Brand names: Doryx, Doxy 100, Monodox, Vibramycin, Vibra-Tabs
Drug class: Tetracyclines

Medically reviewed by Drugs.com on Apr 10, 2024. Written by ASHP.

Introduction

Antibacterial; semisynthetic tetracycline antibiotic derived from oxytetracycline.^{103 111 113 114}

Uses for Doxycycline Calcium

Respiratory Tract Infections

Treatment of respiratory tract infections caused by Mycoplasma pneumoniae.^{111 113 114}

Treatment of respiratory tract infections caused by Haemophilus influenzae, Streptococcus pneumoniae, or Klebsiella.^{111 113 114} Should only be used for treatment of infections caused by these bacteria when in vitro susceptibility tests indicate the organism is susceptible.^{111 113 a}

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

Alternative for treatment of infections caused by Legionella pneumophila^{† [off-label]}; ¹³⁷ used with or without rifampin.¹³⁷

Acne

Adjunctive treatment of moderate to severe inflammatory acne.^{111 a} Not indicated for treatment of noninflammatory acne.^a

Actinomycosis

Treatment of actinomycosis caused by Actinomyces israelii.^{111 113 137} Alternative to penicillin G;^{111 113 137} oral tetracyclines (usually doxycycline or tetracycline) also used as follow-up after initial parenteral penicillin G.¹⁰⁹

Amebiasis

Adjunct to amebicides for treatment of acute intestinal amebiasis.^{111 113} Tetracyclines not included in current recommendations for treatment of amebiasis caused by Entamoeba.^{109 122}

Anthrax

Postexposure prophylaxis to reduce the incidence or progression of disease following a suspected or confirmed exposure to aerosolized Bacillus anthracis spores (inhalational anthrax).^{102 111 113 141 147} Initial drug of choice for such prophylaxis is ciprofloxacin or doxycycline;^{102 141 147} doxycycline is the preferred tetracycline because of ease of administration and proven efficacy in monkey studies.¹⁰²

Treatment of inhalational anthrax.^{102 111 113 142 143 147 o} Monotherapy may be effective for anthrax that occurs as the result of natural or endemic exposures,^{109 o} 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.^{102 143 147} 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.^{102 105 143 147}

Treatment of GI and oropharyngeal anthrax.^{102 143} If occurring in the context of biologic warfare or bioterrorism, use parenteral regimens recommended for inhalational anthrax.^{102 143}

Treatment of cutaneous anthrax.^{102 111 143 147 o} 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.^{102 105 143 147 o}

Bartonella Infections

Treatment of bartonellosis caused by Bartonella bacilliformis.^{111 113 160}

Treatment of infections caused by B. henselae^{† [off-label]} (e.g., cat scratch disease, bacillary angiomatosis, peliosis hepatitis).ⁱ 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.^{109 j k l} Anti-infectives also are indicated in patients with B. henselae infections who develop bacillary angiomatosis, neuroretinitis, or Parinaud’s oculoglandular syndrome.^{109 j k l} Optimum regimens have not been identified; some clinicians recommend erythromycin, azithromycin, doxycycline, ciprofloxacin, rifampin, co-trimoxazole, gentamicin, or third generation cephalosporins.^{109 i j k l}

Treatment of infections caused by B. quintana^{† [off-label]}.¹³⁷ Optimum anti-infective regimens have not been identified;^{e f g} various drugs have been used, including doxycycline, erythromycin, azithromycin, chloramphenicol, or cephalosporins.^{137 f g}

A drug of choice for treatment of bartonellosis in HIV-infected adults and adolescents, especially CNS bartonellosis.¹⁶⁰ 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.^{160 h}

Brucellosis

Treatment of brucellosis;^{103 109 111 113 114 137 147 m} considered a drug of choice.^{109 147} Used in conjunction with other anti-infectives (e.g., streptomycin or gentamicin and/or rifampin),^{103 109 111 113 114 137 147 m} especially for severe infections or when there are complications (e.g., endocarditis, meningitis, osteomyelitis).^{109 147}

Postexposure prophylaxis following a high-risk exposure to Brucella^{† [off-label]109 147} (e.g., needle-stick injury, inadvertent laboratory exposure, confirmed exposure in the context of biologic warfare or bioterrorism).¹⁴⁷ Postexposure prophylaxis not generally recommended after exposure to endemic brucellosis.^{109 147}

Burkholderia Infections

Treatment of melioidosis^† caused by Burkholderia pseudomallei.^{137 147 gg} 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.¹⁴⁷ 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.^{147 gg}

Treatment of glanders^† caused by B. mallei.¹³⁷ Experience is limited regarding treatment of human cases; optimum regimens not identified.^{147 gg} Some clinicians suggest streptomycin used in conjunction with tetracycline or chloramphenicol or imipenem monotherapy.¹³⁷ 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.¹⁴⁷

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.^{147 gg} 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.^{147 gg}

Campylobacter Infections

Treatment of infections caused by Campylobacter fetus.^{103 111 114} Tetracyclines (usually doxycycline) are alternatives,¹⁰⁹ not drugs of choice for C. fetus.¹³⁷

Chancroid

Treatment of chancroid caused by Haemophilus ducreyi.^{103 111 113 114} Not included in CDC recommendations for treatment of chancroid.¹⁰⁷

Chlamydial Infections

Treatment of uncomplicated urethral, endocervical, or rectal infections caused by Chlamydia trachomatis.^{107 108 109 111 114 137} A drug of choice for presumptive treatment of chlamydial infections in patients with gonorrhea.^{107 108}

Treatment of trachoma and inclusion conjunctivitis caused by C. trachomatis.^{109 111 113 114} Consider that anti-infectives may not eliminate C. trachomatis in all cases of chronic trachoma.^{111 113 114}

Treatment of lymphogranuloma venereum (genital, inguinal, or anorectal infections) caused by C. trachomatis.^{103 107 108 111 113 114} Recommended as drug of choice by CDC and others.^{107 108}

Treatment of psittacosis (ornithosis) caused by C. psittaci.^{100 103 109 111 113 114} A drug of choice recommended by CDC.¹⁰⁰

Clostridium Infections

Treatment of infections caused by Clostridium.^{111 113} Tetracyclines are alternatives to metronidazole or penicillin G for adjunctive treatment of C. tetani infections.¹³⁷

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.^{109 137 x z cc}

Treatment of human monocytotropic (or monocytic) ehrlichiosis^† (HME) caused by E. chaffeensis; drug of choice.^{109 137 x cc}

Treatment of ehrlichiosis^† caused by E. ewingii or E. canis; drug of choice.^{109 137 cc}

Enterobacteriaceae Infections

Treatment of infections caused by susceptible Escherichia coli, Enterobacter aerogenes, Klebsiella, or Shigella.^{111 113} Should only be used for treatment of infections caused by these common gram-negative bacteria when other appropriate anti-infectives are contraindicated or ineffective^a and when in vitro susceptibility tests indicate the organism is susceptible.^{111 113 a}

Fusobacterium Infections

Alternative to penicillin G for treatment of infections caused by Fusobacterium fusiforme (Vincent’s infection).^{111 113}

Gonorrhea and Associated Infections

Alternative for treatment of uncomplicated gonorrhea caused by susceptible Neisseria gonorrhoeae.^{111 113 114} However, tetracyclines are considered inadequate therapy and are not recommended by CDC for treatment of gonorrhea.^{107 b}

Empiric treatment of epididymitis most likely caused by N. gonorrhoeae or C. trachomatis; used in conjunction with IM ceftriaxone.^{107 108}

Granuloma Inguinale (Donovanosis)

Treatment of granuloma inguinale (donovanosis) caused by Calymmatobacterium granulomatis.^{107 111 113 114} CDC recommends doxycycline or co-trimoxazole as drugs of choice.¹⁰⁷

Leptospirosis

Alternative to penicillin G for treatment of leptospirosis^†.^{109 137}

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).^{123 153}

Can be used for combined prophylaxis in travelers at increased risk of leptospirosis who also require malaria chemoprophylaxis.¹²³

Listeria Infections

Alternative for treatment of listeriosis caused by Listeria monocytogenes.^{111 113} Not usually considered a drug of choice or alternative for these infections.^{109 137}

Lyme Disease

Treatment of early disseminated Lyme disease^† associated with erythema migrans, in the absence of neurologic involvement or third-degree AV heart block.^{109 115 116 117 118 119 120 121 136 137 140} 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.^{109 115 116 117 118 119 120 121 136 137 140}

Treatment of uncomplicated Lyme arthritis^† without objective evidence of neurologic involvement (e.g., meningitis or radiculopathy).^{109 115 116 117 121 136 140}

Alternative for treatment of neurologic manifestations of Lyme disease^† when β-lactams (e.g., ceftriaxone, penicillin G) cannot be used.¹³⁶

Malaria

Prevention (prophylaxis) of malaria caused by Plasmodium falciparum, including chloroquine-resistant strains.^{111 122 123 139 153} 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;^{122 123} 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.¹²³

Treatment of uncomplicated malaria^† caused by chloroquine-resistant Plasmodium falciparum or chloroquine-resistant P. vivax and when the plasmodial species has not been identified.^{122 158} Used in conjunction with quinine; not effective alone.^{122 158}

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.^{122 158} A regimen of quinine and doxycycline (or tetracycline) generally preferred over quinine and clindamycin,¹⁵⁸ except for young children or pregnant women who should not receive tetracyclines.¹⁵⁸ Quinine in conjunction with tetracycline (or doxycycline) also a regimen of choice for chloroquine-resistant P. vivax malaria.^{122 158}

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.¹⁵⁸

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.¹²² Not recommended by CDC for presumptive self-treatment of malaria; CDC recommends the fixed combination of atovaquone and proguanil.¹²³

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;^{122 123 158} primaquine usually also indicated to eradicate hypnozoites and prevent relapse in patients exposed to or being treated for P. ovale or P. vivax malaria.^{122 123 158}

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].¹²³

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.¹⁵⁸

Mycobacterial Infections

Alternative for treatment of infections caused by Mycobacterium fortuitum^†.¹³⁷

Treatment of cutaneous infections caused by M. marinum^†;^{106 137} a drug of choice.¹⁰⁶

Nocardiosis

Alternative to co-trimoxazole for treatment of nocardiosis^† caused by Nocardia.^{109 137 a}

Nongonococcal Urethritis

Treatment of nongonococcal urethritis (NGU) caused by Ureaplasma urealyticum, C. trachomatis, or Mycoplasma.^{107 108 111 114 b}

Consider that some cases of recurrent urethritis following doxycycline treatment may be caused by tetracycline-resistant U. urealyticum.¹⁰⁷

Pelvic Inflammatory Disease

Treatment of acute pelvic inflammatory disease (PID); used in conjunction with other anti-infectives.^{107 108} Doxycycline is included in PID regimens to provide coverage against Chlamydia.¹⁰⁷

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.^{107 108} A regimen of IV ampicillin and sulbactam and IV doxycycline is an alternative^{107 108} since it provides good coverage against C. trachomatis, N. gonorrhoeae, and anaerobes and is effective for tubo-ovarian abscess.¹⁰⁷ Doxycycline also used as follow-up after a parenteral regimen of clindamycin and gentamicin.¹⁰⁷

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.^{107 108} Although experience is limited, oral amoxicillin and clavulanate and oral doxycycline may be an alternative oral regimen.¹⁰⁷

Plague

Treatment of plague caused by Yersinia pestis,^{103 111 113 114 123 137 144 147} 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.^{137 144 147} Regimen of choice is streptomycin or gentamicin;^{137 144 147} alternatives are doxycycline, tetracycline, ciprofloxacin, or chloramphenicol.^{144 147} For plague meningitis, some experts recommend that treatment regimen include chloramphenicol.¹⁴⁷

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).^{144 147} Doxycycline may be drug of choice;^{109 144 147} alternatives are tetracycline, ciprofloxacin, or chloramphenicol.¹⁴⁷ Prophylaxis not required for asymptomatic contacts of individuals with bubonic plague, but observe such contacts for 1 week and initiate treatment if symptoms occur.¹⁴⁷

Pleural Effusions

Management of pleural effusions^† associated with metastatic tumors.^{126 127 128 132 134 151 152}

Rat-bite Fever

Treatment of rat-bite fever^† caused by Streptobacillus moniliformis or Spirillum minus.^{109 137} Tetracyclines (usually doxycycline) are alternatives to penicillin G.^{109 137}

Relapsing Fever

Treatment of relapsing fever caused by Borrelia recurrentis.^{111 113 137} A drug of choice.¹³⁷

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.^{103 109 111 112 113 114 147 cc} Drug of choice for treatment of most rickettsial infections.^{109 112 147 a cc}

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.^{107 108 109 111 113 160} Use tetracyclines only if compliance and follow-up can be ensured since efficacy not well documented.^{107 160}

Tularemia

Treatment of tularemia caused by Francisella tularensis,^{103 111 113 114 137 145 147} including naturally occurring or endemic tularemia or tularemia that occurs following exposure to F. tularensis in the context of biologic warfare or bioterrorism.^{137 145 147} Drugs of choice are streptomycin or gentamicin; alternatives are tetracyclines (usually doxycycline), ciprofloxacin, or chloramphenicol.^{137 145 147} Risk of relapse and primary treatment failure may be higher with the alternatives.¹⁴⁵

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.^{145 147} Drugs of choice are doxycycline, tetracycline, or ciprofloxacin.^{145 147} 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.¹⁴⁷

Preexposure prophylaxis of tularemia^†.¹⁴⁷ 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.¹⁴⁷

Vibrio Infections

Treatment of cholera caused by Vibrio cholerae.^{109 110 111 137 p} A drug of choice; used as an adjunct to fluid and electrolyte replacement in moderate to severe disease.^{109 110 137 p}

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

Treatment of infections caused by V. vulnificus^†.^{137 p p} Optimum anti-infective therapy has not been identified; a tetracycline or third generation cephalosporin (e.g., cefotaxime, ceftazidime) is recommended.^{137 p q} Because the case fatality rate associated with V. vulnificus is high, initiate anti-infective therapy promptly if indicated.^q

Yaws

Alternative to penicillin G for treatment of yaws caused by Treponema pertenue.^{111 137}

Yersinia Infections

Treatment of plague caused by Yersinia pestis.^{103 111 113 114 137 144 147} (See Plague under Uses.)

Treatment of GI infections caused by Yersinia enterocolitica^† or Y. pseudotuberculosis^†.^{110 p} 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.^{109 110 p} Some suggest the role of oral anti-infectives in management of enterocolitis, pseudoappendicitis syndrome, or mesenteric adenitis caused by Yersinia needs further evaluation.¹⁰⁹

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).^{107 108}

Related/similar drugs

prednisone, amoxicillin, albuterol, doxycycline, ciprofloxacin, cephalexin, azithromycin

Doxycycline Calcium Dosage and Administration

Administration

Administer orally^{101 103 114 111} or by slow IV infusion.¹¹³ Also has been administered by intrapleural infusion.^{126 127 128 132 134 151 152}

Do not administer IM or sub-Q.¹¹³

IV route recommended only when oral therapy is not indicated or feasible; oral should replace IV as soon as possible.¹¹³ Prolonged IV administration may result in thrombophlebitis; avoid extravasation.¹¹³

Oral Administration

Administer capsules and tablets with adequate amounts of fluid to reduce the risk of esophageal irritation and ulceration.^{103 114 111 123} Probably should not be given at bedtime or to patients with esophageal obstruction or compression.^{123 b}

Administer with food or milk to minimize nausea and vomiting and if gastric irritation occurs;^{103 114 111} absorption not markedly influenced by simultaneous ingestion of food or milk.^{103 114 111 146 148 150}

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.¹²³

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.¹¹¹

Doxycycline calcium oral suspension is administered as provided without further dilution and contains 50 mg/5 mL.¹¹¹

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.^{155 156} 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.¹⁵⁵

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.¹¹³

Dilution

Reconstituted solution must be further diluted prior to administration.¹¹³ 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.¹¹³ Concentrations <0.1 mg/mL or >1 mg/mL are not recommended.¹¹³

Rate of Administration

Administer by slow IV infusion, usually over 1–4 hours (depending on the dose).¹¹³ The minimum recommended time to infuse 100 mg in a solution containing 0.5 mg/mL is 1 hour.¹¹³

Intrapleural Administration

Reconstitution and Dilution

Dilute 500 mg of doxycycline with 25–30 mL of 0.9% sodium chloride injection.^{126 127 128 132 134 151 152}

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).^{127 128 130 131 133}

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.^{130 131 133}

Instill diluted doxycycline solution into the pleural space through a thoracostomy tube; clamp tube and subsequently remove the fluid.^{126 127 128 132 134 151 152}

Dosage

Available as doxycycline calcium,¹¹¹ doxycycline hyclate,^{103 111 113} and doxycycline monohydrate;^{111 114} dosage expressed in terms of doxycycline.^{103 111 113 114}

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.^{103 111 114} For severe infections, up to 4.4 mg/kg daily.^{103 111 114}

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.^{103 111 114} For more severe infections, 100 mg every 12 hours.^{103 111 114}

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.¹¹³

Children >8 years of age weighing >45 kg: 200 mg on day 1 in 1 or 2 infusions followed by 100–200 mg daily.¹¹³

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.^{141 147 c} 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.^{102 104 141 147}

Children >8 years of age weighing ≥45 kg: 100 mg twice daily given for ≥60 days.^{104 141 147 c}

Optimum duration of postexposure prophylaxis after an inhalation exposure to B. anthracis spores is unclear,^{147 ff} but prolonged postexposure prophylaxis usually required.^{102 147} 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.^ff 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.^{102 147} 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.¹⁴⁷

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).^{102 147 c}

Children >8 years of age weighing ≥45 kg: 100 mg twice daily.^{102 c} Some experts recommend an initial 200-mg dose, then 100 mg every 12 hours.¹⁴⁷

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).^{102 147} 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.^{102 143 147} 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.¹⁰⁵

IV, then Oral

Children ≤8 years of age^† or weighing <45 kg: 2.2 mg/kg (up to 100 mg) twice daily.^{102 143 147 d}

Children >8 years of age weighing ≥45 kg: 100 mg twice daily.^{102 142 143 147 d}

Used in conjunction with 1 or 2 other anti-infectives predicted to be effective.^{102 143 147} When clinical improvement occurs, switch IV doxycycline to oral doxycycline in the same dosage and continue for a total duration of ≥60 days.^{102 142 143 147 d} 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.¹⁰⁵

Treatment of Cutaneous Anthrax

Oral

Children ≤8 years of age^† or weighing <45 kg: 2.2 mg/kg (up to 100 mg) twice daily.^{102 143 147}

Children >8 years of age weighing ≥45 kg: 100 mg twice daily.^{102 143 147}

For mild, uncomplicated cutaneous anthrax that occurs following natural or endemic exposure, 5–10 days of treatment has been recommended.^{102 143 147}

For cutaneous anthrax that occurs following exposure in the context of biologic warfare or bioterrorism, duration of treatment is ≥60 days.^{102 143 147} 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.^{105 143 147}

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.^{102 105 143 147}

IV, then Oral

Children ≤8 years of age^† or weighing <45 kg: 2.2 mg/kg (up to 100 mg) twice daily.^{102 147}

Children >8 years of age weighing ≥45 kg: 100 mg every 12 hours.^{102 142 143 147}

Used in conjunction with 1 or 2 other anti-infectives predicted to be effective.^{102 143 147} When clinical improvement occurs, switch IV doxycycline to oral doxycycline in the same dosage and continue for a total duration of ≥60 days.^{102 142 143 147 d} 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.^{105 147}

Bartonella Infections

Oral or IV

Adolescents with HIV infection: 100 mg every 12 hours for ≥3 months for bartonellosis (including CNS infections).¹⁶⁰ Also consider doxycycline long-term suppressive therapy^† in those with relapse or reinfection.¹⁶⁰

Brucellosis

Treatment of Brucellosis

Oral

Children ≥8 years of age: 2–4 mg/kg daily (up to 200 mg daily) in 2 divided doses.¹⁰⁹ Some experts recommend 2.2 mg/kg twice daily (up to 200 mg daily).¹⁴⁷

Usual duration of therapy is 4–6 weeks;^{109 147} more prolonged therapy may be required for complicated disease (e.g., hepatitis, splenitis, meningoencephalitis, endocarditis, osteomyelitis).¹⁴⁷ Meningoencephalitis and endocarditis should be treated for ≥90 days and may require ≥6 months of treatment.¹⁴⁷

Usually used in conjunction with rifampin or other anti-infectives to decrease risk of relapse.^{109 147} 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.^{109 147}

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.^gg

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

Initial IV regimen continued for ≥14 days and until clinical improvement occurs.^{147 gg} When appropriate, switch to a prolonged oral maintenance regimen.^{147 gg}

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.¹⁴⁷

Prolonged oral maintenance regimen recommended to reduce risk of relapse after initial treatment with IV ceftazidime, imipenem, or meropenem (with or without IV doxycycline).¹⁴⁷ Maintenance regimen usually continued for ≥4–6 months;^{147 gg} a duration of 6–12 months may be necessary depending on response to therapy and severity of illness.^{147 gg} Lifelong follow-up recommended for all patients to identify relapse.¹⁴⁷

Chlamydial Infections

Uncomplicated Urethral, Endocervical, or Rectal Infections

Oral

Children >8 years of age: 100 mg twice daily given for 7 days.^{107 109}

Presumptive Treatment of Chlamydial Infection in Gonorrhea Patients

Oral

Adolescents: 100 mg twice daily given for 7 days.¹⁰⁷

Lymphogranuloma Venereum

Oral

Adolescents: 100 mg twice daily given for 21 days.^{107 109}

Ehrlichiosis†

Oral or IV

AAP and CDC recommend 2.2 mg/kg (up to 100 mg) twice daily.^{109 cc} Initiate promptly since delay can result in severe disease and fatal outcome.^{109 cc}

Optimum duration of therapy not established.^{109 cc} Usually continued ≥5–10 days and until patient is afebrile for ≥3 days and clinically improved.^{109 x cc} Severe illness may require longer duration of therapy.^{109 cc} 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.^cc

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.^{109 cc}

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.^{107 109}

Granuloma Inguinale (Donovanosis)

Oral

Adolescents: 100 mg twice daily given for ≥3 weeks or until all lesions have healed completely;¹⁰⁷ consider adding IV aminoglycoside (e.g., gentamicin) if improvement is not evident within the first few days of therapy and in HIV-infected patients.¹⁰⁷

Relapse can occur 6–18 months after apparently effective treatment.¹¹⁶

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).^{109 115 116 117 118 119 120 121 124 136 137 140}

Duration of treatment is 14–21 days for most patients with early localized or early disseminated disease in the absence of neurologic involvement.^{109 115 116 117 118 119 120 121 124 136 140} Some experts recommend a duration of 21–28 days for early disseminated disease associated with mild carditis or isolated facial nerve palsy.^{109 115 136 140}

Lyme Arthritis†

Oral

Children ≥8 years of age: 1–2 mg/kg twice daily (up to 100 mg each dose) for 28 days.^{109 115 116 117 119 124 120 121 136}

Malaria

Prevention of Malaria

Oral

Children ≥8 years of age: 2 mg/kg (up to 100 mg) once daily.^{122 123 139 153}

Initiate prophylaxis 1–2 days prior to entering malarious area; continue during the stay and for 4 weeks after leaving area.^{111 122 123 139} 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.¹²³

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.^{122 123}

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).^{122 158}

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).¹⁵⁸

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.¹⁵⁸

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.^{158 159}

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.¹⁵⁸ Used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3–7 days.¹⁵⁸

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.¹⁵⁸ Used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3–7 days.¹⁵⁸

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).¹²² 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.¹²²

Not recommended for self-treatment of malaria in individuals currently taking the drug for prophylaxis.¹²²

Nongonococcal Urethritis

Oral

Adolescents: 100 mg twice daily given for 7 days.¹⁰⁷

Pelvic Inflammatory Disease†

Oral

Adolescents: 100 mg every 12 hours given for 14 days.¹⁰⁷ Used in conjunction with and as follow-up to other anti-infectives (see Uses).¹⁰⁷

IV, then Oral

Adolescents: 100 mg every 12 hours.¹⁰⁷ Initially, IV doxycycline in conjunction with IV cefoxitin or cefotetan.¹⁰⁷ 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.¹⁰⁷

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).¹⁴⁴

Children weighing ≥45 kg: 100 mg twice daily or 200 mg once daily.¹⁴⁴

Prompt initiation of treatment (within 18–24 hours of symptom onset) is essential.^{144 147} Oral doxycycline may be substituted in the same dosage when the patient’s condition improves or if parenteral doxycycline is unavailable.^{144 147} Total duration of treatment is ≥10–14 days.^{144 147}

Postexposure Prophylaxis Following High-risk Exposure†

Oral

Children weighing <45 kg: 2.2 mg/kg twice daily (up to 200 mg daily).¹⁴⁴

Children weighing ≥45 kg: 100 mg twice daily.¹⁴⁴ Alternatively, 2–4 mg/kg daily in 2 equally divided doses.¹⁴⁹

Duration of prophylaxis following exposure to plague aerosol or a patient with suspected pneumonic plague is 7 days^{144 147} or the duration of exposure risk plus 7 days.¹⁴⁷

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.^{103 111 114} For severe infections, up to 4.4 mg/kg daily.^{103 111 114}

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.^{103 111 114}

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

Rocky Mountain Spotted Fever (RMSF)

Oral or IV

CDC recommends 2.2 mg/kg (up to 100 mg) twice daily.^cc Initiate promptly since delay can result in severe disease and fatal outcome.^{109 cc}

Usually continued ≥5–10 days and until patient is afebrile for ≥3 days and clinically improved.^{109 x cc} Severe illness may require longer duration of therapy.^{109 cc}

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.^cc

Q Fever

Oral

CDC recommends 2.2 mg/kg every 12 hours for ≥14 days for treatment of acute Q fever.¹⁴⁷

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.¹⁴⁷

Syphilis

Primary or Secondary Syphilis

Oral

Children >8 years of age: 100 mg twice daily given for 14 days.^{107 109 111 160}

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.^{107 109 111 160}

Tularemia

Treatment

IV, then Oral

Children weighing <45 kg: 2.2 mg/kg (up to 100 mg) twice daily.^{145 147}

Children weighing ≥45 kg: 100 mg twice daily.^{145 147}

Oral doxycycline may be substituted in the same dosage when the patient’s condition improves or if parenteral doxycycline is unavailable.¹⁴⁵ Total duration of treatment is ≥14–21 days.^{145 147}

Postexposure Prophylaxis Following High-risk Exposure†

Oral

Children weighing <45 kg: 2.2 mg/kg (up to 100 mg) twice daily.^{145 147}

Children weighing ≥45 kg: 100 mg twice daily.^{145 147}

Initiate postexposure prophylaxis within 24 hours of exposure and continue for ≥14 days.^{145 147}

Vibrio Infections

Cholera

Oral

Children ≥8 years of age: 6 mg/kg (maximum 300 mg) as a single dose.¹⁰⁹

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.¹⁰⁷

Adults

General Adult Dosage

Oral

100 mg every 12 hours on day 1 followed by 100 mg daily in 1 or 2 divided doses.^{103 111}

For more severe infections, 100 mg every 12 hours.^{103 111}

IV

200 mg on day 1 in 1 or 2 IV infusions followed by 100–200 mg daily.¹¹³

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.^a

For severe infections, 100 mg every 12 hours.^a

Anthrax

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

Oral

100 mg twice daily given for ≥60 days.^{102 141 147 c} Some experts recommend an initial 200-mg dose, then 100 mg every 12 hours.¹⁴⁷

Optimum duration of postexposure prophylaxis after an inhalation exposure to B. anthracis spores is unclear,^{147 ff} but prolonged postexposure prophylaxis usually required.^{102 147} 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.^ff 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.^{102 147} 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.¹⁴⁷

Treatment of Inhalational, GI, or Oropharyngeal Anthrax

Oral

100 mg twice daily.^{102 143} Some experts recommend an initial 200-mg dose, then 100 mg every 12 hours.¹⁴⁷

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).^{102 143} 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.^{102 143 147}

IV, then Oral

100 mg twice daily.^{102 142 143} Some experts recommend an initial 200-mg dose, then 100 mg every 12 hours.¹⁴⁷

Used in conjunction with 1 or 2 other anti-infectives predicted to be effective.^{102 143} When clinical improvement occurs, switch IV doxycycline to oral doxycycline in the same dosage and continue for a total duration of ≥60 days.^{102 142 143 147 d}

Treatment of Cutaneous Anthrax

Oral

100 mg twice daily.^{102 143 147}

For mild, uncomplicated cutaneous anthrax that occurs following natural or endemic exposure, 5–10 days of treatment has been recommended.^{102 143 147}

For cutaneous anthrax that occurs following exposure in the context of biologic warfare or bioterrorism, duration of treatment is ≥60 days.^{102 143 147}

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.^{102 143 147}

IV, then Oral

100 mg twice daily.^{d 143}

Used in conjunction with 1 or 2 other anti-infectives predicted to be effective.^{102 143} When clinical improvement occurs, switch IV doxycycline to oral doxycycline in the same dosage and continue for a total duration of ≥60 days.^{102 142 143 147 d}

Bartonella Infections

Oral or IV

HIV-infected adults: 100 mg every 12 hours for ≥3 months for bartonellosis (including CNS infections).¹⁶⁰ Also consider doxycycline long-term suppressive therapy^† in those with relapse or reinfection.¹⁶⁰

Burkholderia Infections†

Treatment of Localized Disease†

Oral

Mild, localized disease without toxicity: 100 mg twice daily for 60–150 days may be effective.¹⁴⁷

Localized disease without toxicity: 100 mg twice daily for 20 weeks given in conjunction with oral co-trimoxazole.¹⁴⁷

Initial Treatment of Severe Disease†

IV

100 mg twice daily given in conjunction with IV ceftazidime, imipenem, or meropenem.^{147 gg}

Initial IV regimen continued for ≥14 days and until clinical improvement occurs.^{147 gg} When appropriate, switch to a prolonged oral maintenance regimen.^{147 gg}

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

Oral

100 mg twice daily given in conjunction with oral co-trimoxazole.¹⁴⁷

Prolonged oral maintenance regimen recommended to reduce risk of relapse after initial treatment with IV ceftazidime, imipenem, or meropenem (with or without IV doxycycline).¹⁴⁷ Maintenance regimen usually continued for ≥4–6 months;^{147 gg} a duration of 6–12 months may be necessary depending on response to therapy and severity of illness.^{147 gg} Lifelong follow-up recommended for all patients to identify relapse.¹⁴⁷

Postexposure Prophylaxis†

Oral

200 mg once daily in conjunction with oral rifampin.¹⁴⁷ Optimum duration unknown; continue for ≥10 days.¹⁴⁷

Brucellosis

Treatment of Brucellosis

Oral

Some experts recommend 100 mg twice daily.¹⁴⁷

Usual duration is 4–6 weeks;^{109 147} more prolonged therapy may be required for complicated disease (e.g., hepatitis, splenitis, meningoencephalitis, endocarditis, osteomyelitis).¹⁴⁷ Meningoencephalitis and endocarditis should be treated for ≥90 days and may require ≥6 months of treatment.¹⁴⁷

Usually used in conjunction with rifampin or other anti-infectives to decrease risk of relapse.^{109 147} 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.^{109 147}

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

Oral

200 mg once daily given for 3–6 weeks.¹⁴⁷

Chlamydial Infections

Uncomplicated Urethral, Endocervical, or Rectal Infections

Oral

100 mg twice daily given for 7 days.^{103 107 108 111 114}

Presumptive Treatment of Chlamydial Infection in Gonorrhea Patients

Oral

100 mg twice daily given for 7 days.^{107 108 109}

Acute Epididymo-orchitis or Proctitis caused by C. trachomatis

Oral

100 mg twice daily given for ≥10 days.^{107 111}

Lymphogranuloma Venereum

Oral

100 mg twice daily given for 21 days.^{107 108}

Psittacosis (Ornithosis)

Oral

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

IV

4.4 mg/kg daily in 2 divided doses for initial treatment of severely ill patients.¹⁰⁰

Ehrlichiosis†

Oral or IV

CDC and others recommend 100 mg twice daily.^{109 x cc} Initiate promptly since delay can result in severe disease and fatal outcome.^{109 cc}

Optimum duration of therapy not established.^{109 x cc} Usually continued ≥5–10 days and until patient is afebrile for ≥3 days and clinically improved.^{109 x cc} Severe illness may require longer duration of therapy.^{109 cc} 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.^cc

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.^{109 cc}

Gonorrhea and Associated Infections

Uncomplicated Gonorrhea

Oral

100 mg twice daily given for 7 days recommended by manufacturer.¹¹¹ Alternatively, 300 mg followed by another 300-mg dose 1 hour later.¹¹¹

No longer recommended for gonorrhea by CDC or other experts.^{107 108}

Empiric Treatment of Epididymitis

Oral

100 mg twice daily given for 10 days; as follow-up to a single dose of IM ceftriaxone.^{107 108 109}

Epididymo-orchitis or Proctitis

Oral

100 mg twice daily given for ≥10 days for acute epididymo-orchitis or for 7 days for proctitis.^{107 111}

Granuloma Inguinale (Donovanosis)

Oral

100 mg twice daily given for ≥3 weeks or until all lesions have healed completely;¹⁰⁷ consider adding IV aminoglycoside (e.g., gentamicin) if improvement is not evident within the first few days of therapy and in HIV-infected patients.¹⁰⁷

Relapse can occur 6–18 months after apparently effective treatment.¹¹⁶

Leptospirosis†

Treatment†

Oral

100 mg twice daily given for 7 days.^b

Prevention†

Oral

200 mg once weekly beginning 1–2 days prior to and continuing throughout the period of exposure.^{123 153}

Lyme Disease†

Early Localized or Early Disseminated Lyme Disease†

Oral

100 mg twice daily.^{109 115 116 117 118 119 120 121 124 136 140}

Duration of treatment is 14–21 days for most patients with early localized or early disseminated disease in the absence of neurologic involvement.^{109 115 116 117 118 119 120 121 124 136 140} Some experts recommend a duration of 21–28 days for early disseminated disease associated with mild carditis or isolated facial nerve palsy.^{109 115 136 140}

Lyme Arthritis†

Oral

100 mg twice daily given for 28 days.^{109 115 116 117 118 119 120 121 124 136}

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.^{109 115 136 140}

Malaria

Prevention of Malaria

Oral

100 mg once daily.^{111 122 123 139 153}

Initiate prophylaxis 1–2 days prior to entering malarious area; continue during the stay and for 4 weeks after leaving area.^{111 122 153} 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.¹²³

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.^{122 123}

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).^{122 158}

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).¹⁵⁸

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.¹⁵⁸

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.¹⁵⁸

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.¹⁵⁸

Used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3–7 days.¹⁵⁸

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).¹²² 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.¹²²

Not recommended for self-treatment of malaria in individuals currently taking the drug for prophylaxis.¹²²

Mycobacterial Infections†

Mycobacterium marinum Infections†

Oral

100 mg twice daily given for ≥3 months recommended by ATS for treatment of cutaneous infections.¹⁰⁶ A minimum of 4–6 weeks of treatment usually is necessary to determine whether the infection is responding.¹⁰⁶

Nongonococcal Urethritis

Oral

100 mg twice daily given for 7 days.^{103 107 108 111 114}

Pelvic Inflammatory Disease†

Oral

100 mg every 12 hours given for 14 days.^{107 108} Used in conjunction with and as follow-up to other anti-infectives (see Uses).^{107 108}

IV, then Oral

100 mg every 12 hours.^{107 108} Initially, IV doxycycline in conjunction with IV cefoxitin or cefotetan.^{107 108} 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.^{107 108}

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.^{144 147}

Prompt initiation of treatment (within 18–24 hours of symptom onset) is essential.^{144 147} Oral doxycycline may be substituted in the same dosage when the patient’s condition improves or if parenteral doxycycline is unavailable.^{144 147} Total duration of treatment is ≥10–14 days.^{144 147}

Postexposure Prophylaxis Following High-risk Exposure†

Oral

100 mg every 12 hours.^{144 147} Alternatively, 100–200 mg daily in 2 equally divided doses.¹⁴⁹

Duration of prophylaxis following exposure to plague aerosol or a patient with suspected pneumonic plague is 7 days^{144 147} or the duration of exposure risk plus 7 days.¹⁴⁷

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).^{126 127 128 132 134 151 152} Procedure may be repeated to achieve control of the effusion,^{127 128} although repeated administration may have limited effects.¹²⁶

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.¹²⁹ Clamp tube for 24 hours and repeat entire procedure daily until the drainage volume approximates the amount of solution instilled.¹²⁹

Rickettsial Infections

Oral

100 mg every 12 hours on day 1 followed by 100 mg daily in 1 or 2 divided doses.^{103 111 114} For more severe infections, 100 mg every 12 hours.^{103 111 114}

Continue therapy for 3–10 days or until patient is afebrile for approximately 2–3 days.^{b 109} Alternatively, a single dose of 100–200 mg may be effective for louse-borne (epidemic) typhus, Brill-Zinsser disease, or scrub typhus.^b

Rocky Mountain Spotted Fever (RMSF)

Oral or IV

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

Usually continued ≥5–10 days and until patient is afebrile for ≥3 days and clinically improved.^{109 x cc} Severe illness may require longer duration of therapy.^{109 cc}

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.^{cc cc}

Q Fever

Oral

100 mg twice daily given for 2–3 weeks recommended by CDC and others for acute Q fever.^{112 123 147 157}

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.¹⁵⁷ Patients with chronic Q fever endocarditis should receive the doxycycline and hydroxychloroquine regimen for 1.5–3 years.¹⁵⁷

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.¹⁴⁷

Syphilis

Primary or Secondary Syphilis

Oral

100 mg twice daily given for 14 days.^{107 108 111 160}

IV

300 mg daily given for ≥10 days.¹¹³

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.^{107 108 109 111 160}

Tularemia

Treatment

IV, then Oral

100 mg twice daily.^{145 147}

Oral doxycycline may be substituted in the same dosage when the patient’s condition improves or if parenteral doxycycline is unavailable.¹⁴⁵ Total duration of treatment is ≥14–21 days.^{145 147}

Postexposure Prophylaxis Following High-risk Exposure†

Oral

100 mg twice daily.^{145 147}

Initiate postexposure prophylaxis within 24 hours of exposure and continue for ≥14 days.^{145 147}

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.^a For severe infections, 100 mg every 12 hours for 3 days.^a

Alternatively, 300 mg as a single dose may be effective.¹¹⁰

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.¹⁰⁷

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.¹¹¹

Malaria

Treatment of Uncomplicated Chloroquine-resistant P. falciparum Malaria†

Oral

Children ≥8 years of age: Maximum 200 mg daily.¹⁵⁸

Treatment of Uncomplicated P. vivax Malaria†

Oral

Children ≥8 years of age: Maximum 200 mg daily.¹⁵⁸

Treatment of Severe P. falciparum Malaria†

Oral or IV

Children ≥8 years of age: Maximum 200 mg daily.¹⁵⁸

Special Populations

Renal Impairment

Dosage adjustments not necessary.¹¹¹

Cautions for Doxycycline Calcium

Contraindications

• Known hypersensitivity to doxycycline or any tetracycline.^{103 111 113 114}

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.^{111 113} Effects are most common following long-term use, but may occur following repeated short-term use.^{111 113}

Tetracyclines form a stable calcium complex in any bone-forming tissue.^{111 113} Reversible decrease in fibula growth rate has occurred in prematures receiving oral tetracycline.^{111 113}

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.^{109 111 113 cc} (See Pediatric Use under Cautions.)

Superinfection/Clostridium difficile-associated Colitis

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.^{111 113} Discontinue drug and institute appropriate therapy if superinfection occurs.^{111 113}

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

Some mild cases of C. difficile-associated diarrhea and colitis may respond to discontinuance alone.^{c r s t u v} 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.^{c r s t u v}

Fetal/Neonatal Morbidity

Animal studies indicate possible fetal toxicity (e.g., retardation of skeletal development) and embryotoxicity.^{111 113} If used during pregnancy or if patient becomes pregnant while receiving doxycycline, patient should be apprised of the potential hazard to the fetus.¹¹¹ (See Pregnancy under Cautions.)

Renal Effects

Tetracyclines have antianabolic effects and may increase BUN.^{111 113} Dose-related increase in BUN reported.¹¹¹

Studies to date indicate that increased BUN does not occur with use of usual doxycycline doses in patients with impaired renal function.^{111 113}

Sensitivity Reactions

Photosensitivity Reactions

Photosensitivity, manifested by an exaggerated sunburn reaction, reported with tetracyclines.^{111 113}

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.^a Most reactions result from accumulation of tetracyclines in skin and are phototoxic in nature; photoallergic reactions also may occur.^a

Discontinue drug at first evidence of skin erythema.^{111 113}

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.¹¹¹

General Precautions

Nervous System Effects

Possibility of bulging fontanels in infants and benign intracranial hypertension in adults.¹¹¹ Effects resolve when drug discontinued.¹¹¹

Laboratory Monitoring

Periodically assess organ system function, including renal, hepatic and hematopoietic, during long-term therapy.¹¹¹

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.^c

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

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.^{111 113}

Incision and drainage or other surgical procedures should be performed in conjunction with doxycycline therapy when indicated.¹¹¹

Specific Populations

Pregnancy

Category D.¹¹¹ (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.¹¹³

CDC and others state doxycycline can be used when necessary for treatment of inhalational anthrax in pregnant women.^{102 143} 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;¹⁴³ some clinicians recommend periodic liver function testing if used in pregnant women.¹⁰²

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).¹⁵⁸ 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.¹⁵⁸ 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.¹⁵⁸

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.^cc

Lactation

Distributed into milk;^{111 113} discontinue nursing or the drug.¹¹¹

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.^c AAP states maternal use of tetracyclines usually is compatible with breast-feeding since absorption of the drugs by nursing infants is negligible.¹⁰⁹

Pediatric Use

Should not be used in children <8 years of age unless other appropriate drugs are ineffective or are contraindicated.^{109 111 113} (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).^{109 111 cc}

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.^{109 cc}

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.¹⁵⁸

Hepatic Impairment

Pharmacokinetics not studied.

Renal Impairment

Renal impairment does not appear to result in excessive accumulation of the drug.^{103 111 113}

Common Adverse Effects

GI effects (nausea, vomiting, diarrhea, bulky loose stools, anorexia, glossitis, dysphagia); maculopapular and erythematous rash; photosensitivity.^{111 113 a}

Drug Interactions

Specific Drugs

Doxycycline Calcium Pharmacokinetics

Absorption

Bioavailability

90–100% absorbed from GI tract in fasting adults;^b peak serum concentrations attained within 1.5–4 hours.^{111 b}

Food

GI absorption reduced up to 20% by food and/or milk;^b effect not considered clinically important.^{111 b}

Divalent and trivalent cations, including aluminum, calcium, iron, and magnesium, may decrease oral absorption as a result of chelation with the drug.^b

Distribution

Extent

Widely distributed into body tissues and fluids.^a

Only small amounts diffuse into CSF.^a

Readily crosses the placenta^a and is distributed into milk.^{111 a}

Plasma Protein Binding

25–93%.^a

Elimination

Metabolism

Does not appear to be metabolized in the liver, but is partially inactivated in the intestine by chelate formation.^b

Elimination Route

Excreted into the GI tract via bile and by nonbiliary routes.^{111 b} 20–26% of an oral or IV dose excreted in urine and 20–40% excreted in feces.^{111 113 b}

Half-life

14–17 hours after a single dose and 22–24 hours after multiple doses.^b

Special Populations

Patients with severe hepatic impairment or biliary obstruction: Serum concentrations and half-life may be increased.^a

Patients with severe renal impairment: Half-life 18–26 hours after a single dose and 20–30 hours after multiple doses.^b

Stability

Storage

Oral

Capsules

Doxycycline hyclate capsules: <30°C in a tight, light-resistant container.¹¹¹

Doxycycline monohydrate capsules: 15–30°C and protect from light.¹¹⁴

Doxycycline hyclate delayed-release capsules containing partially enteric-coated pellets: <25°C.¹⁰³

For Suspension

<30°C in a tight, light-resistant container.¹¹¹ After reconstitution, stable for 2 weeks at room temperature.^b

Suspension

<30°C in a tight, light-resistant container.¹¹¹

Tablets

Film-coated tablets: <30°C in a tight, light-resistant container.¹¹¹

Tablets: 15–30°C in a tight, light-resistant container.¹⁰¹

Film-coated tablets that have been ground and extemporaneously mixed with food or drinks (chocolate pudding, regular or low-fat chocolate milk, apple juice with table sugar, low-fat milk) are stable for 24 hours at room temperature (22–26°C) or refrigerated at 2–8°C; the ground tablets mixed with low-fat chocolate milk may be stable for 1 week when refrigerated.¹⁵⁶ Ground tablets are stable for at least 6 days when wrapped in aluminum foil and stored at room temperature.¹⁵⁶

Parenteral

Powder for Infusion

IV solutions containing 0.1–1 mg/mL prepared using sodium chloride or 5% dextrose injection are stable for 48 hours at 25°C when protected from direct sunlight or up to 72 hours when refrigerated and protected from both sunlight and artificial light.¹¹³ Once removed from refrigeration, these solutions must be completely infused within 12 hours and any unused solution discarded.¹¹³

IV solutions containing 0.1–1 mg/mL prepared using Ringer’s injection, invert sugar in 10% dextrose injection, Normosol-M or Normosol-R in 5% dextrose injection, or Plasma-Lyte 56 or Plasma-Lyte 148 in 5% dextrose injection are stable for up 12 hours at room temperature or up to 72 hours when refrigerated and protected from sunlight and artificial light.¹¹³ Once removed from refrigeration, these solutions must be completely infused within 12 hours and any unused solution discarded.¹¹³

IV solutions prepared using lactated Ringer’s injection or 5% dextrose in lactated Ringer’s injection must be completely infused within 6 hours after reconstitution and any unused solution discarded.¹¹³ These solutions must be protected from direct sunlight during infusion.¹¹³

Solutions containing 10 mg/mL prepared using sterile water for injection may be frozen immediately after preparation and stored for up to 8 weeks at -20°C.¹¹³ If warmed, take care to avoid heating after thawing is complete.¹¹³ Do not refreeze after thawing.¹¹³

Compatibility

Parenteral

Solution Compatibility

Drug Compatibility

Actions and Spectrum

• Usually bacteriostatic,^{111 113 a} but may be bactericidal in high concentrations or against highly susceptible organisms.^a

• Inhibits protein synthesis^{111 113} in susceptible organisms by reversibly binding to 30S and 50S ribosomal subunits.^a

• The complete mechanisms by which tetracyclines reduce acne lesions have not been fully elucidated.^a The effects appear to result in part from the antibacterial activity of the drugs, but other mechanisms also are involved.^a

• Spectrum of activity includes many gram-positive and -negative bacteria and various other organisms (e.g., Rickettsia, Chlamydia, Mycoplasma, spirochetes).^{111 a} Inactive against fungi and viruses.^{111 a}

• Gram-positive aerobes and anaerobes: Active against Actinomyces israelii, Bacillus anthracis, Clostridium perfringens, C. tetani, Nocardia, Propionibacterium acnes, and some streptococci.^{111 a} Many strains of S. pyogenes and Enterococci are resistant.¹¹¹

• Gram-negative aerobes and anaerobes: Active against Bartonella bacilliformis, Brucella, Calymmatobacterium granulomatis, Francisella tularensis, Haemophilus ducreyi, H. influenzae, Neisseria gonorrhoeae, Vibrio cholerae, Y. enterocolitica, and Y. pestis.^{111 a} Many strains of Acinetobacter, E. aerogenes, E. coli, Klebsiella, and Shigella and nearly all strains of Proteus and Pseudomonas are resistant.^{111 a}

• Other organisms: Active against Rickettsia, Anaplasma phagocytophilum (formerly Ehrlichia phagocytophila, E. equi, agent of HGE),^{z dd ee} E. chaffeensis,^aa Coxiella burnetii, Chlamydia psittaci, C. trachomatis, Helicobacter pylori, Mycoplasma hominis, M. pneumoniae, Ureaplasma urealyticum, Borrelia burgdorferi, B. recurrentis, Leptospira, Treponema pallidum, T. pertenue, and Mycobacterium fortuitum.^{111 a} Active against asexual erythrocytic forms of Plasmodium falciparum, but is not gametocidal and not active against exoerythrocytic forms of P. falciparum.^{111 a}

• Complete cross-resistance usually occurs between doxycycline and other tetracyclines (demeclocycline, minocycline, oxytetracycline, tetracycline).^{111 113 a}

Advice to Patients

• Advise patients that antibacterials (including doxycycline) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).^c

• Importance of completing full course of therapy, even if feeling better after a few days.^{111 c}

• Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with doxycycline or other antibacterials in the future.^c

• Importance of drinking sufficient quantities of fluids when taking capsules or tablets to reduce the risk of esophageal irritation and ulceration.¹¹¹

• Advise patients that doxycycline absorption is reduced when taken with foods, especially those containing calcium, but is not markedly influenced by simultaneous ingestion with food or milk.¹¹¹

• Advise patients that doxycycline may increase the incidence of vaginal candidiasis.¹¹¹

• Advise patients that doxycycline may decrease effectiveness of oral contraceptives and that alternative nonhormonal contraceptive measures should be used.^a

• Advise patients to avoid excessive sunlight or artificial UV light and to discontinue the drug at the first sign of skin erythema and if phototoxicity (e.g., skin eruption) occurs;¹¹¹ consider use of sunscreen or sunblock.¹¹¹

• Advise patients using the drug for malaria prevention that no antimalarial agent (including doxycycline) guarantees protection against malaria.¹¹¹ Importance of using personal protective measures to avoid mosquito bites (e.g., staying in well-screened areas, using mosquito nets, covering body with clothing, using an effective insect repellent), especially from dusk to dawn.¹¹¹

• Advise patients using the drug for malaria prevention that such prophylaxis should begin 1–2 days before travel to the malarious area, be taken daily while in the malarious area, and continued for 4 weeks (but not >4 weeks) after leaving the area.¹¹¹

• Advise travelers who plan presumptive self-treatment in the event of a possible malarial infection to keep an amount of doxycycline and quinine sufficient for self-treatment in their possession during travel and to take the regimen promptly in the event of a febrile illness during or after their travel if professional medical care is not readily available.^{122 158}

• Advise travelers that presumptive self-treatment of malaria is an interim measure and that they should seek medical evaluation as soon as possible.^{122 158}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹¹¹ (See Fetal/Neonatal Morbidity under Cautions.)

• Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, and any concomitant illnesses.¹¹¹

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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