Amoxicillin-clavulanic acid is a combination drug marketed under the trade name Augmentin. Clavulanic acid is a beta-lactamase inhibitor that possesses weak antibacterial activity. Combination with clavulanic acid reestablishes amoxicillin's activity against beta-lactamase-producing bacteria. This makes Augmentin an excellent drug for treating infections due to beta-lactamase-producing H. influenzae and penicillinase-producing anaerobes. The drug is commonly used to treat infections such as acute otitis media, acute sinusitis, acute bacterial cystitis, uncomplicated gonorrhea, and chancroid caused by susceptible organisms. Augmentin was approved by the FDA in August 1984 and is off patent as of December 2002. An extended release dosage form, Augmentin XR, was approved in September 2002 for the treatment of acute bacterial sinusitis or community-acquired pneumonia.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Tuberculosis patients*
-Directly observed therapy (DOT) is recommended for all children as well as adolescents and adults living with HIV.
Route-Specific Administration
Oral Administration
NOTE: The ratio of amoxicillin; clavulanic acid is not equivalent in the different formulations (tablets, chewable tablets, extended-release tablets, and suspension). Therefore, except where noted, different dosage forms should not be interchanged.
-Administer dose at the start of a meal. May be administered without regard to meals, however, oral absorption of amoxicillin and clavulanic acid are enhanced when administered at the start of a light meal. Also, administration with food minimizes gastrointestinal irritation. Avoid high-fat meals as they decrease the absorption of clavulanic acid.
Oral Solid Formulations
-Extended-release tablets: Swallow tablet whole. Do not crush or chew. Scored extended-release tablets are available for patients who have difficulty swallowing. Breaking the scored tablets in half does not affect the release characteristics.
Oral Liquid Formulations
Oral Suspension
-For infants younger than 3 months, the 125 mg/5 mL oral suspension is recommended.
-The various suspensions of amoxicillin; clavulanic acid are not interchangeable due to differences in the amount of clavulanic acid potassium contained in each product.
Reconstitution
-Prior to reconstitution, tap the bottle until all powder flows freely.
-Add approximately 2/3 of the total amount of water for reconstitution and shake well. Add the remainder of the water and shake well.
-ES suspension: 1 drop of FlavoRx may be added for every 5 mL of suspension.
-Storage: Store the reconstituted suspension under refrigeration. Discard any unused suspension after 10 days.
Administration
-Shake well prior to each administration.
-Measure dosage with calibrated spoon, cup, or oral syringe.
Amoxicillin; clavulanic acid 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; clavulanic acid if lesions progress. Other hypersensitivity and dermatologic reactions include contact dermatitis/diaper dermatitis (5% to 6%), rash (3%), and urticaria (3%). Postmarketing adverse reactions include hypersensitivity reactions, anaphylactoid reactions, anaphylactic shock, angioedema, serum sickness-like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, fever), hypersensitivity vasculitis, rash, pruritus, and exfoliative dermatitis. Fever was reported in 4% to 6% of patients.
Crystalluria, hematuria, and interstitial nephritis have been reported during postmarketing experience with amoxicillin; clavulanic acid.
In clinical trials with amoxicillin; clavulanate, diarrhea/loose stools was reported in 2% to 15% of patients. In pediatric trials (aged 2 months to 12 years) with the oral suspension, the incidence of diarrhea was significantly lower in patients receiving the twice daily regimen as compared to those using the every 8 hour regimen (14% vs. 34%, respectively). Also, the incidence of severe diarrhea and the number of patients who withdrew due to diarrhea was lower in the twice daily regimen (3% vs. 8%). In pediatric trials with the Augmentin ES suspension, diarrhea occurred in 4% to 13% of patients. Nausea (2% to 3%), abdominal discomfort/abdominal pain (less than 1%), flatulence (less than 1%), and vomiting (1%) were also reported. In pediatric trials, vomiting occurred in 7% of patients with the Augmentin ES suspension and 8% with regular amoxicillin; clavulanic acid. Gastrointestinal adverse events noted in postmarketing reports include indigestion (dyspepsia), gastritis, stomatitis, glossitis, tongue discoloration (black hairy tongue), and enterocolitis.
Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with amoxicillin; clavulanic acid. 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 has been reported with the use of amoxicillin; clavulanic acid. In pediatric patients, candidal infection of the diaper areas has been reported in 4% to 6% of patients in clinical trials. Vaginitis has been reported in 1% of patients. In trials with the extended-release tablets, vaginal mycosis was reported in 3% of patients. Additionally, upper respiratory tract infection was reported in 3% to 9% of patients.
Headache (less than 1%) has been reported with amoxicillin; clavulanic acid. Other central nervous system reactions reported with amoxicillin; clavulanic acid during postmarketing experience include agitation, anxiety, behavioral changes, aseptic meningitis, confusion, convulsions (seizures), dizziness, insomnia, and reversible hyperactivity. 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.
Hematologic effects reported with penicillins, such as amoxicillin; clavulanic acid, include anemia (including hemolytic anemia), thrombocytopenia, thrombotic thrombocytopenic purpura (TTP), eosinophilia, leukopenia, and agranulocytosis. These adverse hematologic effects are generally reversible after discontinuation of therapy and may be related to hypersensitivity. Thrombocytosis was reported in less than 1% of patients receiving amoxicillin; clavulanic acid in clinical studies. There have also been reports of increased prothrombin time in patients receiving amoxicillin; clavulanic acid and anticoagulant therapy.
Hepatic dysfunction, including hepatitis, cholestatic jaundice (cholestasis), elevated hepatic enzymes (AST and/or ALT), increased serum bilirubin (hyperbilirubinemia), and/or increased alkaline phosphatase, has been infrequently reported with amoxicillin; clavulanic acid; it has been more commonly reported in the elderly, in males, or in patients on prolonged treatment. Discontinue amoxicillin; clavulanic acid if signs or symptoms of hepatitis occur. Hepatotoxicity is usually reversible. Death has rarely been reported and has generally been cases associated with serious underlying diseases or concomitant medications. In a case series of 11 children (1 to 11 years) with hepatotoxicity associated with amoxicillin; clavulanic acid therapy, all cases had received normal doses of amoxicillin; clavulanic acid therapy with a duration of treatment ranging from 3 to 10 days. Hepatotoxicity was detected within 3 to 29 days in all patients and no correlation was found among the cases with regard to age distribution. As in adults, the majority of cases were males (n = 9). Elevated hepatic enzymes normalized within 8 weeks in most of the cases.
Tooth discoloration (brown, yellow, or gray staining) has rarely been 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).
Cough was reported in 7% to 12% of patients during clinical trials with amoxicillin; clavulanic acid.
A false-positive reaction for glucose in the urine has been observed in patients receiving penicillins, such as amoxicillin; clavulanic acid, and using Benedict's solution, Fehling's solution, or Clinitest tablets for urine glucose testing. However, this reaction has not been observed with glucose oxidase tests (e.g., Tes-tape, Clinistix, Diastix). Patients with diabetes mellitus who test their urine for glucose should use glucose tests based on enzymatic glucose oxidase reactions while on amoxicillin; clavulanic acid treatment.
Amoxicillin is a penicillin and should not be used in patients with a penicillin hypersensitivity. Amoxicillin; clavulanic acid should be used cautiously in patients with cephalosporin hypersensitivity or carbapenem hypersensitivity. These patients are more susceptible to hypersensitivity reactions during therapy with amoxicillin; the incidence of true cross-sensitivity has been estimated at roughly 3-5%. Patients with allergies or atopic conditions including asthma, eczema, hives (urticaria), or hay fever may have a greater risk for hypersensitivity reactions to penicillins.
In clinical studies of amoxicillin; clavulanic acid (Augmentin XR and other dosage forms) no overall differences in safety and effectiveness were observed between geriatric subjects and younger adult subjects, and other clinical experience has not reported differences in responses between the elderly and younger patients. A greater sensitivity of some older individuals cannot be ruled out. Because this drug is known to be substantially excreted by the kidney and because the elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function in these patients.
Amoxicillin; clavulanic acid extended-release tablets are contraindicated in patients with severe renal impairment (creatinine clearance < 30 mL/min), renal failure, and in hemodialysis (dialysis) patients. In general, other formulations of amoxicillin; clavulanic acid should be used with caution in patients with renal impairment or renal disease since the drug is eliminated via renal mechanisms. Adjust the dosage in patients with CrCl <= 30 mL/min and in patients with renal failure. Dosage adjustments are also recommended for 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; clavulanic acid, 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; clavulanic acid has been used to treat infections in infants < 3 months of age, including neonates. However, dosages must be modified for these age groups compared to infants >= 3 months of age because of incompletely developed renal function. Certain dosage forms are not for use in small children; for example, the safety and effectiveness of amoxicillin; clavulanic acid extended-release tablets and regular tablets have not been established in pediatric patients weighing less than 40 kg. Children less than 40 kg of body weight should be dosed using oral suspension or chewable tablets. Neonates and infants < 3 months should be dosed using the 125 mg/5 mL oral suspension for dosing only.
While amoxicillin; clavulanate should be used with caution in pregnancy, penicillins are usually considered safe during pregnancy when clearly needed. The effects of amoxicillin; clavulanic acid on pregnant women or the fetus during labor and obstetric delivery are unknown; however, one study in women with premature rupture of fetal membranes reported that prophylactic therapy with amoxicillin; clavulanic acid may be associated with an increased risk of necrotizing enterocolitis in the neonate. Animal data reveal no teratogenic effects; however, there are no adequate and well-controlled studies in pregnant women.
According to the manufacturer, amoxicillin; clavulanic acid should be used cautiously during breast-feeding. However, unless the infant is allergic to penicillins, breast-feeding is generally safe during maternal penicillin therapy. The American Academy of Pediatrics (AAP) considers amoxicillin a medication that is usually compatible with breast-feeding; however, amoxicillin; clavulanic acid has not been evaluated by the AAP. Amoxicillin; clavulanic acid is excreted in breast milk in small amounts. Penicillins may cause diarrhea (due to disruption of GI flora), candidiasis, and skin rash in breast-feeding infants. In a study assessing adverse events in breast-fed infants of mothers exposed to antibiotics, 22.3% (15/67) of infants experienced adverse events after exposure to amoxicillin; clavulanic acid. The adverse events included constipation, rash, diarrhea, irritability, and elevated liver enzymes. The rate of adverse events was positively correlated with the dose of amoxicillin; clavulanic acid.. The infant should be observed for potential effects. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Amoxicillin; clavulanic acid chewable tablets contain phenylalanine in the amount of 2.1 mg per 200 mg tablet and 4.2 mg per 400 mg tablet. The 200 mg/5mL, 400 mg/5mL and 600 mg/5 mL oral suspensions of amoxicillin; clavulanic acid each contain 7 mg of phenylalanine per 5 mL. These formulations should be used cautiously in patients with phenylketonuria. Patients with phenylketonuria should be warned that these items contain phenylalanine. However, other amoxicillin; clavulanic acid formulations do not contain phenylalanine.
According to the manufacturer, amoxicillin; clavulanic acid should not be used in patients with mononucleosis as a high incidence of skin rashes have been reported with amoxicillin in these patients.
Amoxicillin; clavulanic acid is contraindicated for use in any patient with a previous history of drug-induced cholestasis, jaundice, or other hepatic dysfunction induced by this combination of drugs. Amoxicillin; clavulanic acid should be used with caution in those patients with pre-existing hepatic disease. Monitor liver function in these patients during therapy. The amoxicillin component is not appreciably metabolized in the liver and does not undergo biliary secretion. However, hepatic dysfunction due to amoxicillin; clavulanic acid has been reported on rare occasions; occasionally these reactions have been severe.
Serious rash events, such as Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), erythema multiforme, and exfoliative dermatitis have been reported in patients receiving treatment with amoxicillin; clavulanic acid. If a skin rash occurs, monitor patients closely and discontinue amoxicillin; clavulanic acid if lesions progress.
-Dosages listed are based on the amoxicillin component; use the specified dosage forms as listed to ensure proper corresponding clavulanic acid dosage.
-Carefully ensure that the correct amoxicillin; clavulanic acid product is selected. Many products are not interchangeable due to differences in clavulanic acid content. Incorrect product selection may lead to severe diarrhea from higher concentrations of clavulanic acid:-The 250 mg tablet and the 250 mg chewable tablet do not contain the same amount of clavulanic acid. The 250 mg tablet contains 125 mg of clavulanic acid, whereas the 250 mg chewable tablet contains 62.5 mg of clavulanic acid. Therefore, the 250 mg tablet and the 250 mg chewable tablet should not be substituted for each other.
-Immediate-release tablets (250 mg or 500 mg) cannot be used to provide the same dosages as extended-release tablets. The extended-release tablet contains 62.5 mg of clavulanic acid, while the immediate-release tablets each contain 125 mg of clavulanic acid. Also, the extended-release tablet provides an extended time course of plasma amoxicillin concentrations; therefore, two immediate-release 500 mg tablets are not equivalent to one extended-release 1000 mg tablet.
-The ES-600 suspension (600 mg amoxicillin and 42.9 mg clavulanic acid per 5 ml suspension) does not contain the same amount of clavulanic acid (as the potassium salt) as any of the other suspensions of amoxicillin; clavulanic acid. Therefore, this suspension is not interchangeable with any other suspension.
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: Bacteroides fragilis, Bacteroides sp., Eikenella corrodens, Enterobacter sp., Enterococcus faecalis, Escherichia coli, Fusobacterium nucleatum, Fusobacterium sp., Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Haemophilus parainfluenzae, Klebsiella pneumoniae, Klebsiella sp., Moraxella catarrhalis, Neisseria gonorrhoeae, Peptostreptococcus magnus, Peptostreptococcus micros, Peptostreptococcus sp., Proteus mirabilis, Staphylococcus aureus (MSSA), Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococci), Viridans 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: Burkholderia pseudomallei, Nocardia brasiliensis
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: Amoxicillin; clavulanic acid is the preferred initial therapy for children who have received amoxicillin within the past 30 days, who have concurrent conjunctivitis, or those for whom coverage of beta-lactamase-positive H. influenzae and M. catarrhalis is desired.
Oral dosage (immediate-release formulations and non-ES suspensions, standard dose therapy):
Adults: 500 mg amoxicillin with 125 mg clavulanic acid PO every 8 hours (using 500 mg regular tablets; 125 mg or 250 mg chewable tablets; or 125 mg/5 mL or 250 mg/5 mL suspension) or 875 mg amoxicillin with 125 mg clavulanic acid PO every 12 hours (using 875 mg tablet or 200 mg/5 mL or 400 mg/5 mL suspension) for 10 days.
Children and Adolescents weighing 40 kg or more: 500 mg amoxicillin with 125 mg clavulanic acid PO every 8 hours (using 500 mg regular tablets; 125 mg or 250 mg chewable tablets; or 125 mg/5 mL or 250 mg/5 mL suspension) or 875 mg amoxicillin with 125 mg clavulanic acid PO every 12 hours (using 875 mg tablet or 200 mg/5 mL or 400 mg/5 mL suspension) for 10 days.
Infants 3 months and older, Children, and Adolescents weighing less than 40 kg: Due to the higher clavulanic acid content in regular formulations (i.e., chewable tablets, non-ES suspensions) and the need for high-dose therapy (i.e., 90 mg/kg/day), these formulations are not recommended for the treatment of AOM. The formulation containing 600 mg of amoxicillin and 42.9 mg of clavulanic acid per 5 mL (e.g., ES-600) is recommended for high-dose therapy. The FDA-approved dose is 45 mg/kg/day amoxicillin component PO divided every 12 hours (using 200 mg/5 mL or 400 mg/5 mL suspension; 200 mg or 400 mg chewable tablets) or 40 mg/kg/day amoxicillin component PO divided every 8 hours (using 125 mg/5 mL or 250 mg/5 mL suspension; 125 mg or 250 mg chewable tablets; or 500 mg regular tablets) for 10 days.
Infants 1 to 2 months: 30 mg/kg/day amoxicillin component PO divided every 12 hours. Due to limited data supporting the use of other formulations, the 125 mg/5 mL suspension is recommended for use in this age group.
Neonates: 30 mg/kg/day amoxicillin component PO divided every 12 hours. Due to limited data supporting the use of other formulations, the 125 mg/5 mL suspension for use in this age group.
Oral dosage (ES-600; 600 mg amoxicillin and 42.9 mg clavulanic acid per 5 mL suspension, high-dose therapy):
Children 6 to 12 years: 90 mg/kg/day amoxicillin component (Max: 4,000 mg amoxicillin/day) PO divided every 12 hours for 5 to 7 days for mild to moderate disease and 10 days for severe disease.
Children 2 to 5 years: 90 mg/kg/day amoxicillin component PO divided every 12 hours for 7 days for mild to moderate disease and 10 days for severe disease.
Infants and Children 6 to 23 months: 90 mg/kg/day amoxicillin component PO divided every 12 hours for 10 days.
Infants 3 to 5 months: 90 mg/kg/day amoxicillin component PO divided every 12 hours for 10 days.
For the treatment of acute bacterial sinusitis:
Oral dosage (immediate-release formulations and non-ES suspensions, standard dose therapy):
Adults: 500 mg amoxicillin with 125 mg clavulanic acid PO every 8 hours (using 500 mg regular tablets; 125 mg or 250 mg chewable tablets; or 125 mg/5 mL or 250 mg/5 mL suspension) or 875 mg amoxicillin with 125 mg clavulanic acid PO every 12 hours (using 875 mg tablet or 200 mg/5 mL or 400 mg/5 mL suspension) for 5 to 10 days as first-line therapy. High-dose therapy is recommended as initial empiric therapy for patients from geographic areas with high rates of penicillin-resistant S. pneumoniae, those with severe infection, patients older than 65 years, those with recent hospitalization, antibiotic use within the past month, and who are immunocompromised. High-dose therapy is also recommended after initial treatment failure.
Children and Adolescents weighing 40 kg or more: 500 mg amoxicillin with 125 mg clavulanic acid PO every 8 hours (using 500 mg regular tablets; 125 mg or 250 mg chewable tablets; or 125 mg/5 mL or 250 mg/5 mL suspension) or 875 mg amoxicillin with 125 mg clavulanic acid PO every 12 hours (using 875 mg tablet or 200 mg/5 mL or 400 mg/5 mL suspension) for 10 to 14 days as first-line therapy. The every 12 hour regimen is preferred because it associated with less diarrhea than the every 8 hour regimen. High-dose therapy is recommended as initial empiric therapy for patients from geographic areas with high rates of penicillin-resistant S. pneumoniae, those with severe infection, children who attend daycare, those with recent hospitalization, antibiotic use within the past month, and who are immunocompromised. High-dose therapy is also recommended after initial treatment failure.
Infants, Children, and Adolescents 3 months to 17 years weighing less than 40 kg: 40 mg/kg/day amoxicillin component PO divided every 8 hours (using 125 mg/5 mL or 250 mg/5 mL suspension; 125 mg or 250 mg chewable tablets; or 500 mg regular tablets) or 45 mg/kg/day amoxicillin component PO divided every 12 hours (using 200 mg/5 mL or 400 mg/5 mL suspension; 200 mg or 400 mg chewable tablets) for 10 to 14 days as first-line therapy for most patients. The every 12 hour regimen is preferred because it associated with less diarrhea than the every 8 hour regimen. High-dose therapy is recommended as initial empiric therapy for patients from geographic areas with high rates of penicillin-resistant S. pneumoniae, those with severe infection, children who attend daycare, children younger than 2 years, children with recent hospitalization, those with antibiotic use within the past month, and those who are immunocompromised. High-dose therapy is also recommended after initial treatment failure.
Infants 1 to 2 months: 30 mg/kg/day amoxicillin component PO divided every 12 hours for 10 to 14 days as first-line therapy. Due to limited data supporting the use of other formulations, the 125 mg/5 mL suspension is recommended for use in this age group.
Neonates: 30 mg/kg/day amoxicillin component PO divided every 12 hours for 10 to 14 days as first-line therapy. Due to limited data supporting the use of other formulations, the 125 mg/5 mL suspension is recommended for use in this age group.
Oral dosage (extended-release tablets containing 1,000 mg amoxicillin and 62.5 mg clavulanate, high-dose therapy):
Adults: 2,000 mg amoxicillin with 125 mg clavulanic acid PO every 12 hours for 5 to 10 days as first-line therapy. High-dose therapy is recommended as initial empiric therapy for patients from geographic areas with high rates of penicillin-resistant S. pneumoniae, those with severe infection, patients older than 65 years, those with recent hospitalization, antibiotic use within the past month, and who are immunocompromised. High-dose therapy is also recommended after initial treatment failure.
Children and Adolescents weighing 40 kg or more: 2,000 mg amoxicillin with 125 mg clavulanic acid PO every 12 hours for 10 to 14 days as first-line therapy. High-dose therapy is recommended as initial empiric therapy for patients from geographic areas with high rates of penicillin-resistant S. pneumoniae, those with severe infection, children who attend daycare, those with recent hospitalization, antibiotic use within the past month, and who are immunocompromised. High-dose therapy is also recommended after initial treatment failure.
Oral dosage (ES-600; 600 mg amoxicillin and 42.9 mg clavulanic acid per 5 mL suspension, high-dose therapy)*:
Adults: 2,000 mg amoxicillin with 143 mg clavulanic acid PO every 12 hours for 5 to 10 days. High-dose therapy is recommended as initial empiric therapy for patients from geographic areas with high rates of penicillin-resistant S. pneumoniae, those with severe infection, patients older than 65 years, those with recent hospitalization, antibiotic use within the past month, and who are immunocompromised. High-dose therapy is also recommended after initial treatment failure.
Infants, Children, and Adolescents: 90 mg/kg/day amoxicillin component (Max: 4,000 mg amoxicillin/day) PO divided every 12 hours for 10 to 14 days as first-line therapy. High-dose therapy is recommended as initial empiric therapy for patients from geographic areas with high rates of penicillin-resistant S. pneumoniae, those with severe infection, children who attend daycare, children younger than 2 years, children with recent hospitalization, those with antibiotic use within the past month, and those who are immunocompromised. High-dose therapy is also recommended after initial treatment failure.
For the treatment of lower respiratory tract infections (LRTIs), including community-acquired pneumonia (CAP) as well as acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD), including chronic bronchitis or emphysema:
-for the treatment of nonspecific lower respiratory tract infections (LRTIs):
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours or 500 mg amoxicillin with 125 mg clavulanate PO every 8 hours.
Children and Adolescents weighing 40 kg or more: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours or 500 mg amoxicillin with 125 mg clavulanate PO every 8 hours.
Infants, Children, and Adolescents 3 months to 17 years and weighing less than 40 kg: 45 mg/kg/day amoxicillin component PO divided every 12 hours or 40 mg/kg/day amoxicillin component PO divided every 8 hours. The every 12-hour regimen is associated with less diarrhea.
Infants 1 to 2 months: 30 mg/kg/day amoxicillin component PO divided every 12 hours. The 125 mg/5 mL suspension is recommended.
Neonates: 30 mg/kg/day amoxicillin component PO divided every 12 hours. The 125 mg/5 mL suspension is recommended.
-for the treatment of community-acquired pneumonia (CAP):
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours or 500 mg amoxicillin with 125 mg clavulanate PO every 8 hours for at least 5 days as part of combination therapy for outpatients with comorbidities. Guide treatment duration by clinical stability.
Adolescents weighing 40 kg or more: 500 mg amoxicillin with 125 mg clavulanate PO every 8 hours for 5 to 10 days as an alternative to high-dose amoxicillin for mild infections or as step-down therapy for infections due to beta-lactamase-producing H. influenzae. In persons living with HIV, amoxicillin; clavulanate is recommended as part of combination therapy for outpatients.
Adolescents weighing less than 40 kg: 45 mg/kg/day amoxicillin component PO divided every 8 hours for 5 to 10 days as an alternative to high-dose amoxicillin for mild infections or as step-down therapy for infections due to beta-lactamase-producing H. influenzae. In persons living with HIV, amoxicillin; clavulanate is recommended as part of combination therapy for outpatients.
Children weighing 40 kg or more: 500 mg amoxicillin with 125 mg clavulanate PO every 8 hours for 7 to 10 days as an alternative to high-dose amoxicillin for mild infections or as step-down therapy for infections due to beta-lactamase-producing H. influenzae.
Infants and Children 3 months to 12 years and weighing less than 40 kg: 45 mg/kg/day amoxicillin component PO divided every 8 hours for 7 to 10 days as an alternative to high-dose amoxicillin for mild infections or as step-down therapy for infections due to beta-lactamase-producing H. influenzae.
Infants 1 to 2 months: 30 mg/kg/day amoxicillin component PO divided every 12 hours. The 125 mg/5 mL suspension is recommended. If a lower respiratory tract infection is suspected in a young infant, full evaluation and careful clinical workup are warranted. Infants younger than 3 to 6 months are likely to benefit from hospitalization.
Neonates: 30 mg/kg/day amoxicillin component PO divided every 12 hours. The 125 mg/5 mL suspension is recommended. If a lower respiratory tract infection is suspected in a neonate, full evaluation and careful clinical workup are warranted. Neonates are likely to benefit from hospitalization.
Oral dosage (extended-release tablets containing 1,000 mg amoxicillin and 62.5 mg clavulanate per tablet):
Adults: 2,000 mg amoxicillin with 125 mg clavulanate PO every 12 hours for at least 5 days as part of combination therapy for outpatients with comorbidities. Guide treatment duration by clinical stability. FDA-approved labeling recommends treatment for 7 to 10 days.
Adolescents weighing 40 kg or more: 2,000 mg amoxicillin with 125 mg clavulanate PO every 12 hours for 5 to 10 days as an alternative to amoxicillin for empiric therapy in outpatients, for mild infections, or as step-down therapy for infections due to beta-lactamase-producing H. influenzae. In persons living with HIV, amoxicillin; clavulanate is recommended as part of combination therapy for outpatients.
Children weighing 40 kg or more: 2,000 mg amoxicillin with 125 mg clavulanate PO every 12 hours for 7 to 10 days as an alternative to amoxicillin for empiric therapy in outpatients, for mild infections, or as step-down therapy for infections due to beta-lactamase-producing H. influenzae.
Oral dosage (ES-600; suspension containing 600 mg amoxicillin and 42.9 mg clavulanate per 5 mL)*:
Adolescents: 90 mg/kg/day amoxicillin component (Max: 4,000 mg amoxicillin/day) PO divided every 12 hours for 5 to 10 days as an alternative to amoxicillin for empiric therapy in outpatients, for mild infections, or as step-down therapy for infections due to beta-lactamase-producing H. influenzae. In persons living with HIV, amoxicillin; clavulanate is recommended as part of combination therapy for outpatients.
Infants and Children 3 months to 12 years: 90 mg/kg/day amoxicillin component (Max: 4,000 mg amoxicillin/day) PO divided every 12 hours for 7 to 10 days as an alternative to amoxicillin for empiric therapy in outpatients, for mild infections, or as step-down therapy for infections due to beta-lactamase-producing H. influenzae.
-for the treatment of exacerbations of COPD, including chronic bronchitis or emphysema:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 500 mg amoxicillin with 125 mg clavulanate PO every 8 hours for 5 to 7 days.
For the treatment of skin and skin structure infections, including impetigo, cellulitis, erysipelas, animal or human bite wounds, leg ulcer, and diabetic foot ulcer:
-for the treatment of impetigo:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours for 5 to 7 days.
Children and Adolescents weighing 40 kg or more: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours for 5 to 7 days.
Infants, Children, and Adolescents 3 months to 17 years weighing less than 40 kg: 25 mg/kg/day amoxicillin component PO divided every 12 hours for 5 to 7 days.
Infants 1 to 2 months: 30 mg/kg/day amoxicillin component PO divided every 12 hours for 5 to 7 days. Due to limited data supporting the use of other formulations, the FDA-approved labeling recommends the 125 mg/5 mL suspension for use in this age group.
Neonates: 30 mg/kg/day amoxicillin component PO divided every 12 hours for 5 to 7 days. Due to limited data supporting the use of other formulations, the FDA-approved labeling recommends the 125 mg/5 mL suspension for use in this age group.
-for the treatment of nonpurulent skin infections, such as cellulitis and erysipelas:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours or 500 mg amoxicillin with 125 mg clavulanate PO every 8 to 12 hours or 250 mg amoxicillin with 125 mg clavulanate PO every 8 hours for 5 to 14 days.
Children and Adolescents weighing 40 kg or more: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours or 500 mg amoxicillin with 125 mg clavulanate PO every 8 to 12 hours or 250 mg amoxicillin with 125 mg clavulanate PO every 8 hours for 5 to 14 days.
Infants, Children, and Adolescents 3 months to 17 years weighing less than 40 kg: 25 to 45 mg/kg/day amoxicillin component PO divided every 12 hours or 20 to 40 mg/kg/day amoxicillin component PO divided every 8 hours for 5 to 14 days.
Infants 1 to 2 months: 30 mg/kg/day amoxicillin component PO divided every 12 hours for 5 to 14 days. Due to limited data supporting the use of other formulations, the FDA-approved labeling recommends the 125 mg/5 mL suspension for use in this age group.
Neonates: 30 mg/kg/day amoxicillin component PO divided every 12 hours for 5 to 14 days. Due to limited data supporting the use of other formulations, the FDA-approved labeling recommends the 125 mg/5 mL suspension for use in this age group.
-for the treatment of animal bite wounds:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours. In setting of a cat or dog bite, preemptive early antimicrobial therapy for 3 to 5 days is recommended for patients who are immunocompromised, asplenic, have advanced liver disease, have edema of the bite area, have moderate to severe injuries, particularly of the hand or face, or have penetrating injuries to the periosteum or joint capsule.
Children and Adolescents weighing 40 kg or more: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours. In setting of a cat or dog bite, preemptive early antimicrobial therapy for 3 to 5 days is recommended for patients who are immunocompromised, asplenic, have advanced liver disease, have edema of the bite area, have moderate to severe injuries, particularly of the hand or face, or have penetrating injuries to the periosteum or joint capsule.
Infants, Children, and Adolescents 3 months to 17 years weighing less than 40 kg: 25 to 45 mg/kg/day amoxicillin component PO divided every 12 hours. In setting of a cat or dog bite, preemptive early antimicrobial therapy for 3 to 5 days is recommended for patients who are immunocompromised, asplenic, have advanced liver disease, have edema of the bite area, have moderate to severe injuries, particularly of the hand or face, or have penetrating injuries to the periosteum or joint capsule.
Infants 1 to 2 months: 30 mg/kg/day amoxicillin component PO divided every 12 hours. Due to limited data supporting the use of other formulations, the FDA-approved labeling recommends the 125 mg/5 mL suspension for use in this age group. In setting of a cat or dog bite, preemptive early antimicrobial therapy for 3 to 5 days is recommended for patients who are immunocompromised, asplenic, have advanced liver disease, have edema of the bite area, have moderate to severe injuries, particularly of the hand or face, or have penetrating injuries to the periosteum or joint capsule.
Neonates: 30 mg/kg/day amoxicillin component PO divided every 12 hours. Due to limited data supporting the use of other formulations, the FDA-approved labeling recommends the 125 mg/5 mL suspension for use in this age group. In setting of a cat or dog bite, preemptive early antimicrobial therapy for 3 to 5 days is recommended for patients who are immunocompromised, asplenic, have advanced liver disease, have edema of the bite area, have moderate to severe injuries, particularly of the hand or face, or have penetrating injuries to the periosteum or joint capsule.
-for the treatment of human bite wounds:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours.
-for the treatment of leg ulcer:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours or 500 mg amoxicillin with 125 mg clavulanate PO every 8 hours for 7 days.
-for the treatment of mild diabetic foot ulcer:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours or 500 mg amoxicillin with 125 mg clavulanate PO every 8 hours for 7 to 14 days for mild infections in patients with recent antibiotic exposure or moderate or severe infections with no complicating features or with ischemic limb/necrosis/gas forming. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease.
For the treatment of urinary tract infection (UTI), including cystitis, pyelonephritis, and infections with difficult-to-treat resistance:
-for the treatment nonspecific UTI:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 500 mg amoxicillin with 125 mg clavulanic acid PO every 12 hours or 250 mg amoxicillin with 125 mg clavulanic acid PO every 8 hours for mild/moderate infections and 875 mg amoxicillin with 125 mg clavulanic acid PO every 12 hours or 500 mg amoxicillin with 125 mg clavulanic acid PO every 8 hours for severe infections.
Children and Adolescents weighing 40 kg or more: 500 mg amoxicillin with 125 mg clavulanic acid PO every 12 hours or 250 mg amoxicillin with 125 mg clavulanic acid PO every 8 hours for mild/moderate infections and 875 mg amoxicillin with 125 mg clavulanic acid PO every 12 hours or 500 mg amoxicillin with 125 mg clavulanic acid PO every 8 hours for severe infections.
Infants, Children, and Adolescents 3 months to 17 years weighing less than 40 kg: 25 mg/kg/day amoxicillin component PO divided every 12 hours or 20 mg/kg/day amoxicillin component PO divided every 8 hours for mild/moderate infections and 45 mg/kg/day amoxicillin component PO divided every 12 hours or 40 mg/kg/day amoxicillin component PO divided every 8 hours for severe infections. The every 12-hour regimen is preferred in children because it causes less diarrhea.
Infants 1 to 2 months: 30 mg/kg/day amoxicillin component PO divided every 12 hours. Due to limited data supporting the use of other formulations, the FDA-approved labeling states that only the 125 mg/5 mL suspension is recommended for this age group.
Neonates: 30 mg/kg/day amoxicillin component PO divided every 12 hours. Due to limited data supporting the use of other formulations, the FDA-approved labeling states that only the 125 mg/5 mL suspension is recommended for this age group.
-for the treatment of acute uncomplicated cystitis:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 500 mg amoxicillin with 125 mg clavulanic acid PO every 12 hours or 250 mg amoxicillin with 125 mg clavulanic acid PO every 8 hours for 3 to 7 days.
-for the treatment of acute uncomplicated cystitis due to infections with difficult-to-treat resistance:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours for 3 to 7 days.
-for the treatment of acute uncomplicated lower UTI in pediatric patients:
Oral dosage (immediate-release formulations and non-ES suspensions):
Children and Adolescents weighing 40 kg or more: 500 mg amoxicillin with 125 mg clavulanic acid PO every 12 hours or 250 mg amoxicillin with 125 mg clavulanic acid PO every 8 hours for 3 to 5 days.
Infants, Children, and Adolescents 3 months to 17 years weighing less than 40 kg: 25 mg/kg/day amoxicillin component PO divided every 12 hours or 20 mg/kg/day amoxicillin component PO divided every 8 hours for 3 to 5 days. The every 12-hour regimen is preferred in children because it causes less diarrhea.
-for the treatment of severe UTI, including pyelonephritis:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 875 mg amoxicillin with 125 mg clavulanic acid PO every 12 hours or 500 mg amoxicillin with 125 mg clavulanic acid PO every 8 hours for 7 to 14 days. Consider an initial dose of a long-acting IV antibiotic prior to use.
Children and Adolescents weighing 40 kg or more: 875 mg amoxicillin with 125 mg clavulanic acid PO every 12 hours or 500 mg amoxicillin with 125 mg clavulanic acid PO every 8 hours for 7 to 14 days.
Infants, Children, and Adolescents 3 months to 17 years weighing less than 40 kg: 45 mg/kg/day amoxicillin component PO divided every 12 hours or 40 mg/kg/day amoxicillin component PO divided every 8 hours for 7 to 14 days. The every 12-hour regimen is preferred in children because it causes less diarrhea.
Infants 1 to 2 months: 30 mg/kg/day amoxicillin component PO divided every 12 hours. Due to limited data supporting the use of other formulations, the FDA-approved labeling states that only the 125 mg/5 mL suspension is recommended for this age group.
Neonates: 30 mg/kg/day amoxicillin component PO divided every 12 hours. Due to limited data supporting the use of other formulations, the FDA-approved labeling states that only the 125 mg/5 mL suspension is recommended for this age group.
For the treatment of dental infection*, including dentoalveolar infection*, periodontitis*, and pericoronitis*:
-for adolescent aggressive periodontitis* or adult refractory chronic periodontitis* after scaling and root planing:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 250 or 500 mg PO 3 times daily for 10 days.
Children and Adolescents: 20 to 40 mg/kg/day PO in equally divided doses given 3 times daily (Max: 500 mg/dose) for 10 days (using 125 mg/5 mL or 250 mg/5 mL suspension; 125 mg or 250 mg chewable tablets; or 500 mg regular tablets). The 250 mg regular tablets should not be used until the child reaches 40 kg.
-for pericoronitis*:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: For preoperative prophylaxis, 2 g PO single dose 1 hour before surgical intervention. If surgical intervention unable to be performed, treat suppurative acute phase pericoronitis with 2 g PO every 12 hours for 7 days.
Children and Adolescents: Safety and efficacy have not been established.
For the treatment of actinomycotic mycetoma* caused by susceptible strains of Nocardia brasiliensis:
Oral dosage:
Adults: 500 mg amoxicillin with 125 mg clavulanic acid PO every 8 hours for 5-6 months.
For use as oral maintenance therapy in the treatment of melioidosis* due to Burkholderia pseudomallei*:
Oral dosage:
Adults, Adolescents, Children: Following initial parenteral treatment for melioidosis, oral maintenance therapy with amoxicillin; clavulanic acid 30 mg/kg/day divided into 3 doses is given for 3-6 months as a second-line agent in adults and as a first-line agent in children and pregnant women.
For the empiric treatment of febrile neutropenia* in low risk patients:
Oral dosage:
Adults: Guidelines recommend amoxicillin; clavulanate in combination with ciprofloxacin as a first line option in low-risk patients. These recommendations are supported by several studies. Doses of 500 mg (amoxicillin component) PO every 8 hours or 1000 mg (amoxicillin component) PO twice daily have been used, with ciprofloxacin, in studies.
For group A streptococci chronic pharyngeal carriage eradication*:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 40 mg/kg/day amoxicillin component PO divided every 8 hours (Max: 2 g/day) for 10 days. Most chronic streptococcal carriers do not need antimicrobial therapy. Treatment may be considered during a community outbreak of acute rheumatic fever, acute poststreptococcal glomerulonephritis or invasive group A streptococcal (GAS) infection; during an outbreak of GAS pharyngitis in a closed or partially closed community; in the presence of a family or personal history of acute rheumatic fever; in a family with excessive anxiety about GAS infections; or when tonsillectomy is being considered only because of carriage.
Infants, Children, and Adolescents: 40 mg/kg/day amoxicillin component PO divided every 8 hours (Max: 2 g/day) for 10 days. Most chronic streptococcal carriers do not need antimicrobial therapy. Treatment may be considered during a community outbreak of acute rheumatic fever, acute poststreptococcal glomerulonephritis or invasive group A streptococcal (GAS) infection; during an outbreak of GAS pharyngitis in a closed or partially closed community; in the presence of a family or personal history of acute rheumatic fever; in a family with excessive anxiety about GAS infections; or when tonsillectomy is being considered only because of carriage.
For the treatment of drug-resistant tuberculosis infection* paired with a carbapenem as part of combination therapy:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 500 mg amoxicillin with 125 mg clavulanate PO every 6 to 12 hours or 1 g amoxicillin with 250 mg clavulanate PO every 6 to 12 hours depending on the frequency of the carbapenem administered.
Infants, Children, and Adolescents: 75 mg/kg/day amoxicillin component PO divided every 8 hours or 80 mg/kg/day amoxicillin component PO divided every 12 hours (Max: 3 g amoxicillin component/day).
Oral dosage (extended-release tablets containing 1,000 mg amoxicillin and 62.5 mg clavulanate per tablet):
Adults: 2,000 mg amoxicillin with 125 mg clavulanate PO every 12 hours.
Oral dosage (ES-600; suspension containing 600 mg amoxicillin and 42.9 mg clavulanate per 5 mL):
Infants, Children, and Adolescents: 80 mg/kg/day amoxicillin component PO divided every 12 hours (Max: 3 g amoxicillin component/day).
For the treatment of intraabdominal infections*, including peritonitis*, appendicitis*, intraabdominal abscess*, complicated diverticulitis*, and peritoneal dialysis catheter-related infection*:
-for the oral step-down treatment of complicated intraabdominal infections* or for the treatment of complicated diverticulitis*:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours or 500 mg amoxicillin with 125 mg clavulanate PO every 8 hours for a total treatment duration of 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
Infants, Children, and Adolescents: 40 mg/kg/day amoxicillin component (Max: 1,500 mg/day) PO divided every 8 hours for a total treatment duration of 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
-for the treatment of peritoneal dialysis catheter-related infection*:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours for at least 14 days to 21 days.
For the treatment of bartonellosis*, including uncomplicated Oroya fever*:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 1 g amoxicillin with 250 mg clavulanate PO every 12 hours for 14 days with or without chloramphenicol as second-line therapy.
Pregnant or Breast-feeding Persons: 1 g amoxicillin with 250 mg clavulanate PO every 12 hours for 14 days with or without chloramphenicol as first-line therapy.
Infants, Children, and Adolescents: 20 mg/kg/dose amoxicillin component (Max: 1 g amoxicillin component/dose) PO every 12 hours for 14 days with or without chloramphenicol as first-line therapy.
For the treatment of small intestinal bacterial overgrowth*:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours or 500 mg amoxicillin with 125 mg clavulanate PO every 8 hours for 7 to 10 days.
Children and Adolescents: 25 to 45 mg/kg/day (Max: 1,750 mg/day) amoxicillin component PO divided every 12 hours or 20 to 40 mg/kg/day (Max 1,500 mg/day) amoxicillin component PO divided every 8 hours for 7 to 10 days.
For the treatment of bone and joint infections*, including osteomyelitis*, infectious arthritis*, and orthopedic device-related infection*:
-for step-down therapy for osteomyelitis* after initial IV therapy:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours or 500 mg amoxicillin with 125 mg clavulanate PO every 8 hours for 4 to 6 weeks.
Infants, Children, and Adolescents 3 months to 17 years: 50 mg/kg/day amoxicillin component (Max: 1,500 mg amoxicillin/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.
Infants 1 to 2 months: 50 mg/kg/day amoxicillin component 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.
Oral dosage (ES-600; 600 mg amoxicillin and 42.9 mg clavulanic acid per 5 mL suspension, high-dose therapy):
Infants, Children, and Adolescents 3 months to 17 years: 80 to 90 mg/kg/day amoxicillin component (Max: 4,000 mg amoxicillin/day) PO divided every 8 to 12 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.
Infants 1 to 2 months: 80 to 90 mg/kg/day amoxicillin component PO divided every 8 to 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.
-for step-down therapy for infectious arthritis* after initial IV therapy:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours or 500 mg amoxicillin with 125 mg clavulanate PO every 8 hours. Treat for a total duration of 3 to 6 weeks (parenteral plus oral.
Infants, Children, and Adolescents 3 months to 17 years: 50 mg/kg/day amoxicillin component (Max: 1,500 mg amoxicillin/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.
Infants 1 to 2 months: 50 mg/kg/day amoxicillin component 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.
Oral dosage (ES-600; 600 mg amoxicillin and 42.9 mg clavulanic acid per 5 mL suspension, high-dose therapy):
Infants, Children, and Adolescents 3 months to 17 years: 80 to 90 mg/kg/day amoxicillin component (Max: 4,000 mg amoxicillin/day) PO divided every 8 to 12 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.
Infants 1 to 2 months: 80 to 90 mg/kg/day amoxicillin component PO divided every 8 to 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.
-for long-term suppressive therapy of prosthetic joint infections*:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 500 mg amoxicillin with 125 mg clavulanic acid PO every 8 hours.
For the treatment of acute exacerbations of bronchiectasis*:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 500 mg amoxicillin with 125 mg clavulanate PO every 8 hours for 14 days.
Infants, Children, and Adolescents: 40 mg/kg/day amoxicillin component (Max: 1,500 mg amoxicillin/day) PO divided every 8 hours for 14 days.
For the treatment of postpartum endometritis*:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours may be considered for mild disease.
For the treatment of anthrax*:
-for the treatment of cutaneous anthrax* without aerosol exposure or signs and symptoms of meningitis:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours for 7 to 10 days or until clinical criteria for stability are met.
Infants, Children, and Adolescents: 22.5 mg/kg/dose amoxicillin component (Max: 875 mg amoxicillin component/dose) PO every 12 hours for 7 to 10 days or until clinical criteria for stability are met.
Neonates 34 weeks gestation and older: 25 mg/kg/dose amoxicillin component PO every 8 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 amoxicillin component PO every 8 hours for 7 to 10 days or until clinical criteria for stability are met.
Neonates 32 to 33 weeks gestation and 0 to 6 days: 25 mg/kg/dose amoxicillin component PO every 12 hours for 7 to 10 days or until clinical criteria for stability are met.
Oral dosage (extended-release tablets containing 1,000 mg amoxicillin and 62.5 mg clavulanate per tablet):
Adults: 2,000 mg amoxicillin with 125 mg clavulanate PO every 12 hours for 7 to 10 days or until clinical criteria for stability are met.
Children and Adolescents weighing 40 kg or more: 2,000 mg amoxicillin with 125 mg clavulanate PO every 12 hours for 7 to 10 days or until clinical criteria for stability are met.
Oral dosage (ES-600; suspension containing 600 mg amoxicillin and 42.9 mg clavulanate per 5 mL):
Infants, Children, and Adolescents weighing less than 40 kg: 45 mg/kg/dose amoxicillin component PO every 12 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 formulations and non-ES suspensions):
Adults: 875 mg amoxicillin with 125 mg clavulanate 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 42- to 60-day total treatment course depending on vaccine status and immunocompetence.
Infants, Children, and Adolescents: 22.5 mg/kg/dose amoxicillin component (Max: 875 mg amoxicillin component/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 34 weeks gestation and older: 25 mg/kg/dose amoxicillin component 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 32 to 33 weeks gestation and 7 days or older: 25 mg/kg/dose amoxicillin component 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 32 to 33 weeks gestation and 0 to 6 days: 25 mg/kg/dose amoxicillin component 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.
Oral dosage (extended-release tablets containing 1,000 mg amoxicillin and 62.5 mg clavulanate per tablet):
Adults: 2,000 mg amoxicillin with 125 mg clavulanate 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 42- to 60-day total treatment course depending on vaccine status and immunocompetence.
Children and Adolescents weighing 40 kg or more: 2,000 mg amoxicillin with 125 mg clavulanate 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.
Oral dosage (ES-600; suspension containing 600 mg amoxicillin and 42.9 mg clavulanate per 5 mL):
Infants, Children, and Adolescents weighing less than 40 kg: 45 mg/kg/dose amoxicillin component 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.
For postexposure anthrax prophylaxis*:
-for postexposure anthrax prophylaxis* after nonaerosol exposure (cutaneous or ingestion):
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours for 7 days after exposure.
Infants, Children, and Adolescents: 22.5 mg/kg/dose amoxicillin component (Max: 875 mg amoxicillin component/dose) PO every 12 hours for 7 days after exposure.
Neonates 34 weeks gestation and older: 25 mg/kg/dose amoxicillin component PO every 8 hours for 7 days after exposure.
Neonates 32 to 33 weeks gestation and 7 days and older: 25 mg/kg/dose amoxicillin component PO every 8 hours for 7 days after exposure.
Neonates 32 to 33 weeks gestation and 0 to 6 days: 25 mg/kg/dose amoxicillin component PO every 12 hours for 7 days after exposure.
Oral dosage (extended-release tablets containing 1,000 mg amoxicillin and 62.5 mg clavulanate per tablet):
Adults: 2,000 mg amoxicillin with 125 mg clavulanate PO every 12 hours for 7 days after exposure.
Children and Adolescents weighing 40 kg or more: 2,000 mg amoxicillin with 125 mg clavulanate PO every 12 hours for 7 days after exposure.
Oral dosage (ES-600; suspension containing 600 mg amoxicillin and 42.9 mg clavulanate per 5 mL):
Infants, Children, and Adolescents weighing less than 40 kg: 45 mg/kg/dose amoxicillin component PO every 12 hours for 7 days after exposure.
-for postexposure anthrax prophylaxis* after aerosol exposure:
Oral dosage (immediate-release formulations and non-ES suspensions):
Adults 66 years and older: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours for 60 days after exposure.
Adults 18 to 65 years: 875 mg amoxicillin with 125 mg clavulanate PO every 12 hours for 60 days after exposure. For immunocompetent, nonpregnant persons who received the anthrax vaccine, may decrease duration to 42 days after first antibiotic dose or 2 weeks after the last vaccine dose, whichever occurs later.
Infants, Children, and Adolescents: 22.5 mg/kg/dose amoxicillin component (Max: 875 mg amoxicillin component/dose) PO every 12 hours for 60 days after exposure.
Neonates 34 weeks gestation and older: 25 mg/kg/dose amoxicillin component PO every 8 hours for 60 days after exposure.
Neonates 32 to 33 weeks gestation and 7 days and older: 25 mg/kg/dose amoxicillin component PO every 8 hours for 60 days after exposure.
Neonates 32 to 33 weeks gestation and 0 to 6 days: 25 mg/kg/dose amoxicillin component PO every 12 hours for 60 days after exposure.
Oral dosage (extended-release tablets containing 1,000 mg amoxicillin and 62.5 mg clavulanate per tablet):
Adults 66 years and older: 2,000 mg amoxicillin with 125 mg clavulanate PO every 12 hours for 60 days after exposure.
Adults 18 to 65 years: 2,000 mg amoxicillin with 125 mg clavulanate PO every 12 hours for 60 days after exposure. For immunocompetent, nonpregnant persons who received the anthrax vaccine, may decrease duration to 42 days after first antibiotic dose or 2 weeks after the last vaccine dose, whichever occurs later.
Children and Adolescents weighing 40 kg or more: 2,000 mg amoxicillin with 125 mg clavulanate PO every 12 hours for 60 days after exposure.
Oral dosage (ES-600; suspension containing 600 mg amoxicillin and 42.9 mg clavulanate per 5 mL):
Infants, Children, and Adolescents weighing less than 40 kg: 45 mg/kg/dose amoxicillin component PO every 12 hours for 60 days after exposure.
Maximum Dosage Limits:
-Adults
regular tablets, chewable tablets, or suspension: up to 1750 mg/day amoxicillin component PO; XR tablets: 4000 mg/day amoxicillin component PO depending on formulation.
-Geriatric
regular tablets, chewable tablets, or suspension: up to 1750 mg/day amoxicillin component PO; XR tablets: 4000 mg/day amoxicillin component PO depending on formulation.
-Adolescents
40 kg or more: regular tablets, chewable tablets, or suspension: up to 1750 mg/day amoxicillin component PO depending on formulation; XR tablets: 4000 mg/day amoxicillin component PO; ES-600 suspension: safety and efficacy have not been established; however, 90 mg/kg/day amoxicillin component PO (Max: 4000 mg/day amoxicillin component) is used off-label.
less than 40 kg: 90 mg/kg/day amoxicillin component PO using ES-600 suspension; 40 to 45 mg/kg/day amoxicillin component PO for regular suspension and chewable tablets depending on formulation for most indications.
-Children
40 kg or more: regular tablets, chewable tablets, or suspension: up to 1750 mg/day amoxicillin component PO depending on formulation; XR tablets: 4000 mg/day amoxicillin component PO; ES-600 suspension: safety and efficacy have not been established; however, 90 mg/kg/day amoxicillin component PO (Max: 4000 mg/day amoxicillin component) is used off-label.
less than 40 kg: 90 mg/kg/day amoxicillin component PO using ES-600 suspension; 40 to 45 mg/kg/day amoxicillin component PO for regular suspension and chewable tablets depending on formulation for most indications.
-Infants
3 months and older: 90 mg/kg/day amoxicillin component PO using ES-600 suspension; 40 to 45 mg/kg/day amoxicillin component PO for regular suspension depending on formulation for most indications.
younger than 3 months: 30 mg/kg/day amoxicillin component PO.
-Neonates
30 mg/kg/day amoxicillin component PO.
Patients with Hepatic Impairment Dosing
Dose amoxicillin; clavulanic acid with caution in those patients with pre-existing hepatic disease and monitor liver function during therapy. No specific dosage adjustment recommendations are available. The amoxicillin component is not appreciably metabolized in the liver and does not undergo biliary secretion.
Patients with Renal Impairment Dosing
NOTE: The 875-mg tablet is not recommended in patients with renal impairment. The extended-release formulation is contraindicated in patients with a CrCl 30 mL/min or less.
Adult and Pediatric Patients Weighing More Than 40 kg
Dosage adjustments are needed for amoxicillin, but clavulanic acid pharmacokinetics are not changed by the presence of renal impairment unless CrCl is less than 10 mL/min. The manufacturer recommended dosage adjustments for adults are listed below.
CrCl 30 mL/min or more: No dosage adjustment necessary.
CrCl 10 to 30 mL/min: 250 to 500 mg PO amoxicillin component every 12 hours, depending on the severity of the infection.
CrCl less than 10 mL/min: 250 to 500 mg PO amoxicillin component every 24 hours, depending on the severity of the infection.
Pediatric Patients
The following dose adjustments are based on the usual dose in pediatric patients of 20 to 40 mg/kg/day amoxicillin component PO divided every 8 hours, 25 to 45 mg/kg/day amoxicillin component PO divided every 12 hours, or 80 to 90 mg/kg/day PO divided every 12 hours (high dose; ES-600 formulation) :
CrCl 30 mL/min/1.73 m2 or more: No dosage adjustment necessary.
CrCl 10 to 29 mL/min/1.73 m2: 8 to 20 mg/kg/dose amoxicillin component (20 mg/kg/dose for high dose) PO every 12 hours.
CrCl less than 10 mL/min/1.73 m2: 8 to 20 mg/kg/dose amoxicillin component (20 mg/kg/dose for high dose) PO every 24 hours.
Intermittent hemodialysis
For adults and children receiving the adult dosage, 250 to 500 mg PO amoxicillin component every 24 hours, depending on the severity of the infection. According to the manufacturer, a supplemental dose should be administered both during and at the end of a dialysis session. For pediatric patients, the recommended dose is 8 to 20 mg/kg/dose amoxicillin component (20 mg/kg/dose for high dose) PO every 24 hours, after dialysis.
Peritoneal dialysis
For adults and children receiving the adult dosage and receiving continuous ambulatory peritoneal dialysis (CAPD), 250 to 500 mg PO amoxicillin component every 24 hours, depending on the severity of the infection. For pediatric patients, the recommended dose is 8 to 20 mg/kg/dose amoxicillin component (20 mg/kg/dose for high dose) PO every 24 hours.
*non-FDA-approved indication
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Acetaminophen; Aspirin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Allopurinol: (Minor) Use of amoxicillin with allopurinol can increase the incidence of drug-related skin rash.
Aspirin, ASA: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Butalbital; Caffeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Caffeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Carisoprodol; Codeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Dipyridamole: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Omeprazole: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Oxycodone: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Butalbital; Aspirin; Caffeine; Codeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Caffeine; Sodium Benzoate: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Choline Salicylate; Magnesium Salicylate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as penicillins, and sulfonamides. An enhanced effect of the displaced drug may occur.
Demeclocycline: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Desogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Dichlorphenamide: (Moderate) Use dichlorphenamide and amoxicillin together with caution. Dichlorphenamide increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including amoxicillin. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Dienogest; Estradiol valerate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Digoxin: (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Doxycycline: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Drospirenone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Estetrol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Norgestimate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethacrynic Acid: (Minor) Ethacrynic acid may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
Ethinyl Estradiol; Norelgestromin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Etonogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Furosemide: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
Indomethacin: (Minor) Indomethacin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
Leuprolide; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Mafenide: (Minor) Sulfonamides may compete with amoxicillin for renal tubular secretion, increasing amoxicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Magnesium Salicylate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as penicillins, and sulfonamides. An enhanced effect of the displaced drug may occur.
Methotrexate: (Major) Avoid concomitant use of methotrexate with penicillins due to the risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions.
Minocycline: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Mycophenolate: (Moderate) Drugs that alter the gastrointestinal flora may interact with mycophenolate by disrupting enterohepatic recirculation. Amoxicillin;Clavulanic Acid may decrease normal GI flora levels and thus lead to less free mycophenolate available for absorption. The effect of amoxicillin without clavulantic acid on mycophenolate kinetics is unclear.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norgestimate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Omadacycline: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Probenecid: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Probenecid; Colchicine: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Salsalate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites or could displace other highly protein-bound drugs such as penicillins. An enhanced effect of the displaced drug may occur.
Sarecycline: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Sodium Benzoate; Sodium Phenylacetate: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
Sulfadiazine: (Minor) Sulfonamides may compete with amoxicillin for renal tubular secretion, increasing amoxicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Minor) Sulfonamides may compete with amoxicillin for renal tubular secretion, increasing amoxicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Sulfasalazine: (Minor) Sulfonamides may compete with amoxicillin for renal tubular secretion, increasing amoxicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Sulfonamides: (Minor) Sulfonamides may compete with amoxicillin for renal tubular secretion, increasing amoxicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Tetracycline: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Tetracyclines: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Typhoid Vaccine: (Major) Antibiotics which possess bacterial activity against salmonella typhi organisms may interfere with the immunological response to the live typhoid vaccine. Allow 24 hours or more to elapse between the administration of the last dose of the antibiotic and the live typhoid vaccine.
Warfarin: (Moderate) The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary.
Amoxicillin is a semisynthetic antibacterial agent. 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. PBPs 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. PBPs 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.
Clavulanic acid is a beta-lactam drug that acts as a competitive inhibitor of bacterial beta-lactamases. This protects amoxicillin from degradation and effectively extends the antibacterial spectrum of amoxicillin. It binds to the enzyme's active site, preventing the beta-lactamase from inactivating the beta-lactam antibiotic; clavulanic acid is also inactivated by this process, earning it the title "suicide" inhibitor. Clavulanic acid can bind with many plasmid- and chromosomally mediated bacterial beta-lactamases. Penetration of the cell wall allows clavulanic acid to bind both bound and extracellular beta-lactamases. Clavulanic acid does not alter the actions of the beta-lactam antibiotics.
Beta-lactams exhibit concentration-independent or time-dependent killing. In vitro and in vivo animal studies have demonstrated that the major pharmacodynamic parameter that determines efficacy for beta-lactams is the amount of time free (non-protein bound) drug concentrations exceed the minimum inhibitory concentration (MIC) of the organism (free T above MIC). This microbiological killing pattern is due to the mechanism of action, which is acylation of PBPs. There is a maximum proportion of PBPs that can be acylated; therefore, once maximum acylation has occurred, killing rates cannot increase. Free beta-lactam concentrations do not have to remain above the MIC for the entire dosing interval. The percentage of time required for both bacteriostatic and maximal bactericidal activity is different for the various classes of beta-lactams. Penicillins require free drug concentrations to exceed the MIC for 30% of the dosing interval to achieve bacteriostatic activity and 50% of the dosing interval to achieve bactericidal activity.
The susceptibility interpretive criteria for amoxicillin; clavulanic acid are delineated by pathogen. The MICs are defined for Enterobacterales, B. pseudomallei, and Vibrio sp. (excluding V. chlolerae) as susceptible at 8/4 mcg/mL or less, intermediate at 16/8 mcg/mL, and resistant at 32/16 mcg/mL or more. The MICs are defined for S. pneumoniae (excluding meningitis) as susceptible at 2/1 mcg/mL or less, intermediate a 4/2 mcg/mL, and resistant at 8/4 mcg/mL or more. The Clinical and Laboratory Standards Institute (CLSI) and the FDA differ on MIC interpretation for H. influenzae. The MICs are defined for H. influenzae by the FDA as susceptible at 4/2 mcg/mL or less and resistant at 8/4 mcg/mL or more; however, the MICs are defined for H. influenzae and H. parainfluenzae by the CLSI as susceptible at 2/1 mcg/mL or less, intermediate at 4/2 mcg/mL, and resistant at 8/4 mcg/mL or more. The MICs are defined for Aggregatibacter sp., Cardiobacterium sp., E. corrodens, Kingella sp., and M. catarrhalis as susceptible at 4/2 mcg/mL or less and resistant at 8/4 mcg/mL or more. The MICs are defined for anaerobes as susceptible at 4/2 mcg/mL or less, intermediate at 8/4 mcg/mL, and resistant at 16/8 mcg/mL or more. The MICs are defined for Pasteurella sp. as susceptible at 0.5/0.25 mcg/mL or less. The breakpoints are based on a dosage of 875 mg amoxicillin with 125 mg clavulanic acid administered every 12 hours or 500 mg amoxicillin with 125 mg clavulanic acid administered every 8 hours when used for treatment of uncomplicated urinary tract infections (UTIs) due to Enterobacterales, completion of therapy for Enterobacterales systemic infections, and for the treatment of S. pneumoniae, H. influenzae, and H. parainfluenzae. Enterococci susceptible to penicillin are predictably susceptible to amoxicillin; clavulanic acid for non-beta-lactamase producing enterococci. Beta-hemolytic streptococci can be considered susceptible to amoxicillin; clavulanic acid. Considering site of infection and appropriate amoxicillin; clavulanic acid dosing, oxacillin-susceptible Staphylococcus sp. can be considered susceptible to amoxicillin; clavulanic acid.
Amoxicillin; clavulanic acid (clavulanate) is administered orally as tablets, chewable tablets, extended-release tablets, and oral suspension. Protein-binding is approximately 18% for amoxicillin and 25% for clavulanic acid. Amoxicillin and clavulanic acid are distributed into many tissues and body fluids including the liver, gallbladder, prostate, lungs, urine, middle ear effusions, bronchial secretions, maxillary sinus secretions, and synovial, pleural, and peritoneal fluids. Minimal levels are attained within the CSF when meninges are not inflamed; these levels are increased with inflammation. The drugs cross the placenta. Approximately 10% of an amoxicillin dose is metabolized to inactive derivatives; most (50 to 80%) of the drug is eliminated unchanged. Amoxicillin and its metabolites are primarily excreted into the urine primarily via tubular secretion and glomerular filtration. Clearance of clavulanic acid has both a renal (25 to 50%) and a non-renal component. Clavulanic acid appears to be extensively metabolized, although the exact mechanism is not fully established. A small percentage of amoxicillin; clavulanic acid is excreted in breast milk. In patients with normal renal function, the elimination half-lives of amoxicillin and clavulanic acid are roughly 1.3 hours and 1 hour, respectively.
Affected cytochrome P450 isoenzymes: none.
-Route-Specific Pharmacokinetics
Oral Route
Both amoxicillin and clavulanic acid are stable against gastric acid and are well absorbed from the GI tract. Approximately 74 to 92% of a dose of amoxicillin is absorbed. Peak serum levels of both amoxicillin and clavulanic acid occur within 1 to 2.5 hours following an oral dose of either chewable or immediate release tablets or oral suspension. Amoxicillin systemic exposure achieved with extended-release tablets is similar to that produced by the oral administration of equivalent doses of amoxicillin alone. Dosing in the fasted or fed state has minimal effect on the pharmacokinetics of amoxicillin; however, absorption of amoxicillin and clavulanate potassium is greater when the drugs are taken with food relative to the fasted state. High-fat meals decrease the absorption of clavulanic acid. In general, all dosage forms are recommended to be taken at the start of a standard meal.
-Special Populations
Renal Impairment
For amoxicillin; clavulanic acid, the elimination half-lives of both amoxicillin and clavulanic acid increase as renal function declines, up to 7.5 hours for amoxicillin and 4.5 hours for clavulanic acid in patients with end-stage renal disease. Dosages and/or dosage intervals need to be adjusted accordingly.
Pediatrics
Infants, Children, and Adolescents
The elimination half-lives for amoxicillin and clavulanic acid are approximately 1 to 1.5 hours and 1 hour, respectively, in children. This is similar to what has been observed in adults. After administration of a 45/3.2 mg/kg dose of amoxicillin; clavulanic acid in fasting children, mean middle ear fluid (MEF) concentrations of amoxicillin at 2 hours were 3.3 mcg/mL; corresponding plasma concentrations were 15.7 mcg/mL. MEF concentrations of amoxicillin at 1 to 3 hours post-dose were > 1 mcg/mL in 18 specimens (90%) and > 4 mcg/mL in 8 specimens (40%), the amoxicillin MIC90 values for penicillin-intermediate and -resistant strains, respectively.
Neonates
Pharmacokinetic data for amoxicillin; clavulanic acid are unavailable in neonates. Due to the immature renal function in neonates, it is expected that the clearance of amoxicillin; clavulanic acid is prolonged. A dosing interval of every 12 hours is recommended in neonates.