Reconstitution and Administration 
Doxycycline calcium,111 doxycycline hyclate,103,111,171,173 and doxycycline monohydrate111,114,170,172,173 are administered orally.
When oral therapy is not feasible, doxycycline hyclate may be administered by slow IV infusion; however, oral therapy should replace IV therapy as soon as possible.113 If doxycycline is given IV, the risk of thrombophlebitis should be considered.113
Like other tetracyclines, doxycycline should not be used in children younger than 8 years of age unless other appropriate drugs would be ineffective or are contraindicated.103,109,111,113,114,170,171,172,173,174 (See Cautions: Pediatric Precautions in the Tetracyclines General Statement 8:12.24.) However, the manufacturers, American Academy of Pediatrics (AAP), US Centers for Disease Control and Prevention (CDC), and Infectious Diseases Society of America (IDSA) state that use of doxycycline in children younger than 8 years of age can be considered in certain circumstances when the potential benefits outweigh the risks.103,109,111,113,114,136,165,170,171,172,173,174 These circumstances include the treatment or prophylaxis of anthrax (including inhalational anthrax [postexposure]),103,109,111,113,114,170,171,172,173,174 treatment of severe cholera,109 and treatment of presumed or confirmed rickettsial infections, including Rocky Mountain spotted fever (RMSF),109 Q fever, ehrlichiosis†, and anaplasmosis†.109,136,165 In addition, the CDC states that children younger than 8 years of age with uncomplicated chloroquine-resistant Plasmodium falciparum malaria, uncomplicated P. vivax malaria, or severe P. falciparum malaria may receive a regimen that includes doxycycline if other treatment options are not available or not tolerated and the potential benefits outweigh risks.158 Because of concerns regarding long-term doxycycline therapy in infants and children, the treatment duration should be limited whenever possible if use of doxycycline is considered necessary in children younger than 8 years of age.109,136,165
Doxycycline calcium is administered orally as a conventional oral suspension.111 Doxycycline hyclate is administered orally as conventional capsules,111,171 conventional film-coated tablets,111,171 delayed-release capsules,174 and delayed-release tablets.103 Doxycycline monohydrate is administered orally as a conventional oral suspension,111 conventional capsules,114,170,173 or conventional film-coated tablets.172
To reduce the risk of esophageal irritation and ulceration, capsules or tablets containing doxycycline hyclate or doxycycline monohydrate should be administered with adequate amounts of fluid103,111,114,170,171,172,173,174 and probably should not be given at bedtime or to patients with esophageal obstruction or compression.123 Most cases of esophagitis or esophageal ulceration reported with oral doxycycline occurred in patients who took the drug immediately before going to bed.103,111,114,170,171,172,173,174
Some manufacturers and some clinicians suggest that doxycycline may be taken with food22,103,111,114,170,171,172,173,174 or milk103,111,171,174 to minimize nausea and vomiting or if gastric irritation occurs. However, it has been suggested that doxycycline, like some other tetracyclines, should not be administered with milk.177 Although a few manufacturers state that absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk,111,171 this effect appears to be variable and concomitant administration with food or milk can decrease the rate and extent of absorption of the drug.103,114,170,172,173 In some studies, administration of doxycycline with food or milk decreased peak plasma concentrations and/or the area under the plasma-concentration time curve (AUC) by up to 20-35%.38,91,103,175,177 (See Effect of Food or Milk under Pharmacokinetics: Absorption.)
It has been suggested that individuals receiving doxycycline for prevention of malaria should take the drug in the evening (but not at bedtime), avoid prolonged, direct exposure to the sun, and use sunscreens that absorb long-wave UVA radiation to minimize the risk of doxycycline-induced photosensitivity.123
The commercially available powder for oral suspension containing doxycycline monohydrate should be reconstituted at the time of dispensing according to the manufacturer's instructions.111 When reconstituted as directed, the oral suspension contains 25 mg of doxycycline per 5 mL.111
The commercially available oral suspension containing doxycycline calcium is administered as provided without further dilution and contains 50 mg of doxycycline per 5 mL.111
The manufacturer of the delayed-release capsules containing partially enteric-coated pellets of doxycycline hyclate states that the capsules may be administered, if necessary, by carefully opening the capsules and sprinkling the contents on a spoonful of applesauce.174 The prepared dose of applesauce with doxycycline hyclate pellets should be swallowed immediately without chewing, and the patient should drink a full glass of water to ensure that the dose is completely swallowed.174 The applesauce should not be hot, and should be soft enough to be swallowed without chewing.174 The applesauce should be discarded if any loss of doxycycline hyclate pellets occurs during the transfer.174 In addition, if a prepared dose of applesauce with doxycycline hyclate delayed-release pellets cannot be taken immediately, the mixture should be discarded and not stored for future use.174
If necessary because the powder for oral suspension and oral suspensions are not available, it has been suggested that conventional doxycycline film-coated tablets can be ground and mixed with appropriate food or drinks.155,156 (See Chemistry and Stability: Stability.) Results of a limited study in adults indicate that 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 The possibility that concomitant administration with food or milk may decrease the rate and extent of absorption of doxycycline should be considered. (See Effect of Food or Milk under Pharmacokinetics: Absorption.)
IV solutions of doxycycline hyclate should not be given IM or subcutaneously, and extravasation should be avoided.113
Doxycycline hyclate powder for IV administration is reconstituted by adding 10 or 20 mL of sterile water for injection or other compatible IV infusion solution to a vial labeled as containing 100 or 200 mg of doxycycline, respectively; resultant solutions contain 10 mg of doxycycline per mL.113 Prior to administration, each 100 mg of the drug must be further diluted with 100 mL to 1 liter of compatible IV infusion fluid or each 200 mg diluted with 200 mL to 2 liter of compatible IV infusion fluid to provide solutions containing approximately 0.1-1 mg of doxycycline per mL.113 IV solutions containing doxycycline concentrations lower than 0.1 mg/mL or higher than 1 mg/mL are not recommended.113
Depending on the dose, IV infusions of doxycycline hyclate usually are given over 1-4 hours.113 The manufacturer states that 1 hour is the minimum recommended time for infusion of 100 mg of doxycycline in a solution containing 0.5 mg of the drug per mL.113
Dosage of doxycycline calcium, doxycycline hyclate, and doxycycline monohydrate is expressed in terms of doxycycline.
The usual oral dosage of doxycycline for adults is 100 mg every 12 hours on the first day of treatment, followed by 100 mg daily given in 1 or 2 divided doses.103,111,114,170,171,172,173,174 For severe infections, adults should receive 100 mg every 12 hours.103,111,114,170,171,172,173,174
The usual oral dosage of doxycycline for children older than 8 years of age weighing more than 45 kg is 100 mg every 12 hours on the first day of treatment, followed by 100 mg daily given in 1 or 2 divided doses.103,111,114,170,171,172,173,174 Children older than 8 years of age weighing 45 kg or less should receive 4.4 mg/kg given in 2 divided doses on the first day of treatment, followed by 2.2 mg/kg daily given in 1 or 2 divided doses.103,111,114,170,171,172,173,174 For severe infections, children 8 years of age or older weighing more than 45 kg may receive 100 mg every 12 hours and those weighing 45 kg or less may receive up to 4.4 mg/kg daily.103,111,114,170,171,172,173,174 The AAP states that oral doxycycline in inappropriate for severe infections.109
The usual IV dosage of doxycycline for adults is 200 mg on the first day of treatment given in 1 or 2 infusions, followed by 100-200 mg daily.113 If a dosage of 200 mg daily is used, dosage should be given in 1 or 2 infusions.113
The usual IV dosage of doxycycline for children older than 8 years of age weighing more than 45 kg is 200 mg on the first day of treatment given in 1 or 2 infusions, followed by 100-200 mg daily.113 If a dosage of 200 mg daily is used, dosage should be given in 1 or 2 infusions.113 The usual IV dosage for children older than 8 years of age weighing 45 kg or less is 4.4 mg/kg on the first day of treatment given in 1 or 2 infusions, followed by 2.2-4.4 mg/kg daily given in 1 or 2 infusions.113
If doxycycline is used for postexposure prophylaxis following suspected or confirmed exposure to aerosolized anthrax spores in the context of biologic warfare or bioterrorism, the CDC and other experts (e.g., US Working Group on Civilian Biodefense, US Army Medical Research Institute of Infectious Diseases [USAMRIID]) recommends that adults and children older than 8 years of age and weighing more than 45 kg receive a dosage of 100 mg orally twice daily and children 8 years of age or younger and children weighing 45 kg or less receive a dosage of 2.2 mg/kg (up to 100 mg) orally twice daily for at least 60 days.102,141,142,147 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 in children younger than 8 years of age if penicillin susceptibility is confirmed.102,105,141,147
Although the optimum duration of postexposure prophylaxis after an inhalation exposure to B. anthracis spores is unclear,147,168 prolonged postexposure prophylaxis generally is recommended because of the possible persistence of anthrax spores in lung tissue following aerosol exposure.102,104,111,141,147 A duration of 60 days may be adequate for a low-dose exposure, but a duration longer than 4 months may be necessary to reduce the risk following a high-dose exposure.168 The US Working Group on Civilian Biodefense recommends that postexposure prophylaxis following a confirmed exposure (including in laboratory workers with confirmed exposures to B. anthracis cultures and individuals exposed to anthrax spores in the context of biologic warfare or bioterrorism) be continued for at least 60 days.102,143 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 Anthrax
For the initial treatment of inhalational anthrax, the usual dosage of doxycycline for adults and children weighing more than 45 kg is 100 mg IV every 12 hours and the usual dosage for children weighing 45 kg or less is 2.2 mg/kg (up to 100 mg) IV every 12 hours.102,113,142,143,147 If meningitis is suspected, IV doxycycline may be less optimal than IV ciprofloxacin because of poor distribution into CSF.102,143
The CDC and other experts (e.g., US Working Group on Civilian Biodefense, USAMRIID) recommend that treatment of inhalational anthrax be initiated with a multiple-drug regimen that includes ciprofloxacin or doxycycline and 1 or 2 other anti-infectives predicted to be effective.102,143,147 Oral therapy should be substituted for IV therapy as soon as the patient's clinical condition improves.102,105,113,142,143,147 Because of the possible persistence of anthrax spores in lung tissue following an aerosol exposure, the total duration of anti-infective therapy of inhalational anthrax that occurs as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism should be at least 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 younger than 8 years of age if penicillin susceptibility is confirmed.105
IV therapy with a multiple-drug parenteral regimen may not be possible if large numbers of individuals require treatment in a mass casualty setting; in these circumstances, some experts state that treatment with an oral regimen recommended for postexposure prophylaxis is an option.102,147 If oral doxycycline is used for initial treatment of inhalational anthrax 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) or is used to complete a treatment regimen initiated with IV doxycycline, the usual oral dosage for adults and children weighing more than 45 kg is 100 mg twice daily and the usual oral dosage for children weighing 45 kg or less is 2.2 mg/kg (up to 100 mg) twice daily.102,103,105,111,113,114,141,143,147,170,171,172,173,174
Treatment of Cutaneous Anthrax
For the treatment of cutaneous anthrax that occurs as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism, the CDC and other experts (e.g., US Working Group on Civilian Biodefense, USAMRIID) recommend that adults and children older than 8 years of age weighing more than 45 kg receive doxycycline in a dosage of 100 mg orally every 12 hours and that children 8 years of age or younger and children weighing 45 kg or less receive 2.2 mg/kg (up to 100 mg) orally every 12 hours.102,141,143,147 Although 5-10 days of anti-infective therapy has been recommended for the treatment of mild, uncomplicated cutaneous anthrax that occurs as the result of natural or endemic exposures to anthrax,147 treatment should be continued for at least 60 days if the cutaneous infection occurred as the result of exposure to aerosolized anthrax spores since the possibility of inhalational anthrax would also exist.102,143,147 Anti-infective therapy may limit the size of the cutaneous anthrax lesion and the lesion usually becomes sterile within the first 24 hours of treatment, but it will still progress through the black eschar stage despite effective treatment.102
Although oral therapy may be adequate for the treatment of mild, uncomplicated cutaneous anthrax, a multiple-drug parenteral regimen is recommended for initial treatment of cutaneous anthrax when there are signs of systemic involvement, extensive edema, or head and neck lesions.102,105,143,147 Cutaneous anthrax in infants and children younger than 2 years of age should be treated IV initially.105 When a parenteral regimen is indicated for the treatment of cutaneous anthrax, IV dosages recommended for the treatment of inhalational anthrax should be used.102,143,147 If infants and children have clinical improvement while receiving the initial parenteral regimen, an oral regimen of 1 or 2 anti-infectives (including either doxycycline or ciprofloxacin) may be used to complete the first 7-10 days of therapy.102,105,143 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 younger than 8 years of age if penicillin susceptibility is confirmed.105
Treatment of GI and Oropharyngeal Anthrax
The CDC and other experts (e.g., US Working Group on Civilian Biodefense) state that doxycycline dosage regimens recommended for the treatment of inhalational anthrax also are recommended for the treatment of GI and oropharyngeal anthrax.102,143,147
For the treatment of Bartonella infections, an oral or IV doxycycline dosage of 100 mg twice daily usually is recommended.184 For the treatment of complicated cat scratch disease (e.g., retinitis) caused by B. henselae , some clinicians recommend oral doxycycline in a dosage of 100 mg twice daily in conjunction with oral rifampin (300 mg twice weekly) given for 4-6 weeks.184 For the treatment of bacillary angiomatosis (BA) or pelliosis hepatitis (PH), oral doxycycline has been given in a dosage of 100 mg twice weekly for 3 or 4 months;184 concomitant oral rifampin (300 mg twice daily) also is recommended in immunocompromised patients with acute, life-threatening Bartonella infections.184 For documented Bartonella endocarditis, a regimen of doxycycline 100 mg twice daily for 6 weeks in conjunction with IV gentamicin (3 mg/kg daily) for 2 weeks has been recommended.184 A doxycycline regimen of 200 mg once daily or 100 mg twice daily for 4 weeks in conjunction with IV gentamicin (3 mg/kg once daily for 2 weeks) has been used for the treatment of trench fever or chronic bacteremia caused by B. quintana .184
For the treatment of bartonellosis (including CNS infections) in adults and adolescents with human immunodeficiency virus (HIV) infection, the CDC, IDSA, and other clinicians recommend that doxycycline be given orally or IV in a dosage of 100 mg every 12 hours for at least 3 months.160 In addition, long-term suppressive therapy (secondary prophylaxis) with doxycycline should be considered to prevent relapse.160
For the treatment of brucellosis, some clinicians recommend that adults receive 100 mg of oral doxycycline twice daily.147,185,186 The AAP recommends that children 8 years of age or older receive doxycycline in a dosage of 2-4 mg/kg daily in 2 divided doses (up to 200 mg daily).109 Other clinicians recommend 2.2 mg/kg twice daily (up to 200 mg daily) for children 8 years of age or older.147
Doxycycline usually is used in conjunction with another anti-infective (e.g., streptomycin or gentamicin and/or rifampin) to reduce the likelihood of relapse, especially for severe infections and when there are complications such as meningitis, endocarditis, or osteomyelitis.109,147,185,186 Monotherapy is no longer recommended for the treatment of brucellosis since such therapy is associated with a high relapse rate.109,147,185
The usual duration of doxycycline treatment is at least 4-6 weeks;109,147,185,186 streptomycin or gentamicin usually is given concomitantly for up to 2-3 weeks and/or rifampin is given for the full duration of treatment.109,147,185,186 More prolonged therapy may be required for complicated disease (e.g., hepatitis, splenitis, meningoencephalitis, endocarditis, osteomyelitis).147,186 Meningoencephalitis and endocarditis should be treated for at least 90 days and may require a treatment duration of 6 months or more.147
For the treatment of localized or mild melioidosis† caused by Burkholderia pseudomallei , oral doxycycline given in a dosage of 100 mg twice daily for 60-150 days may be effective.147 Alternatively, for the treatment of localized disease without toxicity, 100 mg of oral doxycycline twice daily for 20 weeks given in conjunction with oral co-trimoxazole has been recommended.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 maintenance regimen of oral anti-infectives (e.g., co-trimoxazole with or without doxycycline).147,169,183
For the initial treatment of severe melioidosis† caused by B. pseudomallei , some clinicians recommend that adults and children 8 years of age or older or weighing 45 kg or more may receive 100 mg of IV doxycycline twice daily and children younger than 8 years of age or weighing less than 45 kg may receive 2.2 mg/kg of IV doxycycline twice daily (up to 200 mg daily) in conjunction with IV ceftazidime, imipenem, or meropenem.169 The initial IV regimen should be continued for at least 14 days and until there is clinical improvement.147,169 When appropriate, treatment may be changed to an oral maintenance regimen (e.g., oral co-trimoxazole with or without oral doxycycline) and continued for at least 3-6 months to prevent recrudence or relapse.147,169,182,183 More prolonged oral maintenance therapy (up to 12 months) may be necessary, depending on the response to therapy and severity of initial illness.147,169 Lifelong follow-up is recommended for all patients to identify relapse of melioidosis.147
If doxycycline is used for follow-up after the initial parenteral regimen, some clinicians recommend that adults and children 8 years of age or older or those weighing 45 kg or more receive a prolonged maintenance regimen of 2 mg/kg (up to 100 mg) of doxycycline orally twice daily with or without oral co-trimoxazole.147,182,183
Some experts (e.g., USAMRIID, 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.147,169 Although the benefits of postexposure prophylaxis† are unknown, USAMRIID states that adults can receive 200 mg of doxycycline once daily in conjunction with oral rifampin for postexposure prophylaxis if exposure occurs in the context of biologic warfare or bioterrorism.147 The CDC recommends that laboratory workers with high-risk exposure to melioidosis be offered postexposure prophylaxis with oral doxycycline in a dosage of 2 mg/kg (up to 100 mg) twice daily.182 The optimum duration of postexposure prophylaxis is unknown, but a duration of at least 10 days is recommended.147,182
Although only limited experience is available regarding the treatment of human cases of glanders† caused by B. mallei ,147,169 some clinicians suggest that, pending results of in vitro susceptibility tests, regimens used for the treatment of severe melioidosis also can be used for initial empiric treatment of glanders.147
Uncomplicated Urethral, Endocervical, or Rectal Infections
For the treatment of uncomplicated urethral, endocervical, or rectal infections caused by Chlamydia trachomatis in adults, adolescents, or children 8 years of age or older, the recommended dosage of oral doxycycline is 100 mg twice daily for 7 days.103,107,108,109,111,114,170,171,172,173,174
For the treatment of nongonococcal urethritis caused by C. trachomatis or Ureaplasma urealyticum in adults, the recommended dosage of oral doxycycline is 100 mg twice daily for 7 days.103,107,111,114,170,171,172,173,174,114
Presumptive Treatment of Chlamydial Infections in Gonorrhea Patients
When oral doxycycline is used for the presumptive treatment of coexisting urogenital chlamydial infections in patients being treated for uncomplicated gonorrhea or disseminated gonococcal infections, the usual dosage for adults and children 8 years of age or older is 100 mg twice daily for 7 days.107,108,109,111
For the treatment of genital, inguinal, or anorectal infections caused by a lymphogranuloma venereum serotype of C. trachomatis in adults, the CDC and some clinicians recommend an oral doxycycline dosage of 100 mg twice daily for 21 days.107,108
The CDC states that individuals with Chlamydophila psittaci (formerly Chlamydia psittaci) infection (psittacosis, ornithosis) usually respond to oral doxycycline given in a dosage of 100 mg twice daily.100 Although fever and symptoms usually are controlled within 48-72 hours, therapy should be continued for at least 10-14 days after defervescence to prevent relapse.100 For initial treatment of severely ill patients, an IV regimen of doxycycline in a dosage of 4.4 mg/kg daily given in 2 divided doses (maximum 100 mg per dose) may be indicated.100
For the treatment of human granulocytotropic anaplasmosis† (HGA; formerly human granulocytic ehrlichiosis [HGE]) caused by Anaplasma phagocytophilum (formerly Ehrlichia phagocytophila , E. equi , agent of HGE), the treatment of human monocytotropic ehrlichiosis† (HME) caused by E. chaffeensis , or the treatment of ehrlichiosis† caused by E. ewingii or E. canis , the CDC, AAP, and other experts recommend that adults receive oral or IV doxycycline in a dosage of 100 mg twice daily109,161,165 and that children receive oral or IV doxycycline in a dosage of 2-2.2 mg/kg (up to 100 mg) twice daily.109,165
Treatment should be initiated promptly since a delay can result in severe disease and a fatal outcome.109,165 IV therapy generally is indicated for hospitalized patients; oral therapy generally is appropriate for patients with early disease, outpatients, or hospitalized patients who are not vomiting or obtunded.109,165 The optimum duration of treatment has not been established;109,161,165 however, treatment usually is continued at least 5-10 days and until the patient is afebrile for 3 days or longer and clinically improved.109,161,165 A longer duration of treatment may be required for severe illness.109 For the treatment of HGA, the CDC and IDSA recommend a treatment duration of 10-14 days since this provides an adequate duration of treatment for possible coexisting Borrelia burgdorferi infection and early Lyme disease.136,165 (See Lyme Disease under Dosage and Administration: Dosage.) If fever persists for longer than 48 hours after initiation of doxycycline treatment, the diagnosis of HGA may be incorrect and the remote possibility that the patient may be coinfected with Babesis microti (causative agent of babesiosis) should be considered.136
Gonorrhea and Associated Infections
If oral doxycycline is used as an alternative for the treatment of uncomplicated gonorrhea, the manufacturers recommend that adults receive 100 mg twice daily for 7 days or, alternatively, an initial 300-mg dose of the drug can be given followed by a second 300-mg dose 1 hour later.103,111,114,170,171,172,173,174
Tetracyclines are not included in current CDC recommendations for the treatment of uncomplicated or disseminated gonorrhea;107 however, the CDC and many clinicians recommend use of doxycycline for presumptive treatment of coexisting chlamydial infections in patients being treated for gonococcal infections.107,108,109 (See Chlamydial Infections under Dosage and Administration: Dosage.)
For the treatment of acute, sexually transmitted epididymitis caused by Neisseria gonorrhoeae and/or C. trachomatis in adults, adolescents, and children 8 years of age and older, the CDC, AAP, and other clinicians recommend that oral doxycycline be given in a dosage of 100 mg twice daily for 10 days as follow-up to a single 250-mg dose of IM ceftriaxone.107,108,109
For the treatment of proctitis† likely to be caused by N. gonorrhoeae and/or C. trachomatis , adults and adolescents should receive 100 mg of oral doxycycline twice daily for 7 days after a single 125-mg dose of IM ceftriaxone.107
Granuloma Inguinale (Donovanosis)
For the treatment of granuloma inguinale (donovanosis) caused by Klebsiella granulomatis (formerly Calymmatobacterium granulomatis ), the CDC recommends that adults and adolescents receive oral doxycycline in a dosage of 100 mg twice daily.107 The drug should be continued until all lesions have healed completely; a minimum of 3 weeks of treatment usually is necessary.107 If lesions do not respond within the first few days of therapy, some experts recommend that a parenteral aminoglycoside (e.g., 1 mg/kg of gentamicin IV every 8 hours) be added to the regimen.107 Use of a parenteral aminoglycoside in addition to doxycycline should be strongly considered when treating donovanosis in HIV-infected patients.107
In the treatment of Legionella pneumophila infections† when erythromycin was contraindicated or ineffective, the usual oral dosage of doxycycline has been given either alone or in conjunction with rifampin.
For the treatment of leptospirosis†, oral doxycycline has been given in a dosage of 100 mg twice daily for 7 days.
If doxycycline is used for prophylaxis in individuals at risk for leptospirosis†, such as those participating in recreational water activities (e.g., whitewater rafting, adventure racing, kayaking) in areas where leptospirosis is endemic or epidemic, the CDC and others recommend that oral doxycycline be given in a dosage of 200 mg once every 7 days.123 Such prophylaxis should be initiated 1-2 days before exposure and continued through the period of exposure.123,153
For the prevention of Lyme disease† in individuals in Lyme disease-endemic areas who are bitten by an Ixodes scapularis tick, the IDSA states that adults can receive a single 200-mg dose of oral doxycycline and children 8 years of age or older can receive a single 4-mg/kg oral dose (up to 200 mg).136 The IDSA states that routine use of such prophylaxis is not recommended.136 However, doxycycline prophylaxis can be offered when all of the following circumstances exist: the attached tick can be reliably identified as an adult or nymphal I. scapularis tick, the estimated duration of tick attachment has been at least 36 hours based on the degree of engorgement of the tick or certainty about the time of exposure to the tick, the doxycycline dose can be given within 72 hours of tick removal, the local rate of infection of I. scapularis with B. burgdorferi is 20% or greater, and doxycycline is not contraindicated.136 Prophylaxis after I. pacificus bites generally is not necessary since rates of infection with B. burgdorferi in these ticks are low.136
Accurate and timely identification of tick species or stage of development and determination of the infection status of the tick as well as assessment of the degree of tick engorgement are often difficult.136,138 The best method for preventing infection with B. burgdorferi and other infections transmitted by Ixodes ticks is avoidance of tick-infested areas.136 If exposure to Ixodes ticks is unavoidable, measures should be taken to reduce the risk of infection, including use of protective clothing and tick repellants, daily body checks for ticks, and prompt removal of attached ticks before transmission can occur.136 (See Postexposure Prophylaxis after Tick Bite under Spirochetal Infections: Lyme Disease, in Uses in the Tetracyclines General Statement 8:12.24.)
For the treatment of early localized or early disseminated Lyme disease† manifested as erythema migrans, in the absence of specific neurologic involvement or advanced atrioventricular (AV) heart block, the IDSA, AAP, and other clinicians recommend that adults receive oral doxycycline in a dosage of 100 mg twice daily for 14 days (range 14-21 days).109,115,116,117,118,119,120,121,124,125,136,140 The IDSA recommends that children 8 years of age or older receive oral doxycycline in a dosage of 4 mg/kg daily in 2 divided doses (up to 100 mg per dose) for 14 days (range 14-21 days) for the treatment of early localized or early disseminated Lyme disease.136 Other clinicians have recommended that these children receive oral doxycycline in a dosage of 1-2 mg/kg twice daily (up to 100 mg per dose).115,116,117,118,119,120,121,124,140
Early Neurologic Lyme Disease, Lyme Carditis, or Borrelial Lymphocytoma
If an oral regimen is used for the treatment of early neurologic Lyme disease† in patients with cranial nerve palsy alone without clinical evidence of meningitis, the treatment of Lyme carditis†, or the treatment of borrelial lymphocytoma†, the IDSA recommends that adults receive oral doxycycline in a dosage of 100 mg twice daily and that children 8 years of age or older receive 4 mg/kg daily in 2 divided doses (up to 100 mg per dose) for 14 days (range 14-21 days).136
For the treatment of uncomplicated Lyme arthritis† in patients without clinical evidence of neurologic disease, the IDSA and other clinicians recommend that adults receive oral doxycycline in a dosage of 100 mg twice daily and that children 8 years of age or older receive 4 mg/kg daily in 2 divided doses (up to 100 mg per dose) for 28 days.109,115,116,117,119,120,121,124,136,142
For prevention of malaria in individuals traveling to areas with chloroquine-resistant Plasmodium falciparum , the CDC, WHO, and the manufacturers recommend that adults receive 100 mg of doxycycline once daily and that children 8 years of age or older receive 2 mg/kg (maximum 100 mg) once daily.103,111,114,122,123,139,153,170,171,172,173,174 If necessary (e.g., because the individuals is unable to take chloroquine or hydroxychloroquine), this doxycycline regimen also can be used to prevent malaria in travelers to areas where chloroquine-resistant P. falciparum has not been reported.123
Doxycycline prophylaxis should be initiated 1-2 days prior to entering a malarious area and continued for 4 weeks after leaving the area.103,109,111,114,122,123,139,153,170,171,172,173,174 If concerns exist regarding tolerance or drug interactions in an individual patient, it may be advisable to initiate doxycycline prophylaxis 3-4 weeks prior to departure to ensure that the drug or combination of drugs (in individuals receiving other drugs) is well tolerated and to allow ample time to switch to another antimalarial agent if required.123
Because doxycycline cannot prevent delayed primary attacks or relapse of P. ovale or P. vivax malaria and cannot provide a radical cure in malaria caused by these species, terminal prophylaxis with primaquine may be indicated during the last 2 weeks of doxycycline prophylaxis if exposure occurred in areas where P. ovale or P. vivax are endemic.123 (See Primaquine Phosphate 8:30.08.)
Presumptive Self-treatment of Malaria
If doxycycline is used in conjunction with quinine sulfate for presumptive self-treatment of malaria† in the event of an influenza-like illness (e.g., fever, chills) during travel, some clinicians recommend that adults receive 100 mg orally twice daily for 7 days given in conjunction with 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 For presumptive self-treatment of malaria in children 8 years of age or older, these clinicians recommend that oral doxycycline be given in a dosage of 4 mg/kg daily in 2 equally divided doses for 7 days given in conjunction with oral quinine sulfate (10 mg/kg 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
Travelers should be advised to keep an amount of doxycycline and quinine sufficient for self-treatment in their possession during travel and to take it promptly in the event of a febrile illness during or after their travel if professional medical care is not readily available.122 It must be emphasized that such presumptive self-treatment of a possible malarial infection is only a temporary measure and that professional medical follow-up care should be obtained as soon as possible.122
Treatment of Uncomplicated Malaria
When oral doxycycline is used in conjunction with oral quinine sulfate for the treatment of uncomplicated malaria† caused by chloroquine-resistant P. falciparum , the CDC and other clinicians recommend that adults receive 100 mg twice daily for 7 days given in conjunction with 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).122,158 These experts recommend that children 8 years of age or older receive oral doxycycline in a dosage of 4 mg/kg daily in 2 equally divided doses (maximum 200 mg daily) for 7 days given 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
When oral doxycycline is used in conjunction with quinine sulfate and primaquine phosphate for the treatment of uncomplicated chloroquine-resistant P. vivax malaria†, the CDC and other clinicians recommend that adults receive 100 mg twice daily for 7 days given 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 These experts recommend that children 8 years of age or older receive oral doxycycline in a dosage of 4 mg/kg daily in 2 equally divided doses for 7 days (maximum 200 mg daily) given 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).158,159 In addition, a 14-day regimen of oral primaquine (30 mg once daily in adults or 0.6 mg/kg once daily in children) should be given with the quinine sulfate and tetracycline hydrochloride regimen to provide a radical cure and prevent delayed attacks or relapse of P. vivax malaria.158
For additional information on treatment of uncomplicated malaria, see Uses: Malaria, in Quinine Sulfate 8:30.08.
Treatment of Severe P. falciparum Malaria
When doxycycline is used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) for the treatment of severe malaria caused by P. falciparum †, the drug should be administered orally or IV for a total duration of 7 days; IV doxycycline should be switched to oral doxycycline as soon as it is tolerated to complete the 7-day regimen.158 In patients who cannot tolerate oral therapy, adults should receive doxycycline in a dosage 100 mg IV every 12 hours. Children older than 8 years of age who are intolerant of oral therapy and who weigh less than 45 kg should receive 4 mg/kg IV daily in 2 equally divided doses and those weighing 45 kg or more may receive 100 mg IV every 12 hours.158,159 In patients able to tolerate oral therapy, adults should receive doxycycline in a dosage of 100 mg twice daily and children older than 8 years of age should receive 4 mg/kg daily in 2 equally divided doses.158 Pediatric dosage should not exceed the recommended adult oral dosage.129
For additional information on treatment of severe malaria, see Uses: Malaria, in Quinidine 24:04.04.04.
Mycobacterium marinum Infections
The American Thoracic Society (ATS) has recommended that oral doxycycline be given in a dosage of 100 mg twice daily for at least 3 months for the treatment of cutaneous Mycobacterium marinum infections† and states that a minimum of 4-6 weeks of therapy is necessary to determine whether or not the infection is responding.106
For the treatment of acute pelvic inflammatory disease† (PID) in adults or adolescents when N. gonorrhoeae or C. trachomatis is suspected as the primary pathogen and a parenteral regimen is indicated, the CDC and many clinicians suggest the use of an IV or oral doxycycline dosage of 100 mg twice daily (every 12 hours) in conjunction with either cefoxitin (2 g IV every 6 hours) or cefotetan (2 g IV every 12 hours).107,108 This initial regimen may be discontinued 24 hours after there is clinical improvement and oral doxycycline is then given in a dosage of 100 mg twice daily to complete 14 days of therapy.107,108 If tubo-ovarian abscess is present, many clinicians would include clindamycin or metronidazole with oral doxycycline to provide more effective coverage against anaerobes.107
Another parenteral regimen recommended by the CDC and many clinicians for the treatment of PID includes parenteral clindamycin (900 mg IV every 8 hours) and gentamicin (loading dose of 2 mg/kg IV or IM followed by 1.5 mg/kg every 8 hours or, alternatively, single daily dosing) for the initial phase, followed by oral doxycycline in a dosage of 100 mg twice daily to complete a total of 14 days of therapy.107,108 If tubo-ovarian abscess is present, many clinicians substitute oral clindamycin (450 mg 4 times daily) for oral doxycycline in the second phase of therapy.107
An alternative parenteral regimen recommended by the CDC and others for the treatment of PID is ampicillin and sulbactam (3 g IV every 6 hours) and oral or IV doxycycline given in a dosage of 100 mg every 12 hours;107,114 this regimen has good coverage against C. trachomatis , N. gonorrhoeae , and anaerobes and is effective for patients with tubo-ovarian abscess.107
When an oral regimen is indicated for the treatment of acute PID† in adults or adolescents, the CDC and many clinicians recommend a single IM dose of ceftriaxone, IM cefoxitin (with oral probenecid), or other parenteral third generation cephalosporin (e.g., cefotaxime) and oral doxycycline given in a dosage of 100 mg twice daily for 14 days with or without oral metronidazole (500 mg twice daily for 14 days).107,108
The CDC states that clinical trials of outpatient regimens have provided little information regarding intermediate and long-term outcomes, and patients who do not respond to an oral regimen within 72 hours should be reevaluated to confirm the diagnosis and treated with a parenteral regimen on either an outpatient or inpatient basis.107
If doxycycline is used for the treatment of pneumonic plague that occurs as the result of exposure to Yersinia pestis in the context of biologic warfare or bioterrorism, some experts (e.g., the US Working Group on Civilian Biodefense, USAMRIID) recommend that adults and children weighing 45 kg or more receive a dosage of 100 mg IV every 12 hours or 200 mg IV once daily and that children weighing less than 45 kg receive doxycycline in a dosage of 2.2 mg/kg IV every 12 hours (up to 200 mg daily).144,147
Prompt initiation of anti-infective therapy (within 18-24 hours of symptom onset) is essential in the treatment of pneumonic plague.144,147 Treatment of pneumonic plague should be initiated with a parenteral regimen, although an oral regimen may be substituted when the patient's condition improves or if parenteral therapy is unavailable.144,147 Anti-infective therapy usually is continued for 10 days;144 some experts recommend a duration of at least 10-14 days.147
For postexposure prophylaxis following a high-risk exposure to Y. pestis , including exposure that occurs in the context of biologic warfare or bioterrorism, some experts recommend that adults and children weighing 45 kg or more receive doxycycline in a dosage of 100 mg orally every 12 hours and that children weighing less than 45 kg receive 2.2 mg/kg orally every 12 hours (up to 200 mg daily).144,147 For high-risk exposures to pneumonic plague, the Advisory Committee on Immunization Practices (ACIP) has recommended that adults 18 years of age and older receive 100-200 mg daily in 2 equally divided doses and that children 9-17 years of age receive 2-4 mg/kg daily in 2 equally divided doses.149
The recommended duration of prophylaxis following exposure to plague aerosol or a patient with suspected pneumonic plague is 7 days144,147 or the duration of exposure risk plus 7 days.147 Some experts recommend that postexposure anti-infective prophylaxis be given to all asymptomatic individuals with exposure to plague aerosol and all asymptomatic individuals who have had household, hospital, or other close contact (within about 2 m) with an individual who has pneumonic plague; however, any exposed individual who develops a temperature of 38.5°C or higher or new cough should promptly receive a parenteral anti-infective for treatment of the disease.144,147
When used as a sclerosing agent to control pleural effusions associated with metastatic tumors†, 500 mg of doxycycline has been diluted with 25-30 mL of 0.9% sodium chloride injection and instilled into the pleural space through a thoracostomy tube following drainage of the accumulated pleural fluid; the tube is then clamped and the fluid subsequently removed.126,127,128,132,134,151,152 The pleurodesis procedure has been repeated in some patients to achieve control of the effusion,127,128 although repeated administration may have limited effects.126,135
Prior to instillation of doxycycline in patients with effusions, the pleural cavity is drained by thoracentesis (needle aspiration) or via the 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 the sclerosing agent is introduced into the pleural cavity when fluid drainage from the chest tube exceeds 100 mL per 24 hours.130,131,133 To achieve pleurodesis in patients who have recurrent malignant pleural effusions†, doxycycline also has been administered as a less concentrated solution (500 mg diluted with 250 mL of 0.9% sodium chloride injection) via chest tube lavage and drainage†.129 For this procedure, the tube has been clamped for 24 hours and the entire procedure repeated daily until the drainage volume approximates the amount of solution instilled.129
For the treatment of most rickettsial infections, including Rocky Mountain spotted fever (RMSF), typhus fever and the typhus group, Q fever, rickettsialpox, and tick fever caused by rickettsiae, the CDC and others recommend that adults receive 100 mg of oral or IV doxycycline twice daily.161,165 For the treatment of most rickettsial infections in children, the CDC and AAP recommend 2.2 mg/kg of oral or IV doxycycline (up to 100 mg) twice daily.109,165 Treatment should be initiated promptly since a delay can result in severe disease and a fatal outcome.161,165 Treatment usually is continued for at least 5-7 days and until the patient is afebrile for 3 days or more and clinically improved.109,161,165 Severe illness may require a longer duration of treatment.109,165
IV treatment generally is indicated for hospitalized patients and oral therapy generally is appropriate for patients with early disease, outpatients, or hospitalized patients who are not vomiting or obtunded.161,165
For the treatment of acute Q fever†, the CDC and other clinicians recommend that adults receive doxycycline in a dosage of 100 mg twice daily for 2-3 weeks and that children receive 2.2 mg/kg (up to 100 mg) twice daily for at least 14 days.112,123,147,157 For the treatment of acute Q fever in patients with preexisting valvular heart disease, the CDC recommends a doxycycline dosage of 200 mg daily given in conjunction with hydroxychloroquine (465 mg [600 mg of hydroxychloroquine sulfate] daily; dosage adjusted to maintain plasma concentrations at 1 ± 0.2 mcg/mL); the recommended duration of treatment is 1 year to prevent progression of acute disease to endocarditis.157 For the treatment of chronic Q fever endocarditis, the same regimen of doxycycline and hydroxychloroquine should be given for 1.5-3 years.157
It has been suggested that oral doxycycline given for 5-7 days in a dosage of 100 mg every 12 hours in adults or 2.2 mg/kg twice daily in children may be effective as prophylaxis against Q fever† and may prevent clinical disease if initiated 8-12 days after exposure; however, such prophylaxis is not effective and may only prolong the onset of disease if given immediately (1-7 days) after exposure.147
While parenteral penicillin G is the drug of choice for all stages of syphilis,107,108 the CDC, other clinicians, and some manufacturers state that nonpregnant adults or adolescents with primary or secondary syphilis who are hypersensitive to penicillin can receive 100 mg of doxycycline orally twice daily for 14 days.103,107,108,109,111,171,174 In addition, nonpregnant adults or adolescents with early latent syphilis (syphilis of less than 1-year duration) can receive 100 mg of oral doxycycline twice daily for 14 days and those with late latent syphilis, syphilis of unknown duration, or tertiary syphilis (except neurosyphilis) can receive 100 mg twice daily for 4 weeks.103,107,108,109,111,114,170,171,172,173,174 Some manufacturers state that the recommended dosage for the treatment of primary or secondary syphilis is 300 mg daily given for at least 10 days.113,114,170,172,173
Care should be taken to ensure optimal compliance with these regimens since patient compliance with multiple-day tetracycline regimens may be poor.107 If compliance with the doxycycline regimen and serologic follow-up cannot be ensured, adults and adolescents with a history of penicillin hypersensitivity should be desensitized, if necessary, and treated with penicillin.107 The CDC states that infants and children with syphilis who are hypersensitive to penicillin should be desensitized, if necessary, and treated with penicillin.107 For information on recommendations regarding treatment and follow-up for all stages and forms of syphilis, see Spirochetal Infections: Syphilis, under Uses in the Natural Penicillins General Statement 8:12.16.04.
If doxycycline is used for the treatment of tularemia that occurs as the result of exposure to Francisella tularensis in the context of biologic warfare or bioterrorism, or naturally occurring or endemic tularemia,145,147 some experts (e.g., US Working Group on Civilian Biodefense, USAMRIID) recommend that adults and children weighing 45 kg or more receive 100 mg IV twice daily and that children weighing less than 45 kg receive 2.2 mg/kg (up to 100 mg) IV twice daily.103,111,114,145,147 Treatment should be continued for at least 14-21 days.145,147 Although therapy should be initiated with IV doxycycline, oral doxycycline can be substituted when the patient's condition improves or if parenteral doxycycline is unavailable.145
If doxycycline is used for postexposure prophylaxis 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, some experts (e.g., the US Working Group on Civilian Biodefense, USAMRIID) recommend that adults and children weighing 45 kg or more receive a dosage of 100 mg orally twice daily and that children weighing less than 45 kg receive a dosage of 2.2 mg/kg (up to 100 mg) orally twice daily.145,147 Postexposure prophylaxis should be initiated within 24 hours of exposure and continued for at least 14 days.145,147 Drugs of choice for postexposure prophylaxis following a high-risk laboratory exposure to F. tularensis are doxycycline, tetracycline, or ciprofloxacin.145,147
Postexposure prophylaxis usually is 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
For the treatment of cholera caused by Vibrio cholerae , the usual oral dosage of doxycycline has been given for 3 days in conjunction with fluid and electrolyte replacement. Some clinicians suggest that doxycycline can be given as a single 300-mg dose for the treatment of cholera.110
Prophylaxis in Sexual Assault Victims
The CDC currently states that if empiric anti-infective prophylaxis is indicated in adult or adolescent victims of sexual assault†, a single 2-g dose of oral metronidazole is given in conjunction with a single 125-mg dose of IM ceftriaxone, followed by oral doxycycline given in a dosage of 100 mg twice daily for 7 days.107
Unlike other currently available tetracycline derivatives, usual dosage of doxycycline may be used in patients with impaired renal function.103,111,114,170,171,172,173,174