AMOXICILLIN

Amoxicillin is an oral semisynthetic aminopenicillin similar to ampicillin. The aminopenicillins are not stable to beta-lactamases of either gram-positive or gram-negative bacteria. Amoxicillin is more stable to gastric acid than is penicillin and more bioavailable than oral ampicillin. Because of greater bioavailability, amoxicillin is associated with a lower incidence of diarrhea versus orally-administered ampicillin. Like ampicillin, amoxicillin has a broader spectrum of activity than penicillin, although the carboxy- and ureidopenicillins are much more active against gram-negative rods. Amoxicillin is commonly used to treat infections such as otitis media, pneumonia, sinusitis, and skin infections caused by susceptible organisms. To increase the efficacy of amoxicillin against penicillin-resistant S. pneumoniae in otitis or respiratory infections, higher dosage regimens have been recommended. Amoxicillin is routinely used for endocarditis prophylaxis and is also used in various regimens for the treatment of Helicobacter pylori infection.

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

Route-Specific Administration

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

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

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

Amoxicillin may cause severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and Systemic Symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). Monitor persons who develop skin rash closely and discontinue amoxicillin if lesions progress. Other hypersensitivity and dermatologic reactions reported with amoxicillin include anaphylactic/anaphylactoid reactions (including anaphylactic shock), angioedema, serum sickness-like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, and frequently fever), hypersensitivity vasculitis, erythema multiforme, hypersensitivity vasculitis, rash, pruritus, urticaria, and exfoliative dermatitis. If a hypersensitivity reaction occurs, discontinue amoxicillin and institute appropriate therapy.

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

Nausea, vomiting, and diarrhea have been reported with penicillins, such as amoxicillin. In a tonsillitis and pharyngitis study, 302 adults and pediatrics (12 years or older) were treated with the extended release oral tablet. Reports of diarrhea (1.7%), nausea (1.3%), vomiting (0.7%), and abdominal pain (0.3%) were all similar to those reported with the comparator drug. Additionally, in clinical trials using combination therapy of amoxicillin plus lansoprazole, diarrhea was reported in 8% of patients. In trials with the combination of amoxicillin, lansoprazole, and clarithromycin, diarrhea was reported in 7% of patients and taste perversion (e.g., dysgeusia) was reported in 5% of patients. Tongue discoloration (black hairy tongue) has also been reported with amoxicillin. Amoxicillin has rarely been reported to cause esophagitis in some patients. Amoxicillin may be irritating to the esophagus if transit of an oral solid dosage form through the esophagus is delayed. Odynophagia, mid-chest pain, and dysphagia may be symptoms of esophagitis.

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

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

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

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

Crystalluria has been reported with amoxicillin therapy.

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

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

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

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

Based on manufacturer data, geriatric patients (above 65 years) do not respond differently to amoxicillin treatment than younger patients. However, a greater sensitivity to amoxicillin in elderly patients could not be ruled out. Amoxicillin is known to be substantially excreted via the kidney. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection for elderly patients; renal function monitoring may be useful. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.

Available data from amoxicillin use during human pregnancy have not established drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes. No adverse developmental effects were observed in animal reproduction studies with administration of amoxicillin to pregnant mice and rats at doses up to 12.5 and 25 times the recommended human dose.

Amoxicillin 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. Small studies assessing adverse events in breastfed infants exposed to antibiotics have found adverse event rates of 7.5% to 8.3% after exposure to amoxicillin. The adverse events reported included diarrhea, rash, and somnolence. There are no data on the effects of amoxicillin on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for amoxicillin and any potential adverse effects on the breast-fed child from amoxicillin or from the underlying maternal condition.

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

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

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

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

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

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

For the treatment of group A beta-hemolytic streptococcal (GAS) pharyngitis (primary rheumatic fever prophylaxis) and tonsillitis:
Oral dosage (immediate-release):
Adults: 1,000 mg PO once daily or 500 mg PO every 12 hours for 10 days. The FDA-approved dosage is 250 mg PO every 8 hours or 500 mg PO every 12 hours for mild to moderate infections and 500 mg PO every 8 hours or 875 mg PO every 12 hours for severe infections.
Infants, Children, and Adolescents 4 months to 17 years: 50 mg/kg/dose (Max: 1,000 mg/dose) PO once daily or 25 mg/kg/dose (Max: 500 mg/dose) PO every 12 hours for 10 days. The FDA-approved dosage is 20 mg/kg/day (Max: 750 mg/day) PO divided every 8 hours or 25 mg/kg/day (Max: 1,000 mg/day) PO divided every 12 hours for mild to moderate infections and 40 mg/kg/day (Max: 1,500 mg/day) PO divided every 8 hours or 45 mg/kg/day (Max: 1,750 mg/day) PO divided every 12 hours for severe infections.
Infants 1 to 3 months: 50 mg/kg/dose PO once daily or 25 mg/kg/dose PO every 12 hours for 10 days. The FDA-approved dosage is 30 mg/kg/day PO divided every 12 hours.
Neonates: 50 mg/kg/dose PO once daily or 25 mg/kg/dose PO every 12 hours for 10 days. The FDA-approved dosage is 30 mg/kg/day PO divided every 12 hours.
Oral dosage (extended-release):
Adults: 775 mg PO once daily for 10 days.
Children and Adolescents 12 to 17 years: 775 mg PO once daily for 10 days.

For the treatment of acute otitis media:
NOTE: Guidelines do not recommend doses less than 80 mg/kg/day PO for the treatment of otitis media. Re-evaluate patients failing to respond within 48 to 72 hours. Amoxicillin; clavulanate is the preferred therapy for children who have received amoxicillin within the past 30 days, who have purulent conjunctivitis, or who have a history of recurrent acute otitis media unresponsive to amoxicillin.
Oral dosage (immediate-release):
Adults: 500 mg PO every 12 hours or 250 mg PO every 8 hours for mild to moderate disease and 875 mg PO every 12 hours or 500 mg PO every 8 hours for severe disease.
Children and Adolescents 6 to 17 years: 80 to 90 mg/kg/day (Usual Max: 4 g/day) PO divided every 12 hours for 5 to 7 days for mild to moderate disease and for 10 days for severe disease as first-line therapy. The FDA-approved dosage is 20 mg/kg/day (Max: 750 mg/day) PO every 8 hours or 25 mg/kg/day (Max: 1,000 mg/day) PO divided every 12 hours for mild to moderate infections and 40 mg/kg/day (Max: 1,500 mg/day) PO divided every 8 hours or 45 mg/kg/day (Max: 1,750 mg/day) PO divided every 12 hours for severe infections.
Children 2 to 5 years: 80 to 90 mg/kg/day PO divided every 12 hours for 7 days for mild to moderate disease and 10 days for severe disease as first-line therapy. The FDA-approved dosage is 20 mg/kg/day (Max: 750 mg/day) PO every 8 hours or 25 mg/kg/day (Max: 1,000 mg/day) PO divided every 12 hours for mild to moderate infections and 40 mg/kg/day (Max: 1,500 mg/day) PO divided every 8 hours or 45 mg/kg/day (Max: 1,750 mg/day) PO divided every 12 hours for severe infections.
Infants and Children 6 to 23 months: 80 to 90 mg/kg/day PO divided every 12 hours for 10 days as first-line therapy. The FDA-approved dosage is 20 mg/kg/day PO every 8 hours or 25 mg/kg/day PO divided every 12 hours for mild to moderate infections and 40 mg/kg/day PO divided every 8 hours or 45 mg/kg/day PO divided every 12 hours for severe infections.
Infants 4 to 5 months: 80 to 90 mg/kg/day PO divided every 12 hours for 10 days. The FDA-approved dosage is 20 mg/kg/day PO every 8 hours or 25 mg/kg/day PO divided every 12 hours for mild to moderate infections and 40 mg/kg/day PO divided every 8 hours or 45 mg/kg/day PO divided every 12 hours for severe infections.
Infants 1 to 3 months: 30 mg/kg/day PO divided every 12 hours.

For the treatment of skin and skin structure infections, including cellulitis, erysipelas, and erysipeloid:
-for the treatment of mild to moderate, nonpurulent skin infections, such as cellulitis and erysipelas:
Oral dosage (immediate-release):
Adults: 250 mg PO every 8 hours or 500 mg PO every 12 hours for 5 to 14 days.
Infants, Children, and Adolescents 4 months to 17 years: 20 mg/kg/day (Max: 750 mg/day) PO divided every 8 hours or 25 mg/kg/day (Max: 1,000 mg/day) PO divided every 12 hours for 5 to 14 days.
Infants 1 to 3 months: 30 mg/kg/day PO divided every 12 hours for 5 to 14 days.
Neonates: 30 mg/kg/day PO divided every 12 hours for 5 to 14 days.
-for the treatment of severe, nonpurulent skin infections, such as cellulitis and erysipelas:
Oral dosage (immediate-release):
Adults: 500 mg PO every 8 hours or 875 mg PO every 12 hours for 5 to 14 days.
Infants, Children, and Adolescents 4 months to 17 years: 40 mg/kg/day (Max: 1,500 mg/day) PO divided every 8 hours or 45 mg/kg/day (Max: 1,750 mg/day) PO divided every 12 hours for 5 to 14 days.
Infants 1 to 3 months: 30 mg/kg/day PO divided every 12 hours for 5 to 14 days.
Neonates: 30 mg/kg/day PO divided every 12 hours for 5 to 14 days.
-for the treatment of erysipeloid:
Oral dosage (immediate-release):
Adults: 500 mg PO every 8 hours for 7 to 10 days.

For the treatment of lower respiratory tract infections (LRTIs), including community-acquired pneumonia (CAP):
-for the treatment of nonspecific lower respiratory tract infections (LRTIs):
Oral dosage (immediate-release):
Adults: 875 mg PO every 12 hours or 500 mg PO every 8 hours.
Infants, Children, and Adolescents 4 months to 17 years: 45 mg/kg/day (Max: 1,750 mg/day) PO divided every 12 hours or 40 mg/kg/day (Max: 1,500 mg/day) PO divided every 8 hours.
Infants 1 to 3 months: 30 mg/kg/day PO divided every 12 hours.
Neonates: 30 mg/kg/day PO divided every 12 hours.
-for the empiric treatment of community-acquired pneumonia (CAP):
Oral dosage (immediate-release):
Adults: 1 g PO every 8 hours for at least 5 days as monotherapy for outpatients without comorbidities or risk factors for MRSA or P. aeruginosa or as part of combination therapy for persons living with HIV. Guide treatment duration by clinical stability.
Adolescents: 90 mg/kg/day (Max: 4 g/day) PO in divided doses every 12 hours for 5 to 7 days. Consider the addition of a macrolide for patients who do not have clinical, laboratory, or radiologic evidence to distinguish bacterial CAP from atypical CAP. In persons living with HIV, amoxicillin is recommended as part of combination therapy for outpatients.
Infants and Children 4 months to 12 years: 90 mg/kg/day (Max: 4 g/day) PO in divided doses every 12 hours for 5 to 7 days. Consider the addition of a macrolide for patients 5 years and older who do not have clinical, laboratory, or radiologic evidence to distinguish bacterial CAP from atypical CAP.
-for the treatment of CAP in pediatric patients due to S. pneumoniae, mild infection or step-down therapy (penicillin MIC 2 mcg/mL or less):
Oral dosage (immediate-release):
Infants, Children, and Adolescents 4 months to 17 years: 90 mg/kg/day (Max: 4 g/day) in divided doses every 12 hours or 45 mg/kg/day (Max: 4 g/day) in divided doses every 8 hours for 5 to 7 days.
-for the treatment of CAP in pediatric patients due to S. pneumoniae, relatively resistant (penicillin MIC = 2 mcg/mL):
Oral dosage (immediate-release):
Infants, Children, and Adolescents 4 months to 17 years: 90 mg/kg/day (Max: 4 g/day) PO in divided doses every 8 hours for 5 to 7 days. Dividing 90 mg/kg/day into 3 doses/day vs. 2 doses/day increases the probability of reaching a clinical and microbiological cure to 90% compared to 65%, respectively, in patients with pneumococcal pneumonia (MIC = 2 mcg/mL).
-for the treatment of CAP in pediatric patients due to Group A Streptococcus, mild infection or step-down therapy:
Oral dosage (immediate-release):
Infants, Children, and Adolescents 4 months to 17 years: 50 to 75 mg/kg/day (Max: 4 g/day) PO in divided doses every 12 hours for 5 to 7 days.
-for the treatment of CAP in pediatric patients due to H. influenzae (beta-lactamase negative), mild infection or step-down therapy:
Oral dosage (immediate-release):
Infants, Children, and Adolescents 4 months to 17 years: 75 to 100 mg/kg/day (Max: 4 g/day) in divided doses every 8 hours for 5 to 7 days.

For the treatment of urinary tract infection (UTI), including cystitis:
-for the treatment of mild to moderate nonspecific urinary tract infections:
Oral dosage (immediate-release):
Adults: 500 mg PO every 12 hours or 250 mg PO every 8 hours. Guidelines recommend against empiric use due to resistance.
Infants, Children, and Adolescents 4 months to 17 years: 20 mg/kg/day (Max: 750 mg/day) PO divided every 8 hours or 25 mg/kg/day (Max: 1,000 mg/day) PO divided every 12 hours.
Infants 1 to 3 months: 30 mg/kg/day PO divided every 12 hours.
Neonates: 30 mg/kg/day PO divided every 12 hours.
-for the treatment severe nonspecific urinary tract infections or infections due less susceptible organisms:
Oral dosage (immediate-release):
Adults: 875 mg PO every 12 hours or 500 mg PO every 8 hours. Guidelines recommend against empiric use due to resistance.
Infants, Children, and Adolescents 4 months to 17 years: 40 mg/kg/day (Max: 1,500 mg/day) PO divided every 8 hours or 45 mg/kg/day (Max: 1,750 mg/day) PO divided every 12 hours.
Infants 1 to 3 months: 30 mg/kg/day PO divided every 12 hours.
Neonates: 30 mg/kg/day PO divided every 12 hours.
-for the treatment of acute uncomplicated cystitis in pregnant persons:
Oral dosage (immediate-release):
Pregnant Persons: 500 mg PO every 8 hours for 7 days.
-for the treatment of acute uncomplicated lower urinary tract infection in pediatric patients:
Oral dosage (immediate-release):
Infants, Children, and Adolescents 4 months to 17 years: 40 mg/kg/day (Max: 1,500 mg/day) PO divided every 8 hours for 3 days.
Infants 1 to 3 months: 40 mg/kg/day PO divided every 8 hours for 3 days.

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

For the treatment of pregnant women with chlamydia infection*:
Oral dosage:
Adults: 500 mg PO three times daily for 7 days as an alternative.
Adolescents: 500 mg PO three times daily for 7 days as an alternative.

For the treatment of dental infection*, including dentoalveolar infection*:
-for adolescent aggressive periodontitis* or adult refractory chronic periodontitis* in combination with metronidazole after scaling and root planing:
Oral dosage:
Adults and Adolescents >= 16 years: Amoxicillin 250-375 mg PO three times daily with metronidazole (250 mg PO three times daily) for 7-10 days.
-for acute dental abscess (apical)* and/or dental abscess (periapical)* in combination with surgical incision and drainage:
Oral dosage:
Adults: 1 g PO as a loading dose followed by 500 mg PO three times daily for 3 days.

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

For the treatment of fully sensitive uncomplicated typhoid fever*:
Oral dosage (immediate-release):
Adults: 50 to 100 mg/kg/day PO divided every 6 to 8 hours for 14 days as an alternative. Usual dose: 1 g PO 3 times daily.
Infants, Children, and Adolescents: 50 to 100 mg/kg/day (Max: 3 g/day) PO divided every 6 to 8 hours for 14 days as an alternative.

For Helicobacter pylori (H. pylori) eradication* in the treatment of patients with duodenal ulcer disease (active or a history of duodenal ulcer), gastric ulcer*, dyspepsia*, or gastric mucosa associated lymphoid tissue (MALT) lymphoma*:
NOTE: The American College of Gastroenterology (ACG) recommends 10 to 14 days of a triple-drug regimen containing a proton pump inhibitor (PPI), clarithromycin, and either amoxicillin or metronidazole. Although 10 to 14 days is recommended, ACG also indicates that giving therapy for 2 weeks may be preferred; a meta-analysis of more than 900 patients found that, as compared to a 7-day regimen, the rate of H. pylori eradication was significantly higher in patients taking triple therapy for 14 days (odds ratio 0.62, 95% CI 0.45 to 0.84). Although not significant, there was a trend towards improved eradication rates with 10 days of therapy vs. 7 days of therapy. The same combination for 14 days continues to be recommended as first line therapy in the 2006 global updates from the Maastricht III Consensus Report.
NOTE: Resistance rates of H. pylori to metronidazole in the US are 25%; whereas amoxicillin resistance is rare. Resistance rates for H. pylori to clarithromycin in the US are 13%.
NOTE: In populations where H. pylori infection is common (10% or more), patients presenting with non-ulcer dyspepsia should be tested for H. pylori; those found to be H. pylori positive should be started on combination eradication therapy (also see Prevpac monograph)
NOTE: A large body of data exist to support the importance of H. pylori eradication as the first line treatment of gastric MALT lymphoma. Following H. pylori eradication, long term tumor regression is observed in 60% to 90% of patients.
-in combination with clarithromycin and lansoprazole in adults:
Oral dosage (immediate-release):
Adults: 1,000 mg PO twice daily in combination with clarithromycin (500 mg PO twice daily) and lansoprazole (30 mg PO twice daily) for 10 to 14 days is recommended. Clarithromycin-containing regimens are associated with a high eradication rate and less side effects than regimens that include metronidazole.
-in combination with clarithromycin and omeprazole in adults:
Oral dosage (immediate-release):
Adults: 1,000 mg PO twice daily with clarithromycin (500 mg PO twice daily) and omeprazole (20 mg twice daily) for 10 to 14 days. For patients with an active ulcer, an additional 14 days of omeprazole (20 mg once daily) is recommended for ulcer healing. According to ACG, any standard dose PPI may be substituted for omeprazole in this regimen.
-in combination with metronidazole and omeprazole in adults:
Oral dosage (immediate-release):
Adults: 1,000 mg PO twice daily with metronidazole (500 mg PO twice daily) and omeprazole (20 mg twice daily) for 10 to 14 days. For patients with an active ulcer, an additional 14 days of omeprazole (20 mg once daily) is recommended for ulcer healing. According to ACG, any standard dose PPI may be substituted for omeprazole in this regimen.
-in combination with levofloxacin and rabeprazole in adults:
NOTE: For patients unable to reach the acceptable 80% or more eradication rate with conventional therapy, a combination including levofloxacin is recommended as a third choice therapy. Selection of this type of rescue therapy should be based on antimicrobial susceptibility testing.
Oral dosage (immediate-release):
Adults: A prospective, open label study evaluated the effectiveness of levofloxacin-based dual (levofloxacin/rabeprazole) and triple (levofloxacin/amoxicillin/rabeprazole) therapy in eradicating H. pylori. Patients (n = 160) were randomized into 4 groups (3 dual and 1 triple therapy regimen). The dual regimens consisted of levofloxacin 500 mg PO once daily with rabeprazole (20 mg PO once daily) for 5, 7, or 10 days. The triple regimen included amoxicillin 1,000 mg PO twice daily, levofloxacin (500 mg once daily), and rabeprazole (20 mg once daily) for 7 days. Triple therapy resulted in a significantly higher eradication rate (more than 90%) than dual therapy at any duration (70% or less).
-in combination with lansoprazole in adults:
Oral dosage (immediate-release):
Adults: More effective triple drug regimens are available and recommended. The original FDA-approved dual regimen consists of amoxicillin 1,000 mg PO and lansoprazole (30 mg PO), each given three times daily for 14 days. Clinical trials showed eradication rates of about 70%, which is substantially lower than that achieved with triple-drug therapy regimens; triple-drug therapy was shown to be more effective than all possible dual therapy combinations.
-in combination with metronidazole and a proton pump inhibitor (PPI) in pediatric patients:
Oral dosage (immediate-release):
Children and Adolescents: 25 mg/kg/dose PO twice daily (Max: 1 g/dose) with metronidazole (10 mg/kg/dose PO twice daily [Max: 500 mg/dose]) and a proton pump inhibitor (PPI; 1 to 2 mg/kg/day PO divided every 12 hours [Max: 20 mg/dose]) for 1 to 2 weeks.
-in combination with clarithromycin and a proton pump inhibitor (PPI) in pediatric patients:
Oral dosage (immediate-release):
Children and Adolescents: 25 mg/kg/dose PO twice daily (Max: 1 g/dose) with clarithromycin (10 mg/kg/dose PO twice daily [Max: 500 mg/dose]) and a proton pump inhibitor (PPI; 1 to 2 mg/kg/day PO divided every 12 hours [Max: 20 mg/dose]) for 1 to 2 weeks.
-as part of a sequential therapy regimen in pediatric patients:
Oral dosage (immediate-release):
Children and Adolescents: 25 mg/kg/dose PO twice daily (Max: 1 g/dose) with a proton pump inhibitor (PPI; 1 to 2 mg/kg/day PO divided every 12 hours [Max: 20 mg/dose]) for 5 days, followed-up by a PPI plus clarithromycin (10 mg/kg/dose PO twice daily [Max: 500 mg/dose]) and metronidazole (10 mg/kg/dose PO twice daily [Max: 500 mg/dose]) for 5 days.

For treatment of cutaneous anthrax* infection due to exposure to Bacillus anthracis or as oral follow-up therapy for severe anthrax:
Oral dosage:
Adults: 1 g PO every 8 hours as an alternative for penicillin-susceptible strains for patients who cannot take first-line agents (i.e., ciprofloxacin, doxycycline) or if first-line agents are unavailable. Treat for 7 to 10 days for naturally acquired infection. For a bioterrorism-related event, treat for a total duration of 60 days. Following initial treatment for severe anthrax infection, amoxicillin as a single agent may also be used as follow-up treatment.
Neonates, Infants, Children, and Adolescents: 75 mg/kg/day PO divided every 8 hours (Max: 1 g/dose) as an alternative for penicillin-susceptible strains. Treat for 7 to 10 days for naturally acquired infection. For a bioterrorism-related event, continue treatment for 60 days. As oral follow-up combination therapy after initial IV therapy for severe anthrax (non-CNS infection), use amoxicillin in combination with a protein synthesis inhibitor (i.e., clindamycin, doxycycline, linezolid). Continue therapy to complete a treatment course of at least 14 days; additional prophylaxis to complete an antimicrobial course of up to 60 days may be required.
Premature neonates 32 to 37 weeks gestational age and older than 7 days: 75 mg/kg/day PO divided every 8 hours as an alternative for penicillin-susceptible strains. Treat for 7 to 10 days for naturally acquired infection. For a bioterrorism-related event, continue treatment for 60 days. As oral follow-up combination therapy after initial IV therapy for severe anthrax (non-CNS infection), use amoxicillin in combination with a protein synthesis inhibitor (i.e., clindamycin, linezolid). Continue therapy to complete a treatment course of at least 14 days; additional prophylaxis to complete an antimicrobial course of up to 60 days may be required.
Premature neonates 32 to 37 weeks gestational age and 7 days or younger: 50 mg/kg/day PO divided every 12 hours as an alternative for penicillin-susceptible strains. Treat for 7 to 10 days for naturally acquired infection. For a bioterrorism-related event, continue treatment for 60 days. As oral follow-up combination therapy after initial IV therapy for severe anthrax (non-CNS infection), use amoxicillin in combination with a protein synthesis inhibitor (i.e., clindamycin, linezolid). Continue therapy to complete a treatment course of at least 14 days; additional prophylaxis to complete an antimicrobial course of up to 60 days may be required.

For anthrax prophylaxis* after exposure to Bacillus anthracis:
Oral dosage (immediate-release):
Adults: 1 g PO every 8 hours for 60 days after exposure as an alternative for penicillin-susceptible strains for patients who cannot take first-line agents (i.e., fluoroquinolones, doxycycline) or if first-line agents are unavailable.
Infants, Children, and Adolescents: 75 mg/kg/day (Max: 3 g/day) PO divided every 8 hours for 60 days after exposure for penicillin-susceptible strains.
Neonates: 75 mg/kg/day PO divided every 8 hours for 60 days after exposure for penicillin-susceptible strains.
Premature neonates 32 to 37 weeks gestation and older than 7 days: 75 mg/kg/day PO divided every 8 hours for 60 days after exposure for penicillin-susceptible strains.
Premature neonates 32 to 37 weeks gestation and 0 to 7 days: 50 mg/kg/day PO divided every 12 hours for 60 days after exposure for penicillin-susceptible strains.

For the prolongation of latency and reduction of maternal and neonatal infections and neonatal morbidity in patients with preterm premature rupture of membranes* (PROM):
Oral dosage:
Pregnant Females: 250 mg PO every 8 hours in combination with oral erythromycin for 5 days, following 48 hours of IV therapy. A 7-day course of therapy with broad-spectrum antibiotics is recommended for pregnant women with preterm PROM who are less than 34 0/7 weeks gestation. Administration of broad-spectrum antibiotics has been shown to prolong pregnancy, reduce maternal and neonatal infections, and reduce gestational age-dependent morbidity. Women with preterm PROM who are candidates for group B streptococcal (GBS) intrapartum prophylaxis should receive GBS prophylaxis to prevent vertical transmission regardless of earlier treatments.

For chronic typhoid carriage eradication*:
Oral dosage (immediate-release):
Adults: 100 mg/kg/day PO divided every 6 to 8 hours plus probenecid for 4 to 6 weeks. Usual dose: 2 g PO 3 times daily.
Infants, Children, and Adolescents: 75 to 100 mg/kg/day (Max: 6 g/day) PO divided every 6 to 8 hours plus probenecid for 4 to 6 weeks.

For the treatment of peritoneal dialysis catheter-related infection*:
Oral dosage (immediate-release):
Adults: 250 to 500 mg PO every 12 hours for at least 14 days to 21 days.
Infants, Children, and Adolescents: 10 to 20 mg/kg/dose (Max: 1,000 mg/dose) PO every 24 hours for at least 14 to 28 days.

For the treatment of bartonellosis*, including uncomplicated Oroya fever*:
Oral dosage (immediate-release):
Pregnant or Breast-feeding Persons: 1 g PO every 8 hours for 14 days as second-line therapy.

For the treatment of acute bacterial sinusitis:
Oral dosage (immediate-release, standard dose therapy):
Adults: 500 mg PO every 8 hours or 875 mg PO every 12 hours for 5 to 10 days as first-line therapy. The FDA-approved dosage is 250 mg PO every 8 hours or 500 mg PO every 12 hours for mild to moderate infections and 500 mg PO every 8 hours or 875 mg PO every 12 hours for severe infections.
Children and Adolescents 2 to 17 years: 45 mg/kg/day (Max: 1,750 mg/day) PO divided every 12 hours for 10 to 14 days for mild to moderate uncomplicated disease in children who do not attend daycare and who have not been treated with an antimicrobial agent in the previous 4 weeks. The FDA-approved dosage is 20 mg/kg/day (Max: 750 mg/day) PO divided every 8 hours or 25 mg/kg/day (Max: 1,000 mg/day) PO divided every 12 hours for mild to moderate infections and 40 mg/kg/day (Max: 1,500 mg/day) PO divided every 8 hours or 45 mg/kg/day (Max: 1,750 mg/day) PO divided every 12 hours for severe infections. Due to the high rates of H. influenzae and beta-lactamase-producing pathogens among upper respiratory tract infections in children, amoxicillin; clavulanic acid (and not amoxicillin alone) is recommended as first-line empiric therapy for acute bacterial sinusitis. However, amoxicillin is an option for children 2 years and older with uncomplicated disease in which antimicrobial resistance is not suspected. Children with moderate to severe disease, attending daycare, or who have recently been treated with antimicrobial therapy should receive high-dose amoxicillin; clavulanic acid.
Infants and Children 4 months to 1 year: Not recommended by guidelines. The FDA-approved dosage is 20 mg/kg/day PO divided every 8 hours or 25 mg/kg/day PO divided every 12 hours for mild to moderate infections and 40 mg/kg/day PO divided every 8 hours or 45 mg/kg/day PO divided every 12 hours for severe infections.
Infants 1 to 3 months: Not recommended by guidelines. The FDA-approved dosage is 30 mg/kg/day PO divided every 12 hours.
Neonates: Not recommended by guidelines. The FDA-approved dosage is 30 mg/kg/day PO divided every 12 hours.
Oral dosage (immediate-release, high-dose therapy*):
Adults: 2,000 mg PO every 12 hours for 5 to 10 days as first-line therapy.
Children and Adolescents 2 to 17 years: 80 to 90 mg/kg/day (Max: 4 g/day) PO divided every 12 hours for 10 to 14 days for children in areas with high rates of S. pneumoniae resistance (more than 10%, including intermediate- and high-level resistance). Due to the high rates of H. influenzae and beta-lactamase-producing pathogens among upper respiratory tract infections in children, amoxicillin; clavulanic acid (and not amoxicillin alone) is recommended as first-line empiric therapy for acute bacterial sinusitis. However, amoxicillin is an option for children 2 years and older with uncomplicated disease in which antimicrobial resistance is not suspected. Children with moderate to severe disease, attending daycare, or who have recently been treated with antimicrobial therapy should receive high-dose amoxicillin; clavulanic acid.

For the treatment of leptospirosis*:
Oral dosage (immediate-release):
Adults: 500 mg PO every 6 hours or 1,000 mg PO every 12 hours for 7 days as alternative therapy for mild or moderate disease.
Infants, Children, and Adolescents: 30 to 40 mg/kg/day PO divided every 6 hours or 50 mg/kg/day PO divided every 12 hours (Max: 2 g/day) for 7 to 10 days as alternative therapy for mild or moderate disease.

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

For the treatment of actinomycosis*:
Oral dosage (immediate-release):
Adults: 500 mg PO every 6 hours for 6 to 12 months after IV therapy. Shorter courses may be appropriate for less extensive infections.

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

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

Patients with Renal Impairment Dosing
Adult patients

CrCl more than 30 mL/minute: no dosage adjustment needed.
CrCl 10 to 30 mL/minute: 250 to 500 mg PO every 12 hours, depending on the severity of the infection.
CrCl less than 10 mL/minute: 250 to 500 mg PO every 24 hours, depending on the severity of the infection.

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

Intermittent hemodialysis
Adult patients
250 to 500 mg PO every 24 hours, depending on the severity of the infection. An additional dose should be given both during and at the end of a dialysis session.

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

Peritoneal dialysis*
Adult patients
250 mg PO every 12 hours.

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

*non-FDA-approved indication

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; Butalbital; 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.

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: (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.

Aspirin, ASA; Pravastatin: (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.

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.

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: (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; Levonorgestrel; Folic Acid; 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.

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.

Lesinurad; Allopurinol: (Minor) Use of amoxicillin with allopurinol can increase the incidence of drug-related skin rash.

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.

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.

Mestranol; 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.

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.

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.

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.

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.

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.

Beta-lactam antibiotics such as amoxicillin are mainly bactericidal. Like other penicillins, amoxicillin inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. Penicillin-binding proteins are responsible for several steps in the synthesis of the cell wall and are found in quantities of several hundred to several thousand molecules per bacterial cell. Penicillin-binding proteins vary among different bacterial species. Thus, the intrinisic 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.

Penicillin-resistant strains of S. pneumoniae are increasing in number. The mechanism of resistance is mediated via the development of altered PBPs and the penicillin-resistant strains will generally be resistant to amoxicillin. The addition of clavulanic acid does not overcome this type of resistance. Increased dosages of amoxicillin may be necessary to overcome resistant S. pneumoniae. Community resistance patterns may determine the likelyhood of amoxicillin efficacy against S. pneumoniae.

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

Affected cytochrome P450 isoenzymes: none


-Route-Specific Pharmacokinetics
Oral Route
Amoxicillin is stable against gastric acid and is rapidly absorbed. Oral bioavailability ranges from 74% to 92%. Amoxicillin is more completely absorbed than ampicillin and, for this reason, is often the preferred oral aminopenicillin.

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

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


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

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