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  • CLASSES

    Antiinfectives and Antiseptics for Local Oral Treatment
    Oral Anti-Acne Non-Retinoids
    Oral Rosacea Agents
    Tetracycline Antibiotics

    DEA CLASS

    Rx

    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, Mondoxyne NL, Monodox, Morgidox 1x, Morgidox 1x Kit, Morgidox 2x, Morgidox 2x Kit, NutriDox, Ocudox, Oracea, Oraxyl, Periostat, TARGADOX, Vibra-Tabs, Vibramycin

    HOW SUPPLIED

    Acticlate/Adoxa/Adoxa Pak/Alodox/Avidoxy/Doxycycline Hyclate/Doxycycline Monohydrate/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/Oraxyl/Vibramycin Oral Cap: 20mg, 50mg, 75mg, 100mg, 150mg
    Doryx/Doxycycline Hyclate Oral Cap DR Pellets: 100mg
    Doryx/Doxycycline Hyclate Oral Tab DR: 50mg, 75mg, 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

    DOSAGE & INDICATIONS

    For the treatment of skin and skin structure infections, including cellulitis, due to Staphylococcus aureus.
    NOTE: Tetracyclines are not the drugs of choice in the treatment of any type of staphylococcal infection.
    Intravenous infusion dosage
    Adults, Adolescents, and Children 8 years and older and weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    4.4 mg/kg IV on day 1, administered as 1 or 2 infusions, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses.

    Oral dosage†
    Adults, Adolescents, and Children 8 years and older and weighing 45 kg or more

    100 mg PO every 12 hours for 5 to 10 days for community-acquired MRSA (CA-MRSA) infections per clinical practice guidelines. The addition of a beta-lactam may be warranted if beta-hemolytic streptococci coverage is necessary.

    Children 8 years and older and Adolescents weighing less than 45 kg

    2 mg/kg/dose PO every 12 hours for 5 to 10 days for community-acquired MRSA (CA-MRSA) infections per clinical practice guidelines. The addition of a beta-lactam may be warranted if beta-hemolytic streptococci coverage is necessary.

    For the treatment of bacterial urinary tract infection (UTI).
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.2 mg/kg/dose PO every 12 hours on day 1, then 2.2 mg/kg/dose PO once daily. For severe infections, including chronic urinary tract infections, continue 2.2 mg/kg/dose PO every 12 hours.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.65 mg/kg/dose PO every 12 hours on day 1, then 1.3 mg/kg/dose PO every 12 hours or 2.6 mg/kg/dose PO once daily. For severe infections, including chronic urinary tract infections, 2.6 mg/kg/dose PO every 12 hours.

    Intravenous infusion dosage
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    4.4 mg/kg IV on day 1, administered as 1 or 2 infusions, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses.

    For the treatment of upper respiratory tract infections (e.g., sinusitis).
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours on day 1, then 100 mg PO once daily. For severe infections, 100 mg PO every 12 hours. For sinusitis, clinical practice guidelines recommend 100 mg PO twice daily or 200 mg PO once daily for 5 to 7 days as second line therapy or for patients with a beta-lactam allergy.

    Children 8 years and older and Adolescents weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.2 mg/kg/dose PO every 12 hours on day 1, then 2.2 mg/kg/day PO once daily. For severe infections, 2.2 mg/kg/dose PO every 12 hours.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.65 mg/kg/dose PO every 12 hours on day 1, then 1.3 mg/kg/dose PO every 12 hours or 2.6 mg/kg/dose PO once daily. For severe infections, 2.6 mg/kg/dose PO every 12 hours.

    Intravenous infusion dosage
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    4.4 mg/kg IV on day 1, administered as 1 or 2 infusions, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses.

    For the treatment of lower respiratory tract infections (e.g., pneumonia, community-acquired pneumonia).
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours on day 1, then 100 mg PO once daily. For severe infections, 100 mg PO every 12 hours. For community acquired pneumonia, clinical practice guidelines recommend doxycycline as monotherapy in previously healthy outpatients with no risk factors for drug-resistant S. pneumoniae and without therapy in the preceding 3 months. An oral beta-lactam should be added in outpatients with comorbidities, previous antibiotic use in the preceding 3 months, or risk factors for drug-resistant S. pneumoniae. Patients should be treated for at least 5 days and should be afebrile for 48 to 72 hours with no more than 1 CAP-associated sign of clinical instability before discontinuing therapy. A longer duration may be needed if the initial therapy is not active against identified pathogens or if there are complications.

    Children 8 years and older and Adolescents weighing 45 kg or more

    100 mg PO every 12 hours on day 1, then 100 mg PO once daily. For severe infections, 100 mg PO every 12 hours. For community acquired pneumonia in HIV-infected adolescents, doxycycline plus an oral beta-lactam is recommended as an alternative for empiric therapy in outpatients.

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.2 mg/kg/dose PO every 12 hours on day 1, then 2.2 mg/kg/dose PO once daily. For severe infections, 2.2 mg/kg/dose PO every 12 hours. For community acquired pneumonia in HIV-infected adolescents, doxycycline plus an oral beta-lactam is recommended as an alternative for empiric therapy in outpatients.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.65 mg/kg/dose PO every 12 hours on day 1, then 1.3 mg/kg/dose PO every 12 hours or 2.6 mg/kg/dose PO once daily. For severe infections, 2.6 mg/kg/dose PO every 12 hours.

    Intravenous infusion dosage
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    200 mg IV on day 1, then 100 to 200 mg/day IV with the 200 mg dose administered as 1 or 2 infusions. For community acquired pneumonia in HIV-infected patients, doxycycline plus an IV beta-lactam is recommended as an alternative for empiric therapy in non-ICU hospitalized patients.

    Children 8 years and older and Adolescents weighing less than 45 kg

    4.4 mg/kg IV on day 1, administered as 1 or 2 infusions, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses. For community acquired pneumonia in HIV-infected adolescents, doxycycline plus an IV beta-lactam is recommended as an alternative for empiric therapy in non-ICU hospitalized patients.

    For the treatment of severe acne vulgaris as adjunctive therapy.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    100 mg PO every 12 hours on day 1, then 100 mg PO once daily. Alternately, sub-antimicrobial-dose doxycycline hyclate 20 mg PO twice daily was evaluated for the treatment of moderate acne in 40 adults in a multicenter, double-blind, randomized, placebo-controlled study. After 6 months, doxycycline treated patients had a significantly greater reduction in the number of comedones, inflammatory and non-inflammatory lesions combined, and total inflammatory lesions compared to placebo. Microbial counts did not differ significantly between the 2 groups, and there was no evidence of change in antimicrobial susceptibility or colonization by potential pathogens.

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.2 mg/kg/dose PO every 12 hours on day 1, then 2.2 mg/kg/dose PO once daily.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.65 mg/kg/dose PO every 12 hours on day 1, then 1.3 mg/kg/dose PO every 12 hours or 2.6 mg/kg/dose PO once daily.

    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 of cholera.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    100 mg PO every 12 hours on day 1, then 100 mg PO once daily in conjunction with fluid and electrolyte replacement.

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.2 mg/kg/dose PO every 12 hours on day 1, then 2.2 to 4.4 mg/kg/day in conjunction with fluid and electrolyte replacement.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.65 mg/kg/dose PO every 12 hours on day 1, then 1.3 mg/kg/dose PO every 12 hours or 2.6 mg/kg/dose PO once daily.

    For the treatment of brucellosis.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    100 mg PO every 12 hours on day 1, then 100 mg PO once daily, with streptomycin. For severe infections, 100 mg PO every 12 hours.

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.2 mg/kg/dose PO every 12 hours on day 1, then 2.2 mg/kg/dose PO once daily, with streptomycin. For severe infections, 2.2 mg/kg/dose PO every 12 hours.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.65 mg/kg/dose PO every 12 hours on day 1, then 1.3 mg/kg/dose PO every 12 hours or 2.6 mg/kg/dose PO once daily, with streptomycin. For severe infections, 2.6 mg/kg/dose PO every 12 hours.

    Intravenous infusion dosage
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    4.4 mg/kg IV on day 1, administered as 1 or 2 infusions, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses.

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

    100 mg PO every 12 hours for at least 5 to 7 days or until afebrile for at least 3 days.

    Children 8 years and older and Adolescents

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for at least 5 to 7 days or until afebrile for at least 3 days.

    Infants† and Children 1 to 7 years†

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for at least 5 to 7 days or until afebrile for at least 3 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 for at least 5 to 7 days or until afebrile for at least 3 days.

    Children 8 years and older and Adolescents

    2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for at least 5 to 7 days or until afebrile for at least 3 days.

    Children 1 to 7 years†

    2.6 mg/kg/dose (Max: 120 mg/dose) PO every 12 hours for at least 5 to 7 days or until afebrile for at least 3 days.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours for at least 5 to 7 days or until afebrile for at least 3 days.

    Children 8 years and older and Adolescents

    2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours for at least 5 to 7 days or until afebrile for at least 3 days.

    Infants† and Children 1 to 7 years†

    2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours for at least 5 to 7 days or until afebrile for at least 3 days.

    For the treatment of relapsing fever due to Borrelia recurrentis.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    100 mg PO every 12 hours on day 1, then 100 mg PO once daily.

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.2 mg/kg/dose PO every 12 hours on day 1, then 2.2 to 4.4 mg/kg/day.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.65 mg/kg/dose PO every 12 hours on day 1, then 1.3 mg/kg/dose PO every 12 hours or 2.6 mg/kg/dose PO once daily.

    Intravenous infusion dosage
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    4.4 mg/kg IV on day 1, administered as 1 or 2 infusions, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses.

    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 HIV-infected patients, their efficacy has not been evaluated and should only be used with close clinical and serologic monitoring.
    For primary, secondary, or early latent syphilis (caused by Treponema pallidum) in nonpregnant, penicillin-allergic patients.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    100 mg PO twice daily for 14 days per clinical practice guidelines. If follow-up/compliance uncertain, desensitize patient and treat with penicillin. Some manufacturers recommend 100 mg PO twice daily for 14 days or 300 mg PO once daily 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 8 years and older and Adolescents weighing less than 45 kg

    2.2 mg/kg/dose PO every 12 hours on day 1, then 2.2 to 4.4 mg/kg/day PO for 14 days.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    120 mg PO every 12 hours for 14 days.

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.65 mg/kg/dose PO every 12 hours on day 1, then 1.3 mg/kg/dose PO every 12 hours or 2.6 mg/kg/dose PO once daily for 14 days total.

    Intravenous dosage
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    300 mg IV once daily for at least 10 days for primary or secondary syphilis.

    Children 8 years and older and Adolescents weighing less than 45 kg

    4.4 mg/kg/day IV on day 1, administered as 1 or 2 infusions, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses for 2 weeks for primary or secondary syphilis.

    For late latent syphilis in nonpregnant, penicillin-allergic patients.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.2 mg/kg/dose PO every 12 hours on day 1, then 2.2 to 4.4 mg/kg/day PO for 4 weeks.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    120 mg PO every 12 hours for 4 weeks.

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.65 mg/kg/dose PO every 12 hours on day 1, then 1.3 mg/kg/dose PO every 12 hours or 2.6 mg/kg/dose PO once daily for 4 weeks total.

    For the treatment of psittacosis.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.2 mg/kg/dose PO every 12 hours on day 1, then 2.2 to 4.4 mg/kg/day PO.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.65 mg/kg/dose PO every 12 hours on day 1, then 1.3 mg/kg/dose PO every 12 hours or 2.6 mg/kg/dose PO once daily. For severe infections, 2.6 mg/kg/dose PO every 12 hours.

    Intravenous dosage
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children and Adolescents 8 years and older weighing less than 45 kg

    4.4 mg/kg IV on day 1, administered as 1 or 2 infusions, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses.

    For the treatment of non-gonococcal urethritis (NGU) and chlamydia infection, including trachoma and inclusion bacterial conjunctivitis.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    100 mg PO every 12 hours for 7 days. Use with anti-gonorrhea agent when appropriate.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    120 mg PO every 12 hours for 7 days. Use with anti-gonorrhea agent when appropriate.

    For the treatment of lymphogranuloma venereum caused by Chlamydia trachomatis.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    100 mg PO twice daily for 21 days. Erythromycin is recommended in pregnant and lactating women.

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.2 mg/kg/dose PO twice daily on day 1, then 2.2 mg/kg/dose PO once daily. For severe infections, continue 2.2 mg/kg/dose PO twice daily. Treat for 21 days.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    120 mg PO twice daily for 21 days. Erythromycin is recommended in pregnant and lactating women.

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.65 mg/kg/dose PO twice daily on day 1, then 2.6 mg/kg/dose PO once daily. For severe infections, 2.6 mg/kg/dose PO twice daily. Treat for 21 days.

    Intravenous dosage
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    200 mg IV on day 1, then 100 to 200 mg IV per day, with the 200 mg dose administered as 1 or 2 infusions for 21 days. Erythromycin is recommended in pregnant and lactating women.

    Children 8 years and older and Adolescents weighing less than 45 kg

    4.4 mg/kg IV on day 1, then 2.2 to 4.4 mg/kg/day IV; administered in 1 to 2 divided doses for 21 days.

    For the treatment of granuloma inguinale (Donovanosis) caused by Klebsiella granulomatis.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    100 mg PO twice daily for a minimum of 3 weeks and until all lesions have completely healed. An aminoglycoside such as gentamicin may be added if no improvement in first few days or if patient is HIV-infected. For pregnant and lactating patients, use erythromycin or azithromycin. Doxycycline is recommended as an alternative to azithromycin.

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.2 mg/kg/dose PO twice daily on day 1, then 2.2 mg/kg/dose PO once daily. For severe infections, continue 2.2 mg/kg/dose PO twice daily. Treat for a minimum of 3 weeks and until all lesions have completely healed. The addition of an aminoglycoside, such as gentamicin, should be considered if lesions do not respond within the first few days of therapy or if the patient also has HIV infection. Doxycycline is recommended as an alternative to azithromycin.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    120 mg PO twice daily for a minimum of 3 weeks and until all lesions have completely healed. An aminoglycoside such as gentamicin may be added if no improvement in first few days or if patient is HIV-infected. For pregnant and lactating patients, use erythromycin or azithromycin. Doxycycline is recommended as an alternative to azithromycin.

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.65 mg/kg/dose PO every 12 hours on day 1, then 1.3 mg/kg/dose PO every 12 hours or 2.6 mg/kg/dose PO once daily. For severe infections, 2.6 mg/kg/dose PO every 12 hours. Treat for a minimum of 3 weeks and until all lesions have completely healed. The addition of an aminoglycoside, such as gentamicin, should be considered if lesions do not respond within the first few days of therapy or if the patient also has HIV infection. Doxycycline is recommended as an alternative to azithromycin.

    Intravenous dosage
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    200 mg IV on day 1, then 100 to 200 mg/day IV, with the 200 mg dose administered as 1 or 2 infusions. Treat for a minimum of 3 weeks and until all lesions have completely healed. The addition of an aminoglycoside, such as gentamicin, should be considered if lesions do not respond within the first few days of therapy or if the patient also has HIV infection. Doxycycline is recommended as an alternative to azithromycin.

    Children 8 years and older and Adolescents weighing less than 45 kg

    4.4 mg/kg IV on day 1, administered as 1 or 2 infusions, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses. Treat for a minimum of 3 weeks and until all lesions have completely healed. The addition of an aminoglycoside, such as gentamicin, should be considered if lesions do not respond within the first few days of therapy or if the patient also has HIV infection. Doxycycline is recommended as an alternative to azithromycin.

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

    100 mg PO twice daily for 10 days to eradicate Chlamydia trachomatis in combination with ceftriaxone IM for acute epididymitis most likely caused by gonorrhea and chlamydia. For acute epididymitis likely caused by gonorrhea, chlamydia, and enteric organisms, ceftriaxone and a quinolone are recommended.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults and Adolescents

    120 mg PO twice daily for 10 days to eradicate Chlamydia trachomatis in combination with ceftriaxone IM for acute epididymitis most likely caused by gonorrhea and chlamydia. For acute epididymitis likely caused by gonorrhea, chlamydia, and enteric organisms, ceftriaxone and a quinolone are recommended.

    For malaria prophylaxis in short-term travelers (less than 4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains.
    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, continue once daily during the stay, and for 4 weeks after returning home.

    Children 8 years and older and Adolescents

    2.2 mg/kg/dose (Max: 100 mg/dose) PO once daily. Begin 1 to 2 days prior to travel to the malarious area, continue once daily during the stay, and for 4 weeks after returning home.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    120 mg PO once daily. Begin 1 to 2 days prior to travel to the malarious area, continue once daily during the stay, and for 4 weeks after returning home.

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.4 mg/kg/dose PO once daily. Begin 1 to 2 days prior to travel to the malarious area, continue once daily during the stay, and for 4 weeks after returning home.

    For the treatment of anthrax infection due to exposure to Bacillus anthracis.
    For the treatment of cutaneous anthrax infection.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children weighing 45 kg or more

    100 mg PO every 12 hours. Treat for 7 to 10 days for naturally acquired infection. For a bioterrorism-related event, treat for 60 days. Doxycycline is recommended as a preferred therapy.

    Term Neonates, Infants, Children, and Adolescents weighing less than 45 kg

    2.2 mg/kg/dose PO every 12 hours. Treat for 7 to 10 days for naturally acquired infection. For a bioterrorism-related event, treat for a total duration of 60 days. Doxycycline is recommended as an alternative treatment to ciprofloxacin.

    For the treatment of systemic anthrax infection.
    Intravenous dosage
    Adults, Adolescents, and Children weighing 45 kg or more

     200 mg IV initially, followed by 100 mg IV every 12 hours. Doxycycline is an alternative to clindamycin or linezolid, in combination with a bactericidal antimicrobial (e.g., ciprofloxacin), for the treatment of systemic anthrax without CNS involvement. Treat for at least 14 days or until clinical criteria for stability are met. Prophylaxis to complete an antimicrobial course of up to 60 days is required.

    Term Neonates, Infants, Children, and Adolescents weighing less than 45 kg

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

    For anthrax prophylaxis after exposure to Bacillus anthracis (postexposure prophylaxis, PEP).
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children weighing 45 kg or more

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

    Term Neonates, Infants, Children, and Adolescents weighing less than 45 kg

    2.2 mg/kg/dose PO every 12 hours for 60 days after exposure. Doxycycline is a preferred therapy for postexposure prophylaxis in infants 1 month and older and children and an alternative therapy to ciprofloxacin for 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, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children and Adolescents weighing less than 45 kg

    2.6 mg/kg/dose PO every 12 hours for 60 days after exposure. Doxycycline is a preferred therapy for postexposure prophylaxis in children.

    For the treatment of plague infection due to exposure to Yersinia pestis.
    For the treatment of plague infection in an individual patient or in a contained casualty setting.
    Intravenous infusion dosage
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    100 mg IV every 12 hours or 200 mg IV every 24 hours for 10 days. Switch to oral antibiotic therapy when clinically indicated. The risk of serious infection following plague exposure supports the use of doxycycline if antibiotic susceptibility testing, exhaustion of drug supplies, or allergic reactions preclude the use of streptomycin. Women who are breast-feeding should be treated with the same antibiotic as the infant.

    Children and Adolescents 8 years and older weighing less than 45 kg

    2.2 mg/kg/dose IV every 12 hours for 10 days. Switch to oral therapy when clinically indicated. The risk of serious infection following plague exposure supports the use of doxycycline if antibiotic susceptibility testing, exhaustion of drug supplies, or allergic reactions preclude the use of streptomycin.

    For the treatment of plague infection in a mass casualty setting.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    100 mg PO every 12 hours for 10 days. If antibiotic susceptibility testing allows, oral ciprofloxacin or chloramphenicol could be used as alternatives.

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.2 mg/kg/dose PO every 12 hours for 10 days. If antibiotic susceptibility testing allows, oral ciprofloxacin or chloramphenicol could be used as alternatives.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    120 mg PO every 12 hours for 10 days. If antibiotic susceptibility testing allows, oral ciprofloxacin or chloramphenicol could be used as alternatives.

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.6 mg/kg/dose PO every 12 hours for 10 days. If antibiotic susceptibility testing allows, oral ciprofloxacin or chloramphenicol could be used as alternatives.

    For the initial treatment of tularemia infection due to exposure to Francisella tularensis .
    For the initial treatment of tularemia infection in individual patient or in 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, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children and Adolescents 8 years and older weighing less than 45 kg

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

    For the initial 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, Adolescents, and Children 8 years and older weighing 45 kg or more

    100 mg PO every 12 hours for 14 days. If antibiotic susceptibility testing allows, oral ciprofloxacin could be used as alternative.

    Children and Adolescents 8 years and older weighing less than 45 kg

    2.2 mg/kg/dose PO every 12 hours for 14 days. If antibiotic susceptibility testing allows, oral ciprofloxacin could be used as alternative.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    120 mg PO every 12 hours for 14 days. If antibiotic susceptibility testing allows, oral ciprofloxacin could be used as alternative.

    Children and Adolescents 8 years and older weighing less than 45 kg

    2.6 mg/kg/dose PO every 12 hours for 14 days. If antibiotic susceptibility testing allows, oral ciprofloxacin could be used as alternative.

    For the treatment of intestinal amebiasis as an adjunct to amebicides.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children and Adolescents 8 years and older weighing less than 45 kg

    2.2 mg/kg/dose PO every 12 hours on day 1, then 2.2 mg/kg/dose PO once daily. For severe infections, continue 2.2 mg/kg/dose PO every 12 hours.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.65 mg/kg/dose PO every 12 hours on day 1, then 1.3 mg/kg/dose PO every 12 hours or 2.6 mg/kg/dose PO once daily. For severe infections, 2.6 mg/kg/dose PO every 12 hours.

    Intravenous infusion dosage
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    4.4 mg/kg IV on day 1, administered as 1 or 2 infusions, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses.

    For the treatment of infections caused by sensitive organisms including actinomycosis (Actinomyces israelii), yaws (Treponema pertenue), necrotizing ulcerative gingivitis (Fusospirochetosis or Vincent's infection), and listeriosis (Listeria monocytogenes).
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.2 mg/kg/dose PO every 12 hours on day 1, then 2.2 mg/kg/dose PO once daily. For severe infections, continue 2.2 mg/kg/dose PO every 12 hours.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.65 mg/kg/dose PO every 12 hours on day 1, then 1.3 mg/kg/dose PO every 12 hours or 2.6 mg/kg/dose PO once daily. For severe infections, 2.6 mg/kg/dose PO every 12 hours.

    Intravenous infusion dosage
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    4.4 mg/kg IV on day 1, administered as 1 or 2 infusions, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses.

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

    100 mg PO every 12 hours for 14 days for acute Q fever. For chronic Q fever (endocarditis or vascular infection), treat in combination with hydroxychloroquine for at least 18 months. For postpartum Q fever with serologic profile for chronic Q fever, treat in combination with hydroxychloroquine for 12 months.

    Children 8 years and older and Adolescents

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

    Infants† and Children 1 to 7 years†

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

    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 for acute Q fever. For chronic Q fever (endocarditis or vascular infection), treat in combination with hydroxychloroquine for at least 18 months. For postpartum Q fever with serologic profile for chronic Q fever, treat in combination with hydroxychloroquine for 12 months.

    Children 8 years and older and Adolescents

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

    Children 1 to 7 years†

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

    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 infusions. A treatment course of 14 days is recommended by CDC for acute Q fever.

    Children 8 years and older and Adolescents

    4.4 mg/kg/day (Max: 200 mg/day) IV on day 1, administered as 1 or 2 infusions, then 2.2 to 4.4 mg/kg/day (Max: 200 mg/day) IV in 1 to 2 divided doses; treat for 14 days for acute Q fever.

    Infants† and Children 1 to 7 years†

    4.4 mg/kg/day (Max: 200 mg/day) IV on day 1, administered as 1 or 2 infusions, then 2.2 to 4.4 mg/kg/day (Max: 200 mg/day) IV in 1 to 2 divided doses; treat for 14 days for acute Q fever.

    For the treatment of chancroid (Haemophilus ducreyi) infections.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    Doxycycline is not included in clinical practice guidelines for chancroid treatment. 100 mg PO every 12 hours on day 1, then 100 mg PO once daily. For severe infections, continue 100 mg PO every 12 hours.

    Children 8 years and older and Adolescents weighing less than 45 kg

    Doxycycline is not included in clinical practice guidelines for chancroid treatment. 2.2 mg/kg/dose PO every 12 hours on day 1, then 2.2 mg/kg/dose PO once daily. For severe infections, continue 2.2 mg/kg/dose PO every 12 hours.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    Doxycycline is not included in clinical practice guidelines for chancroid treatment. 120 mg PO every 12 hours on day 1, then 60 mg PO every 12 hours or 120 mg PO once daily. For severe infections, continue 120 mg PO every 12 hours.

    Children 8 years and older and Adolescents weighing less than 45 kg

    Doxycycline is not included in clinical practice guidelines for chancroid treatment. 2.65 mg/kg/dose PO every 12 hours on day 1, then 1.3 mg/kg/dose PO every 12 hours or 2.6 mg/kg/dose PO once daily. For severe infections, 2.6 mg/kg/dose PO every 12 hours.

    Intravenous dosage
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    Doxycycline is not included in clinical practice guidelines for chancroid treatment. 200 mg IV on day 1, then 100 to 200 mg IV per day, with the 200 mg dose administered as 1 or 2 infusions.

    Children 8 years and older and Adolescents weighing less than 45 kg

    Doxycycline is not included in clinical practice guidelines for chancroid treatment. 4.4 mg/kg IV on day 1, administered as 1 or 2 infusions, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses.

    For the treatment of bartonellosis (Bartonella bacilliformis) infections, including Bartonella endocarditis.
    For the treatment of Bartonella sp. infections (bartonellosis) in HIV-infected patients.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours for at least 3 months. Adding rifampin is an option in patients with CNS infections or other severe infections. Add gentamicin for 2 weeks for confirmed endocarditis; rifampin may be substituted in patients with renal insufficiency. Use as a single agent for bacillary angiomatosis, peliosis hepatis, bacteremia, and osteomyelitis.

    Adolescents

    100 mg PO every 12 hours for at least 3 months. Adding rifampin is an option in patients with CNS infections or other severe infections. Add gentamicin for 2 weeks for confirmed endocarditis; rifampin may be substituted in patients with renal insufficiency. Use as a single agent for bacillary angiomatosis, peliosis hepatis, bacteremia, and osteomyelitis.

    Intravenous dosage
    Adults

    100 mg IV every 12 hours for at least 3 months. Adding rifampin is an option in patients with CNS infections or other severe infections. Add gentamicin for 2 weeks for confirmed endocarditis; rifampin may be substituted in patients with renal insufficiency. Use as a single agent for bacillary angiomatosis, peliosis hepatis, bacteremia, and osteomyelitis.

    Adolescents

    100 mg IV every 12 hours for at least 3 months. Adding rifampin is an option in patients with CNS infections or other severe infections. Add gentamicin for 2 weeks for confirmed endocarditis; rifampin may be substituted in patients with renal insufficiency. Use as a single agent for bacillary angiomatosis, peliosis hepatis, bacteremia, and osteomyelitis.

    For long term suppression† of infections caused by Bartonella sp. in HIV-infected patients with relapse or reinfection with CD4 count less than 200 cells/mm3.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults

    100 mg PO every 12 hours. Discontinuation of suppressive therapy may be considered after 3 to 4 months of treatment and CD4 count is more than 200 cells/mm3 for at least 6 months. Some experts suggest that Bartonella titers also decrease by 4-fold prior to discontinuation of suppressive therapy.

    Adolescents

    100 mg PO every 12 hours. Discontinuation of suppressive therapy may be considered after 3 to 4 months of treatment and CD4 count is more than 200 cells/mm3 for at least 6 months. Some experts suggest that Bartonella titers also decrease by 4-fold prior to discontinuation of suppressive 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. For severe infections, continue 100 mg PO every 12 hours. Clinical practice guidelines recommend doxycycline in combination with rifampin for 4 to 6 weeks for retinitis. In trench fever or chronic bacteremia, doxycycline for 4 weeks plus gentamicin for 2 weeks is recommended. For culture-positive endocarditis, doxycycline for 6 weeks plus gentamicin for 2 weeks is recommended; in culture-negative endocarditis, ceftriaxone for 6 weeks plus gentamicin for 2 weeks with or without doxycycline for 6 weeks is recommended. Treat as monotherapy for 3 months for bacillary angiomatosis and 4 months for peliosis hepatis.

    Children and Adolescents 8 to 17 years

    2.2 mg/kg/dose PO every 12 hours on day 1 (Max: 100 mg/dose), then 2.2 mg/kg/day PO every 24 hours or divided every 12 hours (Max: 100 mg/day). For severe infections, 2.2 mg/kg/dose PO every 12 hours (Max: 100 mg/dose). Clinical practice guidelines recommend doxycycline for 6 weeks plus gentamicin for 2 weeks (or alternately, rifampin) for culture-positive endocarditis; for culture-negative endocarditis, ceftriaxone for 6 weeks plus gentamicin for 2 weeks with or without doxycycline for 6 weeks is recommended.

    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. For severe infections, continue 120 mg PO every 12 hours. Clinical practice guidelines recommend doxycycline in combination with rifampin for 4 to 6 weeks for retinitis. In trench fever or chronic bacteremia, doxycycline for 4 weeks plus gentamicin for 2 weeks is recommended. For culture-positive endocarditis, doxycycline for 6 weeks plus gentamicin for 2 weeks is recommended; in culture-negative endocarditis, ceftriaxone for 6 weeks plus gentamicin for 2 weeks with or without doxycycline for 6 weeks is recommended. Treat as monotherapy for 3 months for bacillary angiomatosis and 4 months for peliosis hepatis.

    Children and Adolescents 8 to 17 years

    2.65 mg/kg/dose PO every 12 hours on day 1 (Max: 120 mg/dose), then 1.3 mg/kg/dose PO every 12 hours (Max: 60 mg/dose) or 2.6 mg/kg/dose PO every 24 hours (Max: 120 mg/dose). For severe infections, 2.6 mg/kg/dose PO every 12 hours (Max: 120 mg/dose). Clinical practice guidelines recommend doxycycline for 6 weeks plus gentamicin for 2 weeks (or alternately, rifampin) for culture-positive endocarditis; for culture-negative endocarditis, ceftriaxone for 6 weeks plus gentamicin for 2 weeks with or without doxycycline for 6 weeks is recommended.

    Intravenous dosage
    Adults

    200 mg IV on day 1, then 100 to 200 mg IV per day, with the 200 mg dose administered as 1 or 2 infusions. Clinical practice guidelines recommend doxycycline in combination with rifampin for 4 to 6 weeks for retinitis. In trench fever or chronic bacteremia, doxycycline for 4 weeks plus gentamicin for 2 weeks is recommended. For culture-positive endocarditis, doxycycline for 6 weeks plus gentamicin for 2 weeks is recommended; in culture-negative endocarditis, ceftriaxone for 6 weeks plus gentamicin for 2 weeks with or without doxycycline for 6 weeks is recommended. Treat as monotherapy for 3 months for bacillary angiomatosis and 4 months for peliosis hepatis.

    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 infusions, then 2.2 to 4.4 mg/kg/day IV in 1 to 2 divided doses (Max: 200 mg/day). Clinical practice guidelines recommend doxycycline for 6 weeks plus gentamicin for 2 weeks (or alternately, rifampin) for culture-positive endocarditis; for culture-negative endocarditis, ceftriaxone for 6 weeks plus gentamicin for 2 weeks with or without doxycycline for 6 weeks is recommended.

    For the treatment of enterocolitis†, biliary tract infections†, and intraabdominal infections†.
    Oral dosage
    Adults, Adolescents, and Children 8 years and older and weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    2.2 mg/kg/dose PO every 12 hours on day 1, then 2.2 mg/kg/dose PO once daily. For severe infections, continue 2.2 mg/kg/dose PO every 12 hours.

    Intravenous infusion dosage
    Adults, Adolescents, and Children 8 years and older and weighing 45 kg or more

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

    Children 8 years and older and Adolescents weighing less than 45 kg

    4.4 mg/kg IV on day 1, administered as 1 or 2 infusions, then 2.2 to 4.4 mg/kg IV daily in 1 to 2 divided doses.

    For the treatment of uncomplicated gonorrhea (e.g., cervicitis, urethritis, pharyngitis, proctitis†).
    For the treatment of acute proctitis†.
    Oral dosage (excluding Doryx MPC delayed-release tablets)
    Adults and Adolescents

    100 mg PO twice daily for 7 days plus ceftriaxone IM.

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

    As an alternative, 100 mg PO twice daily for 7 days in combination with ceftriaxone 250 mg IM as a single dose. Doxycycline is only recommended as an alternative therapy in cases of azithromycin allergy. Product labeling recommends 100 mg PO twice daily for 7 days or alternatively 300 mg PO once and then a second 300 mg PO dose 1 hour later.

    Children 8 years and older† and Adolescents weighing 45 kg or more†

    As an alternative, 100 mg PO twice daily for 7 days in combination with ceftriaxone 250 mg IM as a single dose. Doxycycline is only recommended as an alternative therapy in cases of azithromycin allergy.

    Oral dosage (Doryx MPC delayed-release tablets)
    Adults

    As an alternative, 120 mg PO twice daily for 7 days in combination with ceftriaxone 250 mg IM as a single dose. Doxycycline is only recommended as an alternative therapy in cases of azithromycin allergy. Product labeling recommends 120 mg PO twice daily for 7 days or alternatively 360 mg PO once and then a second 360 mg PO dose 1 hour later.

    Intravenous dosage
    Adults

    Due to resistance, the CDC no longer recommends IV doxycycline for gonorrhea. Product labeling recommends 200 mg IV on day 1, then 100 to 200 mg IV per day, with the 200 mg dose administered as 1 or 2 infusions.

    For chlamydial infection prophylaxis† in victims of sexual assault.
    Oral dosage
    Adults and Adolescents

    100 mg PO twice daily for 7 days as an alternative to a single dose of azithromycin, in combination with ceftriaxone plus metronidazole or tinidazole in a single dose per CDC.

    For the treatment of chronic prostatitis† due to Ureaplasma urealyticum.
    Oral dosage
    Adult males

    In a pilot study, doxycycline 100 mg PO twice daily for 21 days was compared to azithromycin 500 mg PO daily for 3 days repeated every week for 3 weeks (total dose: 4500 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 traveler's diarrhea† and traveler's diarrhea prophylaxis†.
    For traveler's diarrhea† commonly caused by enterotoxigenic Escherichia coli.
    Oral dosage
    Adults

    100 mg PO twice daily for 3 days.

    For traveler's diarrhea prophylaxis† commonly caused by enterotoxigenic Escherichia coli.
    Oral dosage
    Adults

    100 mg PO once daily for the duration of the period at risk (up to 3 weeks) and continue for 1 to 2 days after returning home.

    For the treatment of Lyme disease†, including erythema migrans†, Lyme arthritis†, Lyme carditis†, and Lyme meningitis†.
    For early Lyme disease† (erythema migrans†).
    Oral dosage
    Adults

    100 mg PO twice daily for 10 to 21 days. Short courses of therapy (i.e., 10 to 14 days) have been reserved for disease that is limited to a single skin lesion only. However, 1 study compared a 10-day course of doxycycline with or without a single IV dose of ceftriaxone and a 20-day course of doxycycline in patients with erythema migrans and found no added benefit to extending the treatment to 20 days or adding IV ceftriaxone. Oral doxycycline has been found to be as effective as parenteral ceftriaxone in acute, disseminated disease (without meningitis).

    Children 8 years and older and Adolescents

    2 mg/kg/dose (Max: 100 mg/dose) PO twice daily for 10 to 21 days.

    For Lyme arthritis†.
    Oral dosage
    Adults

    100 mg PO twice daily for 28 days.

    Children 8 years and older and Adolescents

    2 mg/kg/dose (Max: 100 mg/dose) PO twice daily for 28 days.

    For Lyme carditis†.
    Oral dosage
    Adults

    100 to 200 mg PO twice daily for 14 days (range, 14 to 21 days) for patients who are intolerant of beta-lactam antibiotics.

    Children 8 years and older and Adolescents

    2 to 4 mg/kg/dose (Max: 200 mg/dose) PO twice daily for 14 days (range, 14 to 21 days) for patients who are intolerant of beta-lactam antibiotics.

    For early neurologic Lyme disease (i.e., Lyme meningitis† or cranial nerve palsy).
    Oral dosage
    Adults

    100 to 200 mg PO twice daily for 10 to 28 days for patients who are intolerant of beta-lactam antibiotics.

    Children 8 years and older and Adolescents

    2 to 4 mg/kg/dose (Max: 200 mg/dose) PO twice daily for 10 to 28 days for patients who are intolerant of beta-lactam antibiotics.

    For Lyme disease prophylaxis†.
    Oral dosage
    Adults

    200 mg PO as a single dose. Following confirmation of a bite from I. scapularis tick, doxycycline 200 mg PO as a single dose was found to be more effective than placebo in preventing clinical manifestations, including erythema migrans, and asymptomatic seroconversion.

    Children 8 years and older and Adolescents

    4 mg/kg/dose (Max: 200 mg/dose) PO as a single dose. Following confirmation of a bite from I. scapularis tick, doxycycline 200 mg PO as a single dose was found to be more effective than placebo in preventing clinical manifestations, including erythema migrans, and asymptomatic seroconversion.

    For the treatment of Legionnaire's disease† caused by Legionella pneumophila.
    Oral or Intravenous infusion dosage
    Adults

    100 mg IV or PO every 12 hours.

    For the management of pleural effusion† as an alternative to injectable tetracycline or other agents.
    Intracavitary dosage
    Adults

    500 mg of doxycycline injection diluted with 250 mL of 0.9% sodium chloride injection, administered via chest tube lavage and drainage. After administering the solution, clamp the chest tube for 24 hours and repeat the procedure daily until the amount of solution drained approximately equals the amount instilled.

    For the treatment of malaria† due to P. falciparum or P. vivax.
    Oral dosage
    Adults

    100 mg PO every 12 hours for 7 days in combination with quinine sulfate for uncomplicated P. falciparum infections; add primaquine phosphate for uncomplicated P. vivax infections per CDC.

    Children and Adolescents 8 years and older

    2.2 mg/kg/dose (Max: 100 mg/dose) PO every 12 hours for 7 days in combination with quinine sulfate for uncomplicated P. falciparum infections; add primaquine phosphate for uncomplicated P. vivax infections per CDC and American Academy of Pediatrics (AAP).

    Intravenous dosage
    Adults

    100 mg IV every 12 hours for 7 days can be used in combination with quinidine gluconate for severe infections; stepdown to oral therapy when able.

    Children and Adolescents 8 years and older

    2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours for 7 days can be used in combination with quinidine gluconate for severe infections; stepdown to oral therapy when able.

    For the treatment of pelvic inflammatory disease (PID)† and tubo-ovarian abscess†.
    Oral or Intravenous infusion dosage
    Adults and Adolescents†

    The CDC recommends doxycycline 100 mg PO, or IV if necessary, every 12 hours for 14 days in combination with cefotetan or cefoxitin as primary therapy. Administer doxycycline orally whenever possible, even in hospitalized patients. Patients can be transitioned to oral doxycycline alone after at least 24 hours of clinical improvement. When tubo-ovarian abscess is present, add clindamycin or metronidazole. A second regimen recommended by the CDC is a combination of clindamycin plus gentamicin, followed by doxycycline 100 mg PO every 12 hours to complete a total of 14 days of therapy. Data also support the use of doxycycline 100 mg PO or IV every 12 hours in combination with ampicillin/sulbactam. Other regimens with limited efficacy data are doxycycline 100 mg PO twice daily for 14 days in combination with ceftriaxone IM, cefoxitin IM plus probenecid, or another parenteral third-generation cephalosporin such as ceftizoxime or cefotaxime, with or without metronidazole.

    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
    Children >= 8 years

    2 mg/kg PO twice daily on day 1, then 2 mg/kg PO as either a single daily dose or divided into 2 equal doses daily for 10 to 14 days.

    For chronic adult periodontitis for a gain in clinical attachment, reduction in probing depth, and reduction in bleeding on probing.
    Oral dosage (regular capsules or tablets)†
    Adults

    100 mg PO twice daily on day 1, followed by 100 mg PO daily as either a single daily dose or as 50 mg PO twice daily for 10 to 21 days. In 1 study, 100 mg PO once daily for 3 weeks was compared to placebo in patients with a history of periodontal abscesses and/or loss of gingival attachment despite active periodontal therapy. During 12 months of follow-up 70% of patients had recurrent active disease and were further randomized to receive doxycycline or placebo. The study showed a relative risk reduction of 43% associated with doxycycline therapy as compared to placebo.

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

    20 mg PO every 12 hours for up to 9 months. The manufacturer recommends that the drug be taken close to meal times and also recommends administering the dose at least 1 hour prior to or 2 hours after meals. A single-dose study of Periostat given with a 1000 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. Manufacturers of other brands of doxycycline state that absorption of oral doxycycline is not markedly influenced by simultaneous ingestion of food or milk (see Interactions). Safety beyond 12 months and efficacy beyond 9 months have not been established.

    Subgingival/Periodontal dosage (Atridox)
    Adults

    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† following exposure to Yersinia pestis.
    Oral dosage
    Adults, Adolescents, and Children >= 8 years and >= 45 kg

    100 mg PO every 12 hours for 7 days. If antibiotic susceptibility testing allows, oral ciprofloxacin or chloramphenicol could be used as alternatives.

    Children and Adolescents >= 8 years and < 45 kg

    2.2 mg/kg PO every 12 hours, not to exceed 200 mg/day, for 7 days. If antibiotic susceptibility testing allows, oral ciprofloxacin or chloramphenicol could be used as alternatives.

    For tularemia prophylaxis† following exposure to Francisella tularensis.
    Oral dosage
    Adults, Adolescents, and Children 8 years and older weighing 45 kg or more

    100 mg PO every 12 hours for 14 days. If antibiotic susceptibility testing allows, oral ciprofloxacin could be used as alternative.

    Children and Adolescents 8 years and older weighing less than 45 kg

    2.2 mg/kg/dose PO every 12 hours for 14 days. If antibiotic susceptibility testing allows, oral ciprofloxacin could be used as alternative.

    For the treatment of Bancroft's filariasis† (elephantiasis) caused by Wuchereria bancrofti†.
    Oral dosage
    Adults and Adolescents

    A placebo-controlled, double-blind study in Tanzanian men age 15 to 68 years reported doxycycline to be effective for treating filariasis including lymphatic filariasis. Patients were randomized to receive doxycycline 200 mg PO daily (n = 34) or placebo (n = 38) for 8 weeks. At the conclusion of the study, doxycycline showed significant reductions in microfilaremia as well as significant macrofilaricidal activity against adult worms. The study noted that doxycycline treatment resulted in a gradual reduction in microfilaremia which tends to cause less inflammatory adverse reactions compared to rapid parasite reduction induced by diethylcarbamazine and ivermectin. Similar reductions in adverse reactions caused by rapid adult worm death (e.g., painful inflammatory scrotal nodules) were predicted due to the gradual macrofilaricidal activity of doxycycline. Although effective, mass treatment with doxycycline is limited by the difficulties in delivering long-term treatment and that it is contraindicated in children less than 8 years of age and pregnant women. Further study is needed to determine the role of doxycycline, other antibiotics, and combinations of antibiotics in treating filariasis.

    For the treatment of melioidosis† due to Burkholderia pseudomallei.
    For use as an adjunct in the treatment of Burkholderia pseudomallei bacteremia†.
    Intravenous infusion dosage
    Adults, Adolescents, and Children

    2 mg/kg IV twice daily, given as adjunctive therapy with ceftazidime for at least 10 to 14 days. If clinical improvement is achieved, switch to oral maintenance therapy with sulfamethoxazole; trimethoprim and doxycycline for 3 to 6 months. Oral maintenance therapy may be given with or without an initial 4-week regimen of chloramphenicol.

    For use as an adjunct in the treatment of localized melioidosis†.
    Intravenous infusion dosage
    Adults, Adolescents, and Children

    2 mg/kg IV twice daily is given with sulfamethoxazole; trimethoprim IV for at least 10 to 14 days. If clinical improvement is achieved, switch to oral maintenance therapy for 3 to 6 months. Oral maintenance therapy may be given with or without an initial 4-week regimen of chloramphenicol.

    For the treatment of leptospirosis† due to Leptospira sp.†.
    For mild leptospirosis†.
    Oral dosage
    Adults and Adolescents >= 15 years

    100 mg PO twice daily for 7 days.

    For severe leptospirosis†.
    Intravenous infusion dosage
    Adults and Adolescents >= 15 years

    A 200 mg IV initial infusion given over 30 minutes, followed by 100 mg IV every 12 hours for 7 days was as effective as penicillin G and cefotaxime in an open-label, randomized comparative study.

    For surgical infection prophylaxis† for gynecologic procedures.
    For surgical infection prophylaxis† for hysterosalpingogram or chromotubation.
    Oral dosage
    Adults

    The American College of Obstetricians and Gynecologists (ACOG) recommends 100 mg PO twice daily for 5 days.

    For surgical infection prophylaxis† for induced abortion/dilation and evacuation.
    Oral dosage
    Adults

    The American College of Obstetricians and Gynecologists (ACOG) recommends 100 mg PO 1 hour before the procedure and 200 mg PO after the procedure.

    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
    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
    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
    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.

    †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: May be administered with food and/or milk if gastric irritation occurs.
    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 can not be consumed immediately, it should be discarded; do not store for later use.
    Dual-release capsules (e.g., Oracea): Administer at least 1 hour before or 2 hours after meals.
    Tablets and capsules for periodontitis: Administer at least 1 hour before morning and evening meals.

    Oral Liquid Formulations

    Shake well prior to each use.
    Use a calibrated oral device (e.g., oral syringe or spoon) to ensure accurate dosage.
    May be taken 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 at 77 degrees F; excursions permitted to 59-86 degrees F
    Adoxa:
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Adoxa Pak:
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Alodox:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Avidoxy:
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Doryx:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Doxal:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Doxy 100:
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in carton until time of use
    Mondoxyne NL:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Monodox:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Morgidox 1x:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Morgidox 1x Kit:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Morgidox 2x :
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Morgidox 2x Kit:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    NutriDox :
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Ocudox :
    - Protect from light
    - Protect from moisture
    - 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 controlled room temperature (between 68 and 77 degrees F)
    TARGADOX:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Vibramycin:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Vibra-Tabs:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Tetracyclines hypersensitivity

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

    Hepatic disease

    Use caution when prescribing doxycycline to patients with severe hepatic disease because hepatic excretion into bile may be delayed and elimination half-life extended.

    Sunlight (UV) exposure

    Doxycycline is associated with photosensitivity reactions after sunlight (UV) exposure, with these reactions occurring somewhat less frequently than with demeclocycline. 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. Reactions can develop from within a few minutes to up to several hours after exposure and will last for 1—2 days after discontinuation of the drug. Advised drug recipients to avoid excess sunlight/artifical ultraviolet light whenever possible, use sunscreens, and to discontinue therapy if phototoxicity occurs (i.e., skin eruption).

    Asthma, sulfite hypersensitivity

    Doxycycline calcium oral suspension contains sodium metabisulfite. Sulfites cause an allergic reaction in some people and this product should be used 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.

    Pregnancy

    Adequate and well-controlled studies of doxycycline use in pregnant women are lacking. The vast majority of reported experience with doxycycline during human pregnancy is short-term, first trimester exposure. There are no human data available to assess the effects of long-term therapy of doxycycline in pregnant women such as that proposed for treatment of anthrax exposure. The tetracyclines as a class of drugs have been noted to have a detrimental effect on the skeletal development and bone growth of the fetus; they usually are not used during pregnancy, especially during the second half of pregnancy, unless benefits from treatment outweigh the risks. 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 two exposed cases.

    Breast-feeding

    Tetracyclines, including doxycycline, are distributed in small amounts into breast milk. According to the manufacturer, because of the potential for serious adverse reactions in nursing babies, a decision should be made whether to discontinue nursing or to discontinue the drug. In general, manufacturers recommend that tetracycline antibiotics not be used 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 effects are nursing babies were not reported. In one study, 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) 3 hours after the dose, and 0.46 mg/L (range 0.3 to 0.91 mg/L) 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. Doxycycline does not have a listed American Academy of Pediatrics breast-feeding category, but another tetracycline antibiotic, tetracycline, is rated as usually compatible with breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    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. The FDA-approved labeling recommends against the use of doxycycline in neonates, infants, and children through 8 years of age except for 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. Studies have failed to demonstrate dental staining, enamel hypoplasia, or tooth color differences in children who have received short-term courses of doxycycline at less 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).

    Colitis, diarrhea, GI disease, inflammatory bowel disease, pseudomembranous colitis, ulcerative colitis

    Almost all antibacterial agents have been associated with pseudomembranous colitis (antibiotic-associated colitis) which may range in severity from mild to life-threatening. In the colon, overgrowth of Clostridia may exist when normal flora is altered subsequent to antibacterial administration. The toxin produced by Clostridium difficile is a primary cause of pseudomembranous colitis. It is known that systemic use of antibiotics predisposes patients to development of pseudomembranous colitis. Consideration should be given to the diagnosis of pseudomembranous colitis in patients presenting with diarrhea following antibacterial administration. Systemic antibiotics should be prescribed with caution to patients with inflammatory bowel disease such as ulcerative colitis or other GI disease. If diarrhea develops during therapy, the drug should be discontinued. Following diagnosis of pseudomembranous colitis, therapeutic measures should be instituted. In milder cases, the colitis may respond to discontinuation of the offending agent. In moderate to severe cases, fluids and electrolytes, protein supplementation, and treatment with an antibacterial effective against Clostridium difficile may be warranted. Products inhibiting peristalsis are contraindicated in this clinical situation. Practitioners should be aware that antibiotic-associated colitis has been observed to occur over two months or more following discontinuation of systemic antibiotic therapy; a careful medical history should be taken.

    Dental disease, periodontal disease

    Doxycycline subgingival formulation (Atridox) has not been clinically evaluated in patients with dental disease/periodontal disease involving extremely severe periodontal defects with very little remaining periodontium. Also, it 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. Periostat and similar oral formulations for peridontitis produce doxycycline concentrations too low to exert a direct antibacterial effect. Clinical studies of patients show that the products have no effect on total anaerobic and facultative bacteria in plaque samples. These products should not be used as an antibiotic in the treatment of periodontitis/periodontal disease.

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

    Doxycycline subgingival (Atridox) and periodontal oral formulations (Periostat, others) have not been clinically tested in patients with predisposition to oral candidiasis, such as patients with immunosuppression due to diabetes mellitus, chemotherapy, or human immunodeficiency virus (HIV) infection.

    Antimicrobial resistance, fungal infection, viral infection

    Doxycycline does not treat fungal infection or viral infection (e.g., common cold). Prescribing doxycycline in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria (antimicrobial resistance). Patients should be told to complete the full course of treatment, even if they feel better earlier. Antibiotic therapy can result in superinfection or suprainfection with nonsusceptible organisms, such as candidiasis. Patients should be monitored closely.

    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.

    Sexually transmitted disease

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

    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.

    Serious rash

    Doxycycline may cause severe serious rash and other severe cutaneous adverse reactions, such as exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). If patients develop skin reactions, discontinue doxycycline and institute appropriate therapy.

    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
    exfoliative dermatitis / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    pericarditis / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    serum sickness / Delayed / Incidence not known
    lupus-like symptoms / 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
    pseudomembranous colitis / Delayed / Incidence not known
    superinfection / Delayed / Incidence not known
    candidiasis / 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

    Mild

    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
    rash (unspecified) / Early / 4.0-4.0
    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
    urticaria / Rapid / Incidence not known
    maculopapular rash / Early / Incidence not known
    purpura / 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

    Acetaminophen; Butalbital: (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.
    Acetaminophen; 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.
    Acetaminophen; 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.
    Acitretin: (Severe) 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: (Major) 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, particularly if the time of administration is within 60 minutes of each other. Aluminum salts should be taken at least 4 hours before or 1 to 2 hours after tetracyclines.
    Aluminum Hydroxide; Magnesium Carbonate: (Major) 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, particularly if the time of administration is within 60 minutes of each other. Aluminum salts should be taken at least 4 hours before or 1 to 2 hours after tetracyclines.
    Aluminum Hydroxide; Magnesium Hydroxide: (Major) 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, particularly if the time of administration is within 60 minutes of each other. Aluminum salts should be taken at least 4 hours before or 1 to 2 hours after tetracyclines.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Major) 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, particularly if the time of administration is within 60 minutes of each other. Aluminum salts should be taken at least 4 hours before or 1 to 2 hours after tetracyclines.
    Aluminum Hydroxide; Magnesium Trisilicate: (Major) 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, particularly if the time of administration is within 60 minutes of each other. Aluminum salts should be taken at least 4 hours before or 1 to 2 hours after tetracyclines.
    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.
    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.
    Atracurium: (Moderate) Tetracyclines may potentiate the neuromuscular effects of nondepolarizing neuromuscular blockers.
    Atropine; Hyoscyamine; Phenobarbital; 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.
    Azelaic Acid; Copper; Folic Acid; Nicotinamide; Pyridoxine; 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.
    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: (Major) Tetracyclines are susceptible to drug interactions with trivalent cations like bismuth. These cations form insoluble complexes with the tetracyclines, thereby reducing the bioavailability of the tetracyclines. Staggering the administration times of bismuth and tetracyclines by 2 hours may be sufficient to avoid this interaction.
    Bismuth Subsalicylate: (Major) Tetracyclines are susceptible to drug interactions with trivalent cations like bismuth. These cations form insoluble complexes with the tetracyclines, thereby reducing the bioavailability of the tetracyclines. Staggering the administration times of bismuth and tetracyclines by 2 hours may be sufficient to avoid this interaction.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Tetracyclines are susceptible to drug interactions with trivalent cations like bismuth. These cations form insoluble complexes with the tetracyclines, thereby reducing the bioavailability of the tetracyclines. Staggering the administration times of bismuth and tetracyclines by 2 hours may be sufficient to avoid this interaction.
    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.
    Calcium Carbonate: (Major) 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: (Major) 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: (Major) 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 Salts: (Major) 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: (Major) 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: (Major) 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: (Major) Carbamazepine may potentially accelerate the hepatic metabolism of doxycycline. Clinicians should be alert to decreased effect of doxycycline. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with doxycycline.
    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.
    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: (Major) 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.
    Cisatracurium: (Moderate) Tetracyclines may potentiate the neuromuscular effects of nondepolarizing neuromuscular blockers.
    Cod Liver Oil: (Moderate) Tetracyclines may interact with vitamin A found in cod liver oil. There have been reports of benign intracranial hypertension (pseudotumor cerebri) during concurrent use of vitamin A and tetracycline. In addition, the combination may also cause additive photosensitivity.
    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.
    Collagenase: (Major) 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.
    Cyanocobalamin, Vitamin B12: (Major) 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.
    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.
    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.
    Doxacurium: (Moderate) Tetracyclines may potentiate the neuromuscular effects of nondepolarizing neuromuscular blockers.
    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.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Major) Iron salts or products that contain iron can decrease the oral bioavailability of tetracyclines. The ability of tetracyclines to chelate with divalent cations such as iron, however, varies depending on the particular antibiotic and when the antibiotic is administered with regard to the iron-containing product. Doxycycline chelates more avidly with iron than other tetracyclines. This pharmacokinetic interaction with iron can be minimized by staggering the doses of the antibiotic and iron by as much as possible. Administering iron-containing products 4 to 6 hours before or 1 hour after the oral tetracycline antibiotic dose will minimize the risk of antibiotic failure due to poor bioavailability.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Major) Iron salts or products that contain iron can decrease the oral bioavailability of tetracyclines. The ability of tetracyclines to chelate with divalent cations such as iron, however, varies depending on the particular antibiotic and when the antibiotic is administered with regard to the iron-containing product. Doxycycline chelates more avidly with iron than other tetracyclines. This pharmacokinetic interaction with iron can be minimized by staggering the doses of the antibiotic and iron by as much as possible. Administering iron-containing products 4 to 6 hours before or 1 hour after the oral tetracycline antibiotic dose will minimize the risk of antibiotic failure due to poor bioavailability.
    Ethotoin: (Major) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of other drugs, including doxycycline, leading to reduced efficacy of the concomitant medication.
    Ferric Citrate: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of tetracyclines will be significantly reduced by other orally administered compounds that contain iron salts. To minimize the potential for this interaction, administer tetracycline antibiotics at least 1 hour before ferric citrate.
    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 containinng 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. There are studies indicating a pharmacokinetic effect of meals containing dairy products on doxycycline absorption. A single-dose study of Periostat given with a 1000 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 (given as Oracea) were reduced by about 45% and 22%, respectively, in healthy volunteers fed a 1000 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 containinng 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. There are studies indicating a pharmacokinetic effect of meals on doxycycline absorption. A single-dose study of Periostat given with a 1000 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 (given as Oracea) were reduced by about 45% and 22%, respectively, in healthy volunteers fed a 1000 calorie, high-fat, high-protein meal which included dairy products. The reductions in AUC and Cmax can be clinically significant.
    Fosphenytoin: (Major) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of other drugs, including doxycycline, leading to reduced efficacy of the concomitant medication.
    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.
    Hetastarch; Dextrose; Electrolytes: (Major) Administration of oral magnesium-containing products with oral tetracycline antibiotics may form nonabsorbable complexes resulting in decreased absorption of tetracyclines. This can compromise therapeutic efficacy of the tetracycline agent. Do not administer oral magnesium-containing laxatives, antacids, dietary supplements, or other drugs within1 to 3 hours of taking an oral tetracycline. (Major) 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.
    Hydantoins: (Major) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of other drugs, including doxycycline, leading to reduced efficacy of the concomitant medication.
    Hydrochlorothiazide, HCTZ; 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.
    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: (Major) 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. (Major) Iron salts or products that contain iron can decrease the oral bioavailability of tetracyclines. The ability of tetracyclines to chelate with divalent cations such as iron, however, varies depending on the particular antibiotic and when the antibiotic is administered with regard to the iron-containing product. Doxycycline chelates more avidly with iron than other tetracyclines. This pharmacokinetic interaction with iron can be minimized by staggering the doses of the antibiotic and iron by as much as possible. Administering iron-containing products 4 to 6 hours before or 1 hour after the oral tetracycline antibiotic dose will minimize the risk of antibiotic failure due to poor bioavailability.
    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.
    Iron: (Major) Iron salts or products that contain iron can decrease the oral bioavailability of tetracyclines. The ability of tetracyclines to chelate with divalent cations such as iron, however, varies depending on the particular antibiotic and when the antibiotic is administered with regard to the iron-containing product. Doxycycline chelates more avidly with iron than other tetracyclines. This pharmacokinetic interaction with iron can be minimized by staggering the doses of the antibiotic and iron by as much as possible. Administering iron-containing products 4 to 6 hours before or 1 hour after the oral tetracycline antibiotic dose will minimize the risk of antibiotic failure due to poor bioavailability.
    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.
    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.
    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: (Major) Administration of oral magnesium citrate solution with oral tetracycline antibiotics may form nonabsorbable complexes resulting in decreased absorption of tetracyclines. Do not administer oral magnesium citrate solution within 1 to 3 hours of taking an oral tetracycline.
    Magnesium Salts: (Major) Administration of oral magnesium-containing products with oral tetracycline antibiotics may form nonabsorbable complexes resulting in decreased absorption of tetracyclines. This can compromise therapeutic efficacy of the tetracycline agent. Do not administer oral magnesium-containing laxatives, antacids, dietary supplements, or other drugs within1 to 3 hours of taking an oral tetracycline.
    Magnesium: (Major) Administration of oral magnesium-containing products with oral tetracycline antibiotics may form nonabsorbable complexes resulting in decreased absorption of tetracyclines. This can compromise therapeutic efficacy of the tetracycline agent. Do not administer oral magnesium-containing laxatives, antacids, dietary supplements, or other drugs within1 to 3 hours of taking an oral tetracycline.
    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.
    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) Oral antibiotics such as tetracyclines may decrease intestinal absorption of methotrexate or interfere with enterohepatic circulation by inhibiting bowel flora and suppressing metabolism of the drug by bacteria. Tetracyclines may displace methotrexate from protein binding sites leading to increased methotrexate levels. A case report describes a patient who received oral doxycycline in combination with her eleventh course of high-dose methotrexate. Methotrexate serum concentrations indicated a prolonged half-life and the patient developed severe gastrointestinal toxicity and myelosuppression including neutropenic fever. This resulted in two prolonged hospital stays and a delay in her next course of chemotherapy.
    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.
    Mivacurium: (Moderate) Tetracyclines may potentiate the neuromuscular effects of nondepolarizing neuromuscular blockers.
    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.
    Neuromuscular blockers: (Moderate) Tetracyclines may potentiate the neuromuscular effects of nondepolarizing neuromuscular blockers.
    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.
    Pancuronium: (Moderate) Tetracyclines may potentiate the neuromuscular effects of nondepolarizing neuromuscular blockers.
    Pantothenic Acid, Vitamin B5: (Major) 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.
    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.
    Phenytoin: (Major) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of other drugs, including doxycycline, leading to reduced efficacy of the concomitant medication.
    Photosensitizing agents: (Moderate) Use photosensitizing agents 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.
    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.
    Polysaccharide-Iron Complex: (Major) Iron salts or products that contain iron can decrease the oral bioavailability of tetracyclines. The ability of tetracyclines to chelate with divalent cations such as iron, however, varies depending on the particular antibiotic and when the antibiotic is administered with regard to the iron-containing product. Doxycycline chelates more avidly with iron than other tetracyclines. This pharmacokinetic interaction with iron can be minimized by staggering the doses of the antibiotic and iron by as much as possible. Administering iron-containing products 4 to 6 hours before or 1 hour after the oral tetracycline antibiotic dose will minimize the risk of antibiotic failure due to poor bioavailability.
    Porfimer: (Moderate) Use photosensitizing agents 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.
    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: (Major) 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.
    Rapacuronium: (Moderate) Tetracyclines may potentiate the neuromuscular effects of nondepolarizing neuromuscular blockers.
    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.
    Rocuronium: (Moderate) Tetracyclines may potentiate the neuromuscular effects of nondepolarizing neuromuscular blockers.
    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.
    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: (Major) Iron salts or products that contain iron can decrease the oral bioavailability of tetracyclines. The ability of tetracyclines to chelate with divalent cations such as iron, however, varies depending on the particular antibiotic and when the antibiotic is administered with regard to the iron-containing product. Doxycycline chelates more avidly with iron than other tetracyclines. This pharmacokinetic interaction with iron can be minimized by staggering the doses of the antibiotic and iron by as much as possible. Administering iron-containing products 4 to 6 hours before or 1 hour after the oral tetracycline antibiotic dose will minimize the risk of antibiotic failure due to poor bioavailability.
    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.
    Soy Isoflavones: (Minor) Bacteria in the intestine produce enzymes which hydrolyze the soy isoflavones to the active isoflavonoids genistein and daidzein; alterations in gut microflora have been correlated with effects on soy isoflavone bioavailability. Tetracyclines significantly reduce the GI microflora and could theoretically prevent the formation of the active components of the soy isoflavones.
    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.
    Succinylcholine: (Moderate) Tetracyclines may potentiate the neuromuscular effects of nondepolarizing neuromuscular blockers.
    Sucralfate: (Major) 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. Sucralfate should be given 2 hours before or after the oral administration of tetracyclines.
    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.
    Tretinoin, ATRA: (Major) The concomitant use of systemic tretinoin, ATRA and systemic tetracyclines should be avoided due to the potential for increased intracranial 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. In addition, a manufacturer of topical tretinoin states that tretinoin, ATRA 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.
    Tubocurarine: (Moderate) Tetracyclines may potentiate the neuromuscular effects of nondepolarizing neuromuscular blockers.
    Vecuronium: (Moderate) Tetracyclines may potentiate the neuromuscular effects of nondepolarizing neuromuscular blockers.
    Verteporfin: (Moderate) Use photosensitizing agents 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.
    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.
    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. (Major) 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.
    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

    Adequate and well-controlled studies of doxycycline use in pregnant women are lacking. The vast majority of reported experience with doxycycline during human pregnancy is short-term, first trimester exposure. There are no human data available to assess the effects of long-term therapy of doxycycline in pregnant women such as that proposed for treatment of anthrax exposure. The tetracyclines as a class of drugs have been noted to have a detrimental effect on the skeletal development and bone growth of the fetus; they usually are not used during pregnancy, especially during the second half of pregnancy, unless benefits from treatment outweigh the risks. 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 two exposed cases.

    Tetracyclines, including doxycycline, are distributed in small amounts into breast milk. According to the manufacturer, because of the potential for serious adverse reactions in nursing babies, a decision should be made whether to discontinue nursing or to discontinue the drug. In general, manufacturers recommend that tetracycline antibiotics not be used 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 effects are nursing babies were not reported. In one study, 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) 3 hours after the dose, and 0.46 mg/L (range 0.3 to 0.91 mg/L) 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. Doxycycline does not have a listed American Academy of Pediatrics breast-feeding category, but another tetracycline antibiotic, tetracycline, is rated as usually compatible with breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    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 30 S 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. Resistance develops when the bacterial cell mutates and the cell wall becomes less permeable.
     
    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 doxycyline, but has no impact on minocycline susceptibility.
     
    The action of tetracyclines in the treatment of acne vulgaris has not been fully established but is believed to be due in part to its antibacterial actions. Several other mechanisms have been proposed but not studied. (See tetracycline monograph for additional information.)
     
    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—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.

    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 regular- 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. Absorption may be delayed by food or milk, but of all the tetracyclines, doxycycline has the least affinity for calcium ions. Therefore, absorption is not significantly affected when the regular- or delayed-release doxycycline products are taken with milk, but can be somewhat delayed. A single-dose study of Periostat given with a 1000-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. 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. 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. 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 1000-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).

    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.