Introduction

Antibacterial; semisynthetic tetracycline antibiotic derived from oxytetracycline.

Uses for Doxycycline (Systemic)

Respiratory Tract Infections

Treatment of respiratory tract infections caused by Mycoplasma pneumoniae.

Treatment of respiratory tract infections caused by Haemophilus influenzae, Streptococcus pneumoniae, or Klebsiella. Should only be used for treatment of infections caused by these bacteria when in vitro susceptibility tests indicate the organism is susceptible.

Empiric treatment of community-acquired pneumonia (CAP) in conjunction with other anti-infectives. Tetracyclines provide coverage against C. pneumoniae, M. pneumoniae, H. influenzae, and Legionella, but S. pneumoniae may be resistant. Doxycycline is the preferred tetracycline for empiric treatment of CAP.

Alternative for treatment of infections caused by Legionella pneumophila^{† [off-label]}; used with or without rifampin.

Acne

Adjunctive treatment of moderate to severe inflammatory acne. Not indicated for treatment of noninflammatory acne.

Actinomycosis

Treatment of actinomycosis caused by Actinomyces israelii. Alternative to penicillin G; oral tetracyclines (usually doxycycline or tetracycline) also used as follow-up after initial parenteral penicillin G.

Amebiasis

Adjunct to amebicides for treatment of acute intestinal amebiasis. Tetracyclines not included in current recommendations for treatment of amebiasis caused by Entamoeba.

Anthrax

Postexposure prophylaxis to reduce the incidence or progression of disease following a suspected or confirmed exposure to aerosolized Bacillus anthracis spores (inhalational anthrax). Initial drug of choice for such prophylaxis is ciprofloxacin or doxycycline; doxycycline is the preferred tetracycline because of ease of administration and proven efficacy in monkey studies.

Treatment of inhalational anthrax. Monotherapy may be effective for anthrax that occurs as the result of natural or endemic exposures, but a multiple-drug parenteral regimen (ciprofloxacin or doxycycline and 1 or 2 other anti-infectives predicted to be effective) is recommended for inhalational anthrax that occurs as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism. Although tetracyclines not usually used in children <8 years of age or in pregnant women, the benefits of doxycycline outweigh the risks and CDC and others state doxycycline can be used when necessary for treatment of inhalational anthrax in these individuals.

Treatment of GI and oropharyngeal anthrax. If occurring in the context of biologic warfare or bioterrorism, use parenteral regimens recommended for inhalational anthrax.

Treatment of cutaneous anthrax. Multiple-drug regimen recommended for initial treatment when there are signs of systemic involvement, extensive edema, or lesions on the head or neck or when cutaneous anthrax occurs in children <2 years of age.

Bartonella Infections

Treatment of bartonellosis caused by Bartonella bacilliformis.

Treatment of infections caused by B. henselae^{† [off-label]} (e.g., cat scratch disease, bacillary angiomatosis, peliosis hepatitis). Cat scratch disease generally is self-limited in immunocompetent individuals and may resolve spontaneously in 2–4 months; some clinicians suggest that anti-infective therapy be considered for acutely or severely ill patients with systemic symptoms, particularly those with hepatosplenomegaly or painful lymphadenopathy, and probably is indicated in immunocompromised patients. Anti-infectives also are indicated in patients with B. henselae infections who develop bacillary angiomatosis, neuroretinitis, or Parinaud’s oculoglandular syndrome. Optimum regimens have not been identified; some clinicians recommend erythromycin, azithromycin, doxycycline, ciprofloxacin, rifampin, co-trimoxazole, gentamicin, or third generation cephalosporins.

Treatment of infections caused by B. quintana^{† [off-label]}. Optimum anti-infective regimens have not been identified; various drugs have been used, including doxycycline, erythromycin, azithromycin, chloramphenicol, or cephalosporins.

A drug of choice for treatment of bartonellosis in HIV-infected adults and adolescents, especially CNS bartonellosis. USPHS/IDSA, CDC, and others suggest that long-term suppression with erythromycin or doxycycline should be considered to prevent recurrence of bartonellosis^{† [off-label]} in HIV-infected adults and adolescents with relapse or reinfection.

Brucellosis

Treatment of brucellosis; considered a drug of choice. Used in conjunction with other anti-infectives (e.g., streptomycin or gentamicin and/or rifampin), especially for severe infections or when there are complications (e.g., endocarditis, meningitis, osteomyelitis).

Postexposure prophylaxis following a high-risk exposure to Brucella^{† [off-label]} (e.g., needle-stick injury, inadvertent laboratory exposure, confirmed exposure in the context of biologic warfare or bioterrorism). Postexposure prophylaxis not generally recommended after exposure to endemic brucellosis.

Burkholderia Infections

Treatment of melioidosis^† caused by Burkholderia pseudomallei. Although optimum regimens not identified, doxycycline monotherapy may be effective for mild, localized disease without toxicity, and doxycycline in conjunction with co-trimoxazole may be effective for localized disease with toxicity. Severe illness requires an initial parenteral regimen of ceftazidime, imipenem, or meropenem (with or without concomitant co-trimoxazole or doxycycline), followed by a prolonged oral maintenance regimen of doxycycline (in conjunction with co-trimoxazole) or amoxicillin-clavulanate.

Treatment of glanders^† caused by B. mallei. Experience is limited regarding treatment of human cases; optimum regimens not identified. Some clinicians suggest streptomycin used in conjunction with tetracycline or chloramphenicol or imipenem monotherapy. Others suggest that, pending results of in vitro susceptibility tests, regimens used for treatment of melioidosis can be used for initial empiric treatment of glanders.

The US Army Medical Research Institute of Infectious Diseases (USAMRIID) and European Commission’s Task Force on Biological and Chemical Agent Threats (BICHAT) state that the same treatment regimens recommended for naturally occurring melioidosis or glanders should be used if these Burkholderia infections occur in the context of biologic warfare or bioterrorism. These experts suggest that postexposure prophylaxis with doxycycline or co-trimoxazole for ≥10 days can be attempted in such situations, but is of unproven benefit.

Campylobacter Infections

Treatment of infections caused by Campylobacter fetus. Tetracyclines (usually doxycycline) are alternatives, not drugs of choice for C. fetus.

Chancroid

Treatment of chancroid caused by Haemophilus ducreyi. Not included in CDC recommendations for treatment of chancroid.

Chlamydial Infections

Treatment of uncomplicated urethral, endocervical, or rectal infections caused by Chlamydia trachomatis. A drug of choice for presumptive treatment of chlamydial infections in patients with gonorrhea.

Treatment of trachoma and inclusion conjunctivitis caused by C. trachomatis. Consider that anti-infectives may not eliminate C. trachomatis in all cases of chronic trachoma.

Treatment of lymphogranuloma venereum (genital, inguinal, or anorectal infections) caused by C. trachomatis. Recommended as drug of choice by CDC and others.

Treatment of psittacosis (ornithosis) caused by C. psittaci. A drug of choice recommended by CDC.

Clostridium Infections

Treatment of infections caused by Clostridium. Tetracyclines are alternatives to metronidazole or penicillin G for adjunctive treatment of C. tetani infections.

Ehrlichiosis

Treatment of human granulocytotropic (or granulocytic) anaplasmosis^† (HGA; formerly human granulocytic ehrlichiosis [HGE]) caused by Anaplasma phagocytophilum (formerly Ehrlichia phagocytophila, E. equi, agent of HGE); drug of choice.

Treatment of human monocytotropic (or monocytic) ehrlichiosis^† (HME) caused by E. chaffeensis; drug of choice.

Treatment of ehrlichiosis^† caused by E. ewingii or E. canis; drug of choice.

Enterobacteriaceae Infections

Treatment of infections caused by susceptible Escherichia coli, Enterobacter aerogenes, Klebsiella, or Shigella. Should only be used for treatment of infections caused by these common gram-negative bacteria when other appropriate anti-infectives are contraindicated or ineffective and when in vitro susceptibility tests indicate the organism is susceptible.

Fusobacterium Infections

Alternative to penicillin G for treatment of infections caused by Fusobacterium fusiforme (Vincent’s infection).

Gonorrhea and Associated Infections

Alternative for treatment of uncomplicated gonorrhea caused by susceptible Neisseria gonorrhoeae. However, tetracyclines are considered inadequate therapy and are not recommended by CDC for treatment of gonorrhea.

Empiric treatment of epididymitis most likely caused by N. gonorrhoeae or C. trachomatis; used in conjunction with IM ceftriaxone.

Granuloma Inguinale (Donovanosis)

Treatment of granuloma inguinale (donovanosis) caused by Calymmatobacterium granulomatis. CDC recommends doxycycline or co-trimoxazole as drugs of choice.

Leptospirosis

Alternative to penicillin G for treatment of leptospirosis^†.

Prevention of leptosporosis^† in travelers to areas where leptospirosis is endemic or epidemic who are at increased risk (e.g., those who engage in recreational water activities such as whitewater rafting, adventure racing, kayaking).

Can be used for combined prophylaxis in travelers at increased risk of leptospirosis who also require malaria chemoprophylaxis.

Listeria Infections

Alternative for treatment of listeriosis caused by Listeria monocytogenes. Not usually considered a drug of choice or alternative for these infections.

Lyme Disease

Treatment of early disseminated Lyme disease^† associated with erythema migrans, in the absence of neurologic involvement or third-degree AV heart block. IDSA, AAP, and others recommend oral doxycycline or oral amoxicillin as first-line therapy for treatment of early localized or early disseminated Lyme disease when oral therapy is appropriate.

Treatment of uncomplicated Lyme arthritis^† without objective evidence of neurologic involvement (e.g., meningitis or radiculopathy).

Alternative for treatment of neurologic manifestations of Lyme disease^† when β-lactams (e.g., ceftriaxone, penicillin G) cannot be used.

Malaria

Prevention (prophylaxis) of malaria caused by Plasmodium falciparum, including chloroquine-resistant strains. Recommended by CDC and others as a drug of choice for prophylaxis in individuals traveling to areas where chloroquine-resistant P. falciparum malaria has been reported; recommended by CDC as an alternative in those traveling to areas where chloroquine-resistant P. falciparum has not been reported and who are unable to take chloroquine or hydroxychloroquine.

Treatment of uncomplicated malaria^† caused by chloroquine-resistant Plasmodium falciparum or chloroquine-resistant P. vivax and when the plasmodial species has not been identified. Used in conjunction with quinine; not effective alone.

CDC and others state treatments of choice for uncomplicated chloroquine-resistant P. falciparum malaria are a regimen of oral quinine in conjunction with oral doxycycline, tetracycline, or clindamycin or a regimen of atovaquone and proguanil. A regimen of quinine and doxycycline (or tetracycline) generally preferred over quinine and clindamycin, except for young children or pregnant women who should not receive tetracyclines. Quinine in conjunction with tetracycline (or doxycycline) also a regimen of choice for chloroquine-resistant P. vivax malaria.

Treatment of severe malaria caused by P. falciparum^†; used in conjunction with IV quinidine gluconate initially and then with oral quinine when an oral regimen is tolerated.

Presumptive self-treatment of malaria^† in travelers who elect not to use prophylaxis, those who require or choose to use a prophylaxis regimen that may not have optimal efficacy, or for long-term travelers receiving effective prophylaxis but who plan to visit very remote areas; used in conjunction with quinine. Not recommended by CDC for presumptive self-treatment of malaria; CDC recommends the fixed combination of atovaquone and proguanil.

Active only against the asexual erythrocytic forms of Plasmodium (not exoerythrocytic stages) and cannot prevent delayed primary attacks or relapse of P. ovale or P. vivax malaria or provide a radical cure; primaquine usually also indicated to eradicate hypnozoites and prevent relapse in patients exposed to or being treated for P. ovale or P. vivax malaria.

Detailed recommendations regarding prevention of malaria available from CDC 24 hours a day from the voice information service (877-394-8747), fax information service (888-232-3299), or Internet at [Web].

Assistance with diagnosis or treatment of malaria available from CDC Malaria Epidemiology Branch by contacting CDC Malaria Hotline at 770-488-7788 from 8:00 a.m. to 4:30 p.m. Eastern Standard Time or CDC Emergency Operation Center at 770-488-7100 after hours, on weekends, and holidays.

Mycobacterial Infections

Alternative for treatment of infections caused by Mycobacterium fortuitum^†.

Treatment of cutaneous infections caused by M. marinum^†; a drug of choice.

Nocardiosis

Alternative to co-trimoxazole for treatment of nocardiosis^† caused by Nocardia.

Nongonococcal Urethritis

Treatment of nongonococcal urethritis (NGU) caused by Ureaplasma urealyticum, C. trachomatis, or Mycoplasma.

Consider that some cases of recurrent urethritis following doxycycline treatment may be caused by tetracycline-resistant U. urealyticum.

Pelvic Inflammatory Disease

Treatment of acute pelvic inflammatory disease (PID); used in conjunction with other anti-infectives. Doxycycline is included in PID regimens to provide coverage against Chlamydia.

When a parenteral regimen is indicated for PID, CDC and others recommend IV cefotetan (or cefoxitin) in conjunction with IV or oral doxycycline as a regimen of choice. A regimen of IV ampicillin and sulbactam and IV doxycycline is an alternative since it provides good coverage against C. trachomatis, N. gonorrhoeae, and anaerobes and is effective for tubo-ovarian abscess. Doxycycline also used as follow-up after a parenteral regimen of clindamycin and gentamicin.

When an oral regimen is indicated, CDC and others recommend a single IM dose of ceftriaxone or cefoxitin (or other parenteral cephalosporin) followed by oral doxycycline (with or without oral metronidazole) as a regimen of choice. Although experience is limited, oral amoxicillin and clavulanate and oral doxycycline may be an alternative oral regimen.

Plague

Treatment of plague caused by Yersinia pestis, including naturally occurring or endemic bubonic, septicemic, or pneumonic plague and plague that occurs following exposure to Y. pestis in the context of biologic warfare or bioterrorism. Regimen of choice is streptomycin or gentamicin; alternatives are doxycycline, tetracycline, ciprofloxacin, or chloramphenicol. For plague meningitis, some experts recommend that treatment regimen include chloramphenicol.

Postexposure prophylaxis following a high-risk exposure to Y. pestis^† (e.g., household, hospital, or other close contact with an individual who has pneumonic plague; laboratory exposure to viable Y. pestis; confirmed exposure to plague aerosol in the context of biologic warfare or bioterrorism). Doxycycline may be drug of choice; alternatives are tetracycline, ciprofloxacin, or chloramphenicol. Prophylaxis not required for asymptomatic contacts of individuals with bubonic plague, but observe such contacts for 1 week and initiate treatment if symptoms occur.

Pleural Effusions

Management of pleural effusions^† associated with metastatic tumors.

Rat-bite Fever

Treatment of rat-bite fever^† caused by Streptobacillus moniliformis or Spirillum minus. Tetracyclines (usually doxycycline) are alternatives to penicillin G.

Relapsing Fever

Treatment of relapsing fever caused by Borrelia recurrentis. A drug of choice.

Rickettsial Infections

Treatment of rickettsial infections including Rocky Mountain spotted fever (RMSF), typhus fever and the typhus group, Q fever, rickettsialpox, and tick fevers caused by Rickettsiae. Drug of choice for treatment of most rickettsial infections.

Syphilis

Alternative to penicillin G benzathine for treatment of primary, secondary, latent, or tertiary syphilis (not neurosyphilis) in nonpregnant adults and adolescents hypersensitive to penicillins, including HIV-infected patients. Use tetracyclines only if compliance and follow-up can be ensured since efficacy not well documented.

Tularemia

Treatment of tularemia caused by Francisella tularensis, including naturally occurring or endemic tularemia or tularemia that occurs following exposure to F. tularensis in the context of biologic warfare or bioterrorism. Drugs of choice are streptomycin or gentamicin; alternatives are tetracyclines (usually doxycycline), ciprofloxacin, or chloramphenicol. Risk of relapse and primary treatment failure may be higher with the alternatives.

Postexposure prophylaxis of tularemia^† following a high-risk laboratory exposure to F. tularensis (e.g., spill, centrifuge accident, needlestick injury) or in individuals exposed to the organism in the context of biologic warfare or bioterrorism. Drugs of choice are doxycycline, tetracycline, or ciprofloxacin. Postexposure prophylaxis usually not recommended after exposure to natural or endemic tularemia (e.g., tick bite, rabbit or other animal exposure) and is unnecessary in close contacts of tularemia patients since human-to-human transmission does not occur.

Preexposure prophylaxis of tularemia^†. Based on results of in vitro susceptibility data, use of doxycycline or ciprofloxacin before exposure possibly may protect against tularemia in the context of biologic warfare or bioterrorism.

Vibrio Infections

Treatment of cholera caused by Vibrio cholerae. A drug of choice; used as an adjunct to fluid and electrolyte replacement in moderate to severe disease.

Treatment of severe V. parahaemolyticus^† infection when anti-infective therapy is indicated in addition to supportive care.

Treatment of infections caused by V. vulnificus^†. Optimum anti-infective therapy has not been identified; a tetracycline or third generation cephalosporin (e.g., cefotaxime, ceftazidime) is recommended. Because the case fatality rate associated with V. vulnificus is high, initiate anti-infective therapy promptly if indicated.

Yaws

Alternative to penicillin G for treatment of yaws caused by Treponema pertenue.

Yersinia Infections

Treatment of plague caused by Yersinia pestis. (See Plague under Uses.)

Treatment of GI infections caused by Yersinia enterocolitica^† or Y. pseudotuberculosis^†. These infections usually are self-limited, but IDSA, AAP, and others recommend anti-infectives for severe infections or when septicemia or other invasive disease occurs. Some suggest the role of oral anti-infectives in management of enterocolitis, pseudoappendicitis syndrome, or mesenteric adenitis caused by Yersinia needs further evaluation.

Prophylaxis in Sexual Assault Victims

Empiric anti-infective prophylaxis in sexual assault victims^†; used in conjunction with a drug effective for gonorrhea (IM ceftriaxone) and a drug effective for bacterial vaginosis and trichomoniasis (oral metronidazole).

Doxycycline (Systemic) Dosage and Administration

Administration

Administer orally or by slow IV infusion. Also has been administered by intrapleural infusion.

Do not administer IM or sub-Q.

IV route recommended only when oral therapy is not indicated or feasible; oral should replace IV as soon as possible. Prolonged IV administration may result in thrombophlebitis; avoid extravasation.

Oral Administration

Administer capsules and tablets with adequate amounts of fluid to reduce the risk of esophageal irritation and ulceration. Probably should not be given at bedtime or to patients with esophageal obstruction or compression.

Administer with food or milk to minimize nausea and vomiting and if gastric irritation occurs; absorption not markedly influenced by simultaneous ingestion of food or milk.

When used for prevention of malaria, CDC recommends taking the drug in the evening (but not at bedtime), avoiding prolonged, direct exposure to the sun, and use of sunscreens that absorb long-wave UVA radiation to minimize the risk of photosensitivity.

Reconstitution

Reconstitute doxycycline monohydrate powder for oral suspension at the time of dispensing according to manufacturer’s directions to provide a suspension containing 25 mg/5 mL.

Doxycycline calcium oral suspension is administered as provided without further dilution and contains 50 mg/5 mL.

If necessary because the commercial powder for oral suspension and oral suspension are not available, doxycycline film-coated tablets can be ground and mixed with food or drinks. Ground doxycycline tablets are most palatable when mixed with chocolate pudding, regular or low-fat chocolate milk, simple syrup with sour apple flavor, apple juice with table sugar, or low-fat milk; the bitterness of the drug is not masked with grape or strawberry jellies or cherry yogurt.

IV Infusion

For solution and drug compatibility information, see Compatibility under Stability.

Reconstitution

Reconstitute vial containing 100 or 200 mg with 10 or 20 mL, respectively, of sterile water for injection or a compatible IV infusion solution (see Compatibility under Stability) to provide a solution containing 10 mg/mL.

Dilution

Reconstituted solution must be further diluted prior to administration. Each 100 mg should be diluted in 100 mL to 1 L of compatible IV infusion solution (see Compatibility under Stability) to provide solutions containing approximately 0.1–1 mg/mL. Concentrations <0.1 mg/mL or >1 mg/mL are not recommended.

Rate of Administration

Administer by slow IV infusion, usually over 1–4 hours (depending on the dose). The minimum recommended time to infuse 100 mg in a solution containing 0.5 mg/mL is 1 hour.

Intrapleural Administration

Reconstitution and Dilution

Dilute 500 mg of doxycycline with 25–30 mL of 0.9% sodium chloride injection.

Intrapleural Administration Technique

Prior to intrapleural instillation of doxycycline solution, drain the pleural cavity by thoracentesis (needle aspiration) or via a thoracostomy tube by gravity or suction (i.e., closed chest tube drainage).

Efficacy of the procedure may be reduced if fluid drainage from the chest tube is >100 mL/24 hours when doxycycline is introduced into the pleural cavity.

Instill diluted doxycycline solution into the pleural space through a thoracostomy tube; clamp tube and subsequently remove the fluid.

Dosage

Available as doxycycline calcium, doxycycline hyclate, and doxycycline monohydrate; dosage expressed in terms of doxycycline.

Pediatric Patients

General Pediatric Dosage

Oral

Children >8 years of age weighing ≤45 kg: 4.4 mg/kg in 2 divided doses on day 1 followed by 2.2 mg/kg daily in 1 or 2 divided doses. For severe infections, up to 4.4 mg/kg daily.

Children >8 years of age weighing >45 kg: 100 mg every 12 hours on day 1 followed by 100 mg daily in 1 or 2 divided doses. For more severe infections, 100 mg every 12 hours.

IV

Children >8 years of age weighing ≤45 kg: 4.4 mg/kg in 1 or 2 divided doses on day 1 followed by 2.2–4.4 mg/kg daily in 1 or 2 infusions.

Children >8 years of age weighing >45 kg: 200 mg on day 1 in 1 or 2 infusions followed by 100–200 mg daily.

Anthrax

Postexposure Prophylaxis Following Exposure in the Context of Biologic Warfare or Bioterrorism

Oral

Children ≤8 years of age^† or weighing <45 kg: 2.2 mg/kg (up to 100 mg) twice daily given for ≥60 days. Because of concerns regarding long-term doxycycline use in infants and children, consider changing (after 10–14 days) to amoxicillin to complete the prophylaxis regimen if penicillin susceptibility is confirmed.

Children >8 years of age weighing ≥45 kg: 100 mg twice daily given for ≥60 days.

Optimum duration of postexposure prophylaxis after an inhalation exposure to B. anthracis spores is unclear, but prolonged postexposure prophylaxis usually required. A duration of 60 days may be adequate for a low-dose exposure, but a duration >4 months may be necessary to reduce the risk following a high-dose exposure. CDC and US Working Group on Civilian Biodefense recommend that postexposure prophylaxis following a confirmed exposure (including in laboratory workers with confirmed exposures to B. anthracis cultures) be continued for 60 days. The US Army Medical Research Institute of Infectious Diseases (USAMRIID) recommends that postexposure prophylaxis be continued for at least 60 days in individuals who are not fully immunized against anthrax and when anthrax vaccine is unavailable or cannot be used for postexposure vaccination.

Treatment of Inhalational, GI, or Oropharyngeal Anthrax

Oral

Children ≤8 years of age^† or weighing <45 kg: 2.2 mg/kg twice daily (up to 200 mg daily).

Children >8 years of age weighing ≥45 kg: 100 mg twice daily. Some experts recommend an initial 200-mg dose, then 100 mg every 12 hours.

Initial parenteral regimen preferred; use oral regimen for initial treatment only when a parenteral regimen is not available (e.g., when there are supply or logistic problems because large numbers of individuals require treatment in a mass casualty setting). Continue for total duration of ≥60 days if inhalational anthrax occurred as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism. Because of concerns regarding long-term doxycycline use in infants and children, consider changing (after 10–14 days) to amoxicillin to complete the treatment regimen in children <8 years of age if penicillin susceptibility is confirmed.

IV, then Oral

Children ≤8 years of age^† or weighing <45 kg: 2.2 mg/kg (up to 100 mg) twice daily.

Children >8 years of age weighing ≥45 kg: 100 mg twice daily.

Used in conjunction with 1 or 2 other anti-infectives predicted to be effective. When clinical improvement occurs, switch IV doxycycline to oral doxycycline in the same dosage and continue for a total duration of ≥60 days. Because of concerns regarding long-term doxycycline use in infants and children, consider changing (after 10–14 days) to amoxicillin to complete the treatment regimen in children <8 years of age if penicillin susceptibility is confirmed.

Treatment of Cutaneous Anthrax

Oral

Children ≤8 years of age^† or weighing <45 kg: 2.2 mg/kg (up to 100 mg) twice daily.

Children >8 years of age weighing ≥45 kg: 100 mg twice daily.

For mild, uncomplicated cutaneous anthrax that occurs following natural or endemic exposure, 5–10 days of treatment has been recommended.

For cutaneous anthrax that occurs following exposure in the context of biologic warfare or bioterrorism, duration of treatment is ≥60 days. Because of concerns regarding long-term doxycycline use in infants and children, consider changing (after 10–14 days) to amoxicillin to complete the treatment regimen in children <8 years of age if penicillin susceptibility is confirmed.

Oral regimen should not be used for initial treatment of cutaneous anthrax if there are signs of systemic involvement, extensive edema, or head and neck lesions and should not be used for initial treatment in infants and children <2 years of age.

IV, then Oral

Children ≤8 years of age^† or weighing <45 kg: 2.2 mg/kg (up to 100 mg) twice daily.

Children >8 years of age weighing ≥45 kg: 100 mg every 12 hours.

Used in conjunction with 1 or 2 other anti-infectives predicted to be effective. When clinical improvement occurs, switch IV doxycycline to oral doxycycline in the same dosage and continue for a total duration of ≥60 days. Because of concerns regarding long-term doxycycline use in infants and children, consider changing (after 10–14 days) to amoxicillin to complete the treatment regimen in children <8 years of age if penicillin susceptibility is confirmed.

Bartonella Infections

Oral or IV

Adolescents with HIV infection: 100 mg every 12 hours for ≥3 months for bartonellosis (including CNS infections). Also consider doxycycline long-term suppressive therapy^† in those with relapse or reinfection.

Brucellosis

Treatment of Brucellosis

Oral

Children ≥8 years of age: 2–4 mg/kg daily (up to 200 mg daily) in 2 divided doses. Some experts recommend 2.2 mg/kg twice daily (up to 200 mg daily).

Usual duration of therapy is 4–6 weeks; more prolonged therapy may be required for complicated disease (e.g., hepatitis, splenitis, meningoencephalitis, endocarditis, osteomyelitis). Meningoencephalitis and endocarditis should be treated for ≥90 days and may require ≥6 months of treatment.

Usually used in conjunction with rifampin or other anti-infectives to decrease risk of relapse. If infection is severe or if endocarditis, meningitis, or osteomyelitis is present, administer IM streptomycin or gentamicin during the first 1–3 weeks of doxycycline therapy.

Burkholderia Infections†

Initial Treatment of Severe Disease†

IV

Children <8 years of age^† or weighing <45 kg: 2.2 mg/kg twice daily (up to 200 mg daily) given in conjunction with IV ceftazidime, imipenem, or meropenem.

Children ≥8 years of age or weighing ≥45 kg: 100 mg twice daily given in conjunction with IV ceftazidime, imipenem, or meropenem.

Initial IV regimen continued for ≥14 days and until clinical improvement occurs. When appropriate, switch to a prolonged oral maintenance regimen.

Follow-up Maintenance Regimen after Initial Treatment of Severe Disease†

Oral

Children ≥8 years of age or weighing ≥45 kg: 100 mg twice daily given in conjunction with oral co-trimoxazole.

Prolonged oral maintenance regimen recommended to reduce risk of relapse after initial treatment with IV ceftazidime, imipenem, or meropenem (with or without IV doxycycline). Maintenance regimen usually continued for ≥4–6 months; a duration of 6–12 months may be necessary depending on response to therapy and severity of illness. Lifelong follow-up recommended for all patients to identify relapse.

Chlamydial Infections

Uncomplicated Urethral, Endocervical, or Rectal Infections

Oral

Children >8 years of age: 100 mg twice daily given for 7 days.

Presumptive Treatment of Chlamydial Infection in Gonorrhea Patients

Oral

Adolescents: 100 mg twice daily given for 7 days.

Lymphogranuloma Venereum

Oral

Adolescents: 100 mg twice daily given for 21 days.

Ehrlichiosis†

Oral or IV

AAP and CDC recommend 2.2 mg/kg (up to 100 mg) twice daily. Initiate promptly since delay can result in severe disease and fatal outcome.

Optimum duration of therapy not established. Usually continued ≥5–10 days and until patient is afebrile for ≥3 days and clinically improved. Severe illness may require longer duration of therapy. CDC recommends a duration of 10–14 days in those with HGA since this provides an appropriate duration of therapy for possible concurrent early Lyme disease.

IV therapy generally indicated for hospitalized patients; oral therapy generally appropriate for patients with early disease, those treated as outpatients, or inpatients who are not vomiting or obtunded.

Gonorrhea and Associated Infections

Empiric Treatment of Epididymitis

Oral

Children ≥8 years of age: 100 mg twice daily given for 10 days; as follow-up to single-dose IM ceftriaxone.

Granuloma Inguinale (Donovanosis)

Oral

Adolescents: 100 mg twice daily given for ≥3 weeks or until all lesions have healed completely; consider adding IV aminoglycoside (e.g., gentamicin) if improvement is not evident within the first few days of therapy and in HIV-infected patients.

Relapse can occur 6–18 months after apparently effective treatment.

Lyme Disease†

Early Localized or Early Disseminated Lyme Disease†

Oral

Children ≥8 years of age: 1–2 mg/kg in 2 divided doses (up to 100 mg each dose).

Duration of treatment is 14–21 days for most patients with early localized or early disseminated disease in the absence of neurologic involvement. Some experts recommend a duration of 21–28 days for early disseminated disease associated with mild carditis or isolated facial nerve palsy.

Lyme Arthritis†

Oral

Children ≥8 years of age: 1–2 mg/kg twice daily (up to 100 mg each dose) for 28 days.

Malaria

Prevention of Malaria

Oral

Children ≥8 years of age: 2 mg/kg (up to 100 mg) once daily.

Initiate prophylaxis 1–2 days prior to entering malarious area; continue during the stay and for 4 weeks after leaving area. If there are concerns about tolerance or drug interactions, it may be advisable to initiate prophylaxis 3–4 weeks prior to travel in individuals receiving other drugs to ensure that the combination of drugs is well tolerated and to allow ample time if a switch to another antimalarial is required.

Terminal prophylaxis with primaquine may be indicated during the final 2 weeks of doxycycline prophylaxis if exposure occurred in areas where P. ovale or P. vivax are endemic.

Treatment of Uncomplicated Chloroquine-resistant P. falciparum Malaria†

Oral

Children ≥8 years of age: 4 mg/kg daily given in 2 equally divided doses (up to 200 mg daily) for 7 days; used in conjunction with oral quinine sulfate (10 mg/kg 3 times daily given for 3 days if infection was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).

Treatment of Uncomplicated P. vivax Malaria†

Oral

Children ≥8 years of age: 4 mg/kg daily in 2 equally divided doses (up to 200 mg daily) for 7 days; used in conjunction with oral quinine sulfate (10 mg/kg 3 times daily given for 3 days if infection was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).

In addition, a 14-day regimen of oral primaquine (0.6 mg/kg once daily) may be indicated to provide a radical cure and prevent delayed attacks or relapse of P. vivax malaria.

Treatment of Severe P. falciparum Malaria†

Oral

Children ≥8 years of age: 4 mg/kg daily in 2 equally divided doses (up to 200 mg daily) given for 7 days; used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3–7 days.

IV, then Oral

Children ≥8 years of age weighing <45 kg: Initially 4 mg/kg daily in 2 equally divided doses IV; when oral therapy can be tolerated, switch to oral doxycycline in a dosage of 4 mg/kg daily in 2 equally divided doses (up to 200 mg daily) for a total duration of IV and oral doxycycline of 7 days. Used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3–7 days.

Children ≥8 years of age weighing ≥45 kg: Initially 100 mg of doxycycline IV every 12 hours; when oral therapy can be tolerated, switch to oral doxycycline in a dosage of 100 mg every 12 hours for a total duration of IV and oral doxycycline of 7 days. Used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3–7 days.

Presumptive Self-treatment of Malaria†

Oral

Children ≥8 years of age: 4 mg/kg daily in 2 equally divided doses for 7 days; used in conjunction with oral quinine sulfate (10 mg/kg 3 times daily given for 3 days if infection was acquired in Africa or South America or for 7 days if acquired in Southeast Asia). Initiate presumptive self-treatment if malaria is suspected (fever, chills, or other influenza-like illness) and professional medical care will not be available within 24 hours.

Not recommended for self-treatment of malaria in individuals currently taking the drug for prophylaxis.

Nongonococcal Urethritis

Oral

Adolescents: 100 mg twice daily given for 7 days.

Pelvic Inflammatory Disease†

Oral

Adolescents: 100 mg every 12 hours given for 14 days. Used in conjunction with and as follow-up to other anti-infectives (see Uses).

IV, then Oral

Adolescents: 100 mg every 12 hours. Initially, IV doxycycline in conjunction with IV cefoxitin or cefotetan. Switch IV doxycycline to oral doxycycline in the same dosage as soon as possible and continue for a total duration of 14 days; continue IV cephamycin for ≥24 hours after clinical improvement occurs.

Plague

Treatment of Pneumonic Plague Occurring in Context of Biologic Warfare or Bioterrorism

IV, then Oral

Children weighing <45 kg: 2.2 mg/kg twice daily (up to 200 mg daily).

Children weighing ≥45 kg: 100 mg twice daily or 200 mg once daily.

Prompt initiation of treatment (within 18–24 hours of symptom onset) is essential. Oral doxycycline may be substituted in the same dosage when the patient’s condition improves or if parenteral doxycycline is unavailable. Total duration of treatment is ≥10–14 days.

Postexposure Prophylaxis Following High-risk Exposure†

Oral

Children weighing <45 kg: 2.2 mg/kg twice daily (up to 200 mg daily).

Children weighing ≥45 kg: 100 mg twice daily. Alternatively, 2–4 mg/kg daily in 2 equally divided doses.

Duration of prophylaxis following exposure to plague aerosol or a patient with suspected pneumonic plague is 7 days or the duration of exposure risk plus 7 days.

Rickettsial Infections

Oral

Children >8 years of age weighing ≤45 kg: 4.4 mg/kg in 2 divided doses on day 1 followed by 2.2 mg/kg daily in 1 or 2 divided doses. For severe infections, up to 4.4 mg/kg daily.

Children >8 years of age weighing >45 kg: 100 mg every 12 hours on day 1 followed by 100 mg daily in 1 or 2 divided doses. For severe infections, 100 mg every 12 hours.

Continue therapy for 3–10 days or until patient is afebrile for approximately 2–3 days. Alternatively, a single 50-mg dose may be effective for louse-borne (epidemic) typhus, Brill-Zinsser disease, or scrub typhus.

Rocky Mountain Spotted Fever (RMSF)

Oral or IV

CDC recommends 2.2 mg/kg (up to 100 mg) twice daily. Initiate promptly since delay can result in severe disease and fatal outcome.

Usually continued ≥5–10 days and until patient is afebrile for ≥3 days and clinically improved. Severe illness may require longer duration of therapy.

IV therapy generally indicated for hospitalized patients; oral therapy generally appropriate for patients with early disease, those treated as outpatients, or inpatients who are not vomiting or obtunded.

Q Fever

Oral

CDC recommends 2.2 mg/kg every 12 hours for ≥14 days for treatment of acute Q fever.

For prophylaxis against Q fever^†, 2.2 mg/kg twice daily given for 5–7 days may prevent clinical disease if initiated 8–12 days after exposure; such prophylaxis is not effective and may only prolong the onset of disease if given immediately (1–7 days) after exposure.

Syphilis

Primary or Secondary Syphilis

Oral

Children >8 years of age: 100 mg twice daily given for 14 days.

Latent Syphilis or Tertiary Syphilis (Except Neurosyphilis)

Oral

Children >8 years of age: 100 mg twice daily given for 14 days for early latent syphilis (duration <1 year) or 100 mg twice daily given for 28 days for late latent syphilis (duration≥1 year), latent syphilis of unknown duration, or tertiary syphilis.

Tularemia

Treatment

IV, then Oral

Children weighing <45 kg: 2.2 mg/kg (up to 100 mg) twice daily.

Children weighing ≥45 kg: 100 mg twice daily.

Oral doxycycline may be substituted in the same dosage when the patient’s condition improves or if parenteral doxycycline is unavailable. Total duration of treatment is ≥14–21 days.

Postexposure Prophylaxis Following High-risk Exposure†

Oral

Children weighing <45 kg: 2.2 mg/kg (up to 100 mg) twice daily.

Children weighing ≥45 kg: 100 mg twice daily.

Initiate postexposure prophylaxis within 24 hours of exposure and continue for ≥14 days.

Vibrio Infections

Cholera

Oral

Children ≥8 years of age: 6 mg/kg (maximum 300 mg) as a single dose.

Prophylaxis in Sexual Assault Victims†

Oral

Adolescents: 100 mg twice daily given for 7 days; used in conjunction with single doses of IM ceftriaxone and oral metronidazole.

Adults

General Adult Dosage

Oral

100 mg every 12 hours on day 1 followed by 100 mg daily in 1 or 2 divided doses.

For more severe infections, 100 mg every 12 hours.

IV

200 mg on day 1 in 1 or 2 IV infusions followed by 100–200 mg daily.

Respiratory Tract Infections

Legionella Infections†

Oral

100 mg every 12 hours on the first day followed by 100 mg daily in 1 or 2 divided doses.

For severe infections, 100 mg every 12 hours.

Anthrax

Postexposure Prophylaxis Following Exposure in the Context of Biologic Warfare or Bioterrorism

Oral

100 mg twice daily given for ≥60 days. Some experts recommend an initial 200-mg dose, then 100 mg every 12 hours.

Optimum duration of postexposure prophylaxis after an inhalation exposure to B. anthracis spores is unclear, but prolonged postexposure prophylaxis usually required. A duration of 60 days may be adequate for a low-dose exposure, but a duration >4 months may be necessary to reduce the risk following a high-dose exposure. CDC and US Working Group on Civilian Biodefense recommend that postexposure prophylaxis following a confirmed exposure (including in laboratory workers with confirmed exposures to B. anthracis cultures) be continued for 60 days. The US Army Medical Research Institute of Infectious Diseases (USAMRIID) recommends that postexposure prophylaxis be continued for at least 60 days in individuals who are not fully immunized against anthrax and when anthrax vaccine is unavailable or cannot be used for postexposure vaccination.

Treatment of Inhalational, GI, or Oropharyngeal Anthrax

Oral

100 mg twice daily. Some experts recommend an initial 200-mg dose, then 100 mg every 12 hours.

Initial parenteral regimen preferred; use oral regimen for initial treatment only when a parenteral regimen is not available (e.g., when there are supply or logistic problems because large numbers of individuals require treatment in a mass casualty setting). Continue for total duration of ≥60 days if inhalational anthrax occurred as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism.

IV, then Oral

100 mg twice daily. Some experts recommend an initial 200-mg dose, then 100 mg every 12 hours.

Used in conjunction with 1 or 2 other anti-infectives predicted to be effective. When clinical improvement occurs, switch IV doxycycline to oral doxycycline in the same dosage and continue for a total duration of ≥60 days.

Treatment of Cutaneous Anthrax

Oral

100 mg twice daily.

For mild, uncomplicated cutaneous anthrax that occurs following natural or endemic exposure, 5–10 days of treatment has been recommended.

For cutaneous anthrax that occurs following exposure in the context of biologic warfare or bioterrorism, duration of treatment is ≥60 days.

Oral regimen should not be used for initial treatment of cutaneous anthrax if there are signs of systemic involvement, extensive edema, or head and neck lesions.

IV, then Oral

100 mg twice daily.

Used in conjunction with 1 or 2 other anti-infectives predicted to be effective. When clinical improvement occurs, switch IV doxycycline to oral doxycycline in the same dosage and continue for a total duration of ≥60 days.

Bartonella Infections

Oral or IV

HIV-infected adults: 100 mg every 12 hours for ≥3 months for bartonellosis (including CNS infections). Also consider doxycycline long-term suppressive therapy^† in those with relapse or reinfection.

Burkholderia Infections†

Treatment of Localized Disease†

Oral

Mild, localized disease without toxicity: 100 mg twice daily for 60–150 days may be effective.

Localized disease without toxicity: 100 mg twice daily for 20 weeks given in conjunction with oral co-trimoxazole.

Initial Treatment of Severe Disease†

IV

100 mg twice daily given in conjunction with IV ceftazidime, imipenem, or meropenem.

Initial IV regimen continued for ≥14 days and until clinical improvement occurs. When appropriate, switch to a prolonged oral maintenance regimen.

Follow-up Maintenance Regimen after Initial Treatment of Severe Disease†

Oral

100 mg twice daily given in conjunction with oral co-trimoxazole.

Prolonged oral maintenance regimen recommended to reduce risk of relapse after initial treatment with IV ceftazidime, imipenem, or meropenem (with or without IV doxycycline). Maintenance regimen usually continued for ≥4–6 months; a duration of 6–12 months may be necessary depending on response to therapy and severity of illness. Lifelong follow-up recommended for all patients to identify relapse.

Postexposure Prophylaxis†

Oral

200 mg once daily in conjunction with oral rifampin. Optimum duration unknown; continue for ≥10 days.

Brucellosis

Treatment of Brucellosis

Oral

Some experts recommend 100 mg twice daily.

Usual duration is 4–6 weeks; more prolonged therapy may be required for complicated disease (e.g., hepatitis, splenitis, meningoencephalitis, endocarditis, osteomyelitis). Meningoencephalitis and endocarditis should be treated for ≥90 days and may require ≥6 months of treatment.

Usually used in conjunction with rifampin or other anti-infectives to decrease risk of relapse. If infection is severe or if endocarditis, meningitis, or osteomyelitis is present, administer IM streptomycin or gentamicin during the first 1–3 weeks of doxycycline therapy.

Postexposure Prophylaxis following Exposure in the Context of Biologic Warfare or Bioterrorism

Oral

200 mg once daily given for 3–6 weeks.

Chlamydial Infections

Uncomplicated Urethral, Endocervical, or Rectal Infections

Oral

100 mg twice daily given for 7 days.

Presumptive Treatment of Chlamydial Infection in Gonorrhea Patients

Oral

100 mg twice daily given for 7 days.

Acute Epididymo-orchitis or Proctitis caused by C. trachomatis

Oral

100 mg twice daily given for ≥10 days.

Lymphogranuloma Venereum

Oral

100 mg twice daily given for 21 days.

Psittacosis (Ornithosis)

Oral

100 mg twice daily given for ≥10–14 days after defervescence.

IV

4.4 mg/kg daily in 2 divided doses for initial treatment of severely ill patients.

Ehrlichiosis†

Oral or IV

CDC and others recommend 100 mg twice daily. Initiate promptly since delay can result in severe disease and fatal outcome.

Optimum duration of therapy not established. Usually continued ≥5–10 days and until patient is afebrile for ≥3 days and clinically improved. Severe illness may require longer duration of therapy. CDC recommends a duration of 10–14 days in those with HGA since this provides an appropriate duration of therapy for possible concurrent early Lyme disease.

IV therapy generally indicated for hospitalized patients; oral therapy generally appropriate for patients with early disease, not requiring hospitalization, or inpatients who are not vomiting or obtunded.

Gonorrhea and Associated Infections

Uncomplicated Gonorrhea

Oral

100 mg twice daily given for 7 days recommended by manufacturer. Alternatively, 300 mg followed by another 300-mg dose 1 hour later.

No longer recommended for gonorrhea by CDC or other experts.

Empiric Treatment of Epididymitis

Oral

100 mg twice daily given for 10 days; as follow-up to a single dose of IM ceftriaxone.

Epididymo-orchitis or Proctitis

Oral

100 mg twice daily given for ≥10 days for acute epididymo-orchitis or for 7 days for proctitis.

Granuloma Inguinale (Donovanosis)

Oral

100 mg twice daily given for ≥3 weeks or until all lesions have healed completely; consider adding IV aminoglycoside (e.g., gentamicin) if improvement is not evident within the first few days of therapy and in HIV-infected patients.

Relapse can occur 6–18 months after apparently effective treatment.

Leptospirosis†

Treatment†

Oral

100 mg twice daily given for 7 days.

Prevention†

Oral

200 mg once weekly beginning 1–2 days prior to and continuing throughout the period of exposure.

Lyme Disease†

Early Localized or Early Disseminated Lyme Disease†

Oral

100 mg twice daily.

Duration of treatment is 14–21 days for most patients with early localized or early disseminated disease in the absence of neurologic involvement. Some experts recommend a duration of 21–28 days for early disseminated disease associated with mild carditis or isolated facial nerve palsy.

Lyme Arthritis†

Oral

100 mg twice daily given for 28 days.

Acute Neurologic Manifestations (e.g., Meningitis, Radiculopathy)†

Oral or IV

100–200 mg twice daily given for 14–28 days for patients who are intolerant of cephalosporins and penicillin.

Malaria

Prevention of Malaria

Oral

100 mg once daily.

Initiate prophylaxis 1–2 days prior to entering malarious area; continue during the stay and for 4 weeks after leaving area. If there are concerns about tolerance or drug interactions, it may be advisable to initiate prophylaxis 3–4 weeks prior to travel in individuals receiving other drugs to ensure that the combination of drugs is well tolerated and to allow ample time if a switch to another antimalarial is required.

Terminal prophylaxis with primaquine may be indicated during the final 2 weeks of doxycycline prophylaxis if exposure occurred in areas where P. ovale or P. vivax are endemic.

Treatment of Uncomplicated Chloroquine-resistant P. falciparum Malaria†

Oral

100 mg twice daily for 7 days; used in conjunction with oral quinine sulfate (650 mg 3 times daily given for 3 days if infection was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).

Treatment of Uncomplicated P. vivax Malaria†

Oral

100 mg twice daily for 7 days; used in conjunction with oral quinine sulfate (650 mg 3 times daily given for 3 days if malaria was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).

In addition, a 14-day regimen of oral primaquine (30 mg once daily) also may be indicated to provide a radical cure and prevent delayed attacks or relapse of P. vivax malaria.

Treatment of Severe P. falciparum Malaria†

Oral

100 mg twice daily given for 7 days; used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3–7 days.

IV, then Oral

Initially, 100 mg of doxycycline IV every 12 hours; when oral therapy can be tolerated, switch to oral doxycycline in a dosage of 100 mg every 12 hours for a total duration of IV and oral doxycycline of 7 days.

Used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3–7 days.

Presumptive Self-treatment of Malaria†

Oral

100 mg twice daily for 7 days; used in conjunction with oral quinine sulfate (650 mg 3 times daily given for 3 days if malaria was acquired in Africa or South America or for 7 days if acquired in Southeast Asia). Initiate presumptive self-treatment if malaria is suspected (fever, chills, or other influenza-like illness) and professional medical care will not be available within 24 hours.

Not recommended for self-treatment of malaria in individuals currently taking the drug for prophylaxis.

Mycobacterial Infections†

Mycobacterium marinum Infections†

Oral

100 mg twice daily given for ≥3 months recommended by ATS for treatment of cutaneous infections. A minimum of 4–6 weeks of treatment usually is necessary to determine whether the infection is responding.

Nongonococcal Urethritis

Oral

100 mg twice daily given for 7 days.

Pelvic Inflammatory Disease†

Oral

100 mg every 12 hours given for 14 days. Used in conjunction with and as follow-up to other anti-infectives (see Uses).

IV, then Oral

100 mg every 12 hours. Initially, IV doxycycline in conjunction with IV cefoxitin or cefotetan. Switch IV doxycycline to oral doxycycline in the same dosage as soon as possible and continue for a total duration of 14 days; continue IV cefoxitin or cefotetan for ≥24 hours after clinical improvement occurs.

Plague

Treatment of Pneumonic Plague Occurring in Context of Biologic Warfare or Bioterrorism

IV, then Oral

100 mg every 12 hours or 200 mg once daily.

Prompt initiation of treatment (within 18–24 hours of symptom onset) is essential. Oral doxycycline may be substituted in the same dosage when the patient’s condition improves or if parenteral doxycycline is unavailable. Total duration of treatment is ≥10–14 days.

Postexposure Prophylaxis Following High-risk Exposure†

Oral

100 mg every 12 hours. Alternatively, 100–200 mg daily in 2 equally divided doses.

Duration of prophylaxis following exposure to plague aerosol or a patient with suspected pneumonic plague is 7 days or the duration of exposure risk plus 7 days.

Pleural Effusions†

Intrapleural

500 mg (diluted with 25–30 mL of 0.9% sodium chloride injection) instilled into the pleural space (see Intrapleural Administration Technique under Dosage and Administration). Procedure may be repeated to achieve control of the effusion, although repeated administration may have limited effects.

For patients with recurrent malignant pleural effusions, administer a less concentrated 500-mg solution (diluted with 250 mL of 0.9% sodium chloride injection) via chest tube lavage and drainage. Clamp tube for 24 hours and repeat entire procedure daily until the drainage volume approximates the amount of solution instilled.

Rickettsial Infections

Oral

100 mg every 12 hours on day 1 followed by 100 mg daily in 1 or 2 divided doses. For more severe infections, 100 mg every 12 hours.

Continue therapy for 3–10 days or until patient is afebrile for approximately 2–3 days. Alternatively, a single dose of 100–200 mg may be effective for louse-borne (epidemic) typhus, Brill-Zinsser disease, or scrub typhus.

Rocky Mountain Spotted Fever (RMSF)

Oral or IV

CDC and others recommend 100 mg twice daily. Initiate promptly since delay can result in severe disease and fatal outcome.

Usually continued ≥5–10 days and until patient is afebrile for ≥3 days and clinically improved. Severe illness may require longer duration of therapy.

IV therapy generally indicated for hospitalized patients; oral therapy generally appropriate for patients with early disease, not requiring hospitalization, or inpatients who are not vomiting or obtunded.

Q Fever

Oral

100 mg twice daily given for 2–3 weeks recommended by CDC and others for acute Q fever.

For acute Q fever with preexisting valvular heart disease, CDC recommends 200 mg daily given in conjunction with hydroxychloroquine for 1 year to prevent progression of acute disease to endocarditis. Patients with chronic Q fever endocarditis should receive the doxycycline and hydroxychloroquine regimen for 1.5–3 years.

For prophylaxis against Q fever^†, 100 mg every 12 hours given for 5–7 days may prevent clinical disease if initiated 8–12 days after exposure; such prophylaxis is not effective and may only prolong the onset of disease if given immediately (1–7 days) after exposure.

Syphilis

Primary or Secondary Syphilis

Oral

100 mg twice daily given for 14 days.

IV

300 mg daily given for ≥10 days.

Latent Syphilis or Tertiary Syphilis (Except Neurosyphilis)

Oral

100 mg twice daily given for 14 days for early latent syphilis (duration <1 year) or 100 mg twice daily given for 28 days for late latent syphilis (duration≥1 year), latent syphilis of unknown duration, or tertiary syphilis.

Tularemia

Treatment

IV, then Oral

100 mg twice daily.

Oral doxycycline may be substituted in the same dosage when the patient’s condition improves or if parenteral doxycycline is unavailable. Total duration of treatment is ≥14–21 days.

Postexposure Prophylaxis Following High-risk Exposure†

Oral

100 mg twice daily.

Initiate postexposure prophylaxis within 24 hours of exposure and continue for ≥14 days.

Vibrio Infections

Cholera

Oral

100 mg every 12 hours on the first day followed by 100 mg daily in 1 or 2 divided doses for 2 days. For severe infections, 100 mg every 12 hours for 3 days.

Alternatively, 300 mg as a single dose may be effective.

Prophylaxis in Sexual Assault Victims†

Oral

100 mg twice daily for 7 days; used in conjunction with single doses of IM ceftriaxone and oral metronidazole.

Prescribing Limits

Pediatric Patients

General Pediatric Dosage

Oral

Maximum 4.4 mg/kg daily for severe infections in children >8 years of age weighing ≤45 kg.

Malaria

Treatment of Uncomplicated Chloroquine-resistant P. falciparum Malaria†

Oral

Children ≥8 years of age: Maximum 200 mg daily.

Treatment of Uncomplicated P. vivax Malaria†

Oral

Children ≥8 years of age: Maximum 200 mg daily.

Treatment of Severe P. falciparum Malaria†

Oral or IV

Children ≥8 years of age: Maximum 200 mg daily.

Special Populations

Renal Impairment

Dosage adjustments not necessary.

Contraindications

• Known hypersensitivity to doxycycline or any tetracycline.

Warnings/Precautions

Warnings

Dental and Bone Effects

Use during tooth development (e.g., pregnancy, children <8 years of age) may cause permanent yellow-gray to brown discoloration of teeth and enamel hypoplasia. Effects are most common following long-term use, but may occur following repeated short-term use.

Tetracyclines form a stable calcium complex in any bone-forming tissue. Reversible decrease in fibula growth rate has occurred in prematures receiving oral tetracycline.

Use not recommended in children <8 years of age unless other appropriate drugs are ineffective or are contraindicated or unless the benefits in certain indications (e.g., anthrax, ehrlichiosis, RMSF) outweigh the risks. (See Pediatric Use under Cautions.)

Superinfection/Clostridium difficile-associated Colitis

Possible emergence and overgrowth of nonsusceptible bacteria or fungi. Discontinue drug and institute appropriate therapy if superinfection occurs.

Treatment with anti-infectives may permit overgrowth of clostridia. Consider Clostridium difficile-associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly.

Some mild cases of C. difficile-associated diarrhea and colitis may respond to discontinuance alone. Manage moderate to severe cases with fluid, electrolyte, and protein supplementation; appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) recommended if colitis is severe.

Fetal/Neonatal Morbidity

Animal studies indicate possible fetal toxicity (e.g., retardation of skeletal development) and embryotoxicity. If used during pregnancy or if patient becomes pregnant while receiving doxycycline, patient should be apprised of the potential hazard to the fetus. (See Pregnancy under Cautions.)

Renal Effects

Tetracyclines have antianabolic effects and may increase BUN. Dose-related increase in BUN reported.

Studies to date indicate that increased BUN does not occur with use of usual doxycycline doses in patients with impaired renal function.

Sensitivity Reactions

Photosensitivity Reactions

Photosensitivity, manifested by an exaggerated sunburn reaction, reported with tetracyclines.

Photosensitivity reactions may develop within a few minutes to several hours after sun exposure and usually persist 1–2 days after discontinuance of the drug. Most reactions result from accumulation of tetracyclines in skin and are phototoxic in nature; photoallergic reactions also may occur.

Discontinue drug at first evidence of skin erythema.

Hypersensitivity Reactions

Oral suspension contains sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.

General Precautions

Nervous System Effects

Possibility of bulging fontanels in infants and benign intracranial hypertension in adults. Effects resolve when drug discontinued.

Laboratory Monitoring

Periodically assess organ system function, including renal, hepatic and hematopoietic, during long-term therapy.

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of doxycycline and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing. In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.

Because many strains of Acinetobacter, Bacteroides, Enterobacter, E. coli, Klebsiella, Shigella, S. pyogenes (group A β-hemolytic streptococci), S. pneumoniae, enterococci, and α-hemolytic streptococci are resistant to doxycycline, in vitro susceptibility tests should be performed if the drug is used for treatment of infections caused by these bacteria.

Incision and drainage or other surgical procedures should be performed in conjunction with doxycycline therapy when indicated.

Specific Populations

Pregnancy

Category D. (See Fetal/Neonatal Morbidity under Cautions.)

Should not be used in pregnant women unless, in the judgment of the clinician, it is essential for the welfare of the patient and benefits outweigh the risks.

CDC and others state doxycycline can be used when necessary for treatment of inhalational anthrax in pregnant women. Since adverse effects on developing teeth and bones are dose-related, CDC suggests the drug might be used for a short period (7–14 days) before 6 months of gestation; some clinicians recommend periodic liver function testing if used in pregnant women.

Malaria infection in pregnant women is associated with high risks of maternal and perinatal morbidity and mortality (e.g., miscarriage, premature delivery, low birth weight, congenital infection and/or perinatal death). CDC recommends prompt treatment with quinine and clindamycin for pregnant women with uncomplicated chloroquine-resistant P. falciparum malaria or with quinine alone for those with uncomplicated P. vivax malaria. However, CDC states a regimen of quinine in conjunction with doxycycline (or tetracycline) may be used for the treatment of uncomplicated malaria in pregnant women in rare circumstances (e.g., if other treatment options are not available or not tolerated) if benefits outweigh risks.

CDC states tetracyclines (e.g., doxycycline) may be warranted in pregnant women with life-threatening illness when clinical suspicion of ehrlichiosis (including HGA and HGE) or RMSF is high.

Lactation

Distributed into milk; discontinue nursing or the drug.

Short-term use in lactating women is not necessarily contraindicated, but the effects of prolonged exposure to doxycycline in breast milk (e.g., 60-day regimen for inhalational anthrax) are unknown. AAP states maternal use of tetracyclines usually is compatible with breast-feeding since absorption of the drugs by nursing infants is negligible.

Pediatric Use

Should not be used in children <8 years of age unless other appropriate drugs are ineffective or are contraindicated. (See Dental and Bone Effects under Cautions.)

Manufacturer, AAP, and CDC state use of tetracyclines (e.g., doxycycline) in children <8 years of age can be considered in certain unusual circumstances when benefits outweigh the risks (e.g., treatment of inhalational anthrax).

Recommended by AAP and CDC as drug of choice for presumed or confirmed Rickettsial infections (including RMSF) or ehrlichiosis^† (including HGA and HME) in children of any age.

CDC states that children <8 years of age with uncomplicated chloroquine-resistant P. falciparum malaria, uncomplicated P. vivax malaria, or severe P. falciparum malaria may receive a regimen that includes doxycycline (or tetracycline) if other treatment options are not available or not tolerated and the potential benefits outweigh risks.

Hepatic Impairment

Pharmacokinetics not studied.

Renal Impairment

Renal impairment does not appear to result in excessive accumulation of the drug.

Common Adverse Effects

GI effects (nausea, vomiting, diarrhea, bulky loose stools, anorexia, glossitis, dysphagia); maculopapular and erythematous rash; photosensitivity.

Administration

Administer orally or by slow IV infusion. Also has been administered by intrapleural infusion.

Do not administer IM or sub-Q.

IV route recommended only when oral therapy is not indicated or feasible; oral should replace IV as soon as possible. Prolonged IV administration may result in thrombophlebitis; avoid extravasation.

Oral Administration

Administer capsules and tablets with adequate amounts of fluid to reduce the risk of esophageal irritation and ulceration. Probably should not be given at bedtime or to patients with esophageal obstruction or compression.

Administer with food or milk to minimize nausea and vomiting and if gastric irritation occurs; absorption not markedly influenced by simultaneous ingestion of food or milk.

When used for prevention of malaria, CDC recommends taking the drug in the evening (but not at bedtime), avoiding prolonged, direct exposure to the sun, and use of sunscreens that absorb long-wave UVA radiation to minimize the risk of photosensitivity.

Reconstitution

Reconstitute doxycycline monohydrate powder for oral suspension at the time of dispensing according to manufacturer’s directions to provide a suspension containing 25 mg/5 mL.

Doxycycline calcium oral suspension is administered as provided without further dilution and contains 50 mg/5 mL.

If necessary because the commercial powder for oral suspension and oral suspension are not available, doxycycline film-coated tablets can be ground and mixed with food or drinks. Ground doxycycline tablets are most palatable when mixed with chocolate pudding, regular or low-fat chocolate milk, simple syrup with sour apple flavor, apple juice with table sugar, or low-fat milk; the bitterness of the drug is not masked with grape or strawberry jellies or cherry yogurt.

IV Infusion

For solution and drug compatibility information, see Compatibility under Stability.

Reconstitution

Reconstitute vial containing 100 or 200 mg with 10 or 20 mL, respectively, of sterile water for injection or a compatible IV infusion solution (see Compatibility under Stability) to provide a solution containing 10 mg/mL.

Dilution

Reconstituted solution must be further diluted prior to administration. Each 100 mg should be diluted in 100 mL to 1 L of compatible IV infusion solution (see Compatibility under Stability) to provide solutions containing approximately 0.1–1 mg/mL. Concentrations <0.1 mg/mL or >1 mg/mL are not recommended.

Rate of Administration

Administer by slow IV infusion, usually over 1–4 hours (depending on the dose). The minimum recommended time to infuse 100 mg in a solution containing 0.5 mg/mL is 1 hour.

Intrapleural Administration

Reconstitution and Dilution

Dilute 500 mg of doxycycline with 25–30 mL of 0.9% sodium chloride injection.

Intrapleural Administration Technique

Prior to intrapleural instillation of doxycycline solution, drain the pleural cavity by thoracentesis (needle aspiration) or via a thoracostomy tube by gravity or suction (i.e., closed chest tube drainage).

Efficacy of the procedure may be reduced if fluid drainage from the chest tube is >100 mL/24 hours when doxycycline is introduced into the pleural cavity.

Instill diluted doxycycline solution into the pleural space through a thoracostomy tube; clamp tube and subsequently remove the fluid.

Dosage

Available as doxycycline calcium, doxycycline hyclate, and doxycycline monohydrate; dosage expressed in terms of doxycycline.

Pediatric Patients

General Pediatric Dosage

Oral

Children >8 years of age weighing ≤45 kg: 4.4 mg/kg in 2 divided doses on day 1 followed by 2.2 mg/kg daily in 1 or 2 divided doses. For severe infections, up to 4.4 mg/kg daily.

Children >8 years of age weighing >45 kg: 100 mg every 12 hours on day 1 followed by 100 mg daily in 1 or 2 divided doses. For more severe infections, 100 mg every 12 hours.

IV

Children >8 years of age weighing ≤45 kg: 4.4 mg/kg in 1 or 2 divided doses on day 1 followed by 2.2–4.4 mg/kg daily in 1 or 2 infusions.

Children >8 years of age weighing >45 kg: 200 mg on day 1 in 1 or 2 infusions followed by 100–200 mg daily.

Anthrax

Postexposure Prophylaxis Following Exposure in the Context of Biologic Warfare or Bioterrorism

Oral

Children ≤8 years of age^† or weighing <45 kg: 2.2 mg/kg (up to 100 mg) twice daily given for ≥60 days. Because of concerns regarding long-term doxycycline use in infants and children, consider changing (after 10–14 days) to amoxicillin to complete the prophylaxis regimen if penicillin susceptibility is confirmed.

Children >8 years of age weighing ≥45 kg: 100 mg twice daily given for ≥60 days.

Optimum duration of postexposure prophylaxis after an inhalation exposure to B. anthracis spores is unclear, but prolonged postexposure prophylaxis usually required. A duration of 60 days may be adequate for a low-dose exposure, but a duration >4 months may be necessary to reduce the risk following a high-dose exposure. CDC and US Working Group on Civilian Biodefense recommend that postexposure prophylaxis following a confirmed exposure (including in laboratory workers with confirmed exposures to B. anthracis cultures) be continued for 60 days. The US Army Medical Research Institute of Infectious Diseases (USAMRIID) recommends that postexposure prophylaxis be continued for at least 60 days in individuals who are not fully immunized against anthrax and when anthrax vaccine is unavailable or cannot be used for postexposure vaccination.

Treatment of Inhalational, GI, or Oropharyngeal Anthrax

Oral

Children ≤8 years of age^† or weighing <45 kg: 2.2 mg/kg twice daily (up to 200 mg daily).

Children >8 years of age weighing ≥45 kg: 100 mg twice daily. Some experts recommend an initial 200-mg dose, then 100 mg every 12 hours.

Initial parenteral regimen preferred; use oral regimen for initial treatment only when a parenteral regimen is not available (e.g., when there are supply or logistic problems because large numbers of individuals require treatment in a mass casualty setting). Continue for total duration of ≥60 days if inhalational anthrax occurred as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism. Because of concerns regarding long-term doxycycline use in infants and children, consider changing (after 10–14 days) to amoxicillin to complete the treatment regimen in children <8 years of age if penicillin susceptibility is confirmed.

IV, then Oral

Children ≤8 years of age^† or weighing <45 kg: 2.2 mg/kg (up to 100 mg) twice daily.

Children >8 years of age weighing ≥45 kg: 100 mg twice daily.

Used in conjunction with 1 or 2 other anti-infectives predicted to be effective. When clinical improvement occurs, switch IV doxycycline to oral doxycycline in the same dosage and continue for a total duration of ≥60 days. Because of concerns regarding long-term doxycycline use in infants and children, consider changing (after 10–14 days) to amoxicillin to complete the treatment regimen in children <8 years of age if penicillin susceptibility is confirmed.

Treatment of Cutaneous Anthrax

Oral

Children ≤8 years of age^† or weighing <45 kg: 2.2 mg/kg (up to 100 mg) twice daily.

Children >8 years of age weighing ≥45 kg: 100 mg twice daily.

For mild, uncomplicated cutaneous anthrax that occurs following natural or endemic exposure, 5–10 days of treatment has been recommended.

For cutaneous anthrax that occurs following exposure in the context of biologic warfare or bioterrorism, duration of treatment is ≥60 days. Because of concerns regarding long-term doxycycline use in infants and children, consider changing (after 10–14 days) to amoxicillin to complete the treatment regimen in children <8 years of age if penicillin susceptibility is confirmed.

Oral regimen should not be used for initial treatment of cutaneous anthrax if there are signs of systemic involvement, extensive edema, or head and neck lesions and should not be used for initial treatment in infants and children <2 years of age.

IV, then Oral

Children ≤8 years of age^† or weighing <45 kg: 2.2 mg/kg (up to 100 mg) twice daily.

Children >8 years of age weighing ≥45 kg: 100 mg every 12 hours.

Used in conjunction with 1 or 2 other anti-infectives predicted to be effective. When clinical improvement occurs, switch IV doxycycline to oral doxycycline in the same dosage and continue for a total duration of ≥60 days. Because of concerns regarding long-term doxycycline use in infants and children, consider changing (after 10–14 days) to amoxicillin to complete the treatment regimen in children <8 years of age if penicillin susceptibility is confirmed.

Bartonella Infections

Oral or IV

Adolescents with HIV infection: 100 mg every 12 hours for ≥3 months for bartonellosis (including CNS infections). Also consider doxycycline long-term suppressive therapy^† in those with relapse or reinfection.

Brucellosis

Treatment of Brucellosis

Oral

Children ≥8 years of age: 2–4 mg/kg daily (up to 200 mg daily) in 2 divided doses. Some experts recommend 2.2 mg/kg twice daily (up to 200 mg daily).

Usual duration of therapy is 4–6 weeks; more prolonged therapy may be required for complicated disease (e.g., hepatitis, splenitis, meningoencephalitis, endocarditis, osteomyelitis). Meningoencephalitis and endocarditis should be treated for ≥90 days and may require ≥6 months of treatment.

Usually used in conjunction with rifampin or other anti-infectives to decrease risk of relapse. If infection is severe or if endocarditis, meningitis, or osteomyelitis is present, administer IM streptomycin or gentamicin during the first 1–3 weeks of doxycycline therapy.

Burkholderia Infections†

Initial Treatment of Severe Disease†

IV

Children <8 years of age^† or weighing <45 kg: 2.2 mg/kg twice daily (up to 200 mg daily) given in conjunction with IV ceftazidime, imipenem, or meropenem.

Children ≥8 years of age or weighing ≥45 kg: 100 mg twice daily given in conjunction with IV ceftazidime, imipenem, or meropenem.

Initial IV regimen continued for ≥14 days and until clinical improvement occurs. When appropriate, switch to a prolonged oral maintenance regimen.

Follow-up Maintenance Regimen after Initial Treatment of Severe Disease†

Oral

Children ≥8 years of age or weighing ≥45 kg: 100 mg twice daily given in conjunction with oral co-trimoxazole.

Prolonged oral maintenance regimen recommended to reduce risk of relapse after initial treatment with IV ceftazidime, imipenem, or meropenem (with or without IV doxycycline). Maintenance regimen usually continued for ≥4–6 months; a duration of 6–12 months may be necessary depending on response to therapy and severity of illness. Lifelong follow-up recommended for all patients to identify relapse.

Chlamydial Infections

Uncomplicated Urethral, Endocervical, or Rectal Infections

Oral

Children >8 years of age: 100 mg twice daily given for 7 days.

Presumptive Treatment of Chlamydial Infection in Gonorrhea Patients

Oral

Adolescents: 100 mg twice daily given for 7 days.

Lymphogranuloma Venereum

Oral

Adolescents: 100 mg twice daily given for 21 days.

Ehrlichiosis†

Oral or IV

AAP and CDC recommend 2.2 mg/kg (up to 100 mg) twice daily. Initiate promptly since delay can result in severe disease and fatal outcome.

Optimum duration of therapy not established. Usually continued ≥5–10 days and until patient is afebrile for ≥3 days and clinically improved. Severe illness may require longer duration of therapy. CDC recommends a duration of 10–14 days in those with HGA since this provides an appropriate duration of therapy for possible concurrent early Lyme disease.

IV therapy generally indicated for hospitalized patients; oral therapy generally appropriate for patients with early disease, those treated as outpatients, or inpatients who are not vomiting or obtunded.

Gonorrhea and Associated Infections

Empiric Treatment of Epididymitis

Oral

Children ≥8 years of age: 100 mg twice daily given for 10 days; as follow-up to single-dose IM ceftriaxone.

Granuloma Inguinale (Donovanosis)

Oral

Adolescents: 100 mg twice daily given for ≥3 weeks or until all lesions have healed completely; consider adding IV aminoglycoside (e.g., gentamicin) if improvement is not evident within the first few days of therapy and in HIV-infected patients.

Relapse can occur 6–18 months after apparently effective treatment.

Lyme Disease†

Early Localized or Early Disseminated Lyme Disease†

Oral

Children ≥8 years of age: 1–2 mg/kg in 2 divided doses (up to 100 mg each dose).

Duration of treatment is 14–21 days for most patients with early localized or early disseminated disease in the absence of neurologic involvement. Some experts recommend a duration of 21–28 days for early disseminated disease associated with mild carditis or isolated facial nerve palsy.

Lyme Arthritis†

Oral

Children ≥8 years of age: 1–2 mg/kg twice daily (up to 100 mg each dose) for 28 days.

Malaria

Prevention of Malaria

Oral

Children ≥8 years of age: 2 mg/kg (up to 100 mg) once daily.

Initiate prophylaxis 1–2 days prior to entering malarious area; continue during the stay and for 4 weeks after leaving area. If there are concerns about tolerance or drug interactions, it may be advisable to initiate prophylaxis 3–4 weeks prior to travel in individuals receiving other drugs to ensure that the combination of drugs is well tolerated and to allow ample time if a switch to another antimalarial is required.

Terminal prophylaxis with primaquine may be indicated during the final 2 weeks of doxycycline prophylaxis if exposure occurred in areas where P. ovale or P. vivax are endemic.

Treatment of Uncomplicated Chloroquine-resistant P. falciparum Malaria†

Oral

Children ≥8 years of age: 4 mg/kg daily given in 2 equally divided doses (up to 200 mg daily) for 7 days; used in conjunction with oral quinine sulfate (10 mg/kg 3 times daily given for 3 days if infection was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).

Treatment of Uncomplicated P. vivax Malaria†

Oral

Children ≥8 years of age: 4 mg/kg daily in 2 equally divided doses (up to 200 mg daily) for 7 days; used in conjunction with oral quinine sulfate (10 mg/kg 3 times daily given for 3 days if infection was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).

In addition, a 14-day regimen of oral primaquine (0.6 mg/kg once daily) may be indicated to provide a radical cure and prevent delayed attacks or relapse of P. vivax malaria.

Treatment of Severe P. falciparum Malaria†

Oral

Children ≥8 years of age: 4 mg/kg daily in 2 equally divided doses (up to 200 mg daily) given for 7 days; used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3–7 days.

IV, then Oral

Children ≥8 years of age weighing <45 kg: Initially 4 mg/kg daily in 2 equally divided doses IV; when oral therapy can be tolerated, switch to oral doxycycline in a dosage of 4 mg/kg daily in 2 equally divided doses (up to 200 mg daily) for a total duration of IV and oral doxycycline of 7 days. Used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3–7 days.

Children ≥8 years of age weighing ≥45 kg: Initially 100 mg of doxycycline IV every 12 hours; when oral therapy can be tolerated, switch to oral doxycycline in a dosage of 100 mg every 12 hours for a total duration of IV and oral doxycycline of 7 days. Used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3–7 days.

Presumptive Self-treatment of Malaria†

Oral

Children ≥8 years of age: 4 mg/kg daily in 2 equally divided doses for 7 days; used in conjunction with oral quinine sulfate (10 mg/kg 3 times daily given for 3 days if infection was acquired in Africa or South America or for 7 days if acquired in Southeast Asia). Initiate presumptive self-treatment if malaria is suspected (fever, chills, or other influenza-like illness) and professional medical care will not be available within 24 hours.

Not recommended for self-treatment of malaria in individuals currently taking the drug for prophylaxis.

Nongonococcal Urethritis

Oral

Adolescents: 100 mg twice daily given for 7 days.

Pelvic Inflammatory Disease†

Oral

Adolescents: 100 mg every 12 hours given for 14 days. Used in conjunction with and as follow-up to other anti-infectives (see Uses).

IV, then Oral

Adolescents: 100 mg every 12 hours. Initially, IV doxycycline in conjunction with IV cefoxitin or cefotetan. Switch IV doxycycline to oral doxycycline in the same dosage as soon as possible and continue for a total duration of 14 days; continue IV cephamycin for ≥24 hours after clinical improvement occurs.

Plague

Treatment of Pneumonic Plague Occurring in Context of Biologic Warfare or Bioterrorism

IV, then Oral

Children weighing <45 kg: 2.2 mg/kg twice daily (up to 200 mg daily).

Children weighing ≥45 kg: 100 mg twice daily or 200 mg once daily.

Prompt initiation of treatment (within 18–24 hours of symptom onset) is essential. Oral doxycycline may be substituted in the same dosage when the patient’s condition improves or if parenteral doxycycline is unavailable. Total duration of treatment is ≥10–14 days.

Postexposure Prophylaxis Following High-risk Exposure†

Oral

Children weighing <45 kg: 2.2 mg/kg twice daily (up to 200 mg daily).

Children weighing ≥45 kg: 100 mg twice daily. Alternatively, 2–4 mg/kg daily in 2 equally divided doses.

Duration of prophylaxis following exposure to plague aerosol or a patient with suspected pneumonic plague is 7 days or the duration of exposure risk plus 7 days.

Rickettsial Infections

Oral

Children >8 years of age weighing ≤45 kg: 4.4 mg/kg in 2 divided doses on day 1 followed by 2.2 mg/kg daily in 1 or 2 divided doses. For severe infections, up to 4.4 mg/kg daily.

Children >8 years of age weighing >45 kg: 100 mg every 12 hours on day 1 followed by 100 mg daily in 1 or 2 divided doses. For severe infections, 100 mg every 12 hours.

Continue therapy for 3–10 days or until patient is afebrile for approximately 2–3 days. Alternatively, a single 50-mg dose may be effective for louse-borne (epidemic) typhus, Brill-Zinsser disease, or scrub typhus.

Rocky Mountain Spotted Fever (RMSF)

Oral or IV

CDC recommends 2.2 mg/kg (up to 100 mg) twice daily. Initiate promptly since delay can result in severe disease and fatal outcome.

Usually continued ≥5–10 days and until patient is afebrile for ≥3 days and clinically improved. Severe illness may require longer duration of therapy.

IV therapy generally indicated for hospitalized patients; oral therapy generally appropriate for patients with early disease, those treated as outpatients, or inpatients who are not vomiting or obtunded.

Q Fever

Oral

CDC recommends 2.2 mg/kg every 12 hours for ≥14 days for treatment of acute Q fever.

For prophylaxis against Q fever^†, 2.2 mg/kg twice daily given for 5–7 days may prevent clinical disease if initiated 8–12 days after exposure; such prophylaxis is not effective and may only prolong the onset of disease if given immediately (1–7 days) after exposure.

Syphilis

Primary or Secondary Syphilis

Oral

Children >8 years of age: 100 mg twice daily given for 14 days.

Latent Syphilis or Tertiary Syphilis (Except Neurosyphilis)

Oral

Children >8 years of age: 100 mg twice daily given for 14 days for early latent syphilis (duration <1 year) or 100 mg twice daily given for 28 days for late latent syphilis (duration≥1 year), latent syphilis of unknown duration, or tertiary syphilis.

Tularemia

Treatment

IV, then Oral

Children weighing <45 kg: 2.2 mg/kg (up to 100 mg) twice daily.

Children weighing ≥45 kg: 100 mg twice daily.

Oral doxycycline may be substituted in the same dosage when the patient’s condition improves or if parenteral doxycycline is unavailable. Total duration of treatment is ≥14–21 days.

Postexposure Prophylaxis Following High-risk Exposure†

Oral

Children weighing <45 kg: 2.2 mg/kg (up to 100 mg) twice daily.

Children weighing ≥45 kg: 100 mg twice daily.

Initiate postexposure prophylaxis within 24 hours of exposure and continue for ≥14 days.

Vibrio Infections

Cholera

Oral

Children ≥8 years of age: 6 mg/kg (maximum 300 mg) as a single dose.

Prophylaxis in Sexual Assault Victims†

Oral

Adolescents: 100 mg twice daily given for 7 days; used in conjunction with single doses of IM ceftriaxone and oral metronidazole.

Adults

General Adult Dosage

Oral

100 mg every 12 hours on day 1 followed by 100 mg daily in 1 or 2 divided doses.

For more severe infections, 100 mg every 12 hours.

IV

200 mg on day 1 in 1 or 2 IV infusions followed by 100–200 mg daily.

Respiratory Tract Infections

Legionella Infections†

Oral

100 mg every 12 hours on the first day followed by 100 mg daily in 1 or 2 divided doses.

For severe infections, 100 mg every 12 hours.

Anthrax

Postexposure Prophylaxis Following Exposure in the Context of Biologic Warfare or Bioterrorism

Oral

100 mg twice daily given for ≥60 days. Some experts recommend an initial 200-mg dose, then 100 mg every 12 hours.

Optimum duration of postexposure prophylaxis after an inhalation exposure to B. anthracis spores is unclear, but prolonged postexposure prophylaxis usually required. A duration of 60 days may be adequate for a low-dose exposure, but a duration >4 months may be necessary to reduce the risk following a high-dose exposure. CDC and US Working Group on Civilian Biodefense recommend that postexposure prophylaxis following a confirmed exposure (including in laboratory workers with confirmed exposures to B. anthracis cultures) be continued for 60 days. The US Army Medical Research Institute of Infectious Diseases (USAMRIID) recommends that postexposure prophylaxis be continued for at least 60 days in individuals who are not fully immunized against anthrax and when anthrax vaccine is unavailable or cannot be used for postexposure vaccination.

Treatment of Inhalational, GI, or Oropharyngeal Anthrax

Oral

100 mg twice daily. Some experts recommend an initial 200-mg dose, then 100 mg every 12 hours.

Initial parenteral regimen preferred; use oral regimen for initial treatment only when a parenteral regimen is not available (e.g., when there are supply or logistic problems because large numbers of individuals require treatment in a mass casualty setting). Continue for total duration of ≥60 days if inhalational anthrax occurred as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism.

IV, then Oral

100 mg twice daily. Some experts recommend an initial 200-mg dose, then 100 mg every 12 hours.

Used in conjunction with 1 or 2 other anti-infectives predicted to be effective. When clinical improvement occurs, switch IV doxycycline to oral doxycycline in the same dosage and continue for a total duration of ≥60 days.

Treatment of Cutaneous Anthrax

Oral

100 mg twice daily.

For mild, uncomplicated cutaneous anthrax that occurs following natural or endemic exposure, 5–10 days of treatment has been recommended.

For cutaneous anthrax that occurs following exposure in the context of biologic warfare or bioterrorism, duration of treatment is ≥60 days.

Oral regimen should not be used for initial treatment of cutaneous anthrax if there are signs of systemic involvement, extensive edema, or head and neck lesions.

IV, then Oral

100 mg twice daily.

Used in conjunction with 1 or 2 other anti-infectives predicted to be effective. When clinical improvement occurs, switch IV doxycycline to oral doxycycline in the same dosage and continue for a total duration of ≥60 days.

Bartonella Infections

Oral or IV

HIV-infected adults: 100 mg every 12 hours for ≥3 months for bartonellosis (including CNS infections). Also consider doxycycline long-term suppressive therapy^† in those with relapse or reinfection.

Burkholderia Infections†

Treatment of Localized Disease†

Oral

Mild, localized disease without toxicity: 100 mg twice daily for 60–150 days may be effective.

Localized disease without toxicity: 100 mg twice daily for 20 weeks given in conjunction with oral co-trimoxazole.

Initial Treatment of Severe Disease†

IV

100 mg twice daily given in conjunction with IV ceftazidime, imipenem, or meropenem.

Initial IV regimen continued for ≥14 days and until clinical improvement occurs. When appropriate, switch to a prolonged oral maintenance regimen.

Follow-up Maintenance Regimen after Initial Treatment of Severe Disease†

Oral

100 mg twice daily given in conjunction with oral co-trimoxazole.

Prolonged oral maintenance regimen recommended to reduce risk of relapse after initial treatment with IV ceftazidime, imipenem, or meropenem (with or without IV doxycycline). Maintenance regimen usually continued for ≥4–6 months; a duration of 6–12 months may be necessary depending on response to therapy and severity of illness. Lifelong follow-up recommended for all patients to identify relapse.

Postexposure Prophylaxis†

Oral

200 mg once daily in conjunction with oral rifampin. Optimum duration unknown; continue for ≥10 days.

Brucellosis

Treatment of Brucellosis

Oral

Some experts recommend 100 mg twice daily.

Usual duration is 4–6 weeks; more prolonged therapy may be required for complicated disease (e.g., hepatitis, splenitis, meningoencephalitis, endocarditis, osteomyelitis). Meningoencephalitis and endocarditis should be treated for ≥90 days and may require ≥6 months of treatment.

Usually used in conjunction with rifampin or other anti-infectives to decrease risk of relapse. If infection is severe or if endocarditis, meningitis, or osteomyelitis is present, administer IM streptomycin or gentamicin during the first 1–3 weeks of doxycycline therapy.

Postexposure Prophylaxis following Exposure in the Context of Biologic Warfare or Bioterrorism

Oral

200 mg once daily given for 3–6 weeks.

Chlamydial Infections

Uncomplicated Urethral, Endocervical, or Rectal Infections

Oral

100 mg twice daily given for 7 days.

Presumptive Treatment of Chlamydial Infection in Gonorrhea Patients

Oral

100 mg twice daily given for 7 days.

Acute Epididymo-orchitis or Proctitis caused by C. trachomatis

Oral

100 mg twice daily given for ≥10 days.

Lymphogranuloma Venereum

Oral

100 mg twice daily given for 21 days.

Psittacosis (Ornithosis)

Oral

100 mg twice daily given for ≥10–14 days after defervescence.

IV

4.4 mg/kg daily in 2 divided doses for initial treatment of severely ill patients.

Ehrlichiosis†

Oral or IV

CDC and others recommend 100 mg twice daily. Initiate promptly since delay can result in severe disease and fatal outcome.

Optimum duration of therapy not established. Usually continued ≥5–10 days and until patient is afebrile for ≥3 days and clinically improved. Severe illness may require longer duration of therapy. CDC recommends a duration of 10–14 days in those with HGA since this provides an appropriate duration of therapy for possible concurrent early Lyme disease.

IV therapy generally indicated for hospitalized patients; oral therapy generally appropriate for patients with early disease, not requiring hospitalization, or inpatients who are not vomiting or obtunded.

Gonorrhea and Associated Infections

Uncomplicated Gonorrhea

Oral

100 mg twice daily given for 7 days recommended by manufacturer. Alternatively, 300 mg followed by another 300-mg dose 1 hour later.

No longer recommended for gonorrhea by CDC or other experts.

Empiric Treatment of Epididymitis

Oral

100 mg twice daily given for 10 days; as follow-up to a single dose of IM ceftriaxone.

Epididymo-orchitis or Proctitis

Oral

100 mg twice daily given for ≥10 days for acute epididymo-orchitis or for 7 days for proctitis.

Granuloma Inguinale (Donovanosis)

Oral

100 mg twice daily given for ≥3 weeks or until all lesions have healed completely; consider adding IV aminoglycoside (e.g., gentamicin) if improvement is not evident within the first few days of therapy and in HIV-infected patients.

Relapse can occur 6–18 months after apparently effective treatment.

Leptospirosis†

Treatment†

Oral

100 mg twice daily given for 7 days.

Prevention†

Oral

200 mg once weekly beginning 1–2 days prior to and continuing throughout the period of exposure.

Lyme Disease†

Early Localized or Early Disseminated Lyme Disease†

Oral

100 mg twice daily.

Duration of treatment is 14–21 days for most patients with early localized or early disseminated disease in the absence of neurologic involvement. Some experts recommend a duration of 21–28 days for early disseminated disease associated with mild carditis or isolated facial nerve palsy.

Lyme Arthritis†

Oral

100 mg twice daily given for 28 days.

Acute Neurologic Manifestations (e.g., Meningitis, Radiculopathy)†

Oral or IV

100–200 mg twice daily given for 14–28 days for patients who are intolerant of cephalosporins and penicillin.

Malaria

Prevention of Malaria

Oral

100 mg once daily.

Initiate prophylaxis 1–2 days prior to entering malarious area; continue during the stay and for 4 weeks after leaving area. If there are concerns about tolerance or drug interactions, it may be advisable to initiate prophylaxis 3–4 weeks prior to travel in individuals receiving other drugs to ensure that the combination of drugs is well tolerated and to allow ample time if a switch to another antimalarial is required.

Terminal prophylaxis with primaquine may be indicated during the final 2 weeks of doxycycline prophylaxis if exposure occurred in areas where P. ovale or P. vivax are endemic.

Treatment of Uncomplicated Chloroquine-resistant P. falciparum Malaria†

Oral

100 mg twice daily for 7 days; used in conjunction with oral quinine sulfate (650 mg 3 times daily given for 3 days if infection was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).

Treatment of Uncomplicated P. vivax Malaria†

Oral

100 mg twice daily for 7 days; used in conjunction with oral quinine sulfate (650 mg 3 times daily given for 3 days if malaria was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).

In addition, a 14-day regimen of oral primaquine (30 mg once daily) also may be indicated to provide a radical cure and prevent delayed attacks or relapse of P. vivax malaria.

Treatment of Severe P. falciparum Malaria†

Oral

100 mg twice daily given for 7 days; used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3–7 days.

IV, then Oral

Initially, 100 mg of doxycycline IV every 12 hours; when oral therapy can be tolerated, switch to oral doxycycline in a dosage of 100 mg every 12 hours for a total duration of IV and oral doxycycline of 7 days.

Used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3–7 days.

Presumptive Self-treatment of Malaria†

Oral

100 mg twice daily for 7 days; used in conjunction with oral quinine sulfate (650 mg 3 times daily given for 3 days if malaria was acquired in Africa or South America or for 7 days if acquired in Southeast Asia). Initiate presumptive self-treatment if malaria is suspected (fever, chills, or other influenza-like illness) and professional medical care will not be available within 24 hours.

Not recommended for self-treatment of malaria in individuals currently taking the drug for prophylaxis.

Mycobacterial Infections†

Mycobacterium marinum Infections†

Oral

100 mg twice daily given for ≥3 months recommended by ATS for treatment of cutaneous infections. A minimum of 4–6 weeks of treatment usually is necessary to determine whether the infection is responding.

Nongonococcal Urethritis

Oral

100 mg twice daily given for 7 days.

Pelvic Inflammatory Disease†

Oral

100 mg every 12 hours given for 14 days. Used in conjunction with and as follow-up to other anti-infectives (see Uses).

IV, then Oral

100 mg every 12 hours. Initially, IV doxycycline in conjunction with IV cefoxitin or cefotetan. Switch IV doxycycline to oral doxycycline in the same dosage as soon as possible and continue for a total duration of 14 days; continue IV cefoxitin or cefotetan for ≥24 hours after clinical improvement occurs.

Plague

Treatment of Pneumonic Plague Occurring in Context of Biologic Warfare or Bioterrorism

IV, then Oral

100 mg every 12 hours or 200 mg once daily.

Prompt initiation of treatment (within 18–24 hours of symptom onset) is essential. Oral doxycycline may be substituted in the same dosage when the patient’s condition improves or if parenteral doxycycline is unavailable. Total duration of treatment is ≥10–14 days.

Postexposure Prophylaxis Following High-risk Exposure†

Oral

100 mg every 12 hours. Alternatively, 100–200 mg daily in 2 equally divided doses.

Duration of prophylaxis following exposure to plague aerosol or a patient with suspected pneumonic plague is 7 days or the duration of exposure risk plus 7 days.

Pleural Effusions†

Intrapleural

500 mg (diluted with 25–30 mL of 0.9% sodium chloride injection) instilled into the pleural space (see Intrapleural Administration Technique under Dosage and Administration). Procedure may be repeated to achieve control of the effusion, although repeated administration may have limited effects.

For patients with recurrent malignant pleural effusions, administer a less concentrated 500-mg solution (diluted with 250 mL of 0.9% sodium chloride injection) via chest tube lavage and drainage. Clamp tube for 24 hours and repeat entire procedure daily until the drainage volume approximates the amount of solution instilled.

Rickettsial Infections

Oral

100 mg every 12 hours on day 1 followed by 100 mg daily in 1 or 2 divided doses. For more severe infections, 100 mg every 12 hours.

Continue therapy for 3–10 days or until patient is afebrile for approximately 2–3 days. Alternatively, a single dose of 100–200 mg may be effective for louse-borne (epidemic) typhus, Brill-Zinsser disease, or scrub typhus.

Rocky Mountain Spotted Fever (RMSF)

Oral or IV

CDC and others recommend 100 mg twice daily. Initiate promptly since delay can result in severe disease and fatal outcome.

Usually continued ≥5–10 days and until patient is afebrile for ≥3 days and clinically improved. Severe illness may require longer duration of therapy.

IV therapy generally indicated for hospitalized patients; oral therapy generally appropriate for patients with early disease, not requiring hospitalization, or inpatients who are not vomiting or obtunded.

Q Fever

Oral

100 mg twice daily given for 2–3 weeks recommended by CDC and others for acute Q fever.

For acute Q fever with preexisting valvular heart disease, CDC recommends 200 mg daily given in conjunction with hydroxychloroquine for 1 year to prevent progression of acute disease to endocarditis. Patients with chronic Q fever endocarditis should receive the doxycycline and hydroxychloroquine regimen for 1.5–3 years.

For prophylaxis against Q fever^†, 100 mg every 12 hours given for 5–7 days may prevent clinical disease if initiated 8–12 days after exposure; such prophylaxis is not effective and may only prolong the onset of disease if given immediately (1–7 days) after exposure.

Syphilis

Primary or Secondary Syphilis

Oral

100 mg twice daily given for 14 days.

IV

300 mg daily given for ≥10 days.

Latent Syphilis or Tertiary Syphilis (Except Neurosyphilis)

Oral

100 mg twice daily given for 14 days for early latent syphilis (duration <1 year) or 100 mg twice daily given for 28 days for late latent syphilis (duration≥1 year), latent syphilis of unknown duration, or tertiary syphilis.

Tularemia

Treatment

IV, then Oral

100 mg twice daily.

Oral doxycycline may be substituted in the same dosage when the patient’s condition improves or if parenteral doxycycline is unavailable. Total duration of treatment is ≥14–21 days.

Postexposure Prophylaxis Following High-risk Exposure†

Oral

100 mg twice daily.

Initiate postexposure prophylaxis within 24 hours of exposure and continue for ≥14 days.

Vibrio Infections

Cholera

Oral

100 mg every 12 hours on the first day followed by 100 mg daily in 1 or 2 divided doses for 2 days. For severe infections, 100 mg every 12 hours for 3 days.

Alternatively, 300 mg as a single dose may be effective.

Prophylaxis in Sexual Assault Victims†

Oral

100 mg twice daily for 7 days; used in conjunction with single doses of IM ceftriaxone and oral metronidazole.

Prescribing Limits

Pediatric Patients

General Pediatric Dosage

Oral

Maximum 4.4 mg/kg daily for severe infections in children >8 years of age weighing ≤45 kg.

Malaria

Treatment of Uncomplicated Chloroquine-resistant P. falciparum Malaria†

Oral

Children ≥8 years of age: Maximum 200 mg daily.

Treatment of Uncomplicated P. vivax Malaria†

Oral

Children ≥8 years of age: Maximum 200 mg daily.

Treatment of Severe P. falciparum Malaria†

Oral or IV

Children ≥8 years of age: Maximum 200 mg daily.

Special Populations

Renal Impairment

Dosage adjustments not necessary.

Doxycycline (systemic) (monograph) Dosage information (more detail)

Specific Drugs