augmentin XR [DSC]

Pharmacologic Category

  • Antibiotic, Penicillin

Pharmacology

Clavulanic acid binds and inhibits beta-lactamases that inactivate amoxicillin resulting in amoxicillin having an expanded spectrum of activity. Amoxicillin 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.

Excretion

Clavulanic acid: Urine (25% to 40% as unchanged drug)

Time to Peak

Clavulanic acid: Serum: 1.5 hours

Half-Life Elimination

Clavulanic acid: 1 hour

Protein Binding

Clavulanic acid: ~25%

Use: Labeled Indications

Oral:

Otitis media, acute:

IR tablets, chewable tablets, oral suspension (400/57 mg per 5 mL, 250/62.5 mg per 5 mL, 200/28.5 mg per 5 mL, and 125/31.25 mg per 5 mL only): Treatment of otitis media caused by beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis.

Oral suspension (600/42.9 mg per 5 mL concentration): Treatment of acute otitis media, recurrent or persistent, caused by Streptococcus pneumoniae (penicillin MIC = 2 mcg/mL or less), H. influenzae (including beta-lactamase-producing strains), and M. catarrhalis (including beta-lactamase-producing strains) in pediatric patients with a history of antibiotic exposure for acute otitis media in the preceding 3 months and who are either ≤2 years of age or attend day care.

Pneumonia:

ER tablets only: Treatment of patients with community-acquired pneumonia (CAP) caused by confirmed or suspected beta-lactamase-producing pathogens (ie, H. influenzae, M. catarrhalis, Haemophilus parainfluenzae, Klebsiella pneumoniae, methicillin-susceptible Staphylococcus aureus) and S. pneumoniae with reduced susceptibility to penicillin (penicillin minimum inhibitory concentration [MIC] = 2 mcg/mL).

Limitations of use: Augmentin XR is not indicated for the treatment of infections caused by S. pneumoniae with penicillin MIC of ≥4 mcg/mL (limited data).

IR tablets, chewable tablets, oral suspension (400/57 mg per 5 mL, 250/62.5 mg per 5 mL, 200/28.5 mg per 5 mL, and 125/31.25 mg per 5 mL only): Treatment of lower respiratory tract infection caused by beta-lactamase-producing strains of H. influenzae and M. catarrhalis.

Rhinosinusitis, acute bacterial:

ER tablets: Treatment of patients with acute bacterial sinusitis caused by confirmed or suspected beta-lactamase-producing pathogens (ie, H. influenzae, M. catarrhalis, H. parainfluenzae, K. pneumoniae, methicillin-susceptible S. aureus) and S. pneumoniae with reduced susceptibility to penicillin (penicillin MIC = 2 mcg/mL).

Limitations of use: Augmentin XR is not indicated for the treatment of infections caused by S. pneumoniae with penicillin MIC of ≥4 mcg/mL (limited data).

IR tablets, chewable tablets, oral suspension (400/57 mg per 5 mL, 250/62.5 mg per 5 mL, 200/28.5 mg per 5 mL, and 125/31.25 mg per 5 mL only): Treatment of sinusitis caused by beta-lactamase-producing strains of H. influenzae and M. catarrhalis.

Skin and skin structure infections: IR tablets, chewable tablets, oral suspension (400/57 mg per 5 mL, 250/62.5 mg per 5 mL, 200/28.5 mg per 5 mL, and 125/31.25 mg per 5 mL only): Treatment of skin and skin structure infections caused by beta-lactamase-producing strains of S. aureus, Escherichia coli, and Klebsiella spp.

Urinary tract infections: IR tablets, chewable tablets, oral suspension (400/57 mg per 5 mL, 250/62.5 mg per 5 mL, 200/28.5 mg per 5 mL, and 125/31.25 mg per 5 mL only): Treatment of urinary tract infections caused by beta-lactamase-producing strains of E. coli, Klebsiella spp, and Enterobacter spp.

IV [Canadian product]: Treatment of severe upper respiratory infections, chronic bronchitis (acute exacerbation), CAP, cystitis, pyelonephritis, skin and soft tissue infections, osteomyelitis, intra-abdominal infections, and female genital infections caused by susceptible organisms in adults and pediatric patients; surgical prophylaxis in procedures involving the GI tract, pelvic cavity, head and neck, or biliary tract in adults.

Off Label Uses

Bite wound, prophylaxis or treatment (animal or human bite)

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTIs), amoxicillin/clavulanate is an effective and recommended treatment or prophylaxis of animal or human bite wounds.

Bronchiectasis, acute exacerbation

Clinical experience suggests the utility of amoxicillin and clavulanate for the treatment of acute exacerbations of bronchiectasis [Barker 2020], [Tsang 2009].

Chronic obstructive pulmonary disease, acute exacerbation

Data from 2 randomized, double-blind studies support the use of amoxicillin and clavulanate for the treatment of bacterial exacerbations of chronic obstructive pulmonary disease (COPD) [Llor 2012], [Wilson 2012].

Based on the Global Initiative for Chronic Obstructive Lung Disease guidelines for the diagnosis, management, and prevention of COPD, amoxicillin and clavulanate is an effective and recommended treatment for COPD exacerbations [GOLD 2020].

Diabetic foot infection

Data from a randomized, open-label trial suggest that amoxicillin and clavulanate may be beneficial for the treatment of diabetic foot infection [Lipsky 2004].

Based on the IDSA clinical practice guideline for the diagnosis and treatment of diabetic foot infections, amoxicillin and clavulanate is an effective and recommended treatment for diabetic foot infection.

Intra-abdominal infection

Data from a randomized, multicenter study support the use of amoxicillin and clavulanate for the treatment of acute uncomplicated diverticulitis [Biondo 2014]. Clinical experience also suggests the utility of amoxicillin and clavulanate as oral step-down therapy for the treatment of intra-abdominal infection [Lucasti 2008].

Based on the Surgical Infection Society (SIS)/IDSA clinical practice guideline for the diagnosis and management of complicated intra-abdominal infection in adults and the SIS clinical practice guideline for the management of intra-abdominal infection, amoxicillin and clavulanate is effective and recommended as oral step-down therapy for intra-abdominal infection once clinically improved on parenteral therapy and patient is able to tolerate an oral diet.

Neutropenic fever, low-risk cancer patients (empiric therapy)

Based on the American Society of Clinical Oncology and IDSA guidelines for treatment of cancer patients with fever and neutropenia, amoxicillin and clavulanate (in combination with ciprofloxacin) is an effective and recommended oral regimen for management of low-risk patients with neutropenic fever.

Odontogenic infection

Data from a prospective, observational study and a prospective, randomized, single-blind study support the use of amoxicillin and clavulanate for the treatment of odontogenic infection [Gerlach 1989], [Tancawan 2015].

Peritonsillar cellulitis or abscess

Data from 2 prospective, observational studies suggest the utility of amoxicillin and clavulanate for the treatment of peritonsillar abscess [Lepelletier 2016], [Sowerby 2013]. Clinical experience also suggests the utility of amoxicillin and clavulanate for the treatment of peritonsillar cellulitis [Wald 2018].

Streptococcus (group A), chronic carriage

Based on the IDSA clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis, amoxicillin and clavulanate is effective and recommended for eradication of group A streptococci in chronic carriers.

Contraindications

Hypersensitivity to amoxicillin, clavulanic acid, other beta-lactam antibacterial drugs (eg, penicillins, cephalosporins), or any component of the formulation; history of cholestatic jaundice or hepatic dysfunction with amoxicillin/clavulanate potassium therapy.

Augmentin XR: Additional contraindications: Severe renal impairment (CrCl <30 mL/minute) and hemodialysis patients.

Canadian labeling: Additional contraindications (not in the US labeling): Oral: Suspected or confirmed mononucleosis.

Dosing: Adult

Note: Dose is based on the amoxicillin component. Dose and frequency are product specific; not all products are interchangeable. For adults who have difficulty swallowing the tablets, the 125 mg/5 mL or 250 mg/5 mL suspension (in appropriate amounts) may be given in place of the 500 mg tablet; the 200 mg/5 mL or 400 mg/5 mL suspension (in appropriate amounts) may be given in place of the 875 mg tablet.

Usual dosing range:

Oral: Immediate release: 500 mg every 8 to 12 hours or 875 mg every 12 hours; Extended release: 2 g every 12 hours.

IV [Canadian product]: 1 g every 8 hours or 2 g every 8 to 12 hours; surgical prophylaxis: 1 to 2 g at induction of anesthesia for procedures <1 hour (for procedures >1 hour may administer up to 2 additional doses in 24 hours).

Bite wound, prophylaxis or treatment (animal or human bite) (off-label use): Oral: Immediate release: 875 mg every 12 hours (IDSA [Stevens 2014]). Note: For prophylaxis, duration is 3 to 5 days (IDSA [Stevens 2014]); for treatment of established infection, duration is typically 5 to 14 days and varies based on clinical response and patient-specific factors (Baddour 2019a; Baddour 2019b).

Chronic obstructive pulmonary disease, acute exacerbation (off-label use): Note: Some experts reserve for patients with risk factors for poor outcomes (eg, age ≥65 years, FEV1 <50% predicted, frequent exacerbations, major comorbidities), but low risk of Pseudomonas infection (Sethi 2020).

Oral: Immediate release: 500 mg every 8 hours or 875 mg every 12 hours for 3 to 7 days (GOLD 2020; Llor 2012; Sethi 2020; Wilson 2012).

Diabetic foot infection (off-label use): Note: May be used alone for mild infections or after clinical response to parenteral therapy in patients without risk factors or concern for infection caused by Pseudomonas aeruginosa (IDSA [Lipsky 2012]; Weintrob 2018).

Oral: Immediate release: 875 mg every 12 hours (IDSA [Lipsky 2012]; Lipsky 2004; Weintrob 2018). Duration of therapy should be tailored to individual clinical circumstances; most patients with infection limited to skin and soft tissue respond to 1 to 2 weeks of therapy (IDSA [Lipsky 2012]; Weintrob 2018).

Intra-abdominal infection (off-label use):

Diverticulitis, acute (for uncomplicated infection that meets criteria for outpatient therapy or as step-down therapy after clinical improvement on initial parenteral therapy): Oral:

Immediate release: 875 mg every 8 hours (Biondo 2014; Mora Lopez 2013).

Extended release: 2 g every 12 hours (Pemberton 2020).

Other intra-abdominal infection, step-down therapy (when clinically improved and able to tolerate oral therapy): Oral: Immediate release: 875 mg 2 to 3 times daily (Barshak 2018; Lucasti 2008; SIS [Mazuski 2017]; SIS/IDSA [Solomkin 2010]).

Duration of therapy is for 4 to 7 days following adequate source control (SIS/IDSA [Solomkin 2010]); for uncomplicated appendicitis and diverticulitis managed nonoperatively, a longer duration is necessary (Barshak 2018; Pemberton 2020).

Neutropenic fever, low-risk cancer patients (empiric therapy) (off-label use): Oral: Immediate release: 500 mg every 8 hours (Freifeld 1999; Kern 1999) or 875 mg every 12 hours (Kern 2013). Combine either dosing regimen with oral ciprofloxacin; continue until resolution of fever and neutropenia. Note: Avoid in patients who have received fluoroquinolone prophylaxis. Administer first dose in the health care setting (after blood cultures are drawn); observe patient for ≥4 hours before discharge (ASCO/IDSA [Taplitz 2018]; IDSA [Freifeld 2011]).

Odontogenic infection (initial therapy for mild infection or step-down therapy after parenteral treatment) (off-label use): Oral: Immediate release: 875 mg twice daily (Tancawan 2015); continue to complete a total of 7 to 14 days of therapy (Chow 2019).

Otitis media, acute: Oral:

Immediate release: 875 mg twice daily (Mira 2001) or 500 mg every 8 hours (WHO 2001).

Extended release: 1 or 2 g twice daily, based on weight and severity of infection; some experts prefer the extended release formulation for patients at high risk of severe infection or resistant S. pneumoniae (Limb 2019).

Duration: 5 to 7 days for mild to moderate infection and 10 days for severe infection (Limb 2019).

Peritonsillar cellulitis or abscess (off-label-use): Note: For step-down therapy after parenteral treatment. Limited data available; dosing based on expert opinion. Reserve for use in regions where Staphylococcus aureus remains susceptible to methicillin or based upon susceptibility results of isolated pathogens, if available. Oral: Immediate release: 875 mg every 12 hours to complete a total of 14 days of therapy (Wald 2018).

Pneumonia:

Aspiration pneumonia (community acquired [mild]): Oral:

Immediate release: 875 mg twice daily (Bartlett 2019).

Extended release: 2 g twice daily (Bartlett 2019).

Duration of therapy: Generally 7 days (Bartlett 2019).

Community acquired, outpatient empiric therapy (patients with comorbidities): Oral:

Immediate release: 500 mg 3 times daily or 875 mg twice daily as part of an appropriate combination regimen (ATS/IDSA [Metlay 2019]).

Extended release: 2 g twice daily as part of an appropriate combination regimen (ATS/IDSA [Metlay 2019]).

Duration of therapy: Minimum of 5 days; patients should be clinically stable with normal vital signs before therapy is discontinued (ATS/IDSA [Metlay 2019]).

Rhinosinusitis, acute bacterial: Note: In uncomplicated acute bacterial rhinosinusitis, initial observation and symptom management without antibiotic therapy is appropriate in most patients (AAO-HNS [Rosenfeld 2015]; Harris 2016).

Standard dose: Oral: Immediate release: 500 mg every 8 hours or 875 mg every 12 hours for 5 to 7 days (IDSA [Chow 2012])

High dose: Oral: Extended release: 2 g every 12 hours. Note: Recommended for patients at risk for poor outcome or pneumococcal resistance based on the following features: age ≥65 years, recent hospitalization, antibiotic use within the past month, immunocompromise, residence in a region with high rates of penicillin-resistant S. pneumoniae, or failure to respond to initial treatment (AAO-HNS [Rosenfeld 2015]; IDSA [Chow 2012]). For initial therapy, the duration is 5 to 7 days; for patients who have failed initial therapy and require re-treatment, the duration is 7 to 10 days (Patel 2020).

Streptococcus (group A), chronic carriage (off-label use): Oral: Immediate release: 40 mg/kg/day in divided doses (eg, 875 mg every 12 hours) (maximum: 2 g/day) for 10 days (IDSA [Shulman 2012]; Mahakit 2006). Note: Most individuals with chronic carriage do not require antibiotics (IDSA [Shulman 2012]).

Urinary tract infection (UTI) (alternative agent): Note: Although evidence is limited, some experts recommend the use of amoxicillin/clavulanate in this setting. Use with caution and only when first-line agents cannot be used (due to decreased efficacy of oral beta-lactams compared to other agents) (ESCMID/IDSA [Gupta 2011]; Hooton 2018a). Closely monitor patient.

Acute uncomplicated cystitis or acute simple cystitis (infection limited to bladder and no signs/symptoms of upper tract or systemic infection): Oral: Immediate release: 500 mg twice daily (Hooton 2005) for 5 to 7 days (ESCMID/IDSA [Gupta 2011]; Hooton 2018a).

Complicated UTI (including pyelonephritis): Oral: Immediate release: 875 mg twice daily for 10 to 14 days (ESCMID/IDSA [Gupta 2011]; Johnson 2018). Note: Oral therapy should follow appropriate parenteral therapy. For outpatient treatment of mild infection, a single dose of a long-acting parenteral agent is acceptable; for outpatients who are more ill or are at risk for more severe illness, consider continuing parenteral therapy until culture and susceptibility results are available (ESCMID/IDSA [Gupta 2011]; Hooton 2018b).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Dosing based on amoxicillin component; dose and frequency are product specific; not all products are interchangeable; using a product with the incorrect amoxicillin:clavulanate ratio could result in subtherapeutic clavulanic acid concentrations or severe diarrhea.

Frequency of dosing generally based on ratio of amoxicillin to clavulanate:

• 2:1 formulations are dosed 3 times daily (amoxicillin 250 mg/clavulanate 125 mg). Note: Per the manufacturer, the amoxicillin 250 mg/clavulanate 125 mg tablet should only be used in patients ≥40 kg due to the amoxicillin to clavulanate ratio.

• 4:1 formulations are dosed 3 times daily (amoxicillin 125 mg/clavulanate 31.25 mg; amoxicillin 250 mg/clavulanate 62.5 mg; amoxicillin 500 mg/clavulanate 125 mg).

• 7:1 formulations are dosed 2 times daily (amoxicillin 200 mg/clavulanate 28.5 mg; amoxicillin 400 mg/clavulanate 57 mg; amoxicillin 875 mg/clavulanate 125 mg).

• 14:1 formulations are dosed 2 times daily (amoxicillin 600 mg/clavulanate 42.9 mg).

• 16:1 formulations (extended release) are dosed 2 times daily (amoxicillin 1,000 mg/clavulanate 62.5 mg).

General dosing, susceptible infection: Note: Dosing determined by formulations amoxicillin:clavulanate ratio:

Immediate-release formulations (Red Book [AAP 2018]): Infants, Children, and Adolescents: Oral:

4:1 formulation: 20 to 40 mg amoxicillin/kg/day in divided doses 3 times daily; maximum daily dose: 1,500 mg/day.

7:1 formulation: 25 to 45 mg amoxicillin/kg/day in divided doses twice daily; maximum daily dose: 1,750 mg/day.

14:1 formulation: 90 mg amoxicillin/kg/day in divided doses twice daily; maximum daily dose: 4,000 mg/day.

Extended-release formulation (16:1): Children and Adolescents >40 kg: Oral: 2,000 mg amoxicillin every 12 hours.

Impetigo: Infants, Children, and Adolescents: Oral: 25 mg amoxicillin/kg/day in divided doses twice daily; maximum dose: 875 mg amoxicillin/dose (IDSA [Stevens 2014]).

Otitis media, acute: Infants ≥3 months and Children: Oral suspension (600 mg/5 mL): Oral: 90 mg amoxicillin/kg/day divided every 12 hours for up to 10 days; recommended for use in children with severe illness, who have received amoxicillin in the past 30 days, who have treatment failure at 48 to 72 hours on first-line therapy, and when coverage for beta-lactamase positive H. influenzae and M. catarrhalis is needed. Variable duration of therapy; the manufacturer suggests 10-day course in all patients; however, new data suggests a shorter course in some cases: If <2 years of age or severe symptoms (any age): 10-day course; if 2 to 5 years of age with mild to moderate symptoms: 7-day course; if ≥6 years of age with mild to moderate symptoms: 5- to 7-day course (AAP [Lieberthal 2013]).

Pneumonia, community-acquired (IDSA/PIDS [Bradley 2011]): Infants ≥3 months, Children, and Adolescents:

Empiric therapy: Oral: 90 mg amoxicillin/kg/day in divided doses twice daily; maximum daily dose: 4,000 mg/day.

H. influenzae, beta-lactamase positive strains, mild infection, or step-down therapy: Oral:

Standard dose: 45 mg amoxicillin/kg/day in divided doses 3 times daily.

High dose: 90 mg amoxicillin/kg/day in divided doses twice daily.

Rhinosinusitis, acute bacterial:

Infants ≥3 months: Oral: 45 mg amoxicillin/kg/day divided every 12 hours or 40 mg/kg/day divided every 8 hours.

Children and Adolescents: Oral:

Standard dose: 45 mg amoxicillin/kg/day divided every 12 hours for 10 to 14 days; usual adult dose: 875 mg amoxicillin/dose (IDSA [Chow 2012]).

High dose: 80 to 90 mg amoxicillin/kg/day divided every 12 hours; maximum dose: 2,000 mg/dose (AAP [Wald 2013]; IDSA [Chow 2012]); treatment duration variable: 10 to 28 days, some have suggested discontinuation of therapy 7 days after resolution of signs and symptoms of infection (AAP [Wald 2013]); some experts recommend a duration of 10 to 14 days (IDSA [Chow 2012]). Note: Recommended for patients who live in areas with high endemic rates of penicillin-nonsusceptible S. pneumonia, patients with moderate to severe infections, daycare attendance, age <2 years, recent hospitalization, antibiotic use within the past month, patients who are immunocompromised or if initial therapy fails (second-line therapy) (AAP [Wald 2013]; IDSA [Chow 2012]).

Streptococci, group A; chronic carrier treatment: Children and Adolescents: Oral: 40 mg amoxicillin/kg/day in divided doses every 8 hours for 10 days; maximum daily dose: 2,000 mg amoxicillin/day (IDSA [Shulman 2012]).

Urinary tract infections: Infants ≥2 months and Children ≤2 years: Oral: 20 to 40 mg amoxicillin/kg/day in divided doses 3 times daily (AAP 2011).

IV dosing (Canadian labeling; not available in US):

Note: Choice of formulation depends upon desired dosages of amoxicillin and clavulanate; for higher daily doses of amoxicillin (as may be used in the empiric coverage of Streptococcus pneumoniae), the 10:1 formulation is preferred to avoid unnecessary high clavulanate exposure.

5:1 formulation:

Infants <3 months or weighing <4 kg: IV: 25 mg amoxicillin/kg/dose every 12 hours.

Infants ≥3 months weighing ≥4 kg, Children, and Adolescents: IV: 25 mg amoxicillin/kg/dose every 8 hours; maximum dose: 1,000 mg amoxicillin/dose.

10:1 formulation:

Infants <3 months or weighing <4 kg: IV: 50 mg amoxicillin/kg/dose every 12 hours.

Infants ≥3 months, Children, and Adolescents weighing 4 to <40 kg: 50 mg amoxicillin/kg/dose every 8 hours; maximum dose: 2,000 mg amoxicillin/dose.

Children and Adolescents weighing ≥40 kg: 2,000 mg amoxicillin every 8 to 12 hours.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Reconstitution

Oral: Reconstitute powder for oral suspension with appropriate amount of water as specified in the manufacturer's labeling. Shake vigorously until suspended.

IV [Canadian product]:

500 mg vial: Reconstitute with 10 mL of SWFI; within 15 minutes, add reconstituted solution to 50 mL of a compatible solution (eg, SWFI, NS).

1 g or 2 g vial: Reconstitute with 20 mL SWFI; within 15 minutes, add reconstituted solution to 100 mL of a compatible solution (eg, SWFI, NS).

Administration

Oral: Administer around-the-clock to promote less variation in peak and trough serum levels. Administer with food to increase absorption and decrease stomach upset; shake suspension well before use. ER tablets should be administered with food.

Bariatric surgery: Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Do not cut, crush, or chew. Switch to IR formulation.

IV [Canadian product]: Administer by slow IV injection over 3 to 4 minutes (1 g dose only) or as an infusion over 30 to 40 minutes.

Dietary Considerations

May be taken with meals or on an empty stomach; take with meals to increase absorption and decrease GI upset; may mix with milk, formula, or juice. Extended release tablets should be taken with food. Some products may contain sodium. Some products contain phenylalanine. All dosage forms contain potassium.

Storage

Oral:

Powder for oral suspension: Store dry powder at or below 25°C (77°F). Reconstituted oral suspension should be kept in refrigerator. Discard unused suspension after 10 days (consult manufacturer's labeling for specific recommendations). Unit-dose antibiotic oral syringes are stable under refrigeration for 24 hours (Tu 1988).

Tablet: Store at or below 25°C (77°F). Dispense in original container.

IV [Canadian product]: Store intact vials at 15°C to 30°C (59°F to 86°F). Solutions diluted for infusion should be used within 1 hour if stored at 25°C (77°F) or within 4 hours if stored at 4°C (30°F); recommendations may vary based on solution used for dilution, refer to manufacturer’s labeling for detailed information.

Drug Interactions

Acemetacin: May increase the serum concentration of Penicillins. Monitor therapy

Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Amoxicillin. Monitor therapy

Aminoglycosides: Penicillins may decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). 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. Avoid combination

Dichlorphenamide: Penicillins may enhance the hypokalemic effect of Dichlorphenamide. Monitor therapy

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Methotrexate: Penicillins may increase the serum concentration of Methotrexate. 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. Monitor therapy

Probenecid: May increase the serum concentration of Betalactamase Inhibitors. Management: Coadministration of probenecid with amoxicillin/clavulanate is not recommended per official package labeling. Consider therapy modification

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. Consider therapy modification

Tetracyclines: May diminish the therapeutic effect of Penicillins. 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. Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Test Interactions

May interfere with urinary glucose tests using cupric sulfate (Benedict's solution, Clinitest, Fehling's solution). Glucose tests based on enzymatic glucose oxidase reactions (eg, Clinistix) are recommended.

Ampicillin may transiently interfere with plasma concentrations of total conjugated estriol, estriol-glucuronide, conjugated estrone and estradiol in pregnant women.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%: Gastrointestinal: Diarrhea (3% to 34%)

1% to 10%:

Dermatologic: Candidal diaper rash (4% to 6%), diaper rash (4%), skin rash (≤3%), urticaria (≤3%)

Gastrointestinal: Nausea (2% to 3%), vomiting (1% to 2%)

Genitourinary: Vaginitis (1%)

Infection: Candidiasis (1%), vaginal mycosis (3%)

<1%:

Gastrointestinal: Abdominal distress, flatulence

Hematologic & oncologic: Thrombocythemia

Nervous system: Headache

Postmarketing:

Cardiovascular: Hypersensitivity angiitis

Dermatologic: Acute generalized exanthematous pustulosis (Hioki 2019 31321789), bullous dermatitis (linear IgA) (Panasiti 2009 19702992), erythema multiforme, exfoliative dermatitis (Barni 2018 30302990), fixed drug eruption (Perez-Ezquerra 2010 20946462), pruritus, Stevens-Johnson syndrome (Mori 2017 28599076), toxic epidermal necrolysis (Rodriguez-Martin 2019 30298362)

Gastrointestinal: Clostridioides difficile associated diarrhea (Brown 2020 32069358; Slimings 2014 24324224), Clostridioides difficile colitis, dyspepsia, enterocolitis, gastritis, glossitis, hemorrhagic colitis (Youn 2018 29713612), melanoglossia, mucocutaneous candidiasis, staining of tooth (Garcia-Lopez 2001 11548760), stomatitis

Genitourinary: Crystalluria (van Noord 2012 22418755), hematuria

Hematologic & oncologic: Agranulocytosis (Armas Villalba 2019 31781425), anemia, eosinophilia, hemolytic anemia, immune thrombocytopenia, leukopenia, thrombocytopenia (Mansour 2014 25477568)

Hepatic: Cholestatic hepatitis (Chalasani 2014; deLemos 2016 27003146), hepatocellular hepatitis (Chalasani 2014; deLemos 2016 27003146)

Hypersensitivity: Anaphylaxis, angioedema, serum sickness-like reaction (Patterson-Fortin 2016 27756758)

Immunologic: Drug reaction with eosinophilia and systemic symptoms (van Kester 2018 29569759)

Nervous system: Agitation, anxiety, behavioral changes (Macknin 1987 3670959), confusion, dizziness, hyperactive behavior (reversible), insomnia, myoclonus (Viloria-Alebesque 2020 32529182)

Renal: Interstitial nephritis

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactic/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, or history of sensitivity to multiple allergens.

• Diarrhea: Incidence of diarrhea is higher than with amoxicillin alone.

• Hepatic effects: Although rarely fatal, hepatic dysfunction (eg, cholestatic jaundice, hepatitis) has been reported. Patients at highest risk include those with serious underlying disease or concomitant medications. Hepatic toxicity is usually reversible. Monitor LFTs at regular intervals in patients with hepatic impairment.

• Prolonged therapy: Monitor renal, hepatic, and hematopoietic function if therapy extends beyond approved duration times.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including Clostridioides (formerly Clostridium) difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment and monitor LFTs at regular intervals.

• Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients.

• Renal impairment: Dosage adjustment recommended in patients with CrCl ≤30 mL/minute.

Dosage form specific issues:

• Clavulanic acid content: Due to differing content of clavulanic acid, not all formulations are interchangeable; use of an inappropriate product for a specific dosage could result in either diarrhea (which may be severe) or subtherapeutic clavulanic acid concentrations leading to decreased clinical efficacy.

• Phenylalanine: Some products contain phenylalanine.

Monitoring Parameters

Assess patient at beginning and throughout therapy for infection; with prolonged therapy, monitor renal, hepatic, and hematologic function periodically; in patients with hepatic impairment, monitor liver function tests at regular intervals; monitor for signs of anaphylaxis during first dose

Pregnancy Risk Factor B Pregnancy Considerations

Both amoxicillin and clavulanic acid cross the placenta (Muller 2009; Weber 1984). An increased risk of necrotizing enterocolitis in neonates or bowel disorders in children may be associated with amoxicillin/clavulanate when exposure occurs near delivery (Kenyon 2001).

Oral ampicillin-class antibiotics are poorly absorbed during labor. Clavulanate does not appear to influence maternal amoxicillin pharmacokinetics following IV administration of amoxicillin/clavulanate prior to delivery (Muller 2009).

As a class, penicillin antibiotics are widely used in pregnant women. 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).

Untreated urinary tract infections (UTI) during pregnancy are associated with an increased risk of developing pyelonephritis, low birth weight, and preterm labor. Amoxicillin/clavulanate may be an option for the treatment of UTI during pregnancy (Betschart 2020; de Rossi 2020; IDSA [Nicolle 2019]; Usta 2011).

Antibiotics are used in the management of preterm prelabor rupture of membranes (PROM) to prolong pregnancy and reduce the risk of infection. However, due to the possible increased risk of necrotizing enterocolitis, amoxicillin/clavulanate is not recommended for this indication (ACOG 217 2020).

Amoxicillin/clavulanate is considered compatible for the of treatment airway diseases in pregnant women. Use should be avoided in women at risk for preterm delivery (due to association with necrotizing enterocolitis) (ERS/TSANZ [Middleton 2020]).

The routine use of antibiotics prior to an operative vaginal delivery (vacuum or forceps delivery) is not currently recommended. However, amoxicillin/clavulanate IV administered after an operative vaginal delivery may decrease the risk of a maternal infection occurring within 6 weeks postpartum. A single dose may be appropriate in specific cases (Knight 2019; Liabsuetrakul 2020).

Patient Education

What is this drug used for?

• It is used to treat bacterial infections.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Nausea

• Vomiting

• Diaper rash (children)

• Diarrhea

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.

• Vaginal irritation

Clostridioides (formerly Clostridium) difficile-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools.

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes.

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Frequently asked questions

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.