Doxycycline (Systemic)
46067 6 AHFS Essentials ASHPI BATCH LEFT top of rh base of rh Doxycycline Doxycycline (Systemic) Antibacterial; semisynthetic tetracycline antibiotic derived from oxytetracycline. Class: Tetracyclines 8:12.24 (AHFS primary); AM250 (VA primary) Brands*: Doryx; Doxy 100; Monodox; Vibramycin; Vibra-Tabs *also available generically Uses Respiratory Tract Infections Treatment of respiratory tract infections caused by Mycoplasma pneumoniae. Treatment of respiratory tract infections caused by Haemophilus influenzae, Streptococcus pneumoniae, or Klebsiella. Should only be used for treatment of infections caused by these bacteria when in vitro susceptibility tests indicate the organism is susceptible. Empiric treatment of community-acquired pneumonia (CAP) in conjunction with other anti-infectives. Tetracyclines provide coverage against C. pneumoniae, M. pneumoniae, H. influenzae, and Legionella, but S. pneumoniae may be resistant. Doxycycline is the preferred tetracycline for empiric treatment of CAP. Alternative for treatment of infections caused by Legionella pneumophila†; used with or without rifampin. Acne Adjunctive treatment of moderate to severe inflammatory acne. Not indicated for treatment of noninflammatory acne. Actinomycosis Alternative to penicillin G for treatment of actinomycosis caused by Actinomyces israelii. Amebiasis Adjunct to amebicides for treatment of acute intestinal amebiasis. Tetracyclines generally not recommended for treatment of amebiasis caused by Entamoeba. Anthrax Postexposure prophylaxis to reduce the incidence or progression of disease following a suspected or confirmed exposure to aerosolized Bacillus anthracis spores (inhalational anthrax). Initial drug of choice for such prophylaxis is ciprofloxacin or doxycycline. Treatment of inhalational anthrax. Monotherapy may be effective for anthrax that occurs as the result of natural or endemic exposures, but a multiple-drug parenteral regimen (ciprofloxacin or doxycycline and 1 or 2 other anti-infectives predicted to be effective) is recommended for inhalational anthrax that occurs as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism. Although tetracyclines not usually used in children ⬍8 years of age or in pregnant women, the benefits of doxycycline outweigh the risks and CDC and others state doxycycline can be used when necessary for treatment of inhalational anthrax in these individuals. Treatment of GI and oropharyngeal anthrax. If occurring in the context of biologic warfare or bioterrorism, use parenteral regimens recommended for inhalational anthrax. Treatment of cutaneous anthrax. Multiple-drug regimen recommended for initial treatment when there are signs of systemic involvement, extensive edema, or lesions on the head or neck or when cutaneous anthrax occurs in children ⬍2 years of age. Bartonella Infections Treatment of bartonellosis caused by Bartonella bacilliformis. Treatment of infections caused by B. quintana†. Optimum anti-infective regimens have not been identified; various drugs have been used, including doxycycline, erythromycin, azithromycin, chloramphenicol, or cephalosporins. Treatment of infections caused by B. henselae† (e.g., cat scratch disease, bacillary angiomatosis, peliosis hepatitis). Cat scratch disease generally is self-limited in immunocompetent individuals and may resolve spontaneously in 2– 4 months; some clinicians suggest that anti-infective therapy be considered for acutely or severely ill patients with systemic symptoms, particularly those with hepatosplenomegaly or painful lymphadenopathy, and probably is indicated in immunocompromised patients. Anti-infectives also are indicated in patients with B. henselae infections who develop bacillary angiomatosis, neuroretinitis, or Parinaud’s oculoglandular syndrome. Optimum regimens have not been identified; some clinicians recommend erythromycin, azithromycin, doxycycline, ciprofloxacin, rifampin, co-trimoxazole, gentamicin, or third generation cephalosporins. A drug of choice for treatment of bartonellosis in HIV-infected adults and adolescents, especially CNS bartonellosis. USPHS/IDSA and others suggest that longterm suppression with erythromycin or doxycycline should be considered to prevent recurrence of bartonellosis† in HIV-infected adults and adolescents with relapse or reinfection. cap height base of text Brucellosis Treatment of brucellosis; considered a drug of choice. Used in conjunction with other anti-infectives (e.g., streptomycin or gentamicin and/or rifampin), especially for severe infections or when there are complications (e.g., endocarditis, meningitis, osteomyelitis). Postexposure prophylaxis following a high-risk exposure to Brucella† (e.g., needlestick injury, inadvertent laboratory exposure, confirmed exposure in the context of biologic warfare or bioterrorism). Postexposure prophylaxis not generally recommended after exposure to endemic brucellosis. Burkholderia Infections Treatment of glanders† caused by Burkholderia mallei; used in conjunction with streptomycin. Alternative for treatment of melioidosis† caused by susceptible B. pseudomallei; used in a multiple-drug regimen with chloramphenicol and co-trimoxazole. Ceftazidime or imipenem monotherapy may be preferred. B. pseudomallei is difficult to eradicate and relapse of melioidosis is common. Campylobacter Infections Treatment of infections caused by Campylobacter fetus. Not a drug of choice. Chancroid Treatment of chancroid caused by Haemophilus ducreyi. Not included in CDC recommendations for treatment of chancroid. Chlamydial Infections Treatment of uncomplicated urethral, endocervical, or rectal infections caused by Chlamydia trachomatis. A drug of choice for presumptive treatment of chlamydial infections in patients with gonorrhea. Treatment of trachoma and inclusion conjunctivitis caused by C. trachomatis. Consider that anti-infectives may not eliminate C. trachomatis in all cases of chronic trachoma. Treatment of lymphogranuloma venereum (genital, inguinal, or anorectal infections) caused by C. trachomatis. Recommended as drug of choice by CDC and others. Treatment of psittacosis (ornithosis) caused by C. psittaci. A drug of choice recommended by CDC. Clostridium Infections Alternative for treatment of infections caused by Clostridium; not considered a drug of choice. Recommended as an alternative to metronidazole or penicillin G for adjunctive treatment of C. tetani infections. Ehrlichia Infections Treatment of ehrlichiosis† caused by Ehrlichia chaffeensis, E. canis, E. ewingii, or E. phagocytophila; drug of choice. Enterobacteriaceae Infections Treatment of infections caused by susceptible Escherichia coli, Enterobacter aerogenes, Klebsiella, or Shigella. Should only be used for treatment of infections caused by these common gram-negative bacteria when other appropriate anti-infectives are contraindicated or ineffective and when in vitro susceptibility tests indicate the organism is susceptible. Fusobacterium Infections Alternative to penicillin G for treatment of infections caused by Fusobacterium fusiforme (Vincent’s infection). Gonorrhea and Associated Infections Alternative for treatment of uncomplicated gonorrhea caused by susceptible Neisseria gonorrhoeae. However, tetracyclines are considered inadequate therapy and are not recommended by CDC for treatment of gonorrhea. Empiric treatment of epididymitis most likely caused by N. gonorrhoeae or C. trachomatis; used in conjunction with IM ceftriaxone. Granuloma Inguinale (Donovanosis) Treatment of granuloma inguinale (donovanosis) caused by Calymmatobacterium granulomatis. CDC recommends doxycycline or co-trimoxazole as drugs of choice. short stand 46067 AHFS Essentials ASHPI BATCH RIGHT Doxycycline Leptospirosis Pelvic Inflammatory Disease Alternative to penicillin G for treatment of leptosporosis†. Prevention of leptosporosis† in travelers to areas where leptospirosis is endemic Treatment of acute pelvic inflammatory disease (PID); used in conjunction with or epidemic who are at increased risk (e.g., those who engage in recreational water activities such as whitewater rafting, adventure racing, kayaking). Can be used for combined prophylaxis in travelers at increased risk of leptospirosis who also require malaria chemoprophylaxis. Listeria Infections Alternative for treatment of listeriosis caused by Listeria monocytogenes. Not usually considered a drug of choice or alternative for these infections. Lyme Disease Treatment of early disseminated Lyme disease† associated with erythema migrans, in the absence of neurologic involvement or third-degree AV heart block. IDSA, AAP, and others recommend oral doxycycline or oral amoxicillin as first-line therapy for treatment of early localized or early disseminated Lyme disease when oral therapy is appropriate. Treatment of uncomplicated Lyme arthritis† without objective evidence of neurologic involvement (e.g., meningitis or radiculopathy). Alternative for treatment of neurologic manifestations of Lyme disease† when lactams (e.g., ceftriaxone, penicillin G) cannot be used. 7 other anti-infectives. Doxycycline is included in PID regimens to provide coverage against Chlamydia. When a parenteral regimen is indicated for PID, CDC and others recommend IV cefotetan (or cefoxitin) in conjunction with IV or oral doxycycline as a regimen of choice. A regimen of IV ampicillin and sulbactam and IV doxycycline is an alternative since it provides good coverage against C. trachomatis, N. gonorrhoeae, and anaerobes and is effective for tubo-ovarian abscess. Doxycycline also used as follow-up after a parenteral regimen of clindamycin and gentamicin. When an oral regimen is indicated, CDC and others recommend a single IM dose of ceftriaxone or cefoxitin (or other parenteral cephalosporin) followed by oral doxycycline (with or without oral metronidazole) as a regimen of choice. Although experience is limited, oral amoxicillin and clavulanate and oral doxycycline may be an alternative oral regimen. Plague Treatment of plague caused by Yersinia pestis, including naturally occurring or en- Malaria demic bubonic, septicemic, or pneumonic plague and plague that occurs following exposure to Y. pestis in the context of biologic warfare or bioterrorism. Regimen of choice is streptomycin (or gentamicin) with or without doxycycline. 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 in the context of biologic warfare or bioterrorism). Prevention (prophylaxis) of malaria caused by Plasmodium falciparum, including Pleural Effusions chloroquine-resistant strains. Recommended by CDC and others as a drug of choice for prophylaxis in individuals traveling to areas where chloroquine-resistant P. falciparum malaria has been reported; recommended by CDC as an alternative in those traveling to areas where chloroquine-resistant P. falciparum has not been reported and who are unable to take chloroquine or hydroxychloroquine. Treatment of uncomplicated malaria† caused by chloroquine-resistant Plasmodium falciparum or chloroquine-resistant P. vivax and when the plasmodial species has not been identified. Used in conjunction with quinine; not effective alone. CDC and others state treatments of choice for uncomplicated chloroquine-resistant P. falciparum malaria are a regimen of oral quinine in conjunction with oral doxycycline, tetracycline, or clindamycin or a regimen of atovaquone and proguanil. A regimen of quinine and doxycycline (or tetracycline) generally preferred over quinine and clindamycin, except for young children or pregnant women who should not receive tetracyclines. Quinine in conjunction with tetracycline (or doxycycline) also a regimen of choice for chloroquine-resistant P. vivax malaria. Treatment of severe malaria caused by P. falciparum†; used in conjunction with IV quinidine gluconate initially and then with oral quinine when an oral regimen is tolerated. Presumptive self-treatment of malaria† in travelers who elect not to use prophylaxis, those who require or choose to use a prophylaxis regimen that may not have optimal efficacy, or for long-term travelers receiving effective prophylaxis but who plan to visit very remote areas; used in conjunction with quinine. Not recommended by CDC for presumptive self-treatment of malaria; CDC recommends the fixed combination of atovaquone and proguanil. Active only against the asexual erythrocytic forms of Plasmodium (not exoerythrocytic stages) and cannot prevent delayed primary attacks or relapse of P. ovale or P. vivax malaria or provide a radical cure; primaquine usually also indicated to eradicate hypnozoites and prevent relapse in patients exposed to or being treated for P. ovale or P. vivax malaria. Detailed recommendations regarding prevention of malaria available from CDC 24 hours a day from the voice information service (877-394-8747), fax information service (888-232-3299), or Internet at http://www.cdc.gov/travel. Assistance with diagnosis or treatment of malaria available from CDC Malaria Epidemiology Branch by contacting CDC Malaria Hotline at 770-488-7788 from 8:00 a.m. to 4:30 p.m. Eastern Standard Time or CDC Emergency Operation Center at 770-488-7100 after hours, on weekends, and holidays. Mycobacterial Infections Alternative for treatment of infections caused by Mycobacterium fortuitum†. Treatment of cutaneous infections caused by M. marinum†; a drug of choice. Nocardiosis Alternative to co-trimoxazole for treatment of nocardiosis† caused by Nocardia. top of rh base of rh cap height base of text Management of pleural effusions† associated with metastatic tumors. Relapsing Fever Treatment of relapsing fever caused by Borrelia recurrentis. A drug of choice. Rickettsial Infections Treatment of rickettsial infections including Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, and tick fevers caused by Rickettsiae. Drug of choice for treatment of most rickettsial infections. Syphilis Alternative to penicillin G benzathine for treatment of primary, secondary, latent, or tertiary syphilis (not neurosyphilis) in nonpregnant adults and adolescents hypersensitive to penicillins, including HIV-infected patients. Use tetracyclines only if compliance and follow-up can be ensured since efficacy not well documented. Tularemia Treatment of tularemia caused by Francisella tularensis, including naturally occurring or endemic tularemia or tularemia that occurs following exposure to F. tularensis in the context of biologic warfare or bioterrorism. Considered an alternative to streptomycin (or gentamicin); risk of relapse and primary treatment failure may be higher than with aminoglycosides. 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. 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. Vibrio Infections Treatment of cholera caused by Vibrio cholerae. A drug of choice; used as an adjunct to fluid and electrolyte replacement in moderate to severe disease. Treatment of severe V. parahaemolyticus† infection when anti-infective therapy is indicated in addition to supportive care. Treatment of infections caused by V. vulnificus†. Optimum anti-infective therapy has not been identified; a tetracycline or third generation cephalosporin (e.g., cefotaxime, ceftazidime) is recommended. Because the case fatality rate associated with V. vulnificus is high, initiate anti-infective therapy promptly if indicated. Yaws Alternative to penicillin G for treatment of yaws caused by Treponema pertenue. Yersinia Infections Nongonococcal Urethritis Treatment of nongonococcal urethritis (NGU) caused by Ureaplasma urealyticum, C. trachomatis, or Mycoplasma. Consider that some cases of recurrent urethritis following doxycycline treatment may be caused by tetracycline-resistant U. urealyticum. Treatment of plague caused by Yersinia pestis. (See Plague under Uses.) Treatment of GI infections caused by Yersinia enterocolitica† or Y. pseudotuberculosis†. These infections usually are self-limited, but IDSA, AAP, and others recommend anti-infectives for severe infections or when septicemia or other invasive disease occurs. Some suggest the role of oral anti-infectives in management of short stand 46067 8 AHFS Essentials ASHPI BATCH LEFT top of rh base of rh Doxycycline enterocolitis, pseudoappendicitis syndrome, or mesenteric adenitis caused by Yersinia needs further evaluation. Prophylaxis in Sexual Assault Victims Empiric anti-infective prophylaxis in sexual assault victims†; used in conjunction with a drug effective for gonorrhea (IM ceftriaxone) and a drug effective for bacterial vaginosis and trichomoniasis (oral metronidazole). Dosage and Administration Administration Administer orally or by slow IV infusion. Also has been administered by intrapleural infusion. Do not administer IM or sub-Q. IV route recommended only when oral therapy is not indicated or feasible; oral should replace IV as soon as possible. Prolonged IV administration may result in thrombophlebitis; avoid extravasation. Oral Administration Administer capsules and tablets with adequate amounts of fluid to reduce the risk of esophageal irritation and ulceration. Probably should not be given at bedtime or to patients with esophageal obstruction or compression. Administer with food or milk to minimize nausea and vomiting and if gastric irritation occurs; absorption not markedly influenced by simultaneous ingestion of food or milk. When used for prevention of malaria, CDC recommends taking the drug in the evening (but not at bedtime), avoiding prolonged, direct exposure to the sun, and use of sunscreens that absorb long-wave UVA radiation to minimize the risk of photosensitivity. Reconstitution Reconstitute doxycycline monohydrate powder for oral suspension at the time of dispensing according to manufacturer’s directions to provide a suspension containing 25 mg/5 mL. Doxycycline calcium oral suspension is administered as provided without further dilution and contains 50 mg/5 mL. If necessary because the commercial powder for oral suspension and oral suspension are not available, doxycycline film-coated tablets can be ground and mixed with food or drinks. Ground doxycycline tablets are most palatable when mixed with chocolate pudding, regular or low-fat chocolate milk, simple syrup with sour apple flavor, apple juice with table sugar, or low-fat milk; the bitterness of the drug is not masked with grape or strawberry jellies or cherry yogurt. IV Infusion For solution and drug compatibility information, see Compatibility under Stability. Reconstitution Reconstitute vial containing 100 or 200 mg with 10 or 20 mL, respectively, of sterile water for injection or a compatible IV infusion solution (see Compatibility under Stability) to provide a solution containing 10 mg/mL. Dilution Reconstituted solution must be further diluted prior to administration. Each 100 mg should be diluted in 100 mL to 1 L of compatible IV infusion solution (see Compatibility under Stability) to provide solutions containing approximately 0.1– 1 mg/mL. Concentrations ⬍0.1 mg/mL or ⬎1 mg/mL are not recommended. Rate of Administration Administer by slow IV infusion, usually over 1– 4 hours (depending on the dose). The minimum recommended time to infuse 100 mg in a solution containing 0.5 mg/ mL is 1 hour. Intrapleural Administration Reconstitution and Dilution Dilute 500 mg of doxycycline with 25– 30 mL of 0.9% sodium chloride injection. Intrapleural Administration Technique Prior to intrapleural instillation of doxycycline solution, drain the pleural cavity by thoracentesis (needle aspiration) or via a thoracostomy tube by gravity or suction (i.e., closed chest tube drainage). Efficacy of the procedure may be reduced if fluid drainage from the chest tube is ⬎100 mL/24 hours when doxycycline is introduced into the pleural cavity. Instill diluted doxycycline solution into the pleural space through a thoracostomy tube; clamp tube and subsequently remove the fluid. Dosage Available as doxycycline calcium, doxycycline hyclate, and doxycycline monohydrate; dosage expressed in terms of doxycycline. Pediatric Patients cap height base of text General Pediatric Dosage Oral: Children ⬎8 years of age weighing ⱕ45 kg: 4.4 mg/kg in 2 divided doses on day 1 followed by 2.2 mg/kg daily in 1 or 2 divided doses. For severe infections, up to 4.4 mg/kg daily. Children ⬎8 years of age weighing ⬎45 kg: 100 mg every 12 hours on day 1 followed by 100 mg daily in 1 or 2 divided doses. For more severe infections, 100 mg every 12 hours. IV: Children ⬎8 years of age weighing ⱕ45 kg: 4.4 mg/kg in 1 or 2 divided doses on day 1 followed by 2.2– 4.4 mg/kg daily in 1 or 2 infusions. Children ⬎8 years of age weighing ⬎45 kg: 200 mg on day 1 in 1 or 2 infusions followed by 100– 200 mg daily. Anthrax ⬎Postexposure Prophylaxis Following Exposure in the Context of Biologic Warfare or Bioterrorism Oral: Children ⱕ8 years of age† or weighing ⬍45 kg: 2.2 mg/kg twice daily given for 60 days. Because of concerns regarding long-term doxycycline use in infants and children, consider changing (after 10– 14 days) to amoxicillin to complete the 60-day regimen if penicillin susceptibility is confirmed. Children ⬎8 years of age weighing ⱖ45 kg: 100 mg twice daily given for 60 days. ⬎Treatment of Inhalational, GI, or Oropharyngeal Anthrax Oral: Children ⱕ8 years of age† or weighing ⬍45 kg: 2.2 mg/kg twice daily. Children ⬎8 years of age weighing ⱖ45 kg: 100 mg twice daily. Initial parenteral regimen preferred; use oral regimen for initial treatment only when a parenteral regimen is not available (e.g., when there are supply or logistic problems because large numbers of individuals require treatment in a mass casualty setting). Continue for total duration of 60 days if inhalational anthrax occurred as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism. Because of concerns regarding long-term doxycycline use in infants and children, consider changing (after 10– 14 days) to amoxicillin to complete the 60-day regimen in children ⬍8 years of age if penicillin susceptibility is confirmed. IV, then Oral: Children ⱕ8 years of age† or weighing ⬍45 kg: 2.2 mg/kg twice daily. Children ⬎8 years of age weighing ⱖ45 kg: 100 mg twice daily. Used in conjunction with 1 or 2 other anti-infectives predicted to be effective. When clinical improvement occurs, switch IV doxycycline to oral doxycycline in the same dosage and continue for a total duration of 60 days. Because of concerns regarding long-term doxycycline use in infants and children, consider changing (after 10– 14 days) to amoxicillin to complete the 60-day regimen in children ⬍8 years of age if penicillin susceptibility is confirmed. ⬎Treatment of Cutaneous Anthrax Oral: Children ⱕ8 years of age† or weighing ⬍45 kg: 2.2 mg/kg twice daily. Children ⬎8 years of age weighing ⱖ45 kg: 100 mg twice daily. For mild, uncomplicated cutaneous anthrax that occurs following natural or endemic exposure, 5– 10 days of treatment has been recommended. For cutaneous anthrax that occurs following exposure in the context of biologic warfare or bioterrorism, duration of treatment is 60 days. Because of concerns regarding long-term doxycycline use in infants and children, consider changing (after 10– 14 days) to amoxicillin to complete the 60day regimen in children ⬍8 years of age if penicillin susceptibility is confirmed. Oral regimen should not be used for initial treatment of cutaneous anthrax if there are signs of systemic involvement, extensive edema, or head and neck lesions and should not be used for initial treatment in infants and children ⬍2 years of age. IV, then Oral: Children ⱕ8 years of age† or weighing ⬍45 kg: 2.2 mg/kg twice daily. Children ⬎8 years of age weighing ⱖ45 kg: 100 mg every 12 hours. Used in conjunction with 1 or 2 other anti-infectives predicted to be effective. When clinical improvement occurs, switch IV doxycycline to oral doxycycline in the same dosage and continue for a total duration of 60 days. Because of concerns regarding long-term doxycycline use in infants and children, consider changing (after 10– 14 days) to amoxicillin to complete the 60-day regimen in children ⬍8 years of age if penicillin susceptibility is confirmed. short stand 46067 AHFS Essentials ASHPI BATCH RIGHT Doxycycline 9 Bartonella Infections Oral or IV: Adolescents with HIV infection: 100 mg every 12 hours for ⱖ3 months for bartonellosis (including CNS infections). Also consider doxycycline long-term suppressive therapy† in those with relapse or reinfection. switch to oral doxycycline in a dosage of 4 mg/kg daily in 2 equally divided doses (up to 200 mg daily) for a total duration of IV and oral doxycycline of 7 days. Used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3– 7 days. Brucellosis Oral: Children ⱖ8 years of age: 2– 4 mg/kg daily (up to 200 mg daily) in 2 divided doses given for 4– 6 weeks. Children ⱖ8 years of age weighing ⱖ45 kg: Initially 100 mg of doxycycline IV every 12 hours; when oral therapy can be tolerated, switch to oral doxycycline in a dosage of 100 mg every 12 hours for a total duration of IV and oral doxycycline of 7 days. Used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3– 7 days. Chlamydial Infections ⬎Uncomplicated Urethral, Endocervical, or Rectal Infections Oral: Children ⬎8 years of age: 100 mg twice daily given for 7 days. ⬎Presumptive Treatment of Chlamydial Infection in Gonorrhea Patients Oral: Adolescents: 100 mg twice daily given for 7 days. ⬎Lymphogranuloma Venereum Oral: Adolescents: 100 mg twice daily given for 21 days. Ehrlichia Infections† Oral: Children ⱖ8 years of age: 3– 4 mg/kg daily in 2 divided doses. Duration of treatment is ⱖ5– 7 days; severe or complicated disease may require longer treatment. Gonorrhea and Associated Infections ⬎Empiric Treatment of Epididymitis Oral: Children ⱖ8 years of age: 100 mg twice daily given for 10 days; as follow-up to single-dose IM ceftriaxone. Granuloma Inguinale (Donovanosis) Oral: Adolescents: 100 mg twice daily given for ⱖ3 weeks or until all lesions have healed completely; consider adding IV aminoglycoside (e.g., gentamicin) if improvement is not evident within the first few days of therapy and in HIV-infected patients. Relapse can occur 6– 18 months after apparently effective treatment. Lyme Disease† ⬎Early Localized or Early Disseminated Lyme Disease† Oral: Children ⱖ8 years of age: 1– 2 mg/kg in 2 divided doses (up to 100 mg each dose). Duration of treatment is 14– 21 days for most patients with early localized or early disseminated disease in the absence of neurologic involvement. Some experts recommend a duration of 21– 28 days for early disseminated disease associated with mild carditis or isolated facial nerve palsy. ⬎Lyme Arthritis† Oral: Children ⱖ8 years of age: 1– 2 mg/kg twice daily (up to 100 mg each dose) for 28 days. Malaria ⬎Prevention of Malaria Oral: Children ⱖ8 years of age: 2 mg/kg (up to 100 mg) once daily. Initiate prophylaxis 1– 2 days prior to entering malarious area; continue during the stay and for 4 weeks after leaving area. If there are concerns about tolerance or drug interactions, it may be advisable to initiate prophylaxis 3– 4 weeks prior to travel in individuals receiving other drugs to ensure that the combination of drugs is well tolerated and to allow ample time if a switch to another antimalarial is required. Terminal prophylaxis with primaquine may be indicated during the final 2 weeks of doxycycline prophylaxis if exposure occurred in areas where P. ovale or P. vivax are endemic. ⬎Treatment of Uncomplicated Chloroquine-resistant P. falciparum Malaria† Oral: Children ⱖ8 years of age: 4 mg/kg daily given in 2 equally divided doses (up to 200 mg daily) for 7 days; used in conjunction with oral quinine sulfate (10 mg/kg 3 times daily given for 3 days if infection was acquired in Africa or South America or for 7 days if acquired in Southeast Asia). ⬎Treatment of Uncomplicated P. vivax Malaria† Oral: Children ⱖ8 years of age: 4 mg/kg daily in 2 equally divided doses (up to 200 mg daily) for 7 days; used in conjunction with oral quinine sulfate (10 mg/kg 3 times daily given for 3 days if infection was acquired in Africa or South America or for 7 days if acquired in Southeast Asia). In addition, a 14-day regimen of oral primaquine (0.6 mg/kg once daily) may be indicated to provide a radical cure and prevent delayed attacks or relapse of P. vivax malaria. ⬎Treatment of Severe P. falciparum Malaria† Oral: Children ⱖ8 years of age: 4 mg/kg daily in 2 equally divided doses (up to 200 mg daily) given for 7 days; used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3– 7 days. IV, then Oral: Children ⱖ8 years of age weighing ⬍45 kg: Initially 4 mg/ kg daily in 2 equally divided doses IV; when oral therapy can be tolerated, top of rh base of rh cap height base of text ⬎Presumptive Self-treatment of Malaria† Oral: Children ⱖ8 years of age: 4 mg/kg daily in 2 equally divided doses for 7 days; used in conjunction with oral quinine sulfate (10 mg/kg 3 times daily given for 3 days if infection was acquired in Africa or South America or for 7 days if acquired in Southeast Asia). Initiate presumptive self-treatment if malaria is suspected (fever, chills, or other influenza-like illness) and professional medical care will not be available within 24 hours. Not recommended for self-treatment of malaria in individuals currently taking the drug for prophylaxis. Nongonococcal Urethritis Oral: Adolescents: 100 mg twice daily given for 7 days. Pelvic Inflammatory Disease† Oral: Adolescents: 100 mg every 12 hours given for 14 days. Used in conjunction with and as follow-up to other anti-infectives (see Uses). IV, then Oral: Adolescents: 100 mg every 12 hours. Initially, IV doxycycline in conjunction with IV cefoxitin or cefotetan. Switch IV doxycycline to oral doxycycline in the same dosage as soon as possible and continue for a total duration of 14 days; continue IV cephamycin for ⱖ24 hours after clinical improvement occurs. Plague ⬎Treatment of Pneumonic Plague Occurring in Context of Biologic Warfare or Bioterrorism IV, then Oral: Children ⬎8 years of age weighing ⬍45 kg: 2.2 mg/kg every 12 hours (up to 200 mg daily). Children ⬎8 years of age weighing ⱖ45 kg: 100 mg every 12 hours or 200 mg once daily. Prompt initiation of treatment (within 18– 24 hours of symptom onset) is essential. Oral doxycycline may be substituted in the same dosage when the patient’s condition improves or if parenteral doxycycline is unavailable. Total duration of treatment is 10– 14 days. ⬎Postexposure Prophylaxis Following High-risk Exposure† Oral: Children ⬎8 years of age weighing ⬍45 kg: 2.2 mg/kg every 12 hours given for 7 days. Children ⬎8 years of age weighing ⱖ45 kg: 100 mg every 12 hours given for 7 days. Alternatively, 2– 4 mg/kg daily in 2 equally divided doses. Rickettsial Infections Oral: Children ⬎8 years of age weighing ⱕ45 kg: 4.4 mg/kg in 2 divided doses on day 1 followed by 2.2 mg/kg daily in 1 or 2 divided doses. For severe infections, up to 4.4 mg/kg daily. Children ⬎8 years of age weighing ⬎45 kg: 100 mg every 12 hours on day 1 followed by 100 mg daily in 1 or 2 divided doses. For severe infections, 100 mg every 12 hours. Continue therapy for 3– 10 days or until patient is afebrile for approximately 2– 3 days. Alternatively, a single 50-mg dose may be effective for louse-borne (epidemic) typhus, Brill-Zinsser disease, or scrub typhus. Syphilis ⬎Primary or Secondary Syphilis Oral: Children ⬎8 years of age: 100 mg twice daily given for 14 days. ⬎Latent Syphilis or Tertiary Syphilis (Except Neurosyphilis) Oral: Children ⬎8 years of age: 100 mg twice daily given for 14 days for early latent syphilis (duration ⬍1 year) or 100 mg twice daily given for 28 days for late latent syphilis (durationⱖ1 year), latent syphilis of unknown duration, or tertiary syphilis. Tularemia ⬎Treatment IV, then Oral: Children ⬎8 years of age weighing ⬍45 kg: 2.2 mg/kg every 12 hours. Children ⬎8 years of age weighing ⱖ45 kg: 100 mg twice daily. Oral doxycycline may be substituted in the same dosage when the patient’s condition improves or if parenteral doxycycline is unavailable. Total duration of treatment is 14– 21 days. short stand 46067 10 AHFS Essentials ASHPI BATCH LEFT top of rh base of rh Doxycycline ⬎Postexposure Prophylaxis Following High-risk Exposure† Oral: Children ⬎8 years of age weighing ⬍45 kg: 2.2 mg/kg every 12 hours given for 14 days. Children ⬎8 years of age weighing ⱖ45 kg: 100 mg twice daily given for 14 days. Vibrio Infections ⬎Cholera Oral: Children ⱖ8 years of age: 6 mg/kg (maximum 300 mg) as a single dose. Prophylaxis in Sexual Assault Victims† Oral: Adolescents: 100 mg twice daily given for 7 days; used in conjunction with single doses of IM ceftriaxone and oral metronidazole. Adults General Adult Dosage Oral: 100 mg every 12 hours on day 1 followed by 100 mg daily in 1 or 2 divided doses. For more severe infections, 100 mg every 12 hours. IV: 200 mg on day 1 in 1 or 2 IV infusions followed by 100– 200 mg daily. Respiratory Tract Infections ⬎Legionella Infections† Oral: 100 mg every 12 hours on the first day followed by 100 mg daily in 1 or 2 divided doses. For severe infections, 100 mg every 12 hours. Anthrax ⬎Postexposure Prophylaxis Following Exposure in the Context of Biologic Warfare or Bioterrorism Oral: 100 mg twice daily given for 60 days. ⬎Treatment of Inhalational, GI, or Oropharyngeal Anthrax Oral: 100 mg twice daily given for 60 days. Initial parenteral regimen preferred; use oral regimen for initial treatment only when a parenteral regimen is not available (e.g., when there are supply or logistic problems because large numbers of individuals require treatment in a mass casualty setting). Continue for total duration of 60 days if inhalational anthrax occurred as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism. IV, then Oral: 100 mg twice daily. Used in conjunction with 1 or 2 other anti-infectives predicted to be effective. When clinical improvement occurs, switch IV doxycycline to oral doxycycline in the same dosage and continue for a total duration of 60 days. ⬎Treatment of Cutaneous Anthrax Oral: 100 mg twice daily. For mild, uncomplicated cutaneous anthrax that occurs following natural or endemic exposure, 5– 10 days of treatment has been recommended. For cutaneous anthrax that occurs following exposure in the context of biologic warfare or bioterrorism, duration of treatment is 60 days. Oral regimen should not be used for initial treatment of cutaneous anthrax if there are signs of systemic involvement, extensive edema, or head and neck lesions. IV, then Oral: 100 mg twice daily. Used in conjunction with 1 or 2 other anti-infectives predicted to be effective. When clinical improvement occurs, switch IV doxycycline to oral doxycycline in the same dosage and continue for a total duration of 60 days. Bartonella Infections Oral or IV: HIV-infected adults: 100 mg every 12 hours for ⱖ3 months for bartonellosis (including CNS infections). Also consider doxycycline longterm suppressive therapy† in those with relapse or reinfection. ⬎Presumptive Treatment of Chlamydial Infection in Gonorrhea Patients Oral: 100 mg twice daily given for 7 days. ⬎Acute Epididymo-orchitis or Proctitis caused by C. trachomatis Oral: 100 mg twice daily given for ⱖ10 days. ⬎Lymphogranuloma Venereum Oral: 100 mg twice daily given for 21 days. ⬎Psittacosis (Ornithosis) Oral: 100 mg twice daily given for ⱖ10– 14 days after defervescence. IV: 4.4 mg/kg daily in 2 divided doses for initial treatment of severely ill patients. Gonorrhea and Associated Infections ⬎Uncomplicated Gonorrhea Oral: 100 mg twice daily given for 7 days recommended by manufacturer. Alternatively, 300 mg followed by another 300-mg dose 1 hour later. No longer recommended for gonorrhea by CDC or other experts. ⬎Empiric Treatment of Epididymitis Oral: 100 mg twice daily given for 10 days; as follow-up to a single dose of IM ceftriaxone. ⬎Epididymo-orchitis or Proctitis Oral: 100 mg twice daily given for ⱖ10 days for acute epididymo-orchitis or for 7 days for proctitis. Granuloma Inguinale (Donovanosis) Oral: 100 mg twice daily given for ⱖ3 weeks or until all lesions have healed completely; consider adding IV aminoglycoside (e.g., gentamicin) if improvement is not evident within the first few days of therapy and in HIV-infected patients. Relapse can occur 6– 18 months after apparently effective treatment. Leptospirosis† ⬎Treatment† Oral: 100 mg twice daily given for 7 days. ⬎Prevention† Oral: 200 mg once weekly beginning 1– 2 days prior to and continuing throughout the period of exposure. Lyme Disease† ⬎Early Localized or Early Disseminated Lyme Disease† Oral: 100 mg twice daily. Duration of treatment is 14– 21 days for most patients with early localized or early disseminated disease in the absence of neurologic involvement. Some experts recommend a duration of 21– 28 days for early disseminated disease associated with mild carditis or isolated facial nerve palsy. ⬎Lyme Arthritis† Oral: 100 mg twice daily given for 28 days. ⬎Acute Neurologic Manifestations (e.g., Meningitis, Radiculopathy)† Oral or IV: 100– 200 mg twice daily given for 14– 28 days for patients who are intolerant of cephalosporins and penicillin. Malaria ⬎Prevention of Malaria Oral: 100 mg once daily. Initiate prophylaxis 1– 2 days prior to entering malarious area; continue during the stay and for 4 weeks after leaving area. If there are concerns about tolerance or drug interactions, it may be advisable to initiate prophylaxis 3– 4 weeks prior to travel in individuals receiving other drugs to ensure that the combination of drugs is well tolerated and to allow ample time if a switch to another antimalarial is required. Terminal prophylaxis with primaquine may be indicated during the final 2 weeks of doxycycline prophylaxis if exposure occurred in areas where P. ovale or P. vivax are endemic. Brucellosis Oral: 200 mg daily for 4 days followed by 100 mg daily for 6– 7 days. Alternatively, dosage may be given for more prolonged periods (i.e., 4– 6 weeks). ⬎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). If infection is severe or if endocarditis, meningitis, or osteomyelitis is present, administer IM streptomycin or gentamicin during the first 7– 14 days of doxycycline therapy. Rifampin can be administered concomitantly to decrease the risk of relapse (with or without an aminoglycoside). ⬎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). Chlamydial Infections ⬎Uncomplicated Urethral, Endocervical, or Rectal Infections Oral: 100 mg twice daily given for 7 days. cap height base of text 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. short stand 46067 AHFS Essentials ASHPI BATCH RIGHT Doxycycline ⬎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. such prophylaxis is not effective and may only prolong the onset of disease if given immediately (1– 7 days) after exposure. IV: 300 mg daily given for ⱖ10 days. ⬎Latent Syphilis or Tertiary Syphilis (Except Neurosyphilis) Oral: 100 mg twice daily given for 14 days for early latent syphilis (duration ⬍1 year) or 100 mg twice daily given for 28 days for late latent syphilis (durationⱖ1 year), latent syphilis of unknown duration, or tertiary syphilis. Used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3– 7 days. ⬎Presumptive Self-treatment of Malaria† Oral: 100 mg twice daily for 7 days; used in conjunction with oral quinine sulfate (650 mg 3 times daily given for 3 days if malaria was acquired in Africa or South America or for 7 days if acquired in Southeast Asia). Initiate presumptive self-treatment if malaria is suspected (fever, chills, or other influenza-like illness) and professional medical care will not be available within 24 hours. Tularemia ⬎Treatment IV, then Oral: 100 mg twice daily. Oral doxycycline may be substituted in the same dosage when the patient’s condition improves or if parenteral doxycycline is unavailable. Total duration of treatment is 14– 21 days. Not recommended for self-treatment of malaria in individuals currently taking the drug for prophylaxis. ⬎Postexposure Prophylaxis Following High-risk Exposure† Oral: 100 mg twice daily given for 14 days. Mycobacterial Infections† ⬎Mycobacterium marinum Infections† Oral: 100 mg twice daily given for ⱖ3 months recommended by ATS for treatment of cutaneous infections. A minimum of 4– 6 weeks of treatment usually is necessary to determine whether the infection is responding. Vibrio Infections ⬎Cholera Oral: 100 mg every 12 hours on the first day followed by 100 mg daily in 1 or 2 divided doses for 2 days. For severe infections, 100 mg every 12 hours for 3 days. Nongonococcal Urethritis Oral: 100 mg twice daily given for 7 days. Alternatively, 300 mg as a single dose may be effective. Prophylaxis in Sexual Assault Victims† Oral: 100 mg twice daily for 7 days; used in conjunction with single doses of IM ceftriaxone and oral metronidazole. Pelvic Inflammatory Disease† Oral: 100 mg every 12 hours given for 14 days. Used in conjunction with and as follow-up to other anti-infectives (see Uses). Prescribing Limits Pediatric Patients General Pediatric Dosage Oral: Maximum 4.4 mg/kg daily for severe infections in children ⬎8 years of age weighing ⱕ45 kg. 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. Malaria ⬎Treatment of Uncomplicated Chloroquine-resistant P. falciparum Malaria† Oral: Children ⱖ8 years of age: Maximum 200 mg daily. Prompt initiation of treatment (within 18– 24 hours of symptom onset) is essential. Oral doxycycline may be substituted in the same dosage when the patient’s condition improves or if parenteral doxycycline is unavailable. Total duration of treatment is 10– 14 days. ⬎Postexposure Prophylaxis Following High-risk Exposure† Oral: 100 mg every 12 hours for 7 days. Alternatively, 100– 200 mg daily in 2 equally divided doses for 7 days. ⬎Treatment of Uncomplicated P. vivax Malaria† Oral: Children ⱖ8 years of age: Maximum 200 mg daily. ⬎Treatment of Severe P. falciparum Malaria† Oral or IV: Children ⱖ8 years of age: Maximum 200 mg daily. Special Populations Pleural Effusions† Intrapleural: 500 mg (diluted with 25– 30 mL of 0.9% sodium chloride injection) instilled into the pleural space (see Intrapleural Administration Technique under Dosage and Administration). Procedure may be repeated to achieve control of the effusion, although repeated administration may have limited effects. Renal Impairment For patients with recurrent malignant pleural effusions, administer a less concentrated 500-mg solution (diluted with 250 mL of 0.9% sodium chloride injection) via chest tube lavage and drainage. Clamp tube for 24 hours and repeat entire procedure daily until the drainage volume approximates the amount of solution instilled. Contraindications Rickettsial Infections Oral: 100 mg every 12 hours on day 1 followed by 100 mg daily in 1 or 2 divided doses. For more severe infections, 100 mg every 12 hours. Continue therapy for 3– 10 days or until patient is afebrile for approximately 2– 3 days. Alternatively, a single dose of 100– 200 mg may be effective for louse-borne (epidemic) typhus, Brill-Zinsser disease, or scrub typhus. ⬎Q Fever Oral: 100 mg twice daily given for 2– 3 weeks recommended by CDC and others for acute Q fever. For acute Q fever with preexisting valvular heart disease, CDC recommends 200 mg daily given in conjunction with hydroxychloroquine for 1 year to prevent progression of acute disease to endocarditis. Patients with chronic Q fever endocarditis should receive the doxycycline and hydroxychloroquine regimen for 1.5– 3 years. For prophylaxis against Q fever†, 100 mg every 12 hours given for 5– 7 days may prevent clinical disease if initiated 8– 12 days after exposure; top of rh base of rh cap height base of text Syphilis ⬎Primary or Secondary Syphilis Oral: 100 mg twice daily given for 14 days. IV, then Oral: Initially, 100 mg of doxycycline IV every 12 hours; when oral therapy can be tolerated, switch to oral doxycycline in a dosage of 100 mg every 12 hours for a total duration of IV and oral doxycycline of 7 days. IV, then Oral: 100 mg every 12 hours. Initially, IV doxycycline in conjunction with IV cefoxitin or cefotetan. Switch IV doxycycline to oral doxycycline in the same dosage as soon as possible and continue for a total duration of 14 days; continue IV cefoxitin or cefotetan for ⱖ24 hours after clinical improvement occurs. 11 Dosage adjustments not necessary. Cautions • Known hypersensitivity to doxycycline or any tetracycline. Warnings/Precautions Warnings Dental and Bone Effects Use during tooth development (e.g., pregnancy, children ⬍8 years of age) may cause permanent yellow-gray to brown discoloration of teeth and enamel hypoplasia. Effects are most common following long-term use, but may occur following repeated short-term use. Tetracyclines form a stable calcium complex in any bone-forming tissue. Reversible decrease in fibula growth rate has occurred in prematures receiving oral tetracycline. Use not recommended in children ⬍8 years of age unless other appropriate drugs are ineffective or are contraindicated or unless the benefits in certain indications (e.g., anthrax) outweigh the risks. (See Pediatric Use under Cautions.) Superinfection/Clostridium difficile-associated Colitis Possible emergence and overgrowth of nonsusceptible bacteria or fungi. Discontinue drug and institute appropriate therapy if superinfection occurs. Treatment with anti-infectives may permit overgrowth of clostridia. Consider Clostridium difficile-associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly. short stand 46067 12 AHFS Essentials ASHPI BATCH LEFT top of rh base of rh Doxycycline Some mild cases of C. difficile-associated diarrhea and colitis may respond to discontinuance alone. Manage moderate to severe cases with fluid, electrolyte, and protein supplementation; appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) recommended if colitis is severe. Fetal/Neonatal Morbidity Animal studies indicate possible fetal toxicity (e.g., retardation of skeletal development) and embryotoxicity. If used during pregnancy or if patient becomes pregnant while receiving doxycycline, patient should be apprised of the potential hazard to the fetus. (See Pregnancy under Cautions.) Renal Effects Tetracyclines have antianabolic effects and may increase BUN. Dose-related increase in BUN reported. Studies to date indicate that increased BUN does not occur with use of usual doxycycline doses in patients with impaired renal function. Sensitivity Reactions Photosensitivity Reactions Photosensitivity, manifested by an exaggerated sunburn reaction, reported with tetracyclines. Photosensitivity reactions may develop within a few minutes to several hours after sun exposure and usually persist 1– 2 days after discontinuance of the drug. Most reactions result from accumulation of tetracyclines in skin and are phototoxic in nature; photoallergic reactions also may occur. Discontinue drug at first evidence of skin erythema. Hypersensitivity Reactions Oral suspension contains sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals. General Precautions Nervous System Effects Possibility of bulging fontanels in infants and benign intracranial hypertension in adults. Effects resolve when drug discontinued. Laboratory Monitoring Periodically assess organ system function, including renal, hepatic and hematopoietic, during long-term therapy. Selection and Use of Anti-infectives To reduce development of drug-resistant bacteria and maintain effectiveness of doxycycline and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria. When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing. In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy. Because many strains of Acinetobacter, Bacteroides, Enterobacter, E. coli, Klebsiella, Shigella, S. pyogenes (group A -hemolytic streptococci), S. pneumoniae, enterococci, and ␣-hemolytic streptococci are resistant to doxycycline, in vitro susceptibility tests should be performed if the drug is used for treatment of infections caused by these bacteria. Incision and drainage or other surgical procedures should be performed in conjunction with doxycycline therapy when indicated. compatible with breast-feeding since absorption of the drugs by nursing infants is negligible. Pediatric Use Should not be used in children ⬍8 years of age unless other appropriate drugs are ineffective or are contraindicated. (See Dental and Bone Effects under Cautions.) Use in children ⬍8 years of age can be considered in certain unusual circumstances when benefits outweigh the risks (e.g., treatment of inhalational anthrax). CDC states that children ⬍8 years of age with uncomplicated chloroquine-resistant P. falciparum malaria, uncomplicated P. vivax malaria, or severe P. falciparum malaria may receive a regimen that includes doxycycline (or tetracycline) if other treatment options are not available or not tolerated and the potential benefits outweigh risks. Hepatic Impairment Pharmacokinetics not studied. Renal Impairment Renal impairment does not appear to result in excessive accumulation of the drug. Common Adverse Effects GI effects (nausea, vomiting, diarrhea, bulky loose stools, anorexia, glossitis, dysphagia); maculopapular and erythematous rash; photosensitivity. Interactions Specific Drugs Drug Interaction Comments Antacids (aluminum-, calcium-, or magnesiumcontaining) Decreased doxycycline absorption Avoid concomitant use Administer antacids containing aluminum, calcium, or magnesium 1– 2 hours before or after doxycycline Anticoagulants, oral Possible increased anticoagu- Monitor PT carefully; adjust lant effect; doxycycline anticoagulant dosage as may impair utilization of needed prothrombin or decrease vitamin K production by intestinal bacteria Anticonvulsants (carbamazepine, barbiturates, phenytoin) Possible decreased doxycycline half-life Demeclocycline, oxytetracycline, or tetracycline may be preferred when a tetracycline is indicated in a patient receiving carbamazepine, barbiturates, or phenytoin Bismuth subsalicylate Possible decreased absorption of doxycycline Concomitant use not recommended Hormonal contraceptives Possible decreased effective- Use alternative nonhormonal ness of oral contraceptives contraceptives Iron-containing preparations Possible decreased absorption of doxycycline Avoid concomitant use Administer doxycycline 2 hours before or 3 hours after an oral iron preparation Methoxyflurane Possible fatal nephrotoxicity Concomitant use not recommended Penicillins Possible antagonism Concomitant use not recommended Specific Populations Pregnancy Category D. (See Fetal/Neonatal Morbidity under Cautions.) Should not be used in pregnant women unless, in the judgment of the clinician, it is essential for the welfare of the patient and benefits outweigh the risks. CDC and others state doxycycline can be used when necessary for treatment of inhalational anthrax in pregnant women. Since adverse effects on developing teeth and bones are dose-related, CDC suggests the drug might be used for a short period (7– 14 days) before 6 months of gestation; some clinicians recommend periodic liver function testing if used in pregnant women. Malaria infection in pregnant women is associated with high risks of maternal and perinatal morbidity and mortality (e.g., miscarriage, premature delivery, low birth weight, congenital infection and/or perinatal death). CDC recommends prompt treatment with quinine and clindamycin for pregnant women with uncomplicated chloroquine-resistant P. falciparum malaria or with quinine alone for those with uncomplicated P. vivax malaria. However, CDC states a regimen of quinine in conjunction with doxycycline (or tetracycline) may be used for the treatment of uncomplicated malaria in pregnant women in rare circumstances (e.g., if other treatment options are not available or not tolerated) if benefits outweigh risks. Lactation Distributed into milk; discontinue nursing or the drug. Short-term use in lactating women is not necessarily contraindicated, but the effects of prolonged exposure to doxycycline in breast milk (e.g., 60-day regimen for inhalational anthrax) are unknown. AAP states maternal use of tetracyclines usually is cap height base of text Pharmacokinetics Absorption Bioavailability 90– 100% absorbed from GI tract in fasting adults; peak serum concentrations attained within 1.5– 4 hours. Food GI absorption reduced up to 20% by food and/or milk; effect not considered clinically important. short stand 46067 AHFS Essentials ASHPI BATCH RIGHT Doxycycline Divalent and trivalent cations, including aluminum, calcium, iron, and magnesium, may decrease oral absorption as a result of chelation with the drug. warmed, take care to avoid heating after thawing is complete. Do not refreeze after thawing. Distribution Compatibility Extent For information on systemic interactions resulting from concomitant use, see Interactions. Widely distributed into body tissues and fluids. Only small amounts diffuse into CSF. Readily crosses the placenta and is distributed into milk. Plasma Protein Binding 13 top of rh base of rh cap height base of text Parenteral Solution Compatibility Compatible 25– 93%. Elimination Metabolism Does not appear to be metabolized in the liver, but is partially inactivated in the intestine by chelate formation. Dextrose 5% in Ringer’s injection, lactated Dextrose 5% in water Invert sugar 10% in water Normosol M in dextrose 5% Normosol R in dextrose 5% Drug Compatibility ⬎Admixture Compatibility Elimination Route Excreted into the GI tract via bile and by nonbiliary routes. 20– 26% of an oral or IV dose excreted in urine and 20– 40% excreted in feces. Compatible Half-life Variable 14– 17 hours after a single dose and 22– 24 hours after multiple doses. Plasma-Lyte 56 or 148 in dextrose 5% Ringer’s injection Ringer’s injection, lactated Sodium chloride 0.9% Ranitidine HCl Meropenem ⬎Y-site Compatibility Special Populations Patients with severe hepatic impairment or biliary obstruction: Serum concentrations and half-life may be increased. Patients with severe renal impairment: Half-life 18– 26 hours after a single dose and 20– 30 hours after multiple doses. Stability Storage Oral Capsules Doxycycline hyclate capsules: ⬍30C in a tight, light-resistant container. Doxycycline monohydrate capsules: 15– 30C and protect from light. Doxycycline hyclate delayed-release capsules containing partially enteric-coated pellets: ⬍25C. For Suspension ⬍30C in a tight, light-resistant container. After reconstitution, stable for 2 weeks at room temperature. Suspension ⬍30C in a tight, light-resistant container. Tablets Film-coated tablets: ⬍30C in a tight, light-resistant container. Tablets: 15– 30C in a tight, light-resistant container. 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– 26C) or refrigerated at 2– 8C; the ground tablets mixed with low-fat chocolate milk may be stable for 1 week when refrigerated. Ground tablets are stable for at least 6 days when wrapped in aluminum foil and stored at room temperature. 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 25C when protected from direct sunlight or up to 72 hours when refrigerated and protected from both sunlight and artificial light. Once removed from refrigeration, these solutions must be completely infused within 12 hours and any unused solution discarded. 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. Once removed from refrigeration, these solutions must be completely infused within 12 hours and any unused solution discarded. 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. These solutions must be protected from direct sunlight during infusion. 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 ⫺20C. If Compatible Acyclovir sodium Amifostine Amiodarone HCl Aztreonam Bivalirudin Cyclophosphamide Dexmedetomidine HCl Diltiazem HCl Docetaxel Etoposide phosphate Fenoldopam mesylate Filgrastim Fludarabine phosphate Gemcitabine HCl Granisetron HCl Hetastarch in lactated electrolyte injection (Hextend) Hydromorphone HCl Linezolid Magnesium sulfate Melphalan HCl Meperidine HCl Morphine sulfate Ondansetron HCl Perphenazine Propofol Remifentanil HCl Sargramostim Tacrolimus Teniposide Theophylline Thiotepa Vinorelbine tartrate Incompatible Allopurinol sodium Heparin sodium Piperacillin sodium and tazobactam sodium Variable Hetastarch in 0.9% sodium chloride Meropenem Actions and Spectrum • • • • • • • Usually bacteriostatic, but may be bactericidal in high concentrations or against highly susceptible organisms. Inhibits protein synthesis in susceptible organisms by reversibly binding to 30S and 50S ribosomal subunits. The complete mechanisms by which tetracyclines reduce acne lesions have not been fully elucidated. The effects appear to result in part from the antibacterial activity of the drugs, but other mechanisms also are involved. Spectrum of activity includes many gram-positive and -negative bacteria and various other organisms (e.g., Rickettsia, Chlamydia, Mycoplasma, spirochetes). Inactive against fungi and viruses. Gram-positive aerobes and anaerobes: Active against Actinomyces israelii, Bacillus anthracis, Clostridium perfringens, C. tetani, Nocardia, Propionibacterium acnes, and some streptococci. Many strains of S. pyogenes and Enterococci are resistant. 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. Many strains of Acinetobacter, E. aerogenes, E. coli, Klebsiella, and Shigella and nearly all strains of Proteus and Pseudomonas are resistant. Other organisms: Active against Rickettsia, Coxiella burnetii, Chlamydia psittaci, C. short stand 46067 AHFS Essentials 14 • ASHPI BATCH top of rh base of rh Doxycycline trachomatis, Helicobacter pylori, Mycoplasma hominis, M. pneumoniae, Ureoplasma urealyticum, Borrelia burgdorferi, B. recurrentis, Leptospira, Treponema pallidum, T. pertenue, and Mycobacterium fortuitum. Active against asexual erythrocytic forms of Plasmodium falciparum, but is not gametocidal and not active against exoerythrocytic forms of P. falciparum. Complete cross-resistance usually occurs between doxycycline and other tetracyclines (demeclocycline, minocycline, oxytetracycline, tetracycline). • • • • • • • • • • • • • • 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). Importance of completing full course of therapy, even if feeling better after a few days. 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. Importance of drinking sufficient quantities of fluids when taking capsules or tablets to reduce the risk of esophageal irritation and ulceration. 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. Advise patients that doxycycline may increase the incidence of vaginal candidiasis. Advise patients that doxycycline may decrease effectiveness of oral contraceptives and that alternative nonhormonal contraceptive measures should be used. 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; consider use of sunscreen or sunblock. Advise patients using the drug for malaria prevention that no antimalarial agent (including doxycycline) guarantees protection against malaria. Importance of using personal protective measures to avoid mosquito bites (e.g., staying in wellscreened areas, using mosquito nets, covering body with clothing, using an effective insect repellent), especially from dusk to dawn. 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. 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 selftreatment 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. Advise travelers that presumptive self-treatment of malaria is an interim measure and that they should seek medical evaluation as soon as possible. Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. (See Fetal/Neonatal Morbidity under Cautions.) Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, and any concomitant illnesses. Importance of informing patients of other important precautionary information. (See Cautions.) cap height base of text Parenteral For injection, for IV use only 100 mg (of doxycycline) Doxy 100 (with ascorbic acid 480 mg and mannitol 300 mg), American Pharmaceutical Partners Vibramycin Hyclate Intravenous (with ascorbic acid 480 mg), Pfizer 200 mg (of doxycycline) Advice to Patients • LEFT Vibramycin Hyclate Intravenous (with ascorbic acid 960 mg), Pfizer *available generically Doxycycline Monohydrate Oral Capsules For suspension 50 mg (of doxycycline)* Doxycycline Monohydrate Capsules, Eon, Par, Ranbaxy, Watson Monodox, Oclassen 100 mg (of doxycycline)* Doxycycline Monohydrate Capsules, Eon, Par, Ranbaxy, Watson Monodox, Oclassen 25 mg (of doxycycline) per 5 mL Vibramycin Monohydrate (with parabens), Pfizer *available generically †Use is not currently included in the labeling approved by the US Food and Drug Administration Selected Revisions July 2005, Copyright, May 2004, American Society of Health-System Pharmacists, Inc. Preparations Doxycycline Calcium Oral Suspension 50 mg (of doxycycline) per 5 mL Vibramycin Calcium Syrup (with parabens, povidone, propylene glycol, and sodium metabisulfite), Pfizer Doxycycline Hyclate Oral Capsules Capsules, delayed-release (containing partially entericcoated pellets) Tablets, filmcoated 50 mg (of doxycycline)* 100 mg (of doxycycline)* 100 mg (of doxycycline) 100 mg (of doxycycline)* Vibramycin Hyclate, Pfizer Vibramycin Hyclate, Pfizer Doryx (with povidone), Warner Chilcott Vibra-Tabs (with propylene glycol), Pfizer short stand
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