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    Penicillinase-Sensitive Penicillin Antibiotics

    DEA CLASS

    Rx

    DESCRIPTION

    Oral semisynthetic aminopenicillin similar to ampicillin; not stable to beta-lactamases of either gram-positive or gram-negative bacteria; more stable to gastric acid than penicillin; more bioavailable than oral ampicillin; commonly used to treat otitis media, bronchitis, sinusitis; also used in combination regimens for H. pylori eradication.

    COMMON BRAND NAMES

    Amoxil, Moxatag, Moxilin, Sumox, Trimox

    HOW SUPPLIED

    Amoxicillin/Amoxicillin Trihydrate/Amoxil Oral Tab Chew: 125mg, 250mg
    Amoxicillin/Amoxicillin Trihydrate/Amoxil Oral Tab: 500mg, 875mg
    Amoxicillin/Amoxicillin Trihydrate/Amoxil/Moxilin/Sumox/Trimox Oral Cap: 250mg, 500mg
    Amoxicillin/Amoxicillin Trihydrate/Amoxil/Moxilin/Sumox/Trimox Oral Pwd F/Recon: 5mL, 125mg, 200mg, 250mg, 400mg
    Moxatag Oral Tab ER: 775mg

    DOSAGE & INDICATIONS

    For the treatment of upper respiratory tract infections (e.g., pharyngitis, tonsillitis).
    For the treatment of tonsillitis and/or pharyngitis (rheumatic fever prophylaxis) secondary to Streptococcus pyogenes.
    Oral dosage (Moxatag 775-mg extended-release tablets)
    Adults, Adolescents, and Children 12 years and older

    775 mg PO once daily, given within 1 hour of completing a meal, for 10 days. The American Heart Association (AHA) recommends amoxicillin extended-release as an alternative to penicillin V for rheumatic fever prophylaxis.

    Oral dosage (immediate-release)
    Adults

    1 g PO once daily or 500 mg PO twice daily for 10 days. The American Heart Association (AHA) recommends extended-release amoxicillin as an alternative to penicillin V for rheumatic fever prophylaxis.

    Infants, Children, and Adolescents

    25 mg/kg/dose (Max: 500 mg/dose) PO twice daily for 10 days is recommended by the Infectious Diseases Society of America (IDSA). Alternatively, 50 mg/kg/dose PO once daily (Max: 1 g/dose) for 10 days is recommended by The American Heart Association (AHA) as an alternative to penicillin V. For ear/nose/throat infections in general, the FDA-approved dosage is 20 mg/kg/day PO in divided doses every 8 hours (Max: 250 mg/dose) or 25 mg/kg/day PO in divided doses every 12 hours (Max: 500 mg/dose) for mild to moderate infections and 40 mg/kg/day PO in divided doses every 8 hours (Max: 500 mg/dose) or 45 mg/kg/day PO in divided doses every 12 hours (Max: 875 mg/dose) for severe infections.

    for the treatment of sinusitis.
    NOTE: Due to the high rates of H. influenzae and beta-lactamase-producing pathogens among upper respiratory tract infections, amoxicillin/clavulanate (and not amoxicillin alone) is recommended as first-line empiric therapy for acute bacterial sinusitis by the Infectious Disease Society of America (IDSA). However, the American Academy of Pediatrics (AAP) considers amoxicillin an option for children 2 years and older with uncomplicated disease in which antimicrobial resistance is not suspected. Children with moderate to severe disease, attending daycare, or who have recently been treated with antimicrobial therapy should receive high-dose amoxicillin; clavulanic acid.
    Oral dosage (immediate-release)
    Children and Adolescents 2 years and older (standard-dose therapy)

    45 mg/kg/day PO in divided doses every 12 hours is the standard dose for children with uncomplicated disease that is mild to moderate in severity who do not attend daycare and who have not been treated with an antimicrobial agent in the previous 4 weeks.

    Children and Adolescents 2 years and older (high-dose therapy)

    80 to 90 mg/kg/day PO in divided doses every 12 hours (Max: 2 g/dose) is recommended for children in areas with high rates of S. pneumoniae resistance (more than 10%, including intermediate- and high-level resistance).

    Children younger than 2 years

    Children younger than 2 years should be treated with amoxicillin; clavulanic acid, not amoxicillin alone.

    Oral dosage (immediate-release)
    Adults

    500 mg PO every 12 hours or 250 mg PO every 8 hours for mild/moderate infections and 875 mg PO every 12 hours or 500 mg PO every 8 hours for severe infections.

    Infants older than 3 months, Children, and Adolescents

    20 mg/kg/day PO in divided doses every 8 hours (Max: 250 mg/dose) or 25 mg/kg/day PO in divided doses every 12 hours (Max: 500 mg/dose) for mild to moderate infections and 40 mg/kg/day PO in divided doses every 8 hours (Max: 500 mg/dose) or 45 mg/kg/day PO in divided doses every 12 hours (Max: 875 mg/dose) for severe infections.

    Neonates and Infants 3 months and younger

    30 mg/kg/day PO given in divided doses every 12 hours.

    For the treatment of acute otitis media.
    NOTE: The American Academy of Pediatrics (AAP) does 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/moderate infections and 875 mg PO every 12 hours or 500 mg PO every 8 hours for severe infections.

    Infants, Children, and Adolescents 6 months to 17 years

    80 to 90 mg/kg/day PO divided every 12 hours is first-line therapy. Treat all patients younger than 2 years and patients 2 years and older with severe disease for 10 days. For children 2 to 5 years with mild to moderate disease, a 7-day course is acceptable. For children 6 years and older with mild to moderate disease, a 5- to 7-day course is acceptable.[53345] Although the FDA-approved dosage ranges from 20 to 45 mg/kg/day PO depending on the severity of infection (Max: 500 mg/dose for every 8 hour dosing and 875 mg/dose for every 12 hour dosing), these low doses are not clinically recommended for the treatment of otitis media.[43844] [53345]

    Infants 4 to 5 months

    80 to 90 mg/kg/day PO divided every 12 hours for 10 days was recommended by experts as first-line therapy in previous guidelines; however, this age group is not addressed in the most current guidelines by the American Academy of Pediatrics (AAP). Although the FDA-approved dosage ranges from 20 to 45 mg/kg/day depending on the severity of infection, these low doses are not clinically recommended for the treatment of otitis media.

    Infants 1 to 3 months

    30 mg/kg/day PO divided every 12 hours is the general FDA-approved dosing. Young infants are less capable of responding to infection, and the clinical manifestations of infection can be subtle. Because of the increased risk for complications of an undiagnosed systemic infection, every young infant presenting with a fever should be carefully evaluated.

    For the treatment of skin and skin structure infections (e.g., cellulitis).
    For mild to moderate infections caused by highly susceptible organisms.
    Oral dosage (immediate-release)
    Adults

    500 mg PO every 12 hours or 250 mg PO every 8 hours.

    Infants older than 3 months, Children, and Adolescents

    20 mg/kg/day PO given in divided doses every 8 hours (Max: 250 mg/dose) or 25 mg/kg/day PO in divided doses given every 12 hours (Max: 500 mg/dose).

    Neonates and Infants 3 months and younger

    30 mg/kg/day PO given in divided doses every 12 hours.

    For severe infections or infections caused by less susceptible organisms.
    Oral dosage
    Adults

    875 mg PO every 12 hours or 500 mg PO every 8 hours.

    Infants older than 3 months, Children, and Adolescents

    40 mg/kg/day PO in divided doses every 8 hours (Max: 500 mg/dose) or 45 mg/kg/day PO in divided doses every 12 hours (Max: 875 mg/dose).

    Neonates and Infants 3 months and younger

    30 mg/kg/day PO given in divided doses every 12 hours.

    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 PO in divided doses every 12 hours or 40 mg/kg/day PO in divided doses every 8 hours (Max: 1,750 mg/day).[43844]

    Neonates and Infants 1 to 3 months

    30 mg/kg/day PO in divided doses every 12 hours.[43844]

    For the 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 HIV-infected outpatients. Guide treatment duration by clinical stability.[34362] [64669]

    Adolescents

    90 mg/kg/day PO in divided doses every 8 to 12 hours (Max: 4 g/day) for 5 to 7 days.[34362] [46963] Dividing 90 mg/kg/day into 3 doses/day increases the probability for reaching a clinical and microbiological cure to 90% compared with the same daily dose divided into 2 doses/day (65%) in patients with pneumococcal pneumonia (MIC of 2 mcg/mL). For less resistant pneumococcal strains (MIC of 0.5 mcg/mL), dividing 90 mg/kg/day into 2 doses will likely achieve a clinical and microbiological cure in more than 99% of children.[51856] 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. Depending on the causative organism, definitive therapy may range from 45 to 100 mg/kg/day PO in divided doses.[46963] In HIV-infected patients, amoxicillin is recommended as part of combination therapy for outpatients.[34362]

    Infants and Children 4 months to 12 years

    90 mg/kg/day PO in divided doses every 8 to 12 hours (Max: 4 g/day).[46963] Dividing 90 mg/kg/day into 3 doses/day increases the probability for reaching a clinical and microbiological cure to 90% compared with the same daily dose divided into 2 doses/day (65%) in patients with pneumococcal pneumonia (MIC of 2 mcg/mL). For less resistant pneumococcal strains (MIC of 0.5 mcg/mL), dividing 90 mg/kg/day into 2 doses will likely achieve a clinical and microbiological cure in more than 99% of children.[51856] 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. Depending on the causative organism, definitive therapy may range from 45 to 100 mg/kg/day PO in divided doses.[46963]

    For the treatment of urinary tract infection (UTI) including cystitis.
    For mild to moderate infections caused by highly susceptible organisms.
    Oral dosage (immediate-release)
    Adults

    500 mg PO every 12 hours or 250 mg PO every 8 hours. The Infectious Diseases Society of America (IDSA) does not recommend amoxicillin for empiric use due to the antimicrobial resistance.

    Infants older than 3 months, Children, and Adolescents

    20 mg/kg/day PO given in divided doses every 8 hours (Max: 250 mg/dose) or 25 mg/kg/day PO given in divided doses every 12 hours (Max: 500 mg/dose).

    Neonates and Infants 3 months and younger

    30 mg/kg/day PO given in divided doses every 12 hours.

    For severe infections or infections caused by less susceptible organisms.
    Oral dosage (immediate-release)
    Adults

    875 mg PO every 12 hours or 500 mg PO every 8 hours. The Infectious Diseases Society of America (IDSA) does not recommend amoxicillin for empiric use due to the antimicrobial resistance.

    Infants older than 3 months, Children, and Adolescents

    40 mg/kg/day PO in divided doses every 8 hours (Max: 500 mg/dose) or 45 mg/kg/day PO in divided doses every 12 hours (Max: 875 mg/dose).

    Neonates and Infants 3 months and younger

    30 mg/kg/day PO given in divided doses every 12 hours.

    for urinary tract infection (UTI) prophylaxis† in infants with hydronephrosis or vesicoureteral reflux.
    NOTE: Guidelines from the Pediatric Vesicoureteral Reflux (VUR) Panel recommend antibiotic prophylaxis for all grades of vesicoureteral reflux in all children less than 1 year. The American Academy of Pediatrics (AAP) states that routine antimicrobial prophylaxis for patients 2 to 24 months with vesicoureteral reflux is not supported by currently available data; however, antimicrobial prophylaxis is still utilized and has biological plausibility. Further research is needed. Amoxicillin is not recommended beyond 2 months of age due to resistance concerns. Sulfamethoxazole; trimethoprim or nitrofurantoin are preferred agents for infants 2 months and older.
    Oral dosage (immediate-release)
    Neonates and Infants younger than 2 months

    10 to 15 mg/kg/dose PO once daily.

    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† including cervicitis† and urethritis†.
    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 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 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 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 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 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 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.

    Neonates, Infants, Children, and Adolescents

    75 mg/kg/day PO divided every 8 hours (Max: 1 g/dose) for 60 days after exposure for penicillin-susceptible strains.

    Premature neonates 32 to 37 weeks gestational age 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 gestational age and 7 days or younger

    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.[64408]

    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.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    1,750 mg/day PO for most labeled indications; however, doses up to 3 g/day PO have been used off-label.

    Geriatric

    1,750 mg/day PO for most labeled indications; however, doses up to 3 g/day PO have been used off-label.

    Adolescents

    1,750 mg/day PO is FDA-approved maximum; however, doses up to 4 g/day PO have been used off-label.

    Children

    45 mg/kg/day PO is FDA-approved maximum; however, doses up to 100 mg/kg/day PO (Max: 4 g/day) have been used off-label.

    Infants

    4 to 11 months: 45 mg/kg/day PO is FDA-approved maximum; however, doses up to 90 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 75 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.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment needed; amoxicillin is not appreciably metabolized in the liver and does not undergo biliary secretion.

    Renal Impairment

    The following dosing recommendations pertain to adults. No specific dosage adjustments for pediatric patients with renal impairment are available at this time; however, dosage intervals should be adjusted.
    CrCl > 30 mL/min: no dosage adjustment needed.
    CrCl 10—30 mL/min: 250—500 mg PO every 12 hours, depending on the severity of the infection. Do not use the 875 mg-tablet strength or the extended-release tablet for dosing.
    CrCl < 10 mL/min: 250—500 mg PO every 24 hours, depending on the severity of the infection. Do not use the 875 mg-tablet strength or the extended-release tablet for dosing.
     
    Intermittent hemodialysis
    For adults, 250—500 mg PO every 24 hours, depending on the severity of the infection. According to the manufacturer, an additional dose should be given both during and at the end of a dialysis session. Do not use the 875 mg-tablet strength or the extended-release tablet for dosing.
     
    Peritoneal dialysis
    Follow dosage recommendations as for renal impairment for CrCl < 10 mL/min for those adults receiving continuous ambulatory peritoneal dialysis (CAPD). Do not use the 875 mg-tablet strength or the extended-release tablet for dosing.
     
    Continuous hemodialysis (CAVHD, CVVHD)
    Amoxicillin is removed by CAVHD or CVVHD.

    ADMINISTRATION

    Oral Administration

    Amoxicillin is administered orally.

    Oral Solid Formulations

    Moxatag extended-release tablets (775 mg): Take within 1 hour of finishing a meal. Do not chew or crush.
    Chewable tablets: Should be chewed before swallowing; do not swallow whole.
    In general, amoxicillin capsules and chewable tablets may be given without regard to meals. The 400mg chewable tablet and the 875mg tablet have been studied only when administered at the start of a light meal.

    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.

    STORAGE

    Generic:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Amoxil:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Moxatag:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Moxilin :
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Sumox:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Trimox:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Asthma, carbapenem hypersensitivity, cephalosporin hypersensitivity, eczema, penicillin hypersensitivity, urticaria

    Amoxicillin is a penicillin and is contraindicated in patients with a penicillin hypersensitivity. In general, amoxicillin should be used cautiously in patients with cephalosporin hypersensitivity or carbapenem hypersensitivity. These patients are more susceptible to hypersensitivity reactions during therapy with amoxicillin; the incidence of true cross-sensitivity has been estimated at roughly 3—5%. Amoxicillin is contraindicated in patients with a known serious hypersensitivity reaction (i.e., anaphylaxis) to other beta-lactams. Patients with allergies or atopic conditions including asthma, eczema, hives (urticaria), or hay fever may have a greater risk for hypersensitivity reactions to penicillins.

    Dialysis, renal failure, renal impairment

    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 <= 30 mL/min 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 <= 30 mL/min.

    C. difficile-associated diarrhea, diarrhea, pseudomembranous colitis

    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.

    Children, infants, neonates, premature neonates

    Amoxicillin has been used to treat infections in infants <= 3 months of age, including neonates and premature neonates. However, dosages must be modified for these age groups compared to infants > 3 months of age because of incompletely developed renal function. Safety and effectiveness of Moxatag extended-release tablets has not been established in neonates, infants, or children < 12 years of age.

    Geriatric

    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.

    Pregnancy

    Amoxicillin is classified in FDA pregnancy risk category B. Animal data reveal no teratogenic effects, however, there are no adequate and well-controlled studies in pregnant women. While amoxicillin should be used with caution in pregnancy, penicillins are usually considered safe during pregnancy when clearly needed.

    Breast-feeding

    According to the manufacturer, amoxicillin should be used cautiously during breast-feeding due to the potential for sensitization of the infant. Unless the infant is allergic to penicillins, breast-feeding is generally safe during maternal penicillin therapy. The American Academy of Pediatrics considers amoxicillin a medication that is usually compatible with breast-feeding. 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 breast fed infants exposed to antibiotics have found adverse event rates of 7.5—8.3% after exposure to amoxicillin. The adverse events reported included diarrhea, rash, and somnolence. The infant should be observed for potential effects. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Phenylketonuria

    Patients with phenylketonuria should be warned that the chewable tablets and the tablets for oral suspension (DisperMox) contain phenylalanine. Amoxicillin chewable tablets contain phenylalanine in the amount of 1.4 mg per 125 mg tablet, 4.5 mg per 200 mg tablet, 2.8 mg per 250 mg tablet, and 9 mg per 400 mg tablet. Each 200 mg and 400 mg DisperMox Tablet for oral suspension contains 5.6 mg phenylalanine and each 600 mg tablet contains 11.23 mg phenylalanine. The oral suspensions do not contain phenylalanine.

    Mononucleosis

    According to the manufacturer, amoxicillin should not be used in patients with mononucleosis as a high incidence of skin rashes have been reported in these patients.

    Sexually transmitted disease

    While amoxicillin may be used to treat certain sexually transmitted diseases (STD), the drug may mask or delay the symptoms of incubating syphilis when given as part of an STD treatment regimen. All patients with a diagnosed or suspected STD should be tested for other STDs, which may include HIV, syphilis, and gonorrhea, at the time of diagnosis. Initiate appropriate therapy and perform follow-up testing as recommended based upon sexually transmitted disease diagnosis.

    Laboratory test interference

    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 Benedict's solution, Fehling's solution, or Clinitest tablets for urine glucose testing. However, this reaction has not been observed with Tes-tape (glucose Enzymatic Test Strip, USP, Lilly) or Clinistix. 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.

    ADVERSE REACTIONS

    Severe

    serum sickness / Delayed / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    vasculitis / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    thrombotic thrombocytopenic purpura (TTP) / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    odynophagia / Delayed / Incidence not known
    seizures / Delayed / Incidence not known

    Moderate

    contact dermatitis / Delayed / 4.0-8.0
    candidiasis / Delayed / 2.0-2.0
    bullous rash / Early / Incidence not known
    platelet dysfunction / Delayed / Incidence not known
    prolonged bleeding time / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    anemia / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known
    dysphagia / Delayed / Incidence not known
    colitis / Delayed / Incidence not known
    esophagitis / Delayed / Incidence not known
    superinfection / Delayed / Incidence not known
    confusion / Early / Incidence not known
    jaundice / Delayed / Incidence not known
    cholestasis / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    dental fluorosis / Delayed / Incidence not known
    crystalluria / Delayed / Incidence not known

    Mild

    rash / Early / 4.0-8.0
    diarrhea / Early / 1.7-8.0
    headache / Early / 1.0-7.0
    dysgeusia / Early / 5.0-5.0
    nausea / Early / 1.3-1.3
    vomiting / Early / 0.7-0.7
    abdominal pain / Early / 0.3-0.3
    maculopapular rash / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    tongue discoloration / Delayed / Incidence not known
    anxiety / Delayed / Incidence not known
    insomnia / Early / Incidence not known
    dizziness / Early / Incidence not known
    agitation / Early / Incidence not known
    tooth discoloration / Delayed / Incidence not known
    Jarisch-Herxheimer reaction / Early / Incidence not known

    DRUG INTERACTIONS

    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; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (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.
    Allopurinol: (Minor) Use of amoxicillin with allopurinol can increase the incidence of drug-related skin rash.
    Amiloride: (Major) The administration of amiloride 2 hours before a dose of amoxicillin oral suspension reduced the bioavailability of amoxicillin by 27% and its Cmax by 25%. No change in the renal clearance of amoxicillin was noted. Although the significance of this pharmacokinetic interaction is unclear, clinicians should avoid administering doses of these two drugs within 2 hours of the other. Staggering the administration times further may avoid this interaction.
    Amiloride; Hydrochlorothiazide, HCTZ: (Major) The administration of amiloride 2 hours before a dose of amoxicillin oral suspension reduced the bioavailability of amoxicillin by 27% and its Cmax by 25%. No change in the renal clearance of amoxicillin was noted. Although the significance of this pharmacokinetic interaction is unclear, clinicians should avoid administering doses of these two drugs within 2 hours of the other. Staggering the administration times further may avoid this interaction.
    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; Dihydrocodeine: (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.
    Erythromycin; Sulfisoxazole: (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.
    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.
    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) Penicillins may reduce the renal clearance of methotrexate. Increased serum concentrations of methotrexate with concomitant hematologic and gastrointestinal toxicity have been observed with concurrent administration of high or low doses of methotrexate and penicillins. Patients should be carefully monitored while receiving this combination.
    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.
    Pyrimethamine; Sulfadoxine: (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.
    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.
    Sulfisoxazole: (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: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    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.

    PREGNANCY AND LACTATION

    Pregnancy

    Amoxicillin is classified in FDA pregnancy risk category B. Animal data reveal no teratogenic effects, however, there are no adequate and well-controlled studies in pregnant women. While amoxicillin should be used with caution in pregnancy, penicillins are usually considered safe during pregnancy when clearly needed.

    According to the manufacturer, amoxicillin should be used cautiously during breast-feeding due to the potential for sensitization of the infant. Unless the infant is allergic to penicillins, breast-feeding is generally safe during maternal penicillin therapy. The American Academy of Pediatrics considers amoxicillin a medication that is usually compatible with breast-feeding. 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 breast fed infants exposed to antibiotics have found adverse event rates of 7.5—8.3% after exposure to amoxicillin. The adverse events reported included diarrhea, rash, and somnolence. The infant should be observed for potential effects. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

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

    PHARMACOKINETICS

    Amoxicillin is administered orally. Approximately 20% of the circulating drug is protein-bound. Amoxicillin is widely distributed into most body tissues and fluids, excluding the brain and spinal fluid except when meninges are inflamed. Amoxicillin does cross the placenta. A small percentage is excreted in breast milk. The unchanged drug and its metabolites are excreted into the urine primarily via tubular secretion and glomerular filtration. 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

    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.