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  • CLASSES

    Antiinfectives and Antiseptics for Local Oral Treatment
    Natural and Semi-Synthetic Tetracycline Antibiotics
    Oral Non-Retinoids for Acne
    Oral Rosacea Agents

    DEA CLASS

    Rx, OTC

    DESCRIPTION

    A tetracycline class agent derived from oxytetracycline. Used to treat acne vulgaris, non-gonococcal urethritis and cervicitis, exacerbations of bronchitis in patients with COPD, and acne vulgaris. Useful in patients with poor renal function. Also commonly used as adjunct to scaling and root planing for adult periodontitis.

    COMMON BRAND NAMES

    Acticlate, Adoxa, Adoxa Pak, Alodox, Avidoxy, Doryx, Doxal, Doxy 100, LYMEPAK, Mondoxyne NL, Monodox, Morgidox 1x, Morgidox 1x Kit, Morgidox 2x, Morgidox 2x Kit, NutriDox, Ocudox, Okebo, Oracea, Oraxyl, Periostat, TARGADOX, Vibra-Tabs, Vibramycin

    HOW SUPPLIED

    Acticlate/Adoxa/Adoxa Pak/Alodox/Avidoxy/Doxycycline Hyclate/Doxycycline Monohydrate/LYMEPAK/Periostat/TARGADOX/Vibra-Tabs Oral Tab: 20mg, 50mg, 75mg, 100mg, 150mg
    Adoxa/Doxal/Doxycycline Hyclate/Doxycycline Monohydrate/Mondoxyne NL/Monodox/Morgidox 1x/Morgidox 1x Kit/Morgidox 2x/Morgidox 2x Kit/NutriDox/Ocudox/Okebo/Oraxyl/Vibramycin Oral Cap: 20mg, 50mg, 75mg, 100mg, 150mg
    Doryx/Doxycycline Hyclate Oral Cap DR Pellets: 100mg
    Doryx/Doxycycline Hyclate Oral Tab DR: 50mg, 60mg, 75mg, 80mg, 100mg, 120mg, 150mg, 200mg
    Doxy 100/Doxycycline Hyclate Intravenous Inj Pwd F/Sol: 100mg
    Doxycycline Monohydrate/Oracea Oral Cap ER: 40mg
    Doxycycline Monohydrate/Vibramycin Oral Pwd F/Recon: 5mL, 25mg
    Vibramycin Oral Susp: 5mL, 50mg

    DOSAGE & INDICATIONS

    For the treatment of skin and skin structure infections, including impetigo, cellulitis, erysipelas, skin abscesses, furunculosis, carbuncle, necrotizing infections, animal or human bite wounds, leg ulcer, and diabetic foot ulcer.
    For the treatment of impetigo when methicillin-resistant S. aureus (MRSA) is suspected or confirmed.
    Oral dosage (excluding Doryx MPC delayed-release tablets)†
    Adults

    100 mg PO every 12 hours for 5 to 7 days.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 5 to 7 days.

    For the treatment of nonpurulent skin infections, such as cellulitis and erysipelas.
    Oral dosage (excluding Doryx MPC delayed-release tablets)†
    Adults

    200 mg PO on day 1, then 100 mg PO once daily or every 12 hours for 5 to 14 days.

    Children and Adolescents 8 to 17 years

    4.4 mg/kg/dose (Max: 200 mg/dose) PO on day 1, then 2.2 mg/kg/dose (Max: 100 mg/dose) PO once daily or every 12 hours for 5 to 14 days.

    For the treatment of purulent skin infections, such as furunculosis, carbuncle, and skin abscesses.
    Oral dosage (excluding Doryx MPC delayed-release tablets)†
    Adults

    200 mg PO on day 1, then 100 mg PO once daily or every 12 hours for 5 to 10 days plus incision and drainage.

    Children and Adolescents 8 to 17 years

    4.4 mg/kg/dose (Max: 200 mg/dose) PO on day 1, then 2.2 mg/kg/dose (Max: 100 mg/dose) PO once daily or every 12 hours for 5 to 10 days plus incision and drainage.  

    For the treatment of necrotizing infections of the skin, fascia, and muscle.
    Intravenous dosage
    Adults

    100 mg IV every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours.  Doxycycline plus ciprofloxacin or ceftriaxone is recommended for infections due to Aeromonas hydrophilia and doxycycline plus ceftriaxone or cefotaxime is recommended for infections due to Vibrio vulnificus.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours.  Doxycycline plus ciprofloxacin or ceftriaxone is recommended for infections due to Aeromonas hydrophilia and doxycycline plus ceftriaxone or cefotaxime is recommended for infections due to Vibrio vulnificus.

    Infants† and Children 1 to 7 years†

    2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours. Doxycycline plus ciprofloxacin or ceftriaxone is recommended for infections due to Aeromonas hydrophilia and doxycycline plus ceftriaxone or cefotaxime is recommended for infections due to Vibrio vulnificus.

    For the treatment of animal bite wounds.
    Oral dosage (excluding Doryx MPC delayed-release tablets)†
    Adults

    100 mg PO every 12 hours. In setting of a cat or dog bite, preemptive early antimicrobial therapy for 3 to 5 days is recommended for patients who are immunocompromised, asplenic, have advanced liver disease, have edema of the bite area, have moderate to severe injuries, particularly of the hand or face, or have penetrating injuries to the periosteum or joint capsule.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours. In setting of a cat or dog bite, preemptive early antimicrobial therapy for 3 to 5 days is recommended for patients who are immunocompromised, asplenic, have advanced liver disease, have edema of the bite area, have moderate to severe injuries, particularly of the hand or face, or have penetrating injuries to the periosteum or joint capsule.

    For the treatment of human bite wounds.
    Oral dosage (excluding Doryx MPC delayed-release tablets)†
    Adults

    100 mg PO every 12 hours.

    For the treatment of leg ulcer.
    Oral dosage (excluding Doryx MPC delayed-release tablets)†
    Adults

    200 mg PO on day 1, then 100 mg PO once daily for 7 days. May increase dose to 200 mg/day.

    Intravenous dosage
    Adults

    200 mg IV on day 1, then 100 mg IV once daily for 7 days. May increase dose to 200 mg/day.

    For the treatment of diabetic foot ulcer.
    Oral dosage (excluding Doryx MPC delayed-release tablets)†
    Adults

    200 mg PO on day 1, then 100 mg PO once daily for 7 to 14 days for mild infections due to methicillin-resistant S. aureus (MRSA) or other staphylococci or streptococci in patients allergic or intolerant to beta-lactams or moderate or severe infections in patients with risk factors for MRSA. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease. 

    Intravenous dosage
    Adults

    200 mg IV on day 1, then 100 to 200 mg/day IV with the 200 mg dose administered as 1 or 2 doses for 7 to 14 days for mild infections due to methicillin-resistant S. aureus (MRSA) or other staphylococci or streptococci in patients allergic or intolerant to beta-lactams or moderate or severe infections in patients with risk factors for MRSA. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease. 

    For the treatment of urinary tract infection (UTI).
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours on day 1, then 100 mg PO once daily. Continue 100 mg PO every 12 hours for severe infections, including chronic urinary tract infections.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours on day 1, then 2.2 mg/kg/day PO every 24 hours or divided every 12 hours (Max: 100 mg/day). Continue 2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for severe infections, including chronic urinary tract infections.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours on day 1, then 60 mg PO every 12 hours or 120 mg PO once daily. Continue 120 mg PO every 12 hours for severe infections, including chronic urinary tract infections.

    Children and Adolescents 8 to 17 years

    2.65 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours on day 1, then 1.3 mg/kg/dose (Max: 60 mg/dose) PO every 12 hours or 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 24 hours. Continue 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for severe infections, including chronic urinary tract infections.

    Intravenous dosage
    Adults

    200 mg IV on day 1, then 100 to 200 mg/day IV with the 200 mg/day dose administered as 1 or 2 doses.

    Children and Adolescents 8 to 17 years

    4.4 mg/kg/day IV on day 1 (Max: 200 mg/day) administered as 1 or 2 doses, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses (Max: 200 mg/day).

    For the treatment of upper respiratory tract infections, including acute bacterial sinusitis.
    For the treatment of unspecified respiratory tract infections.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours on day 1, then 100 mg PO once daily. Continue 100 mg PO every 12 hours for severe infections.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours on day 1, then 2.2 mg/kg/day PO every 24 hours or divided every 12 hours (Max: 100 mg/day). Continue 2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for severe infections.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours on day 1, then 60 mg PO every 12 hours or 120 mg PO once daily. Continue 120 mg PO every 12 hours for severe infections.

    Children and Adolescents 8 to 17 years

    2.65 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours on day 1, then 1.3 mg/kg/dose (Max: 60 mg/dose) PO every 12 hours or 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 24 hours. Continue 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for severe infections.

    Intravenous dosage
    Adults

    200 mg IV on day 1, then 100 to 200 mg/day IV with the 200 mg dose administered as 1 or 2 doses.

    Children and Adolescents 8 to 17 years

    4.4 mg/kg/day IV on day 1 (Max: 200 mg/day) administered as 1 or 2 doses, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses (Max: 200 mg/day).

    For the treatment of acute bacterial sinusitis.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO twice daily or 200 mg PO once daily for 5 to 10 days as second-line therapy or for patients with a beta-lactam allergy.

    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 (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours on day 1, then 100 mg PO once daily. Continue 100 mg PO every 12 hours for severe infections.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours on day 1, then 2.2 mg/kg/day PO once daily (Max: 100 mg/day). Continue 2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for severe infections.[29817]

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours on day 1, then 60 mg PO every 12 hours or 120 mg PO once daily. Continue 120 mg PO every 12 hours for severe infections.[32075]

    Children and Adolescents 8 to 17 years

    2.65 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours on day 1, then 1.3 mg/kg/dose (Max: 60 mg/dose) PO every 12 hours or 2.6 mg/kg/dose (Max: 120 mg/dose) PO once daily. Continue 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for severe infections.[32075]

    Intravenous dosage
    Adults

    200 mg IV on day 1, then 100 to 200 mg/day IV with the 200 mg dose administered as 1 or 2 doses.[55918]

    Children and Adolescents 8 to 17 years

    4.4 mg/kg/day IV on day 1 (Max: 200 mg/day) administered as 1 or 2 doses, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses (Max: 200 mg/day).

    For the treatment of community-acquired pneumonia (CAP).
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 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 outpatients with comorbidities or hospitalized patients with nonsevere pneumonia who have contraindications to or clinical failure with standard therapies. Guide treatment duration by clinical stability.[34362] [64669]

    Adolescents

    2 to 4 mg/kg/day PO in 1 to 2 divided doses (Max: 200 mg/day) for 5 to 10 days as an alternative for empiric therapy in outpatients with presumed atypical pneumonia or as step-down therapy or for mild infections due to M. pneumoniae or C. trachomatis or as an alternative for empiric therapy in outpatients with presumed atypical pneumonia.[34362] [46963] In persons living with HIV, doxycycline is recommended as part of combination therapy for outpatients or hospitalized patients with nonsevere pneumonia as an alternative.[34362]

    Children 8 to 12 years

    2 to 4 mg/kg/day PO in 1 to 2 divided doses (Max: 200 mg/day) for 10 days as an alternative for empiric therapy in outpatients with presumed atypical pneumonia or as step-down therapy or for mild infections due to M. pneumoniae or C. trachomatis or as an alternative for empiric therapy in outpatients with presumed atypical pneumonia.[46963]

    Intravenous dosage
    Adults

    100 mg IV every 12 hours for at least 5 days as part of combination therapy for hospitalized patients with nonsevere pneumonia who have contraindications to or clinical failure with standard therapies. Guide treatment duration by clinical stability.[34362] [64669]

    Adolescents

    4.4 mg/kg/day IV on day 1 (Max: 200 mg/day) administered as 1 or 2 doses, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses (Max: 200 mg/day).[55918] In persons living with HIV, doxycycline is recommended as an alternative as part of combination therapy for hospitalized patients with nonsevere pneumonia.[34362]

    For the treatment of severe acne vulgaris as adjunctive therapy.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours on day 1, then 100 mg PO once daily. Continue 100 mg PO every 12 hours for severe infections.

    Children and Adolescents 8 to 17 years

    50 to 100 mg PO once or twice daily or 150 mg PO once daily. The FDA-approved dose is 2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours on day 1, then 2.2 mg/kg/day PO every 24 hours or divided every 12 hours (Max: 100 mg/day). Continue 2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for severe infections. The second-generation tetracyclines, including doxycycline, are preferred for the treatment of acne due to the ability to dose once daily, greater lipophilicity that is believed to increase follicular penetration, and lower prevalence of resistant P. acnes strains as compared with tetracycline.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours on day 1, then 60 mg PO every 12 hours or 120 mg PO once daily. Continue 120 mg PO every 12 hours for severe infections.

    Children and Adolescents 8 to 17 years

    2.65 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours on day 1, then 1.3 mg/kg/dose (Max: 60 mg/dose) PO every 12 hours or 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 24 hours. Continue 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for severe infections. The second-generation tetracyclines, including doxycycline, are preferred for the treatment of acne due to the ability to dose once daily, greater lipophilicity that is believed to increase follicular penetration, and lower prevalence of resistant P. acnes strains as compared with tetracycline.
     

    For the treatment of acne rosacea.
    Oral dosage (Oracea)
    Adults

    40 mg PO once daily in the morning. Efficacy beyond 16 weeks and safety beyond 9 months have not been established.

    For the treatment infectious diarrhea and gastroenteritis, including cholera.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    300 mg PO as a single dose as first-line therapy. The FDA-approved dose is 100 mg PO every 12 hours on day 1, then 50 mg PO every 12 hours or 100 mg PO once daily. Continue 100 mg PO every 12 hours for severe infections.

    Children and Adolescents 12 to 17 years

    300 mg PO as a single dose as first-line therapy. The FDA-approved dose is 2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours on day 1, then 1.1 mg/kg/dose (Max: 50 mg/dose) PO every 12 hours or 2.2 mg/kg/dose (Max: 100 mg/dose) PO once daily. Continue 2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for severe infections.

    Children 8 to 11 years

    2 to 4.4 mg/kg/dose (Max: 300 mg/dose) PO as a single dose as first-line therapy. The FDA-approved dose is 2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours on day 1, then 1.1 mg/kg/dose (Max: 50 mg/dose) PO every 12 hours or 2.2 mg/kg/dose (Max: 100 mg/dose) PO once daily. Continue 2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for severe infections.

    Infants† and Children 1 to 7 years†

    2 to 4.4 mg/kg/dose (Max: 300 mg/dose) PO as a single dose as first-line therapy.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    360 mg PO as a single dose as first-line therapy. The FDA-approved dose is 120 mg PO every 12 hours on day 1, then 60 mg PO every 12 hours or 120 mg PO once daily. Continue 120 mg PO every 12 hours for severe infections.

    Children and Adolescents 12 to 17 years

    360 mg PO as a single dose as first-line therapy. The FDA-approved dose is 2.65 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours on day 1, then 1.3 mg/kg/dose (Max: 60 mg/dose) PO every 12 hours or 2.6 mg/kg/dose (Max: 120 mg/dose) PO once daily. Continue 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for severe infections.

    Children 8 to 11 years

    2.4 to 5.3 mg/kg/dose (Max: 360 mg/dose) PO as a single dose as first-line therapy. The FDA-approved dose is 2.65 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours on day 1, then 1.3 mg/kg/dose (Max: 60 mg/dose) PO every 12 hours or 2.6 mg/kg/dose (Max: 120 mg/dose) PO once daily. Continue 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for severe infections.

    For the treatment of Rickettsial infections, including Rocky Mountain spotted fever, Rickettsial pox, ehrlichiosis, anaplasmosis, scrub typhus, and murine typhus.
    For the treatment of Rocky Mountain spotted fever.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of at least 5 to 7 days.

    Infants, Children, and Adolescents

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of at least 5 to 7 days.

    Oral dosage (Doryx MPC delayed-release tablets)

    NOTE: Children must be able to swallow tablets whole to receive the Doryx MPC formulation.

    Adults

    120 mg PO every 12 hours until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of at least 5 to 7 days.

    Children and Adolescents

    2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of at least 5 to 7 days.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of at least 5 to 7 days.

    Infants, Children, and Adolescents

    2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of at least 5 to 7 days.

    For the treatment of other spotted fever group Rickettsioses, including Rickettsial pox, and ehrlichiosis.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of at least 5 to 7 days.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of at least 5 to 7 days.

    Infants† and Children 1 to 7 years†

    2.2 mg/kg/dose PO every 12 hours (Max: 100 mg/dose) until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of at least 5 to 7 days.

    Oral dosage (Doryx MPC delayed-release tablets)

    NOTE: Children must be able to swallow tablets whole to receive the Doryx MPC formulation.

    Adults

    120 mg PO every 12 hours until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of at least 5 to 7 days.

    Children and Adolescents 8 to 17 years

    2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of at least 5 to 7 days.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of at least 5 to 7 days.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of at least 5 to 7 days.

    Infants† and Children 1 to 7 years†

    2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of at least 5 to 7 days.

    For the treatment of anaplasmosis.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of at least 5 to 7 days or 10 days if suspect concurrent Lyme disease.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of at least 5 to 7 days or 10 days if suspect concurrent Lyme disease.

    Infants† and Children 1 to 7 years†

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of at least 5 to 7 days or 10 days if suspect concurrent Lyme disease.

    Oral dosage (Doryx MPC delayed-release tablets)

    NOTE: Children must be able to swallow tablets whole to receive the Doryx MPC formulation.

    Adults

    120 mg PO every 12 hours until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of at least 5 to 7 days or 10 days if suspect concurrent Lyme disease.

    Children and Adolescents 8 to 17 years

    2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of at least 5 to 7 days or 10 days if suspect concurrent Lyme disease.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of at least 5 to 7 days or 10 days if suspect concurrent Lyme disease.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of at least 5 to 7 days or 10 days if suspect concurrent Lyme disease.

    Infants† and Children 1 to 7 years†

    2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours until afebrile for at least 3 days and clinical improvement with a minimum treatment duration of at least 5 to 7 days or 10 days if suspect concurrent Lyme disease.

    For the treatment of scrub typhus and endemic murine typhus.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours until afebrile for at least 3 days and clinical improvement.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours until afebrile for at least 3 days and clinical improvement.

    Infants† and Children 1 to 7 years†

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours until afebrile for at least 3 days and clinical improvement.

    Oral dosage (Doryx MPC delayed-release tablets)

    NOTE: Children must be able to swallow tablets whole to receive the Doryx MPC formulation.

    Adults

    120 mg PO every 12 hours until afebrile for at least 3 days and clinical improvement.

    Children and Adolescents 8 to 17 years

    2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours until afebrile for at least 3 days and clinical improvement.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours until afebrile for at least 3 days and clinical improvement.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours until afebrile for at least 3 days and clinical improvement.

    Infants† and Children 1 to 7 years†

    2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours until afebrile for at least 3 days and clinical improvement.

    For the treatment of epidemic typhus.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours until afebrile for at least 3 days and clinical improvement; 200 mg PO as a single dose may be effective in halting outbreaks, although some patients may relapse.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours until afebrile for at least 3 days and clinical improvement; 4.4 mg/kg/dose (Max: 200 mg/dose) PO as a single dose may be effective in halting outbreaks, although some patients may relapse.

    Infants† and Children 1 to 7 years†

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours until afebrile for at least 3 days and clinical improvement; 4.4 mg/kg/dose (Max: 200 mg/dose) PO as a single dose may be effective in halting outbreaks, although some patients may relapse.

    Oral dosage (Doryx MPC delayed-release tablets)

    NOTE: Children must be able to swallow tablets whole to receive the Doryx MPC formulation.

    Adults

    120 mg PO every 12 hours until afebrile for at least 3 days and clinical improvement; 240 mg PO as a single dose may be effective in halting outbreaks, although some patients may relapse.

    Children and Adolescents 8 to 17 years

    2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours until afebrile for at least 3 days and clinical improvement; 5.2 mg/kg/dose (Max: 240 mg/dose) PO as a single dose may be effective in halting outbreaks, although some patients may relapse.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours until afebrile for at least 3 days and clinical improvement; 200 mg IV as a single dose may be effective in halting outbreaks, although some patients may relapse.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours until afebrile for at least 3 days and clinical improvement; 4.4 mg/kg/dose (Max: 200 mg/dose) IV as a single dose may be effective in halting outbreaks, although some patients may relapse.

    Infants† and Children 1 to 7 years†

    2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours until afebrile for at least 3 days and clinical improvement; 4.4 mg/kg/dose (Max: 200 mg/dose) IV as a single dose may be effective in halting outbreaks, although some patients may relapse.

    For the treatment of relapsing fever due to Borrelia recurrentis.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours on day 1, then 100 mg PO once daily. Continue 100 mg PO every 12 hours for severe infection.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours on day 1, then 2.2 mg/kg/day PO every 24 hours or divided every 12 hours (Max: 100 mg/day). Continue 2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for severe infections. Treat for 5 to 10 days.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours on day 1, then 60 mg PO every 12 hours or 120 mg PO once daily. Continue 120 mg PO every 12 hours for severe infections.

    Children and Adolescents 8 to 17 years

    2.65 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours on day 1, then 1.3 mg/kg/dose (Max: 60 mg/dose) PO every 12 hours or 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 24 hours. Continue 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for severe infections. Treat for 5 to 10 days.

    Intravenous dosage
    Adults

    200 mg IV on day 1, then 100 to 200 mg/day IV with the 200 mg dose administered as 1 or 2 doses.

    Children and Adolescents 8 to 17 years

    4.4 mg/kg/day IV on day 1 (Max: 200 mg/day) administered as 1 or 2 doses, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses (Max: 200 mg/day) for 5 to 10 days.

    For the treatment of syphilis.
    NOTE: A Jarisch-Herxheimer reaction may occur within the first 24 hours of therapy.
    NOTE: While clinical practice guidelines recommend non-penicillin alternatives for the treatment of syphilis in patients living with HIV, their efficacy has not been well established, and they should only be used with close clinical and serologic monitoring.
    For primary, secondary, or early latent syphilis in nonpregnant, penicillin-allergic patients.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for 14 days. If follow-up/compliance uncertain, desensitize patient and treat with penicillin. Some manufacturers recommend 150 mg PO every 12 hours for at least 10 days. Empirically treat individuals exposed to a sex partner diagnosed with primary, secondary, or early latent syphilis within the past 90 days as they may be infected even if seronegative. Empirically treat individuals exposed more than 90 days before diagnosis in a sex partner if serologic test results are not immediately available and follow-up is uncertain.

    Children and Adolescents 8 to 17 years weighing 45 kg or more

    100 mg PO every 12 hours for 14 days. If follow-up/compliance uncertain, desensitize patient and treat with penicillin. Some manufacturers recommend 150 mg PO every 12 hours for at least 10 days. Empirically treat individuals exposed to a sex partner diagnosed with primary, secondary, or early latent syphilis within the past 90 days as they may be infected even if seronegative. Empirically treat individuals exposed more than 90 days before diagnosis in a sex partner if serologic test results are not immediately available and follow-up is uncertain.

    Children and Adolescents 8 to 17 years weighing less than 45 kg

    2.2 mg/kg/dose PO every 12 hours for 14 days. If follow-up/compliance uncertain, desensitize patient and treat with penicillin. Empirically treat individuals exposed to a sex partner diagnosed with primary, secondary, or early latent syphilis within the past 90 days as they may be infected even if seronegative. Empirically treat individuals exposed more than 90 days before diagnosis in a sex partner if serologic test results are not immediately available and follow-up is uncertain.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours for 14 days. If follow-up/compliance uncertain, desensitize patient and treat with penicillin. Empirically treat individuals exposed to a sex partner diagnosed with primary, secondary, or early latent syphilis within the past 90 days as they may be infected even if seronegative. Empirically treat individuals exposed more than 90 days before diagnosis in a sex partner if serologic test results are not immediately available and follow-up is uncertain.

    Children and Adolescents 8 to 17 years

    2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for 14 days. If follow-up/compliance uncertain, desensitize patient and treat with penicillin. Empirically treat individuals exposed to a sex partner diagnosed with primary, secondary, or early latent syphilis within the past 90 days as they may be infected even if seronegative. Empirically treat individuals exposed more than 90 days before diagnosis in a sex partner if serologic test results are not immediately available and follow-up is uncertain.

    Intravenous dosage
    Adults

    300 mg IV once daily for 14 days.

    Children and Adolescents 8 to 17 years weighing 45 kg or more

    300 mg IV once daily for 14 days.

    Children and Adolescents 8 to 17 years weighing less than 45 kg

    2.2 mg/kg/dose IV every 12 hours for 14 days.

    For late latent syphilis in nonpregnant, penicillin-allergic patients.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for 4 weeks. If follow-up/compliance uncertain, desensitize the patient and treat with penicillin.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 4 weeks. If follow-up/compliance uncertain, desensitize the patient and treat with penicillin.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours for 4 weeks. If follow-up/compliance uncertain, desensitize the patient and treat with penicillin.

    Children and Adolescents 8 to 17 years

    2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for 4 weeks. If follow-up/compliance uncertain, desensitize the patient and treat with penicillin.

    For the treatment of uncomplicated gonorrhea, including rectal infections in females, cervicitis, and urethritis.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    Not recommended by guidelines. The FDA-approved dosage is 100 mg PO every 12 hours for 7 days, or alternatively, 300 mg PO every 1 hour for 2 doses.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    Not recommended by guidelines. The FDA-approved dosage is 120 mg PO every 12 hours for 7 days, or alternatively, 360 mg PO every 1 hour for 2 doses.

    Intravenous dosage
    Adults

    Not recommended by guidelines. The FDA-approved dosage is 200 mg IV on day 1, then 100 to 200 mg/day IV once daily or divided twice daily.

    For the treatment of psittacosis.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for at least 10 to 14 days after fever resolves.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for at least 10 to 14 days after fever resolves.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours for at least 10 to 14 days after fever resolves.

    Children and Adolescents 8 to 17 years

    2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for at least 10 to 14 days after fever resolves.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours for at least 10 to 14 days after fever resolves.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours for at least 10 to 14 days after fever resolves.

    For the treatment of non-gonococcal urethritis (NGU) and chlamydia infection, including trachoma and chlamydial conjunctivitis.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for 7 days. For persistent NGU, follow therapy with 7 days of moxifloxacin.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 7 days. For persistent NGU, follow therapy with 7 days of moxifloxacin.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours for 7 days. For persistent NGU, follow therapy with 7 days of moxifloxacin.

    Children and Adolescents 8 to 17 years

    2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for 7 days. For persistent NGU, follow therapy with 7 days of moxifloxacin.

    For the treatment of lymphogranuloma venereum caused by C. trachomatis.
    For the primary treatment of lymphogranuloma venereum.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for 21 days.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 21 days. 

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours for 21 days.

    Children and Adolescents 8 to 17 years

    2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for 21 days.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours for 21 days.[40389]

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours for 21 days.

    For the presumptive treatment of chlamydia in the sex partner(s) of a patient with lymphogranuloma venereum.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for 7 days.

    Adolescents

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 7 days.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours for 7 days.

    Adolescents

    2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for 7 days.

    For the treatment of granuloma inguinale (Donovanosis).
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours as an alternative for at least 3 weeks and until all lesions have completely healed. Consider adding a second antibiotic if lesions do not respond within the first few days of therapy. For pregnant and lactating patients, use erythromycin or azithromycin.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours as an alternative for at least 3 weeks and until all lesions have completely healed. Consider adding a second antibiotic if lesions do not respond within the first few days of therapy.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours as an alternative for at least 3 weeks and until all lesions have completely healed. Consider adding a second antibiotic if lesions do not respond within the first few days of therapy. For pregnant and lactating patients, use erythromycin or azithromycin.

    Children and Adolescents 8 to 17 years

    2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours as an alternative for at least 3 weeks and until all lesions have completely healed. Consider adding a second antibiotic if lesions do not respond within the first few days of therapy.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours as an alternative for at least 3 weeks and until all lesions have completely healed. Consider adding a second antibiotic if lesions do not respond within the first few days of therapy. For pregnant and lactating patients, use erythromycin or azithromycin.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours as an alternative for at least 3 weeks and until all lesions have completely healed. Consider adding a second antibiotic if lesions do not respond within the first few days of therapy.

    For the treatment of epididymitis and epididymo-orchitis.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for 10 days in combination with single dose IM ceftriaxone for acute epididymitis most likely due to gonorrhea or chlamydia.

    Children weighing 45 kg or more and Adolescents

    100 mg PO every 12 hours for 10 days in combination with single dose IM ceftriaxone for acute epididymitis most likely due to gonorrhea or chlamydia.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours for 10 days in combination with single dose IM ceftriaxone for acute epididymitis most likely due to gonorrhea or chlamydia.

    Children weighing 45 kg or more and Adolescents

    120 mg PO every 12 hours for 10 days in combination with single dose IM ceftriaxone for acute epididymitis most likely due to gonorrhea or chlamydia.

    For the treatment of brucellosis.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours on day 1, then 100 mg PO once daily plus streptomycin. Continue 100 mg PO every 12 hours for severe infections.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours on day 1, then 2.2 mg/kg/day PO every 24 hours or divided every 12 hours (Max: 100 mg/day) plus rifampin. Continue 2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours and add gentamicin for the first 7 to 14 days for severe infections. Treat for at least 6 weeks. Treatment duration is often extended for 4 to 6 months for severe infections (i.e., endocarditis, meningitis, osteomyelitis).

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours on day 1, then 60 mg PO every 12 hours or either 120 mg PO once daily plus streptomycin. Continue 120 mg PO every 12 hours for severe infections.

    Children and Adolescents 8 to 17 years

    2.65 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours on day 1, then 1.3 mg/kg/dose (Max: 60 mg/dose) PO every 12 hours or 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 24 hours plus rifampin. Continue 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours and add gentamicin for the first 7 to 14 days for severe infections. Treat for at least 6 weeks. Treatment duration is often extended for 4 to 6 months for severe infections (i.e., endocarditis, meningitis, osteomyelitis).

    Intravenous dosage
    Adults

    200 mg IV on day 1, then 100 to 200 mg/day IV with the 200 mg dose administered as 1 or 2 doses.

    Children and Adolescents 8 to 17 years

    4.4 mg/kg/day IV on day 1 (Max: 200 mg/day) administered as 1 or 2 doses, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses (Max: 200 mg/day) plus rifampin for at least 6 weeks. Add gentamicin for the first 7 to 14 days for severe infections. Treatment duration is often extended for 4 to 6 months for severe infections (i.e., endocarditis, meningitis, osteomyelitis).

    For malaria prophylaxis.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO once daily. Begin 1 to 2 days prior to travel to the malarious area and continue during the stay and for 4 weeks after returning home. Guidelines recommend for use in all areas and FDA-labeling includes for use in short-term travelers (less than 4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains.

    Children and Adolescents 8 to 17 years

    2 mg/kg/dose (Max: 100 mg/dose) PO once daily. Begin 1 to 2 days prior to travel to the malarious area and continue during the stay and for 4 weeks after returning home. Guidelines recommend for use in all areas and FDA-labeling includes for use in short-term travelers (less than 4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO once daily. Begin 1 to 2 days prior to travel to the malarious area and continue during the stay and for 4 weeks after returning home. Guidelines recommend for use in all areas and FDA-labeling includes for use in short-term travelers (less than 4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains.

    Children and Adolescents 8 to 17 years weighing 45 kg or more

    120 mg PO once daily. Begin 1 to 2 days prior to travel to the malarious area and continue during the stay and for 4 weeks after returning home. Guidelines recommend for use in all areas and FDA-labeling includes for use in short-term travelers (less than 4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains.

    Children and Adolescents 8 to 17 years weighing less than 45 kg

    2.4 mg/kg/dose (Max: 120 mg/dose) PO once daily. Begin 1 to 2 days prior to travel to the malarious area and continue during the stay and for 4 weeks after returning home. Guidelines recommend for use in all areas and FDA-labeling includes for use in short-term travelers (less than 4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains.

    For the treatment of anthrax infection due to Bacillus anthracis.
    For the treatment of cutaneous anthrax infection.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for 7 to 10 days for naturally acquired infection and for 60 days for a bioterrorism-related event. Doxycycline is a preferred therapy.

    Infants, Children, and Adolescents

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 7 to 10 days for naturally acquired infection and for 60 days for a bioterrorism-related event. Doxycycline is an alternative to ciprofloxacin.

    Term Neonates

    2.2 mg/kg/dose PO every 12 hours for 7 to 10 days for naturally acquired infection or for 60 days for a bioterrorism-related event. Doxycycline is an alternative to ciprofloxacin.

    Oral dosage (Doryx MPC delayed-release tablets)

    NOTE: Children must be able to swallow tablets whole to receive the Doryx MPC formulation.

    Adults

    120 mg every PO 12 hours for 7 to 10 days for naturally acquired infection and for 60 days for a bioterrorism-related event. Doxycycline is a preferred therapy.

    Children and Adolescents

    2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for 7 to 10 days for naturally acquired infection or for 60 days for a bioterrorism-related event. Doxycycline is an alternative to ciprofloxacin.

    For the treatment of systemic anthrax infection.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Infants, Children, and Adolescents

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for at least 14 days or until clinical criteria for stability are met plus a bactericidal antimicrobial (e.g., ciprofloxacin). Prophylaxis to complete an antimicrobial course of up to 60 days may be required. Doxycycline is as an alternative oral follow-up therapy for systemic anthrax without CNS involvement.

    Term Neonates

    2.2 mg/kg/dose PO every 12 hours for at least 14 days or until clinical criteria for stability are met plus a bactericidal antimicrobial (e.g., ciprofloxacin). Prophylaxis to complete an antimicrobial course of up to 60 days may be required. Doxycycline is as an alternative oral follow-up therapy for systemic anthrax without CNS involvement.

    Oral dosage (Doryx MPC delayed-release tablets)

    NOTE: Children must be able to swallow tablets whole to receive the Doryx MPC formulation.

    Children and Adolescents

    2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for at least 14 days or until clinical criteria for stability are met plus a bactericidal antimicrobial (e.g., ciprofloxacin). Prophylaxis to complete an antimicrobial course of up to 60 days may be required. Doxycycline is as an alternative oral follow-up therapy for systemic anthrax without CNS involvement.

    Intravenous dosage
    Adults

    200 mg IV on day 1, then 100 mg IV every 12 hours for at least 14 days or until clinical criteria for stability are met plus a bactericidal antimicrobial (e.g., ciprofloxacin). Prophylaxis to complete an antimicrobial course of up to 60 days is required. Doxycycline is an alternative for the treatment of systemic anthrax without CNS involvement.

    Infants, Children, and Adolescents

    4.4 mg/kg/day IV on day 1 (Max: 200 mg/day), then 2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours for at least 14 days or until clinical criteria for stability are met plus a bactericidal antimicrobial (e.g., ciprofloxacin). Prophylaxis to complete an antimicrobial course of up to 60 days is required. Doxycycline is an alternative for the treatment of systemic anthrax without CNS involvement.

    Term Neonates

    4.4 mg/kg/day IV on day 1, then 2.2 mg/kg/dose IV every 12 hours for at least 14 days or until clinical criteria for stability are met plus a bactericidal antimicrobial (e.g., ciprofloxacin). Prophylaxis to complete an antimicrobial course of up to 60 days is required. Doxycycline is an alternative for the treatment of systemic anthrax without CNS involvement.

    For anthrax prophylaxis after exposure to Bacillus anthracis (postexposure prophylaxis, PEP).
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for 60 days after exposure. Doxycycline is a preferred therapy for postexposure prophylaxis.

    Infants, Children, and Adolescents

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 60 days after exposure. Doxycycline is a preferred therapy for postexposure prophylaxis in pediatric patients older than 1 month.

    Term Neonates

    2.2 mg/kg/dose PO every 12 hours for 60 days after exposure. Doxycycline is as an alternative therapy for postexposure prophylaxis in term neonates.

    Oral dosage (Doryx MPC delayed-release tablets)

    NOTE: Children must be able to swallow tablets whole to receive the Doryx MPC formulation.

    Adults

    120 mg PO every 12 hours for 60 days after exposure. Doxycycline is a preferred therapy for postexposure prophylaxis.

    Children and Adolescents

    2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for 60 days after exposure. Doxycycline is a preferred therapy for postexposure prophylaxis.

    For the treatment of plague infection.
    For the treatment of bubonic or pharyngeal plague.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    200 mg PO on day 1, then 100 mg PO every 12 hours for 10 to 14 days as first-line therapy in most patients and as an alternative therapy in pregnant patients. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment of naturally occurring plague in pregnant patients and patients infected after intentional release of Y. pestis.

    Children and Adolescents 8 to 17 years

    4.4 mg/kg/dose (Max: 200 mg/dose) PO on day 1, then 2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 10 to 14 days as first-line therapy. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.

    Infants† and Children 1 to 7 years†

    4.4 mg/kg/dose (Max: 200 mg/dose) PO on day 1, then 2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 10 to 14 days as first-line therapy. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.

    Neonates†

    4.4 mg/kg/dose PO on day 1, then 2.2 mg/kg/dose PO every 12 hours for 10 to 14 days as first-line therapy. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours for 10 to 14 days as first-line therapy in most patients and as an alternative therapy in pregnant patients. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment of naturally occurring plague in pregnant patients and patients infected after intentional release of Y. pestis.

    Children and Adolescents 8 to 17 years

    2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for 10 to 14 days as first-line therapy. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.

    Intravenous dosage
    Adults

    200 mg IV on day 1, then 100 mg IV every 12 hours for 10 to 14 days as first-line therapy in most patients and as an alternative therapy in pregnant patients. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment of naturally occurring plague in pregnant patients and patients infected after intentional release of Y. pestis.

    Children and Adolescents 8 to 17 years

    4.4 mg/kg/dose (Max: 200 mg/dose) IV on day 1, then 2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours for 10 to 14 days as first-line therapy. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.

    Infants† and Children 1 to 7 years†

    4.4 mg/kg/dose (Max: 200 mg/dose) IV on day 1, then 2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours for 10 to 14 days as first-line therapy. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.

    Neonates†

    4.4 mg/kg/dose IV on day 1, then 2.2 mg/kg/dose IV every 12 hours for 10 to 14 days as first-line therapy. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.

    For the treatment of pneumonic or septicemic plague.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    200 mg PO on day 1, then 100 mg PO every 12 hours for 10 to 14 days as an alternative therapy. Monotherapy can be considered for mild-to-moderate disease in patients with naturally occurring plague. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment of naturally occurring plague in pregnant patients, patients with severe disease, and patients infected after intentional release of Y. pestis.

    Children and Adolescents 8 to 17 years

    4.4 mg/kg/dose (Max: 200 mg/dose) PO on day 1, then 2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 10 to 14 days as an alternative therapy. Monotherapy can be considered for mild-to-moderate disease in patients with naturally occurring plague. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.

    Infants† and Children 1 to 7 years†

    4.4 mg/kg/dose (Max: 200 mg/dose) PO on day 1, then 2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 10 to 14 days as an alternative therapy. Monotherapy can be considered for mild-to-moderate disease in patients with naturally occurring plague. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.

    Neonates†

    4.4 mg/kg/dose PO on day 1, then 2.2 mg/kg/dose PO every 12 hours for 10 to 14 days as an alternative therapy. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours for 10 to 14 days as an alternative therapy. Monotherapy can be considered for mild-to-moderate disease in patients with naturally occurring plague. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment of naturally occurring plague in pregnant patients, patients with severe disease, and patients infected after intentional release of Y. pestis.

    Children and Adolescents 8 to 17 years

    2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for 10 to 14 days as an alternative therapy. Monotherapy can be considered for mild-to-moderate disease in patients with naturally occurring plague. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.

    Intravenous dosage
    Adults

    200 mg IV on day 1, then 100 mg IV every 12 hours for 10 to 14 days as an alternative therapy. Monotherapy can be considered for mild-to-moderate disease in patients with naturally occurring plague. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment of naturally occurring plague in pregnant patients, patients with severe disease, and patients infected after intentional release of Y. pestis.

    Children and Adolescents 8 to 17 years

    4.4 mg/kg/dose (Max: 200 mg/dose) IV on day 1, then 2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours for 10 to 14 days as an alternative therapy. Monotherapy can be considered for mild-to-moderate disease in patients with naturally occurring plague. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.

    Infants† and Children 1 to 7 years†

    4.4 mg/kg/dose (Max: 200 mg/dose) IV on day 1, then 2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours for 10 to 14 days as an alternative therapy. Monotherapy can be considered for mild-to-moderate disease in patients with naturally occurring plague. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.

    Neonates†

    4.4 mg/kg/dose IV on day 1, then 2.2 mg/kg/dose IV every 12 hours for 10 to 14 days as an alternative therapy. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.

    For the treatment of tularemia infection due to Francisella tularensis .
    For the treatment of tularemia infection in individual patient or a contained casualty setting.
    NOTE: Streptomycin is the drug of choice to treat tularemia in most patients; gentamicin is the preferred agent in pregnant women.
    Intravenous dosage
    Adults

    100 mg IV every 12 hours for 14 to 21 days as an alternative to streptomycin or gentamicin. Switch to oral therapy when clinically indicated. The risk of serious infection after tularemia exposure supports the use of doxycycline if antibiotic susceptibility testing, exhaustion of drug supplies, or allergic reactions preclude the use of streptomycin/gentamicin.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours for 14 to 21 days as an alternative to streptomycin or gentamicin. Switch to oral therapy when clinically indicated. The risk of serious infection after tularemia exposure supports the use of doxycycline if antibiotic susceptibility testing, exhaustion of drug supplies, or allergic reactions preclude the use of streptomycin/gentamicin.

    For the treatment of tularemia infection in a mass casualty setting.
    NOTE: It is recommended that pregnant women be treated with ciprofloxacin as a first-line agent; doxycycline is a preferred treatment choice if ciprofloxacin is contraindicated.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for 14 days.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 14 days.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours for 14 days.

    Children and Adolescents 8 to 17 years

    2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for 14 days.

    For the treatment of intestinal amebiasis as an adjunct to amebicides.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours on day 1, then 100 mg PO once daily. Continue 100 mg PO every 12 hours for severe infections.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours on day 1, then 2.2 mg/kg/day PO every 24 hours or divided every 12 hours (Max: 100 mg/day). Continue 2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for severe infections.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours on day 1, then 60 mg PO every 12 hours or 120 mg PO once daily. Continue 120 mg PO every 12 hours for severe infections.

    Children and Adolescents 8 to 17 years

    2.65 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours on day 1, then 1.3 mg/kg/dose (Max: 60 mg/dose) PO every 12 hours or 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 24 hours. Continue 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for severe infections.

    Intravenous dosage
    Adults

    200 mg IV on day 1, then 100 to 200 mg/day IV with the 200 mg dose administered as 1 or 2 doses.

    Children and Adolescents 8 to 17 years

    4.4 mg/kg IV on day 1 (Max: 200 mg/day) administered as 1 or 2 doses, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses (Max: 200 mg/day).

    For the treatment of yaws, necrotizing ulcerative gingivitis (Fusospirochetosis or Vincent's infection), and listeriosis.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours on day 1, then 100 mg PO once daily. Continue 100 mg PO every 12 hours for severe infections.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours on day 1, then 2.2 mg/kg/day PO every 24 hours or divided every 12 hours (Max: 100 mg/day). Continue 2.2 mg/kg/dose PO (Max: 100 mg/dose) every 12 hours for severe infections.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours on day 1, then 60 mg PO every 12 hours or 120 mg PO once daily. Continue 120 mg PO every 12 hours for severe infections.

    Children and Adolescents 8 to 17 years

    2.65 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours on day 1, then 1.3 mg/kg/dose (Max: 60 mg/dose) PO every 12 hours or 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 24 hours. Continue 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for severe infections.

    Intravenous dosage
    Adults

    200 mg IV on day 1, then 100 to 200 mg/day IV with the 200 mg dose administered as 1 or 2 doses.

    Children and Adolescents 8 to 17 years

    4.4 mg/kg/day IV on day 1 (Max: 200 mg/day) administered as 1 or 2 doses, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses (Max: 200 mg/day).

    For the treatment of Q fever.
    For the treatment of acute Q fever.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for 14 days.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 14 days.

    Infants† and Children 1 to 7 years†

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 5 or 14 days. Treat for 5 days for children with mild or uncomplicated illness; if patient remains febrile after 5 days of treatment, switch to sulfamethoxazole; trimethoprim therapy. Treat for 14 days for children with high risk criteria (i.e., hospitalized or severe illness, heart valvulopathy, immunocompromised, or delayed Q fever diagnosis who have experienced illness for more than 14 days without resolution of symptoms).

    Oral dosage (Doryx MPC delayed-release tablets)

    NOTE: Children must be able to swallow tablets whole to receive the Doryx MPC formulation.

    Adults

    120 mg PO every 12 hours for 14 days.

    Children and Adolescents 8 to 17 years

    2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for 14 days.

    Children 1 to 7 years†

    2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for 5 or 14 days. Treat for 5 days for children with mild or uncomplicated illness; if patient remains febrile after 5 days of treatment, switch to sulfamethoxazole; trimethoprim therapy. Treat for 14 days for children with high risk criteria (i.e., hospitalized or severe illness, heart valvulopathy, immunocompromised, or delayed Q fever diagnosis who have experienced illness for more than 14 days without resolution of symptoms).

    Intravenous dosage
    Adults

    100 mg IV every 12 hours for 14 days.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours for 14 days.

    Infants† and Children 1 to 7 years†

    2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours for 5 or 14 days. Treat for 5 days for children with mild or uncomplicated illness; if patient remains febrile after 5 days of treatment, switch to sulfamethoxazole; trimethoprim therapy. Treat for 14 days for children with high risk criteria (i.e., hospitalized or severe illness, heart valvulopathy, immunocompromised, or delayed Q fever diagnosis who have experienced illness for more than 14 days without resolution of symptoms).

    For the treatment of chronic Q fever endocarditis or vascular infection.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours plus hydroxychloroquine for 18 months or more.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours plus hydroxychloroquine for 18 months or more.

    For the treatment of chronic Q fever noncardiac organ disease.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours plus hydroxychloroquine. Duration of treatment is dependent on serologic response.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours plus hydroxychloroquine. Duration of treatment is dependent on serologic response.

    For the treatment of chronic Q fever postpartum in persons with serologic profile positive for Q fever.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Pregnant Persons

    100 mg PO every 12 hours plus hydroxychloroquine for 12 months.

    Oral dosage (Doryx MPC delayed-release tablets)
    Pregnant Persons

    120 mg PO every 12 hours plus hydroxychloroquine for 12 months.

    For the treatment of chancroid.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    Not recommended by guidelines. 100 mg PO every 12 hours on day 1, then 100 mg PO once daily. Continue 100 mg PO every 12 hours for severe infections.

    Children and Adolescents 8 to 17 years

    Not recommended by guidelines. 2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours on day 1, then 2.2 mg/kg/day (Max: 100 mg/day) PO every 24 hours or divided every 12 hours. Continue 2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for severe infections.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    Not recommended by guidelines. 120 mg PO every 12 hours on day 1, then 60 mg PO every 12 hours or 120 mg PO once daily. Continue 120 mg PO every 12 hours for severe infections.

    Children and Adolescents 8 to 17 years

    Not recommended by guidelines. 2.65 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours on day 1, then 1.3 mg/kg/dose (Max: 60 mg/dose) PO every 12 hours or 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 24 hours. Continue 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for severe infections.

    Intravenous dosage
    Adults

    Not recommended by guidelines. 200 mg IV on day 1, then 100 to 200 mg/day IV with the 200 mg dose administered as 1 or 2 doses.

    Children and Adolescents 8 to 17 years

    Not recommended by guidelines. 4.4 mg/kg/day (Max: 200 mg/day) IV on day 1 administered as 1 or 2 doses, then 2.2 to 4.4 mg/kg/day (Max: 200 mg/day) IV in 1 to 2 divided doses.

    For the treatment of actinomycosis.
    Intravenous dosage
    Adults

    100 mg IV every 12 hours for 2 to 6 weeks, followed by oral therapy for 6 to 12 months. Shorter courses may be appropriate for less extensive infections.

    Children and Adolescents 8 to 17 years

    4.4 mg/kg/day IV on day 1 (Max: 200 mg/day) administered as 1 or 2 doses, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses (Max: 200 mg/day).

    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for 6 to 12 months after IV therapy. Shorter courses may be appropriate for less extensive infections.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours on day 1, then 2.2 mg/kg/day PO every 24 hours or divided every 12 hours (Max: 100 mg/day). Continue 2.2 mg/kg/dose PO (Max: 100 mg/dose) every 12 hours for severe infections.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours on day 1, then 60 mg PO every 12 hours or 120 mg PO once daily. Continue 120 mg PO every 12 hours for severe infections.

    Children and Adolescents 8 to 17 years

    2.65 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours on day 1, then 1.3 mg/kg/dose (Max: 60 mg/dose) PO every 12 hours or 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 24 hours. Continue 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for severe infections.

    For chlamydial infection prophylaxis† in victims of sexual assault.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO twice daily for 7 days.

    Adolescents

    100 mg PO twice daily for 7 days.

    For the treatment of chronic prostatitis† due to Ureaplasma urealyticum.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adult males

    100 mg PO twice daily for 21 days. In a pilot study, doxycycline was compared to azithromycin 500 mg PO daily for 3 days repeated every week for 3 weeks (total dose: 4,500 mg). Patients were randomized to the doxycycline (n = 31) or azithromycin (n = 32) regimen; sexual partners were also treated at the same time. Eradication rates and clinical cure rates were similar between the groups.

    For the management of methicillin-resistant Staphylococcus aureus (MRSA)-associated bone and joint infections†, including osteomyelitis†, or orthopedic device-related infection†.
    For the management of methicillin-resistant Staphylococcus aureus (MRSA)-associated osteomyelitis†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours with rifampin for an additional 1 to 3 months (or longer for chronic infection or if no debridement performed) after initial therapy.

    For the management of methicillin-resistant Staphylococcus aureus (MRSA)-associated prosthetic device infections†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours with rifampin for 3 months for hip infections or for 6 months for knee infections after initial therapy.

    For the management of methicillin-resistant Staphylococcus aureus (MRSA)-associated spinal implant infections†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO twice daily with rifampin until spine fusion and after initial therapy. Long-term oral suppressive therapy may be considered in select cases, especially if device removal is not possible.

    For the treatment of bartonellosis, including cat scratch disease†, neuroretinitis†, bacillary angiomatosis†, bacillary peliosis† (peliosis hepatis†), bacteremia†, trench fever†, endocarditis†, osteomyelitis†, and CNS infections†.
    For the general treatment of bartonellosis due to Bartonella bacilliformis.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours on day 1, then 100 mg PO once daily. Continue 100 mg PO every 12 hours for severe infections.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours on day 1, then 2.2 mg/kg/day PO every 24 hours or divided every 12 hours (Max: 100 mg/day). Continue 2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for severe infections.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    120 mg PO every 12 hours on day 1, then 60 mg PO every 12 hours or 120 mg PO once daily. Continue 120 mg PO every 12 hours for severe infections.

    Children and Adolescents 8 to 17 years

    2.65 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours on day 1, then 1.3 mg/kg/dose (Max: 60 mg/dose) PO every 12 hours or 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 24 hours. Continue 2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for severe infections.

    Intravenous dosage
    Adults

    200 mg IV on day 1, then 100 to 200 mg/day with the 200 mg dose administered in 1 to 2 divided doses.

    Children and Adolescents 8 to 17 years

    4.4 mg/kg/day IV on day 1 (Max: 200 mg/day) administered as 1 or 2 doses, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses (Max: 200 mg/day).

    For the treatment of Bartonella infections, including cat scratch disease, bacillary angiomatosis, bacillary peliosis (peliosis hepatis), bacteremia, and osteomyelitis, in immunocompromised patients†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for at least 3 months.

    Adolescents

    100 mg PO every 12 hours for at least 3 months.

    Children 8 to 12 years

    2.2 to 4.4 mg/kg/day PO divided every 12 hours (Max: 200 mg/day) for at least 3 months.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours for at least 3 months.

    Adolescents

    100 mg IV every 12 hours for at least 3 months.

    Children 8 to 12 years

    2.2 to 4.4 mg/kg/day IV divided every 12 hours (Max: 200 mg/day) for at least 3 months.

    For the treatment of Bartonella infections involving the central nervous system in immunocompromised patients†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for at least 3 months with or without rifampin.

    Adolescents

    100 mg PO every 12 hours for at least 3 months with or without rifampin.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours for at least 3 months with or without rifampin.

    Adolescents

    100 mg IV every 12 hours for at least 3 months with or without rifampin.

    For the treatment of documented Bartonella endocarditis in immunocompromised patients†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for at least 3 months plus rifampin for 6 weeks as first-line therapy or gentamicin for 2 weeks as second-line therapy due to nephrotoxicity, as glomerulonephritis frequently complicates Bartonella endocarditis.

    Adolescents

    100 mg PO every 12 hours for at least 3 months plus rifampin for 6 weeks as first-line therapy or gentamicin for 2 weeks as second-line therapy due to nephrotoxicity, as glomerulonephritis frequently complicates Bartonella endocarditis.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours for at least 3 months plus rifampin for 6 weeks as first-line therapy or gentamicin for 2 weeks as second-line therapy due to nephrotoxicity, as glomerulonephritis frequently complicates Bartonella endocarditis.

    Adolescents

    100 mg IV every 12 hours for at least 3 months plus rifampin for 6 weeks as first-line therapy or gentamicin for 2 weeks as second-line therapy due to nephrotoxicity, as glomerulonephritis frequently complicates Bartonella endocarditis.

    For the treatment of severe Bartonella infections, including multifocal disease or with clinical decompensation, in immunocompromised patients†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for at least 3 months plus rifampin.

    Adolescents

    100 mg PO every 12 hours for at least 3 months plus rifampin.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours for at least 3 months plus rifampin.

    Adolescents

    100 mg IV every 12 hours for at least 3 months plus rifampin.

    For the treatment of Bartonella bacteremia or trench fever in immunocompetent patients†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours or 200 mg PO once daily for 4 weeks plus gentamicin for 2 weeks.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours or 200 mg IV once daily for 4 weeks plus gentamicin for 2 weeks.

    For the treatment of bacillary angiomatosis in immunocompetent patients†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for 2 weeks to 3 months for uncomplicated infections. Add rifampin and treat complicated infections for 3 months. Treat relapses for 4 to 6 months.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours for 2 weeks to 3 months for uncomplicated infections. Add rifampin and treat complicated infections for 3 months. Treat relapses for 4 to 6 months.

    For the treatment of bacillary peliosis (peliosis hepatis) in immunocompetent patients†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for 3 to 4 months. Add rifampin and treat for 3 months for complicated infections. Treat relapses for 4 to 6 months.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours for 3 to 4 months. Add rifampin and treat for 3 months for complicated infections. Treat relapses for 4 to 6 months.

    For the treatment of suspected Bartonella endocarditis (culture-negative) in immunocompetent patients†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for 6 weeks plus ceftriaxone for 6 weeks and gentamicin for 2 weeks.

    Children and Adolescents

    2.2 to 4.4 mg/kg/day PO divided every 12 hours (Max: 200 mg/day) for 6 weeks plus ceftriaxone for 6 weeks and gentamicin for 2 weeks.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours for 6 weeks plus ceftriaxone for 6 weeks and gentamicin for 2 weeks.

    Children and Adolescents

    2.2 to 4.4 mg/kg/day IV divided every 12 hours (Max: 200 mg/day) for 6 weeks plus ceftriaxone for 6 weeks and gentamicin for 2 weeks.

    For the treatment of documented Bartonella endocarditis in immunocompetent patients†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for at least 6 weeks plus gentamicin for 2 weeks or rifampin for at least 6 weeks.

    Children and Adolescents

    2.2 to 4.4 mg/kg/day PO divided every 12 hours (Max: 200 mg/day) for at least 6 weeks plus gentamicin for 2 weeks or rifampin for at least 6 weeks.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours for at least 6 weeks plus gentamicin for 2 weeks or rifampin for at least 6 weeks.

    Children and Adolescents

    2.2 to 4.4 mg/kg/day IV divided every 12 hours (Max: 200 mg/day) for at least 6 weeks plus gentamicin for 2 weeks or rifampin for at least 6 weeks.

    For the treatment of Bartonella infections involving the central nervous system in immunocompetent patients†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for 4 to 6 weeks plus rifampin.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours for 4 to 6 weeks plus rifampin.

    For the treatment of typical cat scratch disease in immunocompetent patients†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours plus rifampin as an alternative. Most cases resolve without treatment; however, consider treating patients with extensive lymphadenopathy.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours plus rifampin as an alternative. Most cases resolve without treatment; however, consider treating patients with extensive lymphadenopathy.

    For the treatment of Bartonella-related neuroretinitis in immunocompetent patients†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for 4 to 6 weeks plus rifampin with or without corticosteroids as first-line therapy.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours for 4 to 6 weeks plus rifampin with or without corticosteroids as first-line therapy.

    For the treatment of atypical hepatosplenic or bony cat scratch disease in immunocompetent patients†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for 4 to 6 weeks plus rifampin.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours for 4 to 6 weeks plus rifampin.

    For secondary bartonellosis prophylaxis† (i.e. long-term suppressive therapy†) in immunocompromised patients.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours if a relapse occurs after at least 3 months of treatment. For persons living with HIV, discontinuation may be considered after 3 to 4 months of treatment and CD4 count more than 200 cells/mm3 for at least 6 months. Some experts suggest that Bartonella titers also decrease by 4-fold before discontinuing suppressive therapy.

    Adolescents

    100 mg PO every 12 hours if a relapse occurs after at least 3 months of treatment. For persons living with HIV, discontinuation may be considered after 3 to 4 months of treatment and CD4 count more than 200 cells/mm3 for at least 6 months. Some experts suggest that Bartonella titers also decrease by 4-fold before discontinuing suppressive therapy.

    For the treatment of Lyme disease, including erythema migrans, Lyme arthritis†, Lyme carditis†, Lyme meningitis†, cranial neuropathy†, radiculoneuropathy/radiculoneuritis†, and cranial nerve palsy†, borrelial lymphocytoma†, and acrodermatitis chronica atrophicans†.
    For the treatment of early Lyme disease (erythema migrans), including solitary and multiple erythema migrans.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours or 200 mg PO once daily for 10 to 14 days.

    Children and Adolescents 8 to 17 years weighing 45 kg or more

    100 mg PO every 12 hours for 10 to 14 days.

    Infants†, Children†, and Adolescents† weighing 44 kg or less

    2.2 mg/kg/dose PO every 12 hours for 10 to 14 days. Studies have shown that short course doxycycline therapy (up to 14 days) is generally considered safe in young children. Some clinicians would reserve doxycycline for young children who are unable to tolerate beta-lactam antibiotics.

    For the initial treatment of Lyme arthritis†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours or 200 mg PO once daily for 28 days.

    Infants, Children, and Adolescents

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 28 days. Studies have shown that short course doxycycline therapy (up to 14 days) is generally considered safe in young children. Some clinicians would reserve doxycycline for young children who are unable to tolerate beta-lactam antibiotics.

    For the treatment of Lyme carditis†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours or 200 mg PO once daily 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

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 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). Studies have shown that short course doxycycline therapy (up to 14 days) is generally considered safe in young children. Some clinicians would reserve doxycycline for young children who are unable to tolerate beta-lactam antibiotics.

    For the treatment of neurologic Lyme disease without parenchymal involvement, including Lyme meningitis†, cranial neuropathy†, radiculoneuropathy/radiculoneuritis†, and cranial nerve palsy†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours or 200 mg PO once daily for 14 to 21 days for mildly ill patients or as stepdown after IV therapy. For acutely ill patients or prior to confirmation of Lyme neuroborreliosis, IV therapy is preferred with appropriate stepdown to oral treatment.

    Infants, Children, and Adolescents

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 14 to 21 days for mildly ill patients or as stepdown after IV therapy. For acutely ill patients or prior to confirmation of Lyme neuroborreliosis, IV therapy is preferred with appropriate stepdown to oral treatment.

    For the treatment of recurrent or refractory Lyme arthritis†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours or 200 mg PO once daily 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

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 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. Studies have shown that short course doxycycline therapy (up to 14 days) is generally considered safe in young children. Some clinicians would reserve doxycycline for young children who are unable to tolerate beta-lactam antibiotics.

    For the treatment of borrelial lymphocytoma†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours or 200 mg PO once daily for 14 days.

    Infants, Children, and Adolescents

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 14 days. Studies have shown that short course doxycycline therapy (up to 14 days) is generally considered safe in young children. Some clinicians would reserve doxycycline for young children who are unable to tolerate beta-lactam antibiotics.

    For the treatment of acrodermatitis chronica atrophicans†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours or 200 mg PO once daily for 21 to 28 days.

    Infants, Children, and Adolescents

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 21 to 28 days. Studies have shown that short course doxycycline therapy (up to 14 days) is generally considered safe in young children. Some clinicians would reserve doxycycline for young children who are unable to tolerate beta-lactam antibiotics.

    For post-exposure Lyme disease prophylaxis† after a high-risk tick bite.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    200 mg PO as a single dose within 72 hours of tick removal.

    Infants, Children, and Adolescents

    4.4 mg/kg/dose (Max: 200 mg/dose) PO as a single dose within 72 hours of tick removal.

    For the treatment of Legionnaire's disease† due to Legionella pneumophila.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours.

    For the treatment of pleural effusion† requiring pleurodesis.
    Intrapleural dosage
    Adults

    500 mg or 1 g intrapleurally via chest tube once. Dilute each dose in 0.9% Sodium Chloride Injection to yield 5 to 20 mg/mL. Dose range: 500 mg/dose to 2 g/dose.

    Infants, Children, and Adolescents

    20 mg/kg/dose (Max: 1 g/dose) intrapleurally via chest tube once. Dilute each dose in 0.9% Sodium Chloride Injection to yield 2 to 12.5 mg/mL. Adult dose range: 500 mg/dose to 2 g/dose.

    Neonates

    Limited data. 20 mg/kg/dose intrapleurally via chest tube once. Dilute each dose in 0.9% Sodium Chloride Injection to yield 2 to 8 mg/mL.

    For the treatment of malaria†.
    For the treatment of uncomplicated malaria† due to P. falciparum or P. vivax.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO twice daily for 7 days. Give in combination with quinine sulfate for P. falciparum or in combination with primaquine phosphate or tafenoquine for P. vivax.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO twice daily for 7 days. Give in combination with quinine sulfate for P. falciparum or in combination with primaquine phosphate or tafenoquine (16 years and older) for P. vivax.

    Children 1 to 7 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO twice daily for 7 days. Give in combination with quinine sulfate for P. falciparum or in combination with primaquine phosphate for P. vivax. In rare instances, doxycycline may be used in children younger than 8 years if other options are not available or are not tolerated and benefit of use outweighs risks.

    For the treatment of severe malaria† after IV artesunate therapy is completed.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO twice daily for 7 days.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO twice daily for 7 days.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours in persons unable to tolerate oral medication. Switch to oral therapy as soon as possible for a total treatment duration of 7 days.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours. Switch to oral therapy as soon as possible for a total treatment duration of 7 days.

    For the treatment of pelvic inflammatory disease (PID)† and tubo-ovarian abscess†.
    For the treatment of mild-to-moderate PID†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours in combination with metronidazole for 14 days and either single dose ceftriaxone IM, cefoxitin IM plus probenecid, or another parenteral third-generation cephalosporin. Patients who fail to respond within 72 hours should be reevaluated to confirm diagnosis and switched to IV therapy.

    Adolescents

    100 mg PO every 12 hours in combination with metronidazole for 14 days and either single dose ceftriaxone IM, cefoxitin IM plus probenecid, or another parenteral third-generation cephalosporin. Patients who fail to respond within 72 hours should be reevaluated to confirm diagnosis and switched to IV therapy.

    For the treatment of severe PID† or tubo-ovarian abscess†.
    Intravenous dosage
    Adults

    100 mg IV every 12 hours in combination with IV ceftriaxone plus metronidazole, cefotetan, cefoxitin, or ampicillin; sulbactam. IV therapy should be continued for at least 24 to 48 hours after clinical improvement, and then stepdown to oral metronidazole and doxycycline for a total of 14 days of therapy.

    Adolescents

    100 mg IV every 12 hours in combination with IV ceftriaxone plus metronidazole, cefotetan, cefoxitin, or ampicillin; sulbactam. IV therapy should be continued for at least 24 to 48 hours after clinical improvement, and then stepdown to oral metronidazole and doxycycline for a total of 14 days of therapy.

    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours as part of initial treatment IV ceftriaxone plus metronidazole, cefotetan, cefoxitin or ampicillin; sulbactam and as stepdown from IV treatment with metronidazole for a total of 14 days of therapy.

    Adolescents

    100 mg PO every 12 hours as part of initial treatment IV ceftriaxone plus metronidazole, cefotetan, cefoxitin or ampicillin; sulbactam and as stepdown from IV treatment with metronidazole for a total of 14 days of therapy.

    For the treatment of acute dental infection†, dentoalveolar infection†, or endodontic infection† including periodontitis in combination with conventional treatment (e.g., scaling and root planing).
    For aggressive juvenile periodontitis†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Children and Adolescents 8 to 17 years

    2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours on day 1, then 2 mg/kg/day PO every 24 hours or divided every 12 hours (Max: 100 mg/day).

    For periodontitis for a gain in clinical attachment, reduction in probing depth, and reduction in bleeding on probing.
    Oral dosage (excluding Doryx MPC delayed-release tablets)†
    Adults

    100 mg PO twice daily on day 1, then 100 mg PO once daily or 50 mg PO twice daily for 10 to 21 days.

    Oral dosage (Periodontitis tablets or capsules, e.g., Periostat, others)
    Adults

    20 mg PO every 12 hours for up to 9 months.

    Subgingival/Periodontal dosage (Atridox)
    Adults

    Dose is dependent on the size, shape, and number of pockets being treated. The final blended product is 500 mg of formulation containing 50 mg of doxycycline hyclate (10% doxycycline hyclate).

    Children and Adolescents 7 to 17 years†

    Very limited data. A case was reported of a 7-year-old boy who was successfully treated with Atridox for a paradental cyst mimicking a periodontal pocket. The dose is dependent on the size, shape, and number of pockets being treated. The final blended product is 500 mg of formulation containing 50 mg of doxycycline hyclate (10% doxycycline hyclate).

    For plague prophylaxis†.
    For pre-exposure prophylaxis†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours until 48 hours after the last perceived exposure as first-line therapy in most patients and as an alternative therapy in pregnant patients.

    Infants, Children, and Adolescents

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours until 48 hours after the last perceived exposure as first-line therapy.

    For postexposure prophylaxis†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for 7 days as first-line therapy in most patients and as an alternative therapy in pregnant patients.

    Infants, Children, and Adolescents

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 7 days as first-line therapy.

    Neonates

    2.2 mg/kg/dose PO every 12 hours for 7 days as first-line therapy.

    For tularemia prophylaxis† after exposure to Francisella tularensis.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for 14 days.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 14 days.

    For the treatment of Bancroft's filariasis† (elephantiasis) due to Wuchereria bancrofti†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    200 mg PO once daily for 8 weeks.

    For the treatment of melioidosis† due to Burkholderia pseudomallei.
    For the treatment of bacteremia due to Burkholderia pseudomallei†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 12 to 20 weeks plus sulfamethoxazole; trimethoprim for 12 to 20 weeks with or without chloramphenicol for 8 weeks as maintenance therapy after completing at least 10 to 14 days of parenteral therapy.

    Children and Adolescents 8 to 17 years

    2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 12 to 20 weeks plus sulfamethoxazole; trimethoprim for 12 to 20 weeks with or without chloramphenicol for 8 weeks as maintenance therapy after completing at least 10 to 14 days of parenteral therapy.

    Intravenous dosage
    Adults

    2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours for at least 10 to 14 days plus ceftazidime followed by oral maintenance therapy.

    Children and Adolescents 8 to 17 years

    2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours for at least 10 to 14 days plus ceftazidime followed by oral maintenance therapy.

    For treatment of localized melioidosis†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 12 to 20 weeks plus sulfamethoxazole; trimethoprim.

    Children and Adolescents 8 to 17 years

    2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 12 to 20 weeks plus sulfamethoxazole; trimethoprim.

    For the treatment of leptospirosis†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for 7 days as first-line therapy for mild or moderate disease.

    Children and Adolescents 8 to 17 years

    1 to 2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 7 days as first-line therapy for mild or moderate disease.

    For surgical infection prophylaxis† for gynecologic procedures.
    For surgical infection prophylaxis† for hysterosalpingogram or chromotubation.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO twice daily for 5 days.

    For surgical infection prophylaxis† for induced abortion/dilation and evacuation.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO 1 hour before the procedure and 200 mg PO after the procedure.

    For Helicobacter pylori (H. pylori) eradication†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO once daily in combination with levofloxacin, nitazoxanide, and a proton pump inhibitor for 7 to 10 days. Guidelines recommend this regimen as a first-line treatment option.

    For bacterial endocarditis prophylaxis†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO as a single dose given 30 to 60 minutes before procedure as an alternative for patients allergic to penicillin, cephalosporin, or macrolide. Prophylaxis is recommended for at-risk cardiac patients who are undergoing dental procedures that involve manipulation of gingival tissue, manipulation of the periapical region of teeth, or perforation of the oral mucosa.[61833]

    Children and Adolescents

    4.4 mg/kg/dose (Max: 100 mg/dose) PO as a single dose given 30 to 60 minutes before procedure as an alternative for patients allergic to penicillin, cephalosporin, or macrolide. Prophylaxis is recommended for at-risk cardiac patients who are undergoing dental procedures that involve manipulation of gingival tissue, manipulation of the periapical region of teeth, or perforation of the oral mucosa.[61833]

    For the treatment of acute proctitis†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for 7 days in combination with single dose IM ceftriaxone. Doxycycline course should be extended to 21 days in the presence of bloody discharge, perianal or mucosal ulcers, or tenesmus and a positive rectal chlamydia test.

    For leptospirosis prophylaxis†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    200 mg PO once weekly beginning 1 to 2 days before and continuing through the exposure for persons at high-risk with short term exposures.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    Oral immediate and delayed-release formulations excluding Doryx MPC and periodontal dosage formulations: 300 mg/day PO; 600 mg PO in a single physician's visit for acute gonococcal infections.
    Intravenous formulation: 300 mg/day IV.
    Doryx MPC: 240 mg/day PO; 720 mg PO in a single physician's visit for acute gonococcal infections.
    Oracea or Periostat: 40 mg/day PO.

    Geriatric

    Oral immediate and delayed-release formulations excluding Doryx MPC and periodontal dosage formulations: 300 mg/day PO; 600 mg PO in a single physician's visit for acute gonococcal infections.
    Intravenous formulation: 300 mg/day IV.
    Doryx MPC: 240 mg/day PO; 720 mg PO in a single physician's visit for acute gonococcal infections.
    Oracea or Periostat: 40 mg PO/day.

    Adolescents

    45 kg or more:
    Oral immediate and delayed-release formulations excluding Doryx MPC and periodontal dosage formulations: 300 mg/day PO; 600 mg PO in a single physician's visit for acute gonococcal infections.
    Intravenous formulation: 300 mg/day IV.
    Doryx MPC: 240 mg/day PO; 720 mg PO in a single physician's visit for acute gonococcal infections.
     
    Less than 45 kg:
    Oral immediate and delayed-release formulations excluding Doryx MPC and periodontal dosage formulations: 4.4 mg/kg/day PO.
    Intravenous formulation: 4.4 mg/kg/day IV.
    Doryx MPC: 5.3 mg/kg/day PO.

    Children

    8 years and older and 45 kg or more:
    Oral immediate and delayed-release formulations excluding Doryx MPC and periodontal dosage formulations: 300 mg/day PO; 600 mg PO in a single physician's visit for acute gonococcal infections.
    Intravenous formulation: 300 mg/day IV.
    Doryx MPC: 240 mg/day PO; 720 mg PO in a single physician's visit for acute gonococcal infections.
    Oracea or Periostat: 40 mg PO/day.
    8 years and older and less than 45 kg:
    Oral immediate and delayed-release formulations excluding Doryx MPC and periodontal dosage formulations: 4.4 mg/kg/day PO.
    Intravenous formulation: 4.4 mg/kg/day IV.
    Doryx MPC: 5.3 mg/kg/day PO.
    1 to 7 years: Use generally not recommended; however, may be used for severe or life-threatening infections (e.g., anthrax, Rocky Mountain spotted fever).
    Oral immediate and delayed-release formulations excluding Doryx MPC and periodontal dosage formulations: 4.4 mg/kg/day PO.
    Intravenous formulation: 4.4 mg/kg/day IV.
    Doryx MPC: 5.3 mg/kg/day PO.

    Infants

    Use generally not recommended; however, doses up to 4.4 mg/kg/day PO/IV may be used for severe or life-threatening infections (e.g., anthrax, Rocky Mountain spotted fever).

    Neonates

    Use generally not recommended; however, doses up to 4.4 mg/kg/day PO/IV may be used for severe or life-threatening infections (e.g., anthrax, Rocky Mountain spotted fever).

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Doxycycline is cleared both renally and fecally without hepatic metabolism; it appears no dosage adjustments are needed in mild impairment. However, dose adjustment may be necessary when prescribing doxycycline to patients with severe hepatic disease because hepatic excretion into bile may be delayed and elimination half-life extended.

    Renal Impairment

    No dosage adjustment needed.
     
    Intermittent hemodialysis
    No dosage adjustment needed.

    ADMINISTRATION

    Oral Administration

    To reduce the risk of esophageal irritation and ulceration, administer with adequate amounts of fluid.
    For patients with esophageal obstruction or compression, do not administer at bedtime in order to reduce the risk of esophageal irritation or ulceration.
    Divalent and trivalent cations significantly affect absorption. Do not administer sucralfate (contains aluminum), oral iron supplements, or aluminum-, magnesium-, or calcium-containing antacids in conjunction with oral doxycycline. Multivitamins containing manganese or zinc salts will also decrease absorption.

    Oral Solid Formulations

    Immediate-release tablets or capsules and Delayed-release tablets: Of all the tetracyclines, doxycycline has the least affinity for calcium ions. Therefore, overall absorption is not significantly affected when the immediate- or delayed-release doxycycline products are taken with milk or other dairy products, but absorption may be delayed.[27974] [29817] [60812] The FDA-approved product labeling states that these products may be administered with food and/or milk if gastric irritation occurs.[29817] [60812]
    Delayed-release tablets: May be swallowed whole or may also be administered by carefully breaking up the tablet and sprinkling the tablet contents (delayed-release pellets) on a spoonful of applesauce. The delayed-release pellets must not be crushed or damaged when breaking up the tablet. The applesauce should not be hot and should be swallowed immediately without chewing. If desired, follow with a cool 8-ounce glass of water. If the prepared dose cannot be consumed immediately, it should be discarded; do not store for later use.[60812]
    Dual-release capsules (e.g., Oracea): Administer at least 1 hour before or 2 hours after meals.[32240]
    Tablets and capsules for periodontitis: Administer at least 1 hour before morning and evening meals.[34113] [44000]

    Oral Liquid Formulations

    Shake well prior to each use.
    Use a calibrated oral device (e.g., oral syringe or spoon) to ensure accurate dosage.
    Of all the tetracyclines, doxycycline has the least affinity for calcium ions. Therefore, overall absorption is not significantly affected when the immediate-release doxycycline products are taken with milk or other dairy products, but absorption may be delayed. The FDA-approved product labeling states that the oral suspension may be administered with food and/or milk if gastric irritation occurs.
     
    Reconstitution
    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 water in 2 portions and shake well after each addition.
    Storage: Store reconstituted suspension at room temperature; discard after 14 days.

    Extemporaneous Compounding-Oral

    In cases where doxycycline oral suspension is not readily available, the FDA has issued guidance for preparing emergency dosages of doxycycline for patients unable to swallow solid oral dosage formulations using doxycycline tablets. Further, detailed information regarding the proper preparation, administration, and storage of doxycycline emergency doses may be obtained on the FDA website.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    (Doxycycline hyclate only)
    Doxycycline hyclate IV solutions should not be given IM or subcutaneous.
    Oral therapy should replace IV infusion as soon as possible to reduce the risk of thrombophlebitis.
     
    Reconstitution:
    Reconstitute 100 or 200 mg vial with 10 or 20 mL, respectively, of Sterile Water for Injection or other compatible IV solution to give a concentration of 10 mg/mL. Each 100 mg of doxycycline must be further diluted with 100 to 1000 mL of a compatible IV infusion solution to give concentrations of 0.1 to 1 mg/mL.
     
    Intravenous infusion:
    Rapid administration is to be avoided.
    Extravasation of doxycycline should be avoided.
    According to the manufacturer, a 0.5 mg/mL IV solution containing 100 mg of doxycycline hyclate should be infused over at least 1 hour.

    Other Administration Route(s)

    Subgingival Administration
    Atridox is locally applied and placed gently below the gum line into periodontal pockets.
    Atridox does not require local anesthesia for placement. Follow the directions for preparing the formulation provided by the manufacturer. To administer, bend the cannula to resemble a periodontal probe and explore the periodontal pocket in a manner similar to periodontal probing. Keeping the cannula tip near the base of the pocket, express the product into the pocket until the formulation reaches the top of the gingival margin. Withdraw the cannula tip from the pocket. In order to separate the tip from the formulation, turn the tip of the cannula towards the tooth, press the tip against the tooth surface, and pinch the string of formulation from the tip of the cannula. Variations on this technique may be needed to achieve separation between the formulation and cannula.
    If desired, using an appropriate dental instrument, the formulation may be packed into the pocket. Dipping the edge of the instrument in water before packing will help keep the formulation from sticking to the instrument, and will help speed coagulation of the formulation. A few drops of water dripped onto the surface of the formulation once in the pocket well also aid in coagulation. If necessary, add more formulation as described above and pack it into the pocket until the pocket is full.
    Cover the pockets containing the formulation with either Coe-Pak periodontal dressing or Octyldent dental adhesive.
    Instruct patient on appropriate home care after application; the patient will not brush or floss the treated area for 7 days; an oral rinse may be used. If small amounts are dislodged, the medicine is harmless if swallowed.

    STORAGE

    Acticlate:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Adoxa:
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Adoxa Pak:
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Alodox:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Avidoxy:
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Doryx:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    - Store in a dry, well ventilated place
    Doxal:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Doxy 100:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not refreeze once thawed
    - Protect from direct sunlight
    - Protect from light
    - Reconstituted product must be stored under refrigeration (36 to 46 degrees F) and any unused product discarded after 72 hours
    - See package insert for detailed storage information
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in carton until time of use
    LYMEPAK:
    - Store between 68 to 77 degrees F
    Mondoxyne NL:
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Monodox:
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Morgidox 1x:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Morgidox 1x Kit:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Morgidox 2x :
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Morgidox 2x Kit:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    NutriDox :
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Ocudox :
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Okebo:
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Oracea:
    - Store at room temperature (between 59 to 86 degrees F)
    Oraxyl:
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Periostat:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    TARGADOX:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Vibramycin:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Vibra-Tabs:
    - Store between 68 to 77 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Tetracyclines hypersensitivity

    Doxycycline and other tetracycline antibiotics are contraindicated in patients with known tetracyclines hypersensitivity.

    Sunlight (UV) exposure

    Doxycycline is associated with photosensitivity reactions after sunlight (UV) exposure, with these reactions occurring somewhat less frequently than with demeclocycline. Reactions can develop from within a few minutes to up to several hours after exposure and will last for 1 to 2 days after discontinuation of the drug. Advise drug recipients to avoid excess sunlight/artificial ultraviolet light whenever possible, to use sunscreens, and to discontinue therapy if phototoxicity occurs (i.e., skin eruption). Photosensitivity reactions are believed to be due to accumulation of the drug in the skin and are mostly phototoxic in nature, but photoallergic reactions also can occur with select drugs.

    Asthma, sulfite hypersensitivity

    Doxycycline calcium oral suspension contains sodium metabisulfite. Sulfites cause an allergic reaction in some people; use this product with caution in patients with a known sulfite hypersensitivity. This sensitivity reaction is more common in patients with asthma than in non-asthmatic patients.

    Achlorhydria

    Increases in gastric pH may reduce the absorption of doxycycline. For example, the bioavailability of doxycycline may be reduced in patients on proton pump inhibitor therapy or with achlorhydria.[32242]

    Children, infants, neonates

    Tetracyclines, like doxycycline, may have a serious effect on the bones and teeth in young children. Tetracyclines are incorporated into bones and teeth that are undergoing calcification. This may cause permanent yellow or brown discoloration and enamel hypoplasia in developing teeth or reversible inhibition of bone growth. Use doxycycline in neonates, infants, and children younger than 8 years only when the potential benefits are expected to outweigh the risks in severe or life-threatening infections (e.g., anthrax, Rocky Mountain spotted fever), particularly when no other alternative therapies are available. However, studies have failed to demonstrate dental staining, enamel hypoplasia, or tooth color differences in children who have received short-term courses of doxycycline at younger than 8 years of age and suggest that this concern may be unwarranted. Doxycycline is the treatment of choice for children of any age for certain infections (i.e., anthrax prophylaxis, Rickettsial diseases). Guidelines suggest doxycycline may be used for the treatment of uncomplicated malaria in children younger than 8 years in rare instances if other options are not available or are not tolerated and benefit of use outweighs risks.

    Geriatric

    In general, doxycycline dose selection for the geriatric patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) of long-term care facilities (LTCFs). 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.

    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 doxycycline, 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.

    Periodontal disease

    Subgingival doxycycline has not been clinically evaluated in patients with conditions involving extremely severe periodontal disease or defects with very little remaining periodontium. Similarly, subgingival doxycycline has not been clinically tested for use in the regeneration of alveolar bone, either in preparation for or in conjunction with the placement of endosseous (dental) implants or in the treatment of failing implants. The dosage of doxycycline achieved with Periostat or similar oral doxycycline formulations is well below the concentration required to inhibit microorganisms commonly associated with adult periodontitis. Clinical studies with this product demonstrated no effect on total anaerobic and facultative bacteria in plaque samples from patients administered this dose regimen for 9 to 18 months. Do not use Periostat or equivalents for reducing the numbers of or eliminating those microorganisms associated with periodontitis.

    Chemotherapy, diabetes mellitus, human immunodeficiency virus (HIV) infection, immunosuppression, radiation therapy

    Subgingival doxycycline has not been clinically tested in immunocompromised patients, such as patients with immunosuppression due to diabetes mellitus, chemotherapy, radiation therapy, or human immunodeficiency virus (HIV) infection. Use doxycycline with caution in patients with a history of or predisposition to oral candidiasis. The safety and effectiveness of doxycycline have not been established for the treatment of periodontitis, in particular, in patients with coexistent oral candidiasis.

    Increased intracranial pressure, obesity

    Doxycycline has been associated with increased intracranial pressure in adults and bulging fontanels in infants. Women of childbearing age with obesity or a prior history of intracranial hypertension are at higher risk for developing doxycycline-associated intracranial hypertension. Since blurred vision, diplopia, and permanent vision loss are potential clinical manifestations of intracranial hypertension, ophthalmologic evaluations (i.e., fundoscopy) are advised for patients developing visual symptoms while receiving doxycycline. Stopping the drug usually resolves intracranial hypertension; however, pressures may remain elevated for weeks after treatment discontinuation. Continue to monitor patients until they stabilize. In addition, avoid concurrent use of doxycycline with isotretinoin, as isotretinoin is also associated with increased intracranial pressures.

    Laboratory test interference

    Administration of doxycycline may result in laboratory test interference. False elevations of urinary catecholamine concentrations may occur due to interference with the fluorescence test. Additionally, antimicrobials are 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 doxycycline in the 4 weeks prior to the test.

    Pregnancy

    There are no adequate and well-controlled studies on the use of doxycycline in pregnant women. There are no data available on the risk of miscarriage after doxycycline exposure. Most reported experience with doxycycline during human pregnancy is short-term, first-trimester exposure. Available data over decades have not shown a difference in major birth defect risk compared to unexposed pregnancies with doxycycline exposure during the first trimester of pregnancy. There are no human data available to assess the effects of long-term therapy of doxycycline in pregnant women. Tetracyclines may cause discoloration of deciduous teeth and reversible inhibition of bone growth when administered during the second and third trimester of pregnancy. Advise the patient of the potential risk to the fetus if doxycycline is used during pregnancy. In a nested, case-control study (n = 87,020 controls; 8,702 cases) within the Quebec Pregnancy Cohort, tetracycline use during early pregnancy was associated with an increased risk of spontaneous abortion (adjusted odds ratio (aOR) 2.59, 95% CI: 1.97 to 3.41, 67 exposed cases); residual confounding by severity of infection may be a potential limitation of this study. Additionally, in a large population-based cohort study (n = 139,938 live births) assessing antibiotic exposure during the first trimester of pregnancy (n = 15,469 exposures) and the risk of major birth defects, doxycycline was associated with an increased risk of circulatory system malformation, cardiac malformations, and ventricular/atrial septal defect (aOR 2.38, 95% CI: 1.21 to 4.67, 9 exposed cases; aOR 2.46, 95% CI: 1.21 to 4.99, 8 exposed cases; aOR 3.19, 95% CI: 1.57 to 6.48, 8 exposed cases, respectively). Possible study limitations include potential unmeasured confounders (i.e., smoking, folic acid, and alcohol intake) as well as that the study was underpowered to detect associations between individual antibiotics and specific malformations due to the small number of exposed cases. In another case-control study (n = 32,804 controls; 18,515 cases), there was a weak but marginally statistically significant association with total malformations and use of doxycycline (n = 64 (0.19%) of the controls and 56 (0.3%) of the cases treated with doxycycline) anytime during pregnancy. No association was seen when the analysis was confined to maternal treatment during the period of organogenesis (i.e., in the second and third months of gestation) with the exception of a marginal relationship with neural tube defect based on only 2 exposed cases. Guidelines suggest doxycycline may be used for the treatment of uncomplicated malaria during pregnancy in rare instances if other options are not available or are not tolerated and benefit of use outweighs risks.

    Breast-feeding

    Tetracyclines, including doxycycline, are distributed in small amounts into breast milk. There are no data on the effects of doxycycline on the breast-fed infant or milk production. Because of the potential for serious adverse reactions in nursing infants, breast-feeding is not recommended during treatment with doxycycline and for 5 days after the last dose. In general, tetracycline antibiotics are not recommended for use in breast-feeding mothers due to a theoretical risk of causing tooth discoloration, enamel hypoplasia, inhibition of linear skeletal growth, oral and vaginal thrush, or photosensitivity reactions in the nursing infant. However, because tetracyclines bind to calcium in the maternal breast milk, the risk for oral absorption by the infant is minimal. Data are available regarding doxycycline milk concentrations in breast-feeding women; however, infant serum concentrations and any effects on breast-feeding infants were not reported. Doxycycline (100 mg PO daily) was given to 10 mothers. On the second day of treatment, milk doxycycline averaged 0.82 mg/L (range 0.37 to 1.24 mg/L) at 3 hours after the dose, and 0.46 mg/L (range 0.3 to 0.91 mg/L) at 24 hours after the dose. Using the average of the peak and trough milk concentrations in this study, the estimated average intake of an exclusively breast-fed infant would be about 6% of the maternal weight-adjusted dosage. Further available data indicate that after doses of 100 to 200 mg PO, milk concentrations do not exceed an average of 1.8 mg/L. Studies of long-term tetracycline use in breast-feeding are lacking. Previous American Academy of Pediatrics recommendations did not address doxycycline but classified another tetracycline antibiotic, tetracycline, as usually compatible with breast-feeding.

    Infertility, reproductive risk

    Doxycycline may be associated with reproductive risk. Based on findings from a fertility study in animals, doxycycline may cause infertility in both males and females. The reversibility of this finding is unclear.

    ADVERSE REACTIONS

    Severe

    enterocolitis / Delayed / Incidence not known
    odynophagia / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    esophageal ulceration / Delayed / Incidence not known
    hepatic failure / Delayed / Incidence not known
    C. difficile-associated diarrhea / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    azotemia / Delayed / Incidence not known
    papilledema / Delayed / Incidence not known
    increased intracranial pressure / Early / Incidence not known

    Moderate

    hypertension / Early / 3.0-3.0
    elevated hepatic enzymes / Delayed / 2.0-2.0
    hyperglycemia / Delayed / 1.0-1.0
    hepatitis / Delayed / Incidence not known
    glossitis / Early / Incidence not known
    dysphagia / Delayed / Incidence not known
    esophagitis / Delayed / Incidence not known
    candidiasis / Delayed / Incidence not known
    superinfection / Delayed / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known
    erythema / Early / Incidence not known
    enamel hypoplasia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    phlebitis / Rapid / Incidence not known
    blurred vision / Early / Incidence not known
    pseudotumor cerebri / Delayed / Incidence not known
    infertility / Delayed / Incidence not known
    growth inhibition / Delayed / Incidence not known

    Mild

    Jarisch-Herxheimer reaction / Early / 0-30.0
    influenza / Delayed / 2.0-11.0
    nausea / Early / 8.0-8.0
    diarrhea / Early / 5.0-6.0
    dyspepsia / Early / 6.0-6.0
    musculoskeletal pain / Early / 1.0-6.0
    pharyngitis / Delayed / 5.0-5.0
    throat irritation / Early / 5.0-5.0
    cough / Delayed / 4.0-4.0
    sinusitis / Delayed / 3.0-3.0
    back pain / Delayed / 1.0-3.0
    abdominal pain / Early / 1.0-2.0
    anxiety / Delayed / 2.0-2.0
    nasal congestion / Early / 2.0-2.0
    xerostomia / Early / 1.0-1.0
    vomiting / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    paresthesias / Delayed / Incidence not known
    onycholysis / Delayed / Incidence not known
    photosensitivity / Delayed / Incidence not known
    headache / Early / Incidence not known
    tooth discoloration / Delayed / Incidence not known
    skin hyperpigmentation / Delayed / Incidence not known
    nail discoloration / Delayed / Incidence not known
    injection site reaction / Rapid / Incidence not known
    diplopia / Early / Incidence not known

    DRUG INTERACTIONS

    Acitretin: (Contraindicated) The concomitant use of acitretin and systemic tetracyclines is contraindicated, due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with systemic retinoid use alone and early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances.
    Aluminum Hydroxide: (Moderate) Separate administration of oral doxycycline and antacids by 2 to 3 hours. Coadministration may impair absorption of doxycycline which may decrease its efficacy.
    Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Separate administration of oral doxycycline and antacids by 2 to 3 hours. Coadministration may impair absorption of doxycycline which may decrease its efficacy.
    Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Separate administration of oral doxycycline and antacids by 2 to 3 hours. Coadministration may impair absorption of doxycycline which may decrease its efficacy.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Separate administration of oral doxycycline and antacids by 2 to 3 hours. Coadministration may impair absorption of doxycycline which may decrease its efficacy.
    Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Separate administration of oral doxycycline and antacids by 2 to 3 hours. Coadministration may impair absorption of doxycycline which may decrease its efficacy.
    Amobarbital: (Major) Phenobarbital has been shown to affect the pharmacokinetics of doxycycline. Doxycycline half-life was decreased from 15.3 hours to 11.1 hours. It is likely that other barbiturates may exert the same effect. Clinicians should keep in mind that larger doses of doxycycline may be necessary in patients receiving barbiturates. This interaction may not apply to other tetracyclines since they are less dependent on hepatic metabolism for elimination.
    Amoxicillin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Amoxicillin; Clarithromycin; Omeprazole: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Amoxicillin; Clavulanic Acid: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Ampicillin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Ampicillin; Sulbactam: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Antacids: (Moderate) Separate administration of oral doxycycline and antacids by 2 to 3 hours. Coadministration may impair absorption of doxycycline which may decrease its efficacy.
    Aspirin, ASA; Butalbital; Caffeine: (Major) Phenobarbital has been shown to affect the pharmacokinetics of doxycycline. Doxycycline half-life was decreased from 15.3 hours to 11.1 hours. It is likely that other barbiturates may exert the same effect. Clinicians should keep in mind that larger doses of doxycycline may be necessary in patients receiving barbiturates. This interaction may not apply to other tetracyclines since they are less dependent on hepatic metabolism for elimination.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Phenobarbital has been shown to affect the pharmacokinetics of doxycycline. Doxycycline half-life was decreased from 15.3 hours to 11.1 hours. It is likely that other barbiturates may exert the same effect. Clinicians should keep in mind that larger doses of doxycycline may be necessary in patients receiving barbiturates. This interaction may not apply to other tetracyclines since they are less dependent on hepatic metabolism for elimination.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Early reports noted an increase in the excretion of tetracyclines during coadministration with sodium bicarbonate, and that the oral absorption of tetracyclines is reduced by sodium bicarbonate via increased gastric pH. However, conflicting data have been reported, and further study is needed. Two recent studies show no effect of oral sodium bicarbonate administration on tetracycline oral bioavailability. In one of these trials, coadministration with sodium bicarbonate was reported to have no effect on tetracycline urinary excretion, Cmax, or AUC. Until more information is available, avoid simultaneous administration of sodium bicarbonate and tetracyclines. When concurrent therapy is needed, stagger administration times by several hours to minimize the potential for interaction, and monitor for antimicrobial efficacy.
    Bacillus Calmette-Guerin Vaccine, BCG: (Major) Doxycycline may interfere with the effectiveness of Bacillus Calmette-Guerin Live, BCG. The TheraCys product is made from the Connaught strain of Bacillus Calmette and Guerin, which is an attenuated strain of Mycobacterium bovis. Sensitivity of the Connaught strain to several antibiotics was tested in vitro. Bacteria were susceptible to doxycycline. Urinary concentrations of doxycycline could interfere with the therapeutic effectiveness of BCG. Although the TICE BCG product is obtained from a different strain (Tice strain), similar antimicrobial sensitivities may occur. Postpone instillation of BCG if the patient is receiving antibiotics. Antituberculosis drugs should not be used to prevent or treat local, irritative toxicities associated with BCG Live treatment (see Adverse Reactions). Also, BCG Live should not be used in patients with an active infection.
    Barbiturates: (Major) Phenobarbital has been shown to affect the pharmacokinetics of doxycycline. Doxycycline half-life was decreased from 15.3 hours to 11.1 hours. It is likely that other barbiturates may exert the same effect. Clinicians should keep in mind that larger doses of doxycycline may be necessary in patients receiving barbiturates. This interaction may not apply to other tetracyclines since they are less dependent on hepatic metabolism for elimination.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Phenobarbital has been shown to affect the pharmacokinetics of doxycycline. Doxycycline half-life was decreased from 15.3 hours to 11.1 hours. It is likely that other barbiturates may exert the same effect. Clinicians should keep in mind that larger doses of doxycycline may be necessary in patients receiving barbiturates. This interaction may not apply to other tetracyclines since they are less dependent on hepatic metabolism for elimination.
    Bexarotene: (Major) The concomitant use of systemic retinoid therapy, such as bexarotene, and systemic tetracyclines should be avoided due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with systemic retionoid use alone and early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Separate administration of oral tetracyclines and bismuth subsalicylate by at least 2 to 3 hours. Coadministration may impair absorption of oral tetracyclines which may decrease their efficacy. Some data suggest that this interaction may only apply to administration with bismuth subsalicylate suspension.
    Bismuth Subsalicylate: (Moderate) Separate administration of oral tetracyclines and bismuth subsalicylate by at least 2 to 3 hours. Coadministration may impair absorption of oral tetracyclines which may decrease their efficacy. Some data suggest that this interaction may only apply to administration with bismuth subsalicylate suspension.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Separate administration of oral tetracyclines and bismuth subsalicylate by at least 2 to 3 hours. Coadministration may impair absorption of oral tetracyclines which may decrease their efficacy. Some data suggest that this interaction may only apply to administration with bismuth subsalicylate suspension.
    Butabarbital: (Major) Phenobarbital has been shown to affect the pharmacokinetics of doxycycline. Doxycycline half-life was decreased from 15.3 hours to 11.1 hours. It is likely that other barbiturates may exert the same effect. Clinicians should keep in mind that larger doses of doxycycline may be necessary in patients receiving barbiturates. This interaction may not apply to other tetracyclines since they are less dependent on hepatic metabolism for elimination.
    Butalbital; Acetaminophen: (Major) Phenobarbital has been shown to affect the pharmacokinetics of doxycycline. Doxycycline half-life was decreased from 15.3 hours to 11.1 hours. It is likely that other barbiturates may exert the same effect. Clinicians should keep in mind that larger doses of doxycycline may be necessary in patients receiving barbiturates. This interaction may not apply to other tetracyclines since they are less dependent on hepatic metabolism for elimination.
    Butalbital; Acetaminophen; Caffeine: (Major) Phenobarbital has been shown to affect the pharmacokinetics of doxycycline. Doxycycline half-life was decreased from 15.3 hours to 11.1 hours. It is likely that other barbiturates may exert the same effect. Clinicians should keep in mind that larger doses of doxycycline may be necessary in patients receiving barbiturates. This interaction may not apply to other tetracyclines since they are less dependent on hepatic metabolism for elimination.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Phenobarbital has been shown to affect the pharmacokinetics of doxycycline. Doxycycline half-life was decreased from 15.3 hours to 11.1 hours. It is likely that other barbiturates may exert the same effect. Clinicians should keep in mind that larger doses of doxycycline may be necessary in patients receiving barbiturates. This interaction may not apply to other tetracyclines since they are less dependent on hepatic metabolism for elimination.
    Calcium Acetate: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Calcium Carbonate: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Calcium Carbonate; Magnesium Hydroxide: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Calcium Carbonate; Risedronate: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Calcium Carbonate; Simethicone: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Calcium Chloride: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Calcium Gluconate: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Calcium: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Calcium; Vitamin D: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Carbamazepine: (Moderate) Monitor for decreased efficacy of doxycycline if coadministered with carbamazepine. Carbamazepine may potentially accelerate the hepatic metabolism of doxycycline.
    Carbenicillin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Carbetapentane; Guaifenesin; Phenylephrine: (Major) Concurrent administration of oral zinc salts with oral tetracyclines can decrease the absorption of these antiinfectives and possibly interfere with their therapeutic response. This is a result of the formation of insoluble chelates between zinc and the antiinfective. Oral zinc supplements should be administered at least 6 hours before or 2 hours after administering tetracyclines.
    Carbetapentane; Phenylephrine: (Major) Concurrent administration of oral zinc salts with oral tetracyclines can decrease the absorption of these antiinfectives and possibly interfere with their therapeutic response. This is a result of the formation of insoluble chelates between zinc and the antiinfective. Oral zinc supplements should be administered at least 6 hours before or 2 hours after administering tetracyclines.
    Chlorpheniramine; Pseudoephedrine: (Major) Concurrent administration of oral zinc salts with oral tetracyclines can decrease the absorption of these antiinfectives and possibly interfere with their therapeutic response. This is a result of the formation of insoluble chelates between zinc and the antiinfective. Oral zinc supplements should be administered at least 6 hours before or 2 hours after administering tetracyclines.
    Cholera Vaccine: (Major) Avoid the live cholera vaccine in patients that have received doxycycline within 14 days prior to vaccination. Concurrent administration of the live cholera vaccine with antibiotics active against cholera, such as doxycycline, may diminish vaccine efficacy and result in suboptimal immune response. A duration of fewer than 14 days between stopping antibiotics and vaccination might also be acceptable in some clinical settings if travel cannot be avoided before 14 days have elapsed after stopping antibiotics.
    Cholestyramine: (Major) Colestipol has been shown to reduce tetracycline absorption by roughly 50%. It is likely this is enough to cause a clinically significant effect. Although no data are available for other tetracyclines, or for cholestyramine, it should be assumed that any tetracycline antibiotic may be affected similarly by either cholestyramine or colestipol. Staggering oral doses of each agent is recommended to minimize this pharmacokinetic interaction. To minimize drug interactions, administer tetracyclines at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine. Since doxycycline undergoes enterohepatic recirculation, it may be even more susceptible to this drug interaction than the other tetracyclines.
    Chromium: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Colesevelam: (Moderate) Colesevelam may decrease the bioavailability of tetracyclines. To minimize potential for interactions, consider administering oral tetracyclines at least 4 hours before colesevelam. The manufacturer for colesevelam suggests monitoring serum drug concentrations and/or clinical effects for those drugs for which alterations in serum blood concentrations have a clinically significant effect on safety or efficacy.
    Colestipol: (Major) Colestipol has been shown to reduce tetracycline absorption by roughly 50%. It is likely this is enough to cause a clinically significant effect. Although no data are available for other tetracyclines, it should be assumed that any tetracycline antibiotic may be affected similarly by colestipol. Staggering oral doses of each agent is recommended to minimize this pharmacokinetic interaction; administer tetracyclines at least 1 hour before or at least 4 to 6 hours after the administration of colestipol. Since doxycycline undergoes enterohepatic recirculation, it may be even more susceptible to this drug interaction than the other tetracyclines.
    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.
    Dicloxacillin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Didanosine, ddI: (Major) Tetracyclines should not be administered simultaneously with didanosine, ddI chewable tablets or powder for oral solution. The buffering agents contained in didanosine tablets and powder reduce tetracycline absorption. Administer oral doses of tetracycline antibiotics 1 hour before or 4 hours after didanosine tablet or powder administration. The delayed-release didanosine capsules do not contain a buffering agent and would not be expected to interact with tetracycline antibiotics.
    Dienogest; Estradiol valerate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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. (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: (Major) Measure serum digoxin concentrations before initiating tetracyclines. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30 to 50% or by modifying the dosing frequency, and continue monitoring. In approximately 10% of patients, a small portion of a digoxin dose is metabolized in the gut by intestinal Eubacterium lentum, an anaerobic bacillus, to inactive digoxin reduction products (DRPs). DRPs have little cardiac activity due to poor cardiac receptor binding and rapid excretion. Certain antibiotics can reduce the activity of intestinal bacteria, which, in turn, may enhance digoxin bioavailability via decreased DRP formation and increased enterohepatic recycling of digoxin in some patients. The addition of tetracycline to digoxin therapy has been reported to increase the serum digoxin concentration by 100%. Digoxin toxicity has been reported in patients previously stabilized on digoxin who receive antibiotics that affect E. lentum, such as tetracyclines. Other antibiotics that have activity against E. lentum may produce similar effects on digoxin metabolism.
    Drospirenone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Estetrol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Elagolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Estradiol Cypionate; Medroxyprogesterone: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject 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: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen 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 oral contraceptives (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 levels of oral contraceptives. 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 of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Estradiol; Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Estradiol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Estradiol; Norgestimate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    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.
    Ethotoin: (Moderate) Monitor for decreased efficacy of doxycycline if coadministered with hydantoins. Hydantoins decrease the half-life of doxycycline.
    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.
    Ferric Maltol: (Moderate) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
    Food: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of certain tetracycline class antibiotics will be reduced by agents containing these cations (e.g., calcium) and it is often recommended to avoid administration within 1 to 2 hours of interfering foods (e.g., dairy products). However, the oral absorption of doxycycline appears to be less affected by food interactions than tetracycline. Some manufacturers state that absorption of oral doxycycline is not markedly influenced by simultaneous ingestion of food or milk and recommend taking doxycycline with food or milk if gastric irritation occurs upon administration. However, there are studies describing altered doxycycline pharmacokinetics when given with meals containing dairy products. A single-dose study of Periostat given with a 1,000 calorie, high-fat, high-protein meal, which included dairy products, resulted in a decrease in the rate and extent of absorption and delay in the time to maximum concentrations. The dual-release capsules (Oracea) are not bioequivalent to other doxycycline products; absorption may be decreased when given with meals. In a single-dose food effect study, the Cmax and AUC of doxycycline (as Oracea) were reduced by about 45% and 22%, respectively, in healthy volunteers fed a 1,000 calorie, high-fat, high-protein meal which included dairy products. The reductions in AUC and Cmax can be clinically significant. (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of certain tetracycline class antibiotics will be reduced by agents containing these cations (e.g., iron) and it is often recommended to avoid administration within at least 1 to 2 hours of interfering foods (e.g., foods containing high amounts of iron). However, the oral absorption of doxycycline appears to be less affected by food interactions than tetracycline. Some manufacturers state that absorption of oral doxycycline is not markedly influenced by simultaneous ingestion of food or milk and recommend taking doxycycline with food or milk if gastric irritation occurs upon administration. However, there are studies describing altered doxycycline pharmacokinetics when given with meals. A single-dose study of Periostat given with a 1,000 calorie, high-fat, high-protein meal, which included dairy products, resulted in a decrease in the rate and extent of absorption and delay in the time to maximum concentrations. The dual-release capsules (Oracea) are not bioequivalent to other doxycycline products; absorption may be decreased when given with meals. In a single-dose food effect study, the Cmax and AUC of doxycycline (as Oracea) were reduced by about 45% and 22%, respectively, in healthy volunteers fed a 1,000 calorie, high-fat, high-protein meal which included dairy products. The reductions in AUC and Cmax can be clinically significant.
    Fosphenytoin: (Moderate) Monitor for decreased efficacy of doxycycline if coadministered with hydantoins. Hydantoins decrease the half-life of doxycycline.
    Halobetasol; Tazarotene: (Moderate) The manufacturer states that tazarotene should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as tetracyclines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Heparin: (Minor) Tetracyclines may partially counteract the anticoagulant actions of heparin, according to the product labels. However, this interaction is not likely of clinical significance in most patients since heparin therapy is adjusted to the partial thromboplastin time (aPTT) and other clinical parameters of the patient.
    Hydantoins: (Moderate) Monitor for decreased efficacy of doxycycline if coadministered with hydantoins. Hydantoins decrease the half-life of doxycycline.
    Insoluble Prussian Blue: (Moderate) The binding of Insoluble Prussian Blue to some orally administered therapeutic drugs and essential nutrients is possible. The blood concentrations and/or clinical response to critical coadministered products should be monitored during Insoluble Prussian Blue therapy.
    Iron Salts: (Moderate) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
    Iron Sucrose, Sucroferric Oxyhydroxide: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of tetracyclines will be significantly reduced by orally administered compounds that contain iron salts. To minimize the potential for this interaction, administer tetracycline antibiotics at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide.
    Iron: (Moderate) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Although doxycycline is not appreciably metabolized by the liver, concomitant use of rifampin has been shown to substantially increase doxycycline clearance. It is possible that extrahepatic sites of metabolism (e.g., intestinal mucosa) may be involved since P-450 cytochrome enzymes have been identified in areas such as adrenal cortex, intestinal mucosa, and kidney. A similar effect on doxycycline clearance and half-life has been noted for carbamazepine, pentobarbital, phenobarbital, phenytoin, and primidone. It is likely that all barbiturates exert the same effect on doxycycline pharmacokinetics. The possibility of antibiotic failure should also be considered whenever these enzyme inducers are used with doxycycline.
    Isoniazid, INH; Rifampin: (Major) Although doxycycline is not appreciably metabolized by the liver, concomitant use of rifampin has been shown to substantially increase doxycycline clearance. It is possible that extrahepatic sites of metabolism (e.g., intestinal mucosa) may be involved since P-450 cytochrome enzymes have been identified in areas such as adrenal cortex, intestinal mucosa, and kidney. A similar effect on doxycycline clearance and half-life has been noted for carbamazepine, pentobarbital, phenobarbital, phenytoin, and primidone. It is likely that all barbiturates exert the same effect on doxycycline pharmacokinetics. The possibility of antibiotic failure should also be considered whenever these enzyme inducers are used with doxycycline.
    Isotretinoin: (Major) Avoid the concomitant use of isotretinoin and systemic tetracyclines due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with both systemic retinoid and tetracycline use alone. Early signs and symptoms include papilledema, headache, nausea, vomiting, and visual disturbances.
    Lansoprazole; Amoxicillin; Clarithromycin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Lanthanum Carbonate: (Major) Oral compounds known to interact with antacids, like tetracyclines, should not be taken within 2 hours of dosing with lanthanum carbonate. If these agents are used concomitantly, space the dosing intervals appropriately. Monitor serum concentrations and clinical condition.
    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.
    Lomitapide: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as tetracyclines. The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
    Magnesium Citrate: (Moderate) Administer magnesium citrate at least 3 hours before or 3 hours after orally administered tetracyclines. Tetracycline absorption may be reduced as tetracycline antibiotics can chelate with divalent or trivalent cations.
    Magnesium Hydroxide: (Moderate) Separate administration of oral doxycycline and antacids by 2 to 3 hours. Coadministration may impair absorption of doxycycline which may decrease its efficacy.
    Magnesium Salts: (Moderate) Administer oral magnesium-containing products at least 3 hours before or 3 hours after orally administered tetracyclines. Tetracycline absorption may be reduced as tetracycline antibiotics can chelate with divalent or trivalent cations.
    Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: (Major) Administer tetracyclines at least 2 hours before or 6 hours after administration of magnesium sulfate; potassium sulfate; sodium sulfate. The absorption of tetracyclines may be reduced by chelation with magnesium sulfate.
    Magnesium: (Moderate) Administer oral magnesium-containing products at least 3 hours before or 3 hours after orally administered tetracyclines. Tetracycline absorption may be reduced as tetracycline antibiotics can chelate with divalent or trivalent cations.
    Mephobarbital: (Major) Phenobarbital has been shown to affect the pharmacokinetics of doxycycline. Doxycycline half-life was decreased from 15.3 hours to 11.1 hours. It is likely that other barbiturates may exert the same effect. Clinicians should keep in mind that larger doses of doxycycline may be necessary in patients receiving barbiturates. This interaction may not apply to other tetracyclines since they are less dependent on hepatic metabolism for elimination.
    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.
    Methohexital: (Major) Phenobarbital has been shown to affect the pharmacokinetics of doxycycline. Doxycycline half-life was decreased from 15.3 hours to 11.1 hours. It is likely that other barbiturates may exert the same effect. Clinicians should keep in mind that larger doses of doxycycline may be necessary in patients receiving barbiturates. This interaction may not apply to other tetracyclines since they are less dependent on hepatic metabolism for elimination.
    Methotrexate: (Moderate) Monitor for methotrexate-related adverse reactions during concomitant tetracyclines use. Tetracyclines may decrease intestinal absorption of methotrexate or interfere with the enterohepatic circulation by inhibiting bowel flora and suppressing metabolism of methotrexate by bacteria.
    Methoxsalen: (Moderate) Use methoxsalen and tetracyclines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Mipomersen: (Moderate) Caution should be exercised when mipomersen is used with other medications known to have potential for hepatotoxicity, such as tetracyclines. The effect of concomitant administration of mipomersen with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
    Molindone: (Major) The tablet formulation of molindone contains calcium sulfate as an excipient and the calcium ions may interfere with the absorption of tetracyclines. It may be advisable to consider an alternative to tetracycline treatment during molindone administration.
    Nafcillin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and tetracyclines may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    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. (Moderate) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
    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. (Moderate) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
    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.
    Omeprazole; Amoxicillin; Rifabutin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Omeprazole; Sodium Bicarbonate: (Major) Early reports noted an increase in the excretion of tetracyclines during coadministration with sodium bicarbonate, and that the oral absorption of tetracyclines is reduced by sodium bicarbonate via increased gastric pH. However, conflicting data have been reported, and further study is needed. Two recent studies show no effect of oral sodium bicarbonate administration on tetracycline oral bioavailability. In one of these trials, coadministration with sodium bicarbonate was reported to have no effect on tetracycline urinary excretion, Cmax, or AUC. Until more information is available, avoid simultaneous administration of sodium bicarbonate and tetracyclines. When concurrent therapy is needed, stagger administration times by several hours to minimize the potential for interaction, and monitor for antimicrobial efficacy.
    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.
    Oxacillin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Penicillin G Benzathine: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Penicillin G Benzathine; Penicillin G Procaine: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Penicillin G Procaine: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Penicillin G: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Penicillin V: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Penicillins: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Pentobarbital: (Major) Phenobarbital has been shown to affect the pharmacokinetics of doxycycline. Doxycycline half-life was decreased from 15.3 hours to 11.1 hours. It is likely that other barbiturates may exert the same effect. Clinicians should keep in mind that larger doses of doxycycline may be necessary in patients receiving barbiturates. This interaction may not apply to other tetracyclines since they are less dependent on hepatic metabolism for elimination.
    Phenobarbital: (Major) Phenobarbital has been shown to affect the pharmacokinetics of doxycycline. Doxycycline half-life was decreased from 15.3 hours to 11.1 hours. It is likely that other barbiturates may exert the same effect. Clinicians should keep in mind that larger doses of doxycycline may be necessary in patients receiving barbiturates. This interaction may not apply to other tetracyclines since they are less dependent on hepatic metabolism for elimination.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Phenobarbital has been shown to affect the pharmacokinetics of doxycycline. Doxycycline half-life was decreased from 15.3 hours to 11.1 hours. It is likely that other barbiturates may exert the same effect. Clinicians should keep in mind that larger doses of doxycycline may be necessary in patients receiving barbiturates. This interaction may not apply to other tetracyclines since they are less dependent on hepatic metabolism for elimination.
    Phenytoin: (Moderate) Monitor for decreased efficacy of doxycycline if coadministered with hydantoins. Hydantoins decrease the half-life of doxycycline.
    Photosensitizing agents (topical): (Moderate) Tetracyclines cause photosensitivity and may increase the photosensitizing effects photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation and the use of protective clothing and sunscreens on exposed skin.
    Piperacillin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Piperacillin; Tazobactam: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Polycarbophil: (Major) Coadministration of calcium polycarbophil with orally administered tetracyclines can decrease the absorption of tetracyclines; oral doses of tetracyclines should be given 2 hours before or after the administration of calcium polycarbophil. Each 625 mg of calcium polycarbophil contains a substantial amount of calcium (approximately 125 mg). This effect is presumably due to the chelation of the antibiotic by the calcium.
    Polyethylene Glycol; Electrolytes: (Major) Administer tetracyclines at least 2 hours before or 6 hours after administration of magnesium sulfate; potassium sulfate; sodium sulfate. The absorption of tetracyclines may be reduced by chelation with magnesium sulfate.
    Polyethylene Glycol; Electrolytes; Ascorbic Acid: (Major) Administer tetracyclines at least 2 hours before or 6 hours after administration of magnesium sulfate; potassium sulfate; sodium sulfate. The absorption of tetracyclines may be reduced by chelation with magnesium sulfate.
    Polysaccharide-Iron Complex: (Moderate) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
    Porfimer: (Major) Avoid coadministration of porfimer with tetracyclines due to the risk of increased photosensitivity. Porfimer is a light-activated drug used in photodynamic therapy; all patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like tetracyclines may increase the risk of a photosensitivity reaction.
    Primidone: (Major) Phenobarbital has been shown to affect the pharmacokinetics of doxycycline. Doxycycline half-life was decreased from 15.3 hours to 11.1 hours. It is likely that other barbiturates may exert the same effect. Clinicians should keep in mind that larger doses of doxycycline may be necessary in patients receiving barbiturates. This interaction may not apply to other tetracyclines since they are less dependent on hepatic metabolism for elimination.
    Pyridostigmine: (Moderate) Parenteral administration of high doses of certain antibiotics such as tetracyclines may intensify or produce neuromuscular block through their own pharmacologic actions. If unexpected prolongation of neuromuscular block or resistance to its reversal with pyridostigmine occurs, consider the possibility of an antibiotic effect.
    Pyridoxine, Vitamin B6: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Quinapril: (Major) Tetracycline absorption is reduced by about 28 to 37% with coadministration with quinapril, presumably due to the magnesium in the quinapril tablet.This interaction should be taken into account when prescribing tetracyclines with quinapril.
    Quinapril; Hydrochlorothiazide, HCTZ: (Major) Tetracycline absorption is reduced by about 28 to 37% with coadministration with quinapril, presumably due to the magnesium in the quinapril tablet.This interaction should be taken into account when prescribing tetracyclines with quinapril.
    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.
    Rifampin: (Major) Although doxycycline is not appreciably metabolized by the liver, concomitant use of rifampin has been shown to substantially increase doxycycline clearance. It is possible that extrahepatic sites of metabolism (e.g., intestinal mucosa) may be involved since P-450 cytochrome enzymes have been identified in areas such as adrenal cortex, intestinal mucosa, and kidney. A similar effect on doxycycline clearance and half-life has been noted for carbamazepine, pentobarbital, phenobarbital, phenytoin, and primidone. It is likely that all barbiturates exert the same effect on doxycycline pharmacokinetics. The possibility of antibiotic failure should also be considered whenever these enzyme inducers are used with doxycycline.
    Rifapentine: (Moderate) According to the manufacturer, doxycycline dosage adjustments may be required if administered concurrently with rifapentine. Rifapentine is an inducer of hepatic isoenzymes CYP3A4 and CYP2C8/9, and although doxycycline is not appreciably metabolized by the liver, its clearance has been shown to be substantially increased when administered in combination with other enzyme inducers, including rifampin.
    Secobarbital: (Major) Phenobarbital has been shown to affect the pharmacokinetics of doxycycline. Doxycycline half-life was decreased from 15.3 hours to 11.1 hours. It is likely that other barbiturates may exert the same effect. Clinicians should keep in mind that larger doses of doxycycline may be necessary in patients receiving barbiturates. This interaction may not apply to other tetracyclines since they are less dependent on hepatic metabolism for elimination.
    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 Bicarbonate: (Major) Early reports noted an increase in the excretion of tetracyclines during coadministration with sodium bicarbonate, and that the oral absorption of tetracyclines is reduced by sodium bicarbonate via increased gastric pH. However, conflicting data have been reported, and further study is needed. Two recent studies show no effect of oral sodium bicarbonate administration on tetracycline oral bioavailability. In one of these trials, coadministration with sodium bicarbonate was reported to have no effect on tetracycline urinary excretion, Cmax, or AUC. Until more information is available, avoid simultaneous administration of sodium bicarbonate and tetracyclines. When concurrent therapy is needed, stagger administration times by several hours to minimize the potential for interaction, and monitor for antimicrobial efficacy.
    Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Moderate) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
    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.
    Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Moderate) Administer oral magnesium-containing products at least 3 hours before or 3 hours after orally administered tetracyclines. Tetracycline absorption may be reduced as tetracycline antibiotics can chelate with divalent or trivalent cations.
    St. John's Wort, Hypericum perforatum: (Moderate) St. John's Wort is known to cause photosensitivity. In theory it is possible that additive photosensitizing effects may result from the concomitant use of St. John's Wort with other photosensitizing drugs such as tetracyclines.
    Sucralfate: (Moderate) Sucralfate should be given 2 hours before or after the oral administration of tetracyclines. Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain aluminum salts, calcium salts, iron salts, magnesium salts, and/or zinc salts. Sucralfate, because it contains aluminum in its structure and due to its mechanism of action, can bind with tetracyclines in the GI tract, reducing the bioavailability of these agents.
    Sulfonylureas: (Moderate) Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents including tetracyclines. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin.
    Tazarotene: (Moderate) The manufacturer states that tazarotene should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as tetracyclines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Thiopental: (Major) Phenobarbital has been shown to affect the pharmacokinetics of doxycycline. Doxycycline half-life was decreased from 15.3 hours to 11.1 hours. It is likely that other barbiturates may exert the same effect. Clinicians should keep in mind that larger doses of doxycycline may be necessary in patients receiving barbiturates. This interaction may not apply to other tetracyclines since they are less dependent on hepatic metabolism for elimination.
    Ticarcillin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Ticarcillin; Clavulanic Acid: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Tretinoin, ATRA: (Major) Avoid the concomitant use of tretinoin and systemic tetracyclines due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with both systemic retinoid and tetracycline use alone. Early signs and symptoms include papilledema, headache, nausea, vomiting, and visual disturbances.
    Verteporfin: (Moderate) Use caution if coadministration of verteporfin with tetracyclines is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like tetracyclines may increase the risk of a photosensitivity reaction.
    Vitamin C: (Moderate) Monitor for decreased efficacy of doxycycline during coadministration; discontinue ascorbic acid therapy if decreased efficacy is suspected. Coadministration may result in decreased efficacy of doxycycline.
    Vonoprazan; Amoxicillin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Vonoprazan; Amoxicillin; Clarithromycin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
    Warfarin: (Moderate) Tetracyclines may increase the action of warfarin and other oral anticoagulants by either impairing prothrombin utilization or, possibly, decreasing production of vitamin K because of its antiinfective action on gut bacteria. 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.
    Zinc Salts: (Major) Concurrent administration of oral zinc salts with oral tetracyclines can decrease the absorption of these antiinfectives and possibly interfere with their therapeutic response. This is a result of the formation of insoluble chelates between zinc and the antiinfective. Oral zinc supplements should be administered at least 6 hours before or 2 hours after administering tetracyclines.
    Zinc: (Major) Concurrent administration of oral zinc salts with oral tetracyclines can decrease the absorption of these antiinfectives and possibly interfere with their therapeutic response. This is a result of the formation of insoluble chelates between zinc and the antiinfective. Oral zinc supplements should be administered at least 6 hours before or 2 hours after administering tetracyclines.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate and well-controlled studies on the use of doxycycline in pregnant women. There are no data available on the risk of miscarriage after doxycycline exposure. Most reported experience with doxycycline during human pregnancy is short-term, first-trimester exposure. Available data over decades have not shown a difference in major birth defect risk compared to unexposed pregnancies with doxycycline exposure during the first trimester of pregnancy. There are no human data available to assess the effects of long-term therapy of doxycycline in pregnant women. Tetracyclines may cause discoloration of deciduous teeth and reversible inhibition of bone growth when administered during the second and third trimester of pregnancy. Advise the patient of the potential risk to the fetus if doxycycline is used during pregnancy. In a nested, case-control study (n = 87,020 controls; 8,702 cases) within the Quebec Pregnancy Cohort, tetracycline use during early pregnancy was associated with an increased risk of spontaneous abortion (adjusted odds ratio (aOR) 2.59, 95% CI: 1.97 to 3.41, 67 exposed cases); residual confounding by severity of infection may be a potential limitation of this study. Additionally, in a large population-based cohort study (n = 139,938 live births) assessing antibiotic exposure during the first trimester of pregnancy (n = 15,469 exposures) and the risk of major birth defects, doxycycline was associated with an increased risk of circulatory system malformation, cardiac malformations, and ventricular/atrial septal defect (aOR 2.38, 95% CI: 1.21 to 4.67, 9 exposed cases; aOR 2.46, 95% CI: 1.21 to 4.99, 8 exposed cases; aOR 3.19, 95% CI: 1.57 to 6.48, 8 exposed cases, respectively). Possible study limitations include potential unmeasured confounders (i.e., smoking, folic acid, and alcohol intake) as well as that the study was underpowered to detect associations between individual antibiotics and specific malformations due to the small number of exposed cases. In another case-control study (n = 32,804 controls; 18,515 cases), there was a weak but marginally statistically significant association with total malformations and use of doxycycline (n = 64 (0.19%) of the controls and 56 (0.3%) of the cases treated with doxycycline) anytime during pregnancy. No association was seen when the analysis was confined to maternal treatment during the period of organogenesis (i.e., in the second and third months of gestation) with the exception of a marginal relationship with neural tube defect based on only 2 exposed cases. Guidelines suggest doxycycline may be used for the treatment of uncomplicated malaria during pregnancy in rare instances if other options are not available or are not tolerated and benefit of use outweighs risks.

    Tetracyclines, including doxycycline, are distributed in small amounts into breast milk. There are no data on the effects of doxycycline on the breast-fed infant or milk production. Because of the potential for serious adverse reactions in nursing infants, breast-feeding is not recommended during treatment with doxycycline and for 5 days after the last dose. In general, tetracycline antibiotics are not recommended for use in breast-feeding mothers due to a theoretical risk of causing tooth discoloration, enamel hypoplasia, inhibition of linear skeletal growth, oral and vaginal thrush, or photosensitivity reactions in the nursing infant. However, because tetracyclines bind to calcium in the maternal breast milk, the risk for oral absorption by the infant is minimal. Data are available regarding doxycycline milk concentrations in breast-feeding women; however, infant serum concentrations and any effects on breast-feeding infants were not reported. Doxycycline (100 mg PO daily) was given to 10 mothers. On the second day of treatment, milk doxycycline averaged 0.82 mg/L (range 0.37 to 1.24 mg/L) at 3 hours after the dose, and 0.46 mg/L (range 0.3 to 0.91 mg/L) at 24 hours after the dose. Using the average of the peak and trough milk concentrations in this study, the estimated average intake of an exclusively breast-fed infant would be about 6% of the maternal weight-adjusted dosage. Further available data indicate that after doses of 100 to 200 mg PO, milk concentrations do not exceed an average of 1.8 mg/L. Studies of long-term tetracycline use in breast-feeding are lacking. Previous American Academy of Pediatrics recommendations did not address doxycycline but classified another tetracycline antibiotic, tetracycline, as usually compatible with breast-feeding.

    MECHANISM OF ACTION

    Doxycycline is generally bacteriostatic against a wide variety of organisms, both gram-positive and gram-negative. In gram-negative bacteria, transportation of the drug into the cell occurs either by passive diffusion or through an energy-dependent active transport system. The latter system is also believed to exist in gram-positive bacteria. Doxycycline and minocycline are more lipophilic than the other tetracyclines, which allows them to pass easily through the lipid bilayer of bacteria where reversible binding to the 30S ribosomal subunits occurs. Binding of doxycycline blocks the binding of aminoacyl transfer RNA (tRNA) to the messenger RNA (mRNA). Bacterial protein synthesis is inhibited, which ultimately accounts for the antibacterial action. High concentrations of antibiotic also can interfere with protein synthesis in mammalian cells, but these cells lack the active transport systems found in bacteria.[29817] [57360] [57369]
     
    Tetracycline resistance occurs via efflux, alterations in binding to the ribosome via ribosomal protection proteins, and decreased permeability. Tetracycline resistance in community-acquired MRSA (CA-MRSA) isolates is primarily associated with the tetK gene. The tetM resistance gene confers resistance to the entire class; however, the tetK gene confers resistance to tetracycline and an inducible resistance to doxycycline, but has no impact on minocycline susceptibility.[29817] [26456] [46693] [59628]
     
    The susceptibility interpretive criteria for doxycycline are delineated by pathogen. The MICs for Enterobacterales, Acinetobacter sp., other non-Enterobacterales, Enterococcus sp., and Staphylococcus sp. are defined as susceptible at 4 mcg/mL or less, intermediate at 8 mcg/mL, and resistant at 16 mcg/mL or more. The MICs for S. pneumoniae are defined as susceptible at 0.25 mcg/mL or less, intermediate at 0.5 mcg/mL, and resistant at 1 mcg/mL or more.[63320] [63321]
     
    The action of tetracyclines in the treatment of acne vulgaris has not been fully established but is believed to be due in part to their antibacterial actions. Skin bacteria produce lipase that breaks down triglycerides present in sebum into free fatty acids, which are comedogenic and may be the cause of the inflammatory lesions of acne. Reduction in the number of lipase-producing bacteria or inhibition of lipase production are 2 possible mechanisms of tetracyclines. Several other mechanisms have been proposed but not studied. The second-generation tetracyclines, doxycycline and minocycline, are preferred for the treatment of acne because of lower prevalence of resistant P. acnes strains as compared with tetracycline and their greater lipophilicity is believed to increase follicular penetration.[54585]
     
    In the treatment of periodontitis, it is thought that doxycycline works by inhibiting collagenase. Collagenase breaks down connective tissue which leads to the separation of the gum from the tooth. Products (e.g., Periostat) used for treatment of periodontitis contain lower amounts of doxycycline. Doxycycline concentrations produced by Periostat are too low to exert a direct antibacterial effect. Clinical studies of patients receiving Periostat for 9 to 18 months show that Periostat has no effect on total anaerobic and facultative bacteria in plaque samples. Periostat should not be used as an antibiotic in the treatment of periodontitis.[34113]

    PHARMACOKINETICS

    Doxycycline is administered orally, intravenously, and via the subgingival route. Protein binding ranges from 80% to 90%. Distribution is extensive due to the relatively high lipid solubility of doxycycline compared to other tetracyclines, although only small amounts diffuse into CSF. Only minocycline is more lipid-soluble.
     
    Doxycycline is not hepatically metabolized. The major route of doxycycline excretion is via the feces with minimal amounts excreted renally (e.g., the renal clearance of doxycycline is roughly 30 to 35 mL/minute). Doxycycline undergoes enterohepatic recirculation; it may be partially inactivated by chelation with iron or other cations in the intestine. In patients with normal renal function, excretion of the active drug is about 30% to 40% in the urine with the remainder eliminated in the feces within 48 hours of dosage. Serum half-life ranges from 12 to 25 hours, depending on single or multiple dosage, in adults with normal renal function.
     
    Affected cytochrome P450 isoenzymes and drug transporters: none

    Oral Route

    Oral absorption of doxycycline from immediate- and delayed-release products is 90% to 100%. Peak serum doxycycline concentrations of 1.5 to 3.6 mcg/mL occur after usual oral doses of regular- or delayed-release products and are achieved in approximately 3 hours in adults.[57360] [57369] Of all the tetracyclines, doxycycline has the least affinity for calcium ions. Therefore, overall absorption is not significantly affected when the immediate- or delayed-release doxycycline products are taken with milk or other dairy products, but absorption may be delayed.[27974] [29817] [60812] A single-dose study of Periostat given with a 1,000-calorie, high-fat, high-protein meal, which included dairy products, resulted in a decrease in the rate and extent of absorption and delay in the time to maximum concentrations.[34113] When the delayed-release doxycycline tablets were given with a high-fat meal, the Cmax and AUC were reduced by 24% and 13%, respectively, after a single dose of 100 mg, while the mean Cmax was 19% lower and the AUC was unchanged after single dose administration of 150 mg; the clinical significance of these reductions is unknown.[60812] After administration of a single dose of the Doryx MPC formulation under fasting conditions in healthy adult subjects, the 120 mg MPC formulation was found to bioequivalent to the regular delayed-release 100 mg tablets. When a single dose of Doryx MPC was administered with a high-fat, high-calorie meal, the Cmax was approximately 30% lower, but there was no significant difference in AUC compared to fasting conditions.[32075] The dual-release capsules (Oracea) are not bioequivalent to other doxycycline products; absorption may be decreased when given with meals. In a single-dose food effect study, the Cmax and AUC of doxycycline (given as Oracea) were reduced by about 45% and 22%, respectively, in healthy volunteers fed a 1,000-calorie, high-fat, high-protein meal which included dairy products. These reductions in AUC and Cmax can be clinically significant. After dosing with dual-release capsules, peak serum concentrations were 510 ng/mL after a single-dose and 600 ng/mL after 7 days (steady-state). Chelation does occur with other cations; administration with bismuth subsalicylate, proton pump inhibitors (PPIs), aluminum-, calcium-, or magnesium-containing antacids, or with iron-containing products will decrease absorption significantly. The bioavailability of doxycycline may be reduced in patients with high gastric pH or achlorhydria (e.g., PPI therapy, gastrectomy, gastric bypass surgery).[32240]

    Other Route(s)

    Subgingival Route
    After subgingival application of doxycycline, gingival crevicular fluid (GCF) concentrations peak in about 2 hours. Local concentrations of doxycycline remained significantly above the minimum inhibitory concentration (MIC90) for periodontal pathogens (6 mcg/mL or less) for at least 7 days. Small amounts of doxycycline are absorbed systemically following subgingival administration.