Note: Doxycycline is available as hyclate, monohydrate, and calcium salts. All doses are expressed as doxycycline base.
Anthrax: Very limited data available (Ref): Term neonates:
Prophylaxis; post-exposure (inhalation or cutaneous); prior to susceptibility testing or penicillin-resistant strains: Oral: 2.2 mg/kg/dose every 12 hours for 60 days.
Treatment:
Cutaneous infection without systemic involvement: Note: Doxycycline is an option if first-line therapy (ie, ciprofloxacin) is unavailable or patient unable to tolerate; for naturally-occurring infection, usual treatment duration is 7 to 10 days; in the event of biological weapon exposure, additional therapy (as prophylaxis for inhaled spores) is necessary for a total course of 60 days from onset of illness.
Oral: 2.2 mg/kg/dose every 12 hours.
Systemic anthrax excluding meningitis: Note: Not recommended for meningitis or disseminated infection when meningitis cannot be ruled out. Doxycycline is an alternative to clindamycin as protein synthesis inhibitor and should be used in combination with a bactericidal antimicrobial (eg, fluoroquinolone, carbapenem, or vancomycin). Duration of therapy at least 14 days or longer until patient clinically stable. Additional therapy (as prophylaxis for inhaled spores) is necessary for a total course of 60 days from onset of illness.
Initial: IV: Loading dose: 4.4 mg/kg once, then 2.2 mg/kg/dose every 12 hours; treat for ≥2 to 3 weeks until condition stable.
Step-down: Oral: 2.2 mg/kg/dose every 12 hours.
Note: Doxycycline is available as hyclate, monohydrate, and calcium salts. All doses are expressed as doxycycline base. Doxycycline was traditionally avoided in ages <8 years, but use has more recently been accepted for short courses (≤14 to 21 days) for all ages when necessary (Ref).
General dosing:
Children and Adolescents: Oral, IV: 2.2 mg/kg/dose every 12 hours; maximum dose: 100 mg/dose.
Acne vulgaris, moderate to severe, treatment: Limited data available: Children ≥8 years and Adolescents: Oral: 50 to 100 mg once or twice daily or 150 mg once daily (Ref).
Anthrax (Ref): Note: Consult public health officials for event-specific recommendations.
Prophylaxis; postexposure (inhalation or cutaneous); prior to susceptibility testing or penicillin-resistant strains: Note: Doxycycline is a preferred option or ciprofloxacin: Infants, Children, and Adolescents: Treatment duration: 60 days.
Patient weight <45 kg: Oral: 2.2 mg/kg/dose every 12 hours.
Patient weight ≥45 kg: Oral: 100 mg every 12 hours.
Treatment; susceptible strains:
Cutaneous infection without systemic involvement: Note: Doxycycline is an option if first-line therapy (ie, ciprofloxacin) is unavailable or patient unable to tolerate; for naturally-occurring infection, usual treatment duration is 7 to 10 days; in the event of biological weapon exposure, additional therapy (as prophylaxis for inhaled spores) is necessary for a total course of 60 days from onset of illness.
Infants, Children, and Adolescents:
Patient weight <45 kg: Oral: 2.2 mg/kg/dose every 12 hours.
Patient weight ≥45 kg: Oral: 100 mg every 12 hours.
Systemic anthrax, excluding meningitis: Note: Not recommended for meningitis or disseminated infection when meningitis cannot be ruled out. Doxycycline is an alternative to clindamycin as protein synthesis inhibitor and should be used in combination with a bactericidal antimicrobial (eg, fluoroquinolone, carbapenem, vancomycin). Duration of therapy at least 14 days or longer until patient clinically stable; additional therapy (as prophylaxis for inhaled spores) is necessary for a total course of 60 days from onset of illness.
Infants, Children, and Adolescents:
Patient weight <45 kg:
Initial: IV: Loading dose: 4.4 mg/kg once, then 2.2 mg/kg/dose every 12 hours; may transition to oral therapy for patients without signs of active infection who are able to tolerate oral therapy and patient/caregiver adherent to therapy.
Step-down: Oral: 2.2 mg/kg/dose every 12 hours.
Patient weight ≥45 kg:
Initial: IV: Loading dose: 200 mg once, then 100 mg every 12 hours; may transition to oral therapy for patients without signs of active infection who are able to tolerate oral therapy and patient/caregiver adherent to therapy.
Step-down: Oral: 100 mg every 12 hours.
Brucellosis: Limited data available: Children ≥8 years and Adolescents: Oral: 2.2 mg/kg/dose twice daily for at least 6 weeks; maximum dose: 100 mg/dose; use in combination with rifampin; for serious infections, gentamicin should be added for initial 1 to 2 weeks and therapy may be extended for up to 4 to 6 months (Ref).
Cholera (Vibrio cholerae), treatment: Note: Due to resistance concerns, antibiotic choice during an outbreak or epidemic should be guided by local isolate susceptibility (Ref).
Children <6 years: Oral: 4 mg/kg as a single dose in combination with hydration; maximum dose: 300 mg/dose (Ref). Note: In children ≥6 years of age, a higher dose of 6 mg/kg was associated with a slightly shorter duration of diarrhea; data with 6 mg/kg are not available for children <6 years of age (Ref). Although doses as low as 2 mg/kg have been recommended, they represent a lower dosing strategy as compared to 300 mg adult dose (Ref).
Children ≥6 years and Adolescents: Oral: 4 to 6 mg/kg as a single dose in combination with hydration; maximum dose: 300 mg/dose (Ref). Note: Although doses as low as 2 mg/kg have been recommended, they represent a lower dosing strategy as compared to 300 mg adult dose (Ref).
Lyme disease (Borrelia spp. infection): Limited data available:
Prophylaxis, postexposure: Infants, Children, and Adolescents: Oral: 4.4 mg/kg/dose as a single dose; maximum dose: 200 mg/dose. Note: Prophylaxis is used only in patients who meet all of the following criteria for a high-risk bite: Ixodes spp. tick attached for ≥36 hours, prophylaxis can be given within 72 hours of tick removal, and tick bite occurred in a highly endemic area (ie, local rate of Ixodes spp. tick infection with Borrelia burgdorferi is ≥20%) (Ref).
Treatment: Infants, Children, and Adolescents: Oral: 2.2 mg/kg/dose twice daily; maximum dose: 100 mg/dose. Duration of therapy depends on clinical syndrome; treat erythema migrans for 10 days; borrelial lymphocytoma for 14 days; meningitis, radiculopathy, cranial nerve palsy, or carditis for 14 to 21 days; arthritis (initial, recurrent, or refractory) for 28 days; and acrodermatitis chronica atrophicans for 21 to 28 days (Ref).
Malaria:
Prophylaxis: Children ≥8 years and Adolescents: Oral: 2.2 mg/kg/dose once daily starting 1 to 2 days before travel to the area with endemic infection, continuing daily during travel and for 4 weeks after leaving endemic area; maximum daily dose: 100 mg/day (Ref).
Treatment: Children and Adolescents: Oral, IV: 2.2 mg/kg/dose twice daily for 7 days; maximum dose: 100 mg/dose; use in combination with quinine sulfate (plus primaquine for Plasmodium vivax) (Ref). Note: Use of doxycycline in children <8 years should be reserved for when alternatives are not available or are not tolerated; benefits should outweigh risks.
Pneumonia, community-acquired; presumed or proven atypical infection (Mycoplasma pneumoniae, Chlamydophila pneumoniae): Children ≥8 years and Adolescents: Oral: 1 to 2 mg/kg/dose twice daily for 10 days (Ref).
Q fever (Coxiella burnetii) (preferred therapy): Children and Adolescents: Oral: 2.2 mg/kg/dose twice daily for 14 days; maximum dose: 100 mg/dose; in children <8 years with mild or uncomplicated disease, may consider treatment duration of 5 days, and if longer treatment required, may consider alternate therapy (trimethoprim/sulfamethoxazole) (Ref).
Skin/soft tissue infections; MRSA or community-acquired cellulitis (purulent) (Ref): Children ≥8 years and Adolescents:
≤45 kg: Oral: 2 mg/kg/dose every 12 hours for 5 to 10 days.
>45 kg: Oral: 100 mg twice daily for 5 to 10 days.
Tickborne rickettsial disease (Rocky Mountain spotted fever), ehrlichiosis, or anaplasmosis: Children and Adolescents: Oral, IV: 2.2 mg/kg/dose every 12 hours; maximum dose: 100 mg/dose; treat for minimum of 5 to 7 days; continue for at least 3 days after defervescence and clinical improvement observed. Severe or complicated disease may require longer treatment; anaplasmosis should be treated for 10 days (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children and Adolescents: IV, Oral: Limited data available:
Mild to severe kidney impairment: Based on adult information, no dosage adjustment is necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Poorly dialyzed (0% to 5%); based on adult information, no supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Poorly dialyzed; based on adult information, no dosage adjustment necessary (Ref).
Continuous renal replacement therapy (CRRT): Based on adult information, no dosage adjustment necessary (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Doxycycline: Drug information")
Note: Doxycycline is available as hyclate, monohydrate, and calcium salts. All doses are expressed as doxycycline base.
Usual dosage range:
Oral: IR and most ER formulations: 100 to 200 mg/day in 1 to 2 divided doses. Note: 60 mg of modified polymer-coated tablet (Doryx MPC) is equivalent to 50 mg conventional delayed-release tablet and 120 mg of modified polymer-coated tablet (Doryx MPC) is equivalent to 100 mg conventional delayed-release tablet.
IV: 100 mg every 12 hours. Note: IV form may cause phlebitis.
Acne vulgaris, inflammatory, moderate to severe (off-label dose):
Note: Use in combination with topical acne therapy. Treatment should ideally be limited to 3 to 4 months to minimize the risk of resistance (Ref).
Oral:
Immediate release: 50 to 100 mg twice daily or 100 mg once daily (Ref).
Extended release: 100 mg twice daily on day 1, then 100 mg once daily (Ref).
Subantimicrobial dosing: 20 mg twice daily (immediate release) or 40 mg once daily (delayed release) (Ref).
Anthrax: Note: Consult public health officials for event-specific recommendations.
Inhalational exposure (postexposure prophylaxis [PEP]): Oral: 100 mg every 12 hours for 42 to 60 days (Ref).
Note: Anthrax vaccine should also be administered to exposed individuals (Ref). Duration of therapy: If the PEP anthrax vaccine series is administered on schedule (for all regimens), antibiotics may be discontinued in immunocompetent adults aged 18 to 65 years at 42 days after initiation of vaccine or 2 weeks after the last dose of the vaccine (whichever comes last and not to exceed 60 days); if the vaccination series cannot be completed, antibiotics should continue for 60 days (Ref). In addition, adults with immunocompromising conditions or receiving immunosuppressive therapy, patients >65 years of age, and patients who are pregnant or breastfeeding should receive antibiotics for 60 days (Ref).
Cutaneous (without systemic involvement), treatment: Oral: 100 mg every 12 hours for 7 to 10 days after naturally acquired infection; treat for 60 days for bioterrorism-related cases (Ref). Note: Patients with cutaneous lesions of the head or neck or extensive edema should be treated for systemic involvement.
Systemic (meningitis excluded; alternative agent), treatment: IV: Initial: 200 mg as a single dose, then 100 mg every 12 hours, in combination with a bactericidal agent; treat for 2 weeks or until clinically stable, whichever is longer. Note: Antitoxin should also be administered for systemic anthrax. Following a course of IV combination therapy, patients exposed to aerosolized spores require oral doxycycline monotherapy to complete an antimicrobial course of 60 days (Ref).
Bartonella spp. infection:
Patients with HIV:
Treatment: Note: Duration of therapy is ≥3 months; continuation of therapy depends on clinical condition and response to therapy (Ref).
Bacillary angiomatosis, cat scratch disease, peliosis hepatis, bacteremia, and osteomyelitis: Oral, IV: 100 mg every 12 hours (Ref). Note: Some experts use in combination with gentamicin for the first 2 weeks of therapy for patients with Bartonella bacteremia (Ref).
CNS infections: Oral, IV: 100 mg every 12 hours; may use in combination with rifampin (Ref).
Endocarditis: Oral, IV: 100 mg every 12 hours; use in combination with rifampin for the first 6 weeks (or gentamicin for first 2 weeks if rifampin cannot be used) (Ref).
Other severe infections: Oral, IV: 100 mg every 12 hours in combination with rifampin (Ref); some experts initiate with IV therapy and transition to oral when patient becomes clinically stable (Ref).
Suppressive therapy: Note: For patients who experience a relapse after receiving a ≥3-month course of primary treatment.
Oral: 100 mg every 12 hours. Continue until patient has received ≥3 months of therapy and CD4 count is >200 cells/mm3 for ≥6 months; some experts discontinue therapy only if Bartonella titers have also decreased 4-fold (Ref).
Patients without HIV:
Bacteremia without endocarditis: Oral: 200 mg once daily or 100 mg twice daily for 4 weeks with gentamicin (or rifampin if gentamicin cannot be used) for first 2 weeks (Ref).
Cat scratch disease, CNS infection, and neuroretinitis: Oral, IV: 100 mg twice daily in combination with rifampin (Ref).
Endocarditis: Oral, IV: 100 mg every 12 hours for 3 months; use in combination with rifampin for the first 6 weeks (or gentamicin for first 2 weeks if rifampin cannot be used) (Ref).
Bite wound infection, prophylaxis or treatment (animal or human bite) (alternative agent) (off-label use): Oral, IV: 100 mg twice daily. Duration is 3 to 5 days for prophylaxis (Ref); duration of treatment for established infection is typically 5 to 14 days (Ref). Note: Some experts use in combination with an appropriate agent for anaerobes (Ref).
Brucellosis:
Treatment:
Endocarditis or neurobrucellosis: Limited data available: IV, Oral: 100 mg twice daily for at least 12 weeks (may be needed for up to 6 months); use as part of an appropriate combination regimen (Ref).
Uncomplicated (nonfocal): Oral: 100 mg twice daily for 6 weeks as part of an appropriate combination regimen (Ref).
Spondylitis: Oral: 100 mg twice daily for at least 12 weeks as part of an appropriate combination regimen (Ref).
Postexposure prophylaxis (high-risk laboratory exposure): Oral: 100 mg twice daily with rifampin for 3 weeks (Ref); for exposure to B. abortus RB51 strains, some experts give doxycycline plus trimethoprim-sulfamethoxazole (Ref).
Cholera (Vibrio cholerae), treatment (adjunctive therapy for severely ill patients): Oral: 300 mg as a single dose. Note: Due to resistance concerns, antimicrobial therapy during an outbreak or epidemic should be guided by isolate susceptibility (Ref).
Endocarditis prophylaxis, dental or invasive respiratory tract procedure (alternative agent for patients with penicillin allergy) (off-label use): Oral: 100 mg administered 30 to 60 minutes prior to procedure; if inadvertently not given prior to the procedure, may be administered up to 2 hours after the procedure. Note: Reserve for select situations (cardiac condition with the highest risk of adverse endocarditis outcomes and procedure likely to result in bacteremia with an organism that can cause endocarditis) (Ref).
Hidradenitis suppurativa (off-label use): Oral: 100 mg once or twice daily (Ref).
Lyme disease (Borrelia spp. infection) (off-label use):
Prophylaxis: Oral: 200 mg as a single dose. Note: Prophylaxis is used only in patients who meet all of the following criteria: Ixodes spp. tick attached for ≥36 hours, prophylaxis can be given within 72 hours of tick removal, and local rate of Ixodes spp. tick infection with Borrelia burgdorferi is ≥20% (Ref).
Treatment, erythema migrans : Oral: 100 mg twice daily for 10 days (Ref).
Treatment, acute neurologic disease (isolated facial nerve palsy, meningitis, or radiculoneuropathy): Oral: 100 mg twice daily for 14 to 21 days (Ref).
Treatment, carditis (initial therapy for mild disease [first-degree atrioventricular block with PR interval <300 msec] or step-down therapy after initial parenteral treatment for more severe disease once PR interval <300 msec): Oral: 100 mg twice daily for 14 to 21 days (Ref).
Treatment, arthritis without neurologic involvement: Oral: 100 mg twice daily for 28 days (Ref).
Malaria:
Prophylaxis: Oral (immediate release and delayed release): 100 mg daily; initiate 1 to 2 days prior to travel to endemic area; continue daily during travel and for 4 weeks after leaving endemic area.
Treatment (alternative agent) (off-label use): Oral: 100 mg twice daily for 7 days in combination with quinine sulfate (quinine sulfate duration is region specific). Note: If used for P. vivax or P. ovale, use this regimen in combination with primaquine. If used for severe malaria (after completion of IV therapy), use full 7-day schedule of doxycycline (Ref).
Otitis media, acute (alternative agent if unable to tolerate penicillins and cephalosporins) (off-label use): Oral: 100 mg every 12 hours; duration of therapy is 5 to 7 days (mild to moderate infection) or 10 days (severe infection) (Ref).
Plague (Yersinia pestis):
Note: Consult public health officials for event-specific recommendations.
Postexposure prophylaxis: Oral: 100 mg every 12 hours for 7 days (Ref).
Treatment of bubonic, pharyngeal, pneumonic, or septicemic plague (alternative agent for pneumonic or septicemic plague): Oral, IV: 200 mg initially then 100 mg every 12 hours for 10 to 14 days and for at least a few days after clinical resolution (Ref).
Pregnant patients (alternative agent): Oral, IV: 200 mg IV initially, then 100 mg orally or IV every 12 hours or 200 mg IV every 24 hours (Ref).
Pleurodesis, chemical (sclerosing agent for pleural effusion) (off-label use): Intrapleural: 500 mg as a single dose in 30 to 100 mL NS (Ref); may require a repeat dose (Ref); some experts combine with or administer following instillation of a local anesthetic (eg, lidocaine, 10 mL [100 mg] of 1% solution (Ref) or mepivacaine 20 mL [400 mg] of 2% solution (Ref)).
Pneumonia, community-acquired, empiric therapy:
Outpatients with no risk factors for antibiotic resistant pathogens: Oral: 100 mg twice daily; must be used as part of an appropriate combination regimen in outpatients with comorbidities (Ref). Some experts prefer to use as part of an appropriate combination regimen in all outpatients, regardless of comorbidities (Ref).
Inpatients (alternative agent): Oral, IV: 100 mg twice daily as part of an appropriate combination regimen (Ref).
Duration: Minimum of 5 days; patients should be clinically stable with normal vital signs before discontinuing therapy (Ref).
Prosthetic joint infection (off-label use):
Treatment: Oral continuation therapy for S. aureus (following pathogen-specific IV therapy in patients undergoing 1-stage exchange or debridement with retention of prosthesis) (alternative agent): Oral: 100 mg twice daily in combination with rifampin; duration is a minimum of 3 months, depending on patient-specific factors (Ref).
Chronic suppression for staphylococci (methicillin resistant) and Cutibacterium acnes (alternative agent for C. acnes): Oral: 100 mg twice daily (Ref).
Q fever (C. burnetii) :
Acute symptomatic: Note: Treatment is most effective if given within the first 3 days of symptoms (Ref).
Oral: 100 mg every 12 hours for 14 days (Ref). Note: Some experts use in combination with hydroxychloroquine and for a prolonged duration in select patients (eg, those with valvulopathy/cardiomyopathy, acute endocarditis, or antiphospholipid antibodies) (Ref).
Persistent localized infection (eg, endocarditis, osteomyelitis, vascular infection, prosthetic joint infection): Oral: 100 mg every 12 hours in combination with hydroxychloroquine for ≥18 months, depending on site of infection and serologic response; in prosthetic valve disease or vascular infection, extend treatment to ≥24 months (Ref).
Rhinosinusitis, acute bacterial (alternative agent):
Note: In uncomplicated acute bacterial rhinosinusitis, initial observation and symptom management without antibiotic therapy is appropriate in most patients. Reserve antibiotic therapy for poor follow-up or lack of improvement over the observation period (Ref).
Oral: 200 mg/day in 1 to 2 divided doses for 5 to 7 days (Ref).
Rocky Mountain spotted fever: Oral, IV: 100 mg twice daily for 5 to 7 days or for at least 3 days after fever subsides, whichever is longer; initiate treatment as soon as possible. Severe or complicated disease may require longer treatment (Ref). Note: Some experts recommend an initial loading dose of 200 mg for critically ill patients (Ref).
Rosacea, moderate to severe or unresponsive to topical therapy: Oral:
Traditional dosing (off-label dose): Initial: 50 to 100 mg twice daily for 4 to 12 weeks; may follow with a topical agent and/or subantimicrobial doxycycline dosing for long-term management. Alternatively, may initiate therapy with subantimicrobial dosing (Ref).
Subantimicrobial dosing: 40 mg once daily (delayed release; Oracea) or 20 mg twice daily (immediate release) (Ref).
Sexually transmitted infections:
Cervical infection, empiric therapy for cervicitis or pathogen-directed therapy for Chlamydia trachomatis: Oral: 100 mg twice daily for 7 days (Ref) or 200 mg delayed release once daily for 7 days (Geisler 2012); for empiric therapy, give in combination with ceftriaxone if the patient is at high risk for gonorrhea, if follow up is a concern, or if local prevalence of gonorrhea is elevated (>5%) (Ref).
Empiric treatment following sexual assault (off-label use): Oral: 100 mg twice daily for 7 days, as part of an appropriate combination regimen (Ref).
Epididymitis, acute (off-label use): Empiric therapy for chlamydia and gonorrhea: Oral: 100 mg twice daily for 10 days with single dose of ceftriaxone. Note: An alternative regimen is recommended in patients who practice insertive anal sex (Ref).
Granuloma inguinale (donovanosis) (alternative agent): Oral: 100 mg twice daily for >3 weeks and until resolution of lesions. Note: If symptoms do not improve within the first few days of therapy, addition of a second agent may be considered (Ref).
Lymphogranuloma venereum: Oral: 100 mg twice daily for 21 days (Ref).
Pelvic inflammatory disease (off-label use):
Mild to moderate pelvic inflammatory disease, outpatient therapy: Oral: 100 mg every 12 hours for 14 days as part of an appropriate combination regimen (Ref).
Severe pelvic inflammatory disease, inpatient therapy: Oral, IV: 100 mg every 12 hours as part of an appropriate combination regimen; transition to oral therapy after 24 to 48 hours of sustained clinical improvement to complete a 14-day total course (Ref).
Rectal infection, empiric therapy for acute proctitis or proctocolitis or pathogen-directed therapy for Chlamydia trachomatis (off-label use): Oral: 100 mg twice daily for 7 days; for empiric therapy, give in combination with a single dose of ceftriaxone. Note: Extend doxycycline duration to 21 days for presumptive therapy of lymphogranuloma venereum if patient has severe rectal symptoms (eg, bloody discharge, tenesmus, perianal ulcers or mucosal ulcers) and a positive rectal chlamydia NAAT or HIV infection (Ref).
Syphilis (alternative agent for nonpregnant patients with penicillin allergy):
Note: Limited data support use of doxycycline as an alternative to penicillin, and close serologic and clinical follow-up is warranted (Ref).
Early syphilis (primary, secondary, and early latent [<1-year duration]): Oral: 100 mg twice daily for 14 days (Ref).
Late syphilis (late latent [>1-year duration] or tertiary syphilis with normal CSF examination): Note: For tertiary syphilis, reserve use for patients who are unable to be desensitized to penicillin (Ref).
Oral: 100 mg twice daily for 28 days (Ref).
Urethral infection, empiric therapy for urethritis or pathogen-directed therapy for Chlamydia trachomatis: Oral: 100 mg twice daily for 7 days or 200 mg delayed release once daily for 7 days (Ref); give in combination with ceftriaxone if there is microscopic evidence of gonococcal urethritis or if there is high clinical suspicion of gonococcal infection (Ref).
Skin and soft tissue infection:
Cellulitis, nonpurulent with risk for methicillin-resistant S. aureus: Oral: 100 mg twice daily in combination with an additional agent (eg, amoxicillin, cephalexin) for coverage of beta-hemolytic streptococci (Ref).
Cellulitis, purulent or abscess: Oral: 100 mg twice daily. Note: Systemic antibiotics only indicated for abscess in certain instances (eg, immunocompromised patients, signs of systemic infection, large or multiple abscesses, indwelling device, high risk for adverse outcome with endocarditis). If at risk for gram-negative bacilli, use in combination with an appropriate agent (Ref).
Duration: Treat for ≥5 days but may extend up to 14 days depending on severity and clinical response (Ref).
Impetigo or ecthyma if methicillin-resistant S. aureus is suspected or confirmed: Note: For impetigo, reserve systemic therapy for patients with numerous lesions or in outbreak settings to decrease transmission (Ref).
Oral: 100 mg twice daily for 7 days (Ref).
Surgical prophylaxis, uterine evacuation (induced abortion or pregnancy loss) (off-label use): Oral: 200 mg as a single dose 1 hour prior to uterine aspiration (Ref); may be administered up to 12 hours before the procedure (Ref). Note: The optimal dosing regimen has not been established; various protocols are in use (Ref).
Tularemia (Francisella tularensis):
Treatment (mild infection) (alternative agent): Oral: 100 mg twice daily for 14 to 21 days (Ref).
Postexposure prophylaxis (nonbioterrorism event, high-risk exposure): Oral: 100 mg twice daily for 14 days (Ref).
Bioterrorism event: Note: Consult public health officials for event-specific recommendations.
Mass casualty management or postexposure prophylaxis (when used as a biological weapon): Oral: 100 mg twice daily for 14 days (Ref).
Contained casualty management (when used as a biological weapon): IV (may transition to oral if clinically appropriate): 100 mg every 12 hours for 14 to 21 days (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
IV, Oral:
Mild to severe impairment: No dosage adjustment necessary (Ref)
Hemodialysis, intermittent (thrice weekly): Poorly dialyzed (0% to 5%); no supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Poorly dialyzed; no dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral, as hyclate [strength expressed as base]:
Morgidox: 50 mg [DSC], 100 mg [DSC] [contains fd&c blue #1 (brilliant blue)]
Vibramycin: 100 mg [contains fd&c blue #1 (brilliant blue)]
Generic: 50 mg, 100 mg
Capsule, Oral, as monohydrate [strength expressed as base]:
Mondoxyne NL: 75 mg [DSC], 100 mg [contains quinoline yellow (d&c yellow #10)]
Okebo: 75 mg [DSC]
Generic: 50 mg, 75 mg, 100 mg, 150 mg
Capsule Delayed Release, Oral, as monohydrate [strength expressed as base]:
Oracea: 40 mg
Generic: 40 mg
Kit, Combination, as hyclate [strength expressed as base]:
Morgidox: 1 x 50 mg [DSC], 1 x 100 mg [DSC], 2 x 100 mg [DSC] [contains cetyl alcohol, edetate (edta) disodium, fd&c blue #1 (brilliant blue)]
Solution Reconstituted, Intravenous, as hyclate [strength expressed as base]:
Generic: 100 mg (1 ea)
Solution Reconstituted, Intravenous, as hyclate [strength expressed as base, preservative free]:
Doxy 100: 100 mg (1 ea)
Generic: 100 mg (1 ea)
Suspension Reconstituted, Oral, as monohydrate [strength expressed as base]:
Vibramycin: 25 mg/5 mL (60 mL) [contains fd&c blue #1 (brilliant blue), methylparaben, propylparaben; raspberry flavor]
Generic: 25 mg/5 mL (60 mL)
Syrup, Oral, as calcium [strength expressed as base]:
Vibramycin: 50 mg/5 mL (473 mL [DSC]) [contains butylparaben, propylene glycol, propylparaben, sodium metabisulfite]
Vibramycin: 50 mg/5 mL (473 mL [DSC]) [contains butylparaben, propylene glycol, propylparaben, sodium metabisulfite; raspberry-apple flavor]
Tablet, Oral, as hyclate [strength expressed as base]:
Acticlate: 75 mg [contains fd&c blue #1 (brilliant blue), fd&c yellow #6 (sunset yellow)]
Acticlate: 150 mg [scored; contains fd&c blue #2 (indigotine)]
Lymepak: 100 mg [contains fd&c blue #1 (brilliant blue), fd&c yellow #6 (sunset yellow), quinoline yellow (d&c yellow #10)]
TargaDOX: 50 mg [contains fd&c blue #2 (indigotine), fd&c yellow #6 (sunset yellow)]
Generic: 20 mg, 50 mg, 75 mg, 100 mg, 150 mg
Tablet, Oral, as monohydrate [strength expressed as base]:
Avidoxy: 100 mg [contains fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Generic: 50 mg, 75 mg, 100 mg, 150 mg
Tablet Delayed Release, Oral, as hyclate:
Doryx MPC: 60 mg [contains corn starch]
Tablet Delayed Release, Oral, as hyclate [strength expressed as base]:
Doryx: 50 mg [contains corn starch]
Doryx: 80 mg, 200 mg [scored; contains corn starch]
Doryx MPC: 120 mg [contains corn starch]
Generic: 50 mg, 75 mg, 80 mg, 100 mg, 150 mg, 200 mg
May be product dependent
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Periostat: 20 mg
Capsule, Oral, as hyclate [strength expressed as base]:
Generic: 100 mg
Capsule Delayed Release, Oral, as monohydrate [strength expressed as base]:
Apprilon: 40 mg
Generic: 40 mg
Tablet, Oral, as hyclate [strength expressed as base]:
Generic: 100 mg
Morgidox kits contain doxycycline capsules 100 mg, plus AcuWash moisturizing Daily Cleanser
NizAzel Doxy kits contain doxycycline tablets 100 mg, plus NicAzel FORTE dietary supplement tablets
Oral: Administer capsules or tablets with adequate amounts of fluid and remain in an upright position following administration (to avoid throat irritation); may be administered with food or milk to decrease GI upset (though absorption may be slightly reduced). Shake suspension well before use.
Acticlate:
Capsule: Swallow capsule whole; do not break, open, crush, dissolve, or chew the capsule.
Tablet (150 mg): May be broken into 1/3 to provide 50 mg dose or 2/3 to provide 100 mg/dose.
Doryx: May break up the tablet and sprinkle the delayed-release pellets on a spoonful of applesauce. Do not crush or damage the delayed-release pellets; loss or damage of pellets prevents using the dose. Swallow the Doryx/applesauce mixture immediately without chewing. Discard mixture if it cannot be used immediately.
Parenteral: For IV use only; administer over 1 to 4 hours; avoid rapid infusion.
Oral administration is preferable unless patient has significant nausea and vomiting; IV and oral routes are bioequivalent.
Oral: In general, administer with meals to decrease GI upset; however, some manufacturer labeling recommends administration on an empty stomach (see below). Administer capsules and tablets with at least 8 ounces (240 mL) of water and have patient sit up for at least 30 minutes or 1 to 2 hours (Canadian labeling) after taking to reduce the risk of esophageal irritation and ulceration.
Acticlate: Swallow capsule whole; do not break, open, crush, dissolve, or chew. The 150 mg tablet may be broken into 2/3 or 1/3 to provide a 100 mg and 50 mg strength, respectively.
Doxycycline 20 mg tablet, Oracea, Apprilon [Canadian product]: Administer on an empty stomach 1 hour before or 2 hours after meals.
Doryx: Do not chew or crush tablets. May be administered by carefully breaking up the tablet and sprinkling tablet contents on a spoonful of cold applesauce; applesauce should be soft enough to swallow without chewing. The delayed-release pellets must not be crushed or damaged when breaking up tablet. Should be administered immediately after preparation and without chewing; follow with a cool 8-ounce (240 mL) glass of water to ensure complete swallowing. If applesauce/pellet mixture is not administered immediately, discard (do not store for future use).
Doryx MPC: Do not chew or crush tablets.
JAMP-doxycycline [Canadian product]: Administer with a full glass of water and with or after a meal to minimize GI upset; patient should not lay down after administration and should not go to bed within 1 to 2 hours of administration.
Periostat [Canadian product]: Administer 1 hour before breakfast and evening meal.
Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate.
Capsule, delayed release: Delayed-release capsule may not be opened. Switch to IR formulation (capsule, tablet, or oral suspension) at closest possible dose.
Tablet, extended release: Delayed-release tablet can be cut into small pieces but not crushed.
IV: Infuse IV doxycycline over 1 to 4 hours. Avoid extravasation (may be an irritant). Prolonged IV administration may cause thrombophlebitis. Oral administration is preferable unless patient has significant nausea and vomiting; IV and oral routes are bioequivalent.
Intrapleural (off-label route): Instill diluted doxycycline (combined with or following instillation of a local anesthetic) into chest tube; clamp chest tube for 2 hours (Ref).
Capsule, tablet, delayed-release tablet: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Protect from light and moisture.
Syrup, oral suspension: Store below 30°C (86°F); protect from light.
Injection: Store intact vials at 20°C to 25°C (68°F to 77°F); protect from light. Stability of IV infusion varies based on solution; refer to manufacturer's labeling.
Treatment of infections caused by susceptible Rickettsia including Rocky Mountain spotted fever; treatment of sexually transmitted infections caused by susceptible Chlamydia, Ureaplasma, Klebsiella, Neisseria, and Haemophilus species; treatment of respiratory tract infections caused by susceptible Mycoplasma, Chlamydophila, Haemophilus, Klebsiella, and Streptococcus species; treatment of infections caused by susceptible gram-negative and gram-positive organisms including Borrelia, Ureaplasma, Haemophilus, Yersinia, Francisella, Vibrio, Campylobacter, Brucella, Bartonella, Calymmatobacterium, Escherichia, Enterobacter, Shigella, Acinetobacter, and Klebsiella species; treatment of ophthalmic infections caused by susceptible Chlamydia species; treatment of anthrax (Bacillus anthracis); treatment of plague (Yersinia pestis); treatment of cholera (Vibrio cholerae); treatment of brucellosis in combination with streptomycin; alternative treatment for infections caused by susceptible bacteria when penicillin is contraindicated including Treponema (eg, syphilis), Listeria, Fusobacterium, Actinomyces, and Clostridium species; adjunctive treatment for acute intestinal amebiasis and severe acne; alternative for malaria prophylaxis in travelers to areas with resistant strains (All indications: FDA approved in ages ≥8 years and adults and in patients <8 years in severe or life-threatening illness); treatment of inflammatory lesions (papules and pustules) associated with rosacea (Oracea: FDA approved in adults). Has also been used for community-acquired methicillin-resistant Staphylococcus aureus cellulitis and ehrlichiosis.
Doxycycline may be confused with dicyclomine, doxepin, doxylamine
Doxy100 may be confused with Doxil
Monodox may be confused with Maalox
Oracea may be confused with Orencia
Vibramycin may be confused with vancomycin, Vibativ
Oracea (US brand name) is marketed in Canada under the brand name Apprilon
Bone growth suppression, as evidenced by growth retardation (fibula), has been reported in premature infants treated with tetracycline; growth restriction up to 40% has been associated with oral tetracycline therapy but is reversible when short-term treatment is discontinued. Upon discontinuation of tetracycline, rapid compensatory bone growth is observed (Ref). There are limited/no data with doxycycline; therefore, the risk for bone growth suppression is extrapolated from data with tetracycline.
Mechanism: Dose-related; tetracycline binds to calcium in growing bones and negatively affects calcium orthophosphate metabolism (Ref); doxycycline appears to bind to calcium less than tetracycline (Ref).
Onset: Intermediate; deposition of tetracycline in bone has been shown after one dose and treatment with tetracycline for 9 to 12 days has resulted in restricted bone growth (Ref).
Risk factors:
• Dose; tetracycline 25 mg/kg/dose every 6 hours in premature infants (Ref)
• Age: Premature infants (Ref)
Esophagitis, esophageal ulcer, and/or esophageal stenosis may occur; patients with sudden onset of chest pain, dysphagia, odynophagia, and/or retrosternal pain may require assessment (Ref). Esophagitis is more frequent with doxycycline than minocycline (Ref).
Mechanism: Local caustic injury due to direct local contact as doxycycline has a pH <3 (Ref).
Onset: Varied; 3 to 12 days after initiation. In treatment of chronic conditions such as acne vulgaris, it can occur any time during treatment (Ref).
Risk factors:
• Administration at bedtime or prior to lying down (Ref)
• Altered esophageal anatomy or underlying esophageal strictures
• Inadequate fluid intake with administration (Ref)
• Preexisting esophageal disorders (eg, gastroesophageal reflux disease)
Doxycycline may cause skin photosensitivity reactions ranging from mild sunburn-like reactions to photodermatitis (Ref). Phototoxic reactions are restricted to exposed skin, usually develop shortly after sun exposure and appear to be dose-related (Ref). Photo-onycholysis has also been reported with tetracyclines (Ref). The main wavelength causing doxycycline’s phototoxic reactions is UVA1 (340-400 nm) (Ref). Chronic tetracycline use (>2 months) may increase the risk of basal cell carcinoma by 11% (Ref).
Mechanism: Doxycycline is activated by the radiation in the long UVA1 spectrum (340-400 nm), increasing sensitivity to sunlight (Ref).
Onset: Photosensitivity: Occurs <24 hours after sun exposure (Ref).
Risk factors:
• Children even at very low doses (20 mg daily) may have increased susceptibility (Ref)
• Fitzpatrick skin types I and II (white, always burns, never tans or tans minimally) (Ref)
• Higher doses (Ref)
• Lack of adherence to suggested sun avoidance, sun-protective clothing, and broad- spectrum sunscreen (UVA and UVB) (Ref)
• Living in a country with high solar radiation; even low doses can precipitate a reaction (Ref)
• Use of sunscreens with primary UVA protection offered by oxybenzone (absorbs shorter UVA radiation) (Ref)
Doxycycline may induce diffuse skin hyperpigmentation (brown, bluish-grey, black discoloration) including nails, skin of hands, arms, legs, dorsal side of feet, interdigital areas, or around scars. Risk of dental staining (staining of tooth) and enamel hypoplasia with doxycycline during tooth development is controversial; however, studies have not validated these issues and most recommend short-term use (<21 days) in children regardless of age (Ref). Local pain with the change in pigment has been reported (Ref). Many patients were receiving doxycycline at higher doses for prolonged periods of time as in treatment of Q fever. For treatment of Q fever, doxycycline is administered concurrently with hydroxychloroquine, which also may cause skin hyperpigmentation (Ref). Hyperpigmentation may be more prevalent with minocycline than doxycycline and associated with a greater variety of tissues (eg, bone, conjunctiva and sclera, ear tympanic membrane, internal organs, nails, subcutaneous fat, teeth and oral mucosa, and thyroid) (Ref). Partially reversible or reversible within 1 to 12 months of discontinuation (Ref).
Mechanism: Dose- and time-related; doxycycline may mineralize tissue as it binds to calcium/iron to form a tetracycline-calcium/iron orthophosphate complex and/or activate melanocytes in the upper dermis (Ref).
Onset: Varied; 2 weeks to 37 months (Ref).
Risk factors:
• Higher doses (Ref)
• Long-term use (Ref)
• Pediatric: Treatment course >21 days (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Endocrine & metabolic: Increased lactate dehydrogenase (2%), increased serum glucose (1%)
Gastrointestinal: Abdominal distention (1%), abdominal pain (1%), diarrhea (5%), upper abdominal pain (2%), xerostomia (1%)
Genitourinary: Vulvovaginal candidiasis (Shapiro 1997)
Postmarketing:
Dermatologic: Erythema multiforme (Shapiro 1997), erythematous rash, exfoliative dermatitis, maculopapular rash, onycholysis (photo-onycholysis skin hyperpigmentation; chronic use) (Dowlati 2015), skin hyperpigmentation (rare: <1%) (Akcam 2005; Keijmel 2015), skin photosensitivity (more frequent to common: ≥4% to ≥10%) (Goetze 2017; Lebrun 2012; Shapiro 1997), Stevens-Johnson syndrome (rare: <1%) (Cac 2007; Shapiro 1997), urticaria (Shapiro 1997)
Endocrine & metabolic: Growth retardation (fibula; based on tetracycline data) (Cohlan 1963)
Gastrointestinal: Anorexia, Clostridioides difficile associated diarrhea (not associated with increased risk) (Deshpanda 2013; Tariq 2018), enamel hypoplasia (Stultz 2019), esophageal stenosis (rare: <1%) (Bonavina 1989), esophageal ulcer (rare: <1%) (Guo 2019), esophagitis (rare: <1%) (Kim 2014), glossitis, nausea (Shapiro 1997), staining of tooth (Stultz 2019), vomiting (Shapiro 1997)
Hematologic & oncologic: Basal cell carcinoma of skin (chronic use) (Li 2018)
Hepatic: Hepatotoxicity (rare: <1%; cholestatic, hepatocellular, or mixed hepatitis; may be accompanied by DRESS symptoms) (Bjornsson 1997; Heaton 2007; LiverTox 2019)
Hypersensitivity: Angioedema (Shapiro 1997), hypersensitivity reaction (Shapiro 1997), nonimmune anaphylaxis (Raeder 1984), serum sickness (Shapiro 1997)
Immunologic: Drug reaction with eosinophilia and systemic symptoms (Lebrun-Vignes 2012)
Nervous system: Bulging fontanel (based on tetracycline data) (Fields 1961; Opfer 1963), idiopathic intracranial hypertension (causality not established; females of childbearing age who are overweight or have a history of intracranial hypertension may be at greater risk)
Renal: Increased blood urea nitrogen
Hypersensitivity to doxycycline, other tetracyclines, or any component of the formulation.
Doxytab, JAMP-doxycycline [Canadian products]: Additional contraindications: Myasthenia gravis; concurrent use with isotretinoin.
Periostat, Apprilon [Canadian products]: Additional contraindications: Use in infants and children <8 years of age or during second or third trimester of pregnancy; breast-feeding.
Concerns related to adverse effects:
• Increased BUN: May be associated with increases in BUN secondary to antianabolic effects; this does not occur with use of doxycycline in patients with renal impairment.
• Intracranial hypertension: Intracranial hypertension (pseudotumor cerebri) has been reported; headache, blurred vision, diplopia, vision loss, and/or papilledema may occur. Women of childbearing age who are overweight or have a history of intracranial hypertension are at greater risk. Intracranial hypertension typically resolves after discontinuation of treatment; however, permanent visual loss is possible. If visual symptoms develop during treatment, prompt ophthalmologic evaluation is warranted. Intracranial pressure can remain elevated for weeks after drug discontinuation; monitor patient until stable.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection.
Disease-related concerns
• Oral candidiasis: Safety and effectiveness have not been established for treatment of periodontitis in patients with coexistent oral candidiasis; use with caution in patients with a history or predisposition to oral candidiasis.
Special populations:
• Pediatric: May cause tissue hyperpigmentation; manufacturer states to use in children ≤8 years of age only when the potential benefits outweigh the risks in severe or life threatening conditions (eg, anthrax, Rocky Mountain spotted fever), particularly when there are no alternative therapies. Limited use between 6 to 7 years of age has minimal effect on the color of permanent incisors (CDC [Biggs 2016]). Recommended in prevention and treatment of anthrax (AAP [Bradley 2014]), treatment of tickborne rickettsial diseases (CDC [Biggs 2016]), and Q fever (CDC [Anderson 2013]).
Dosage form specific issues:
• Oracea, Apprilon [Canadian product]: Should not be used for the treatment or prophylaxis of bacterial infections because the lower dose of drug per capsule may be subefficacious and promote resistance.
• Sulfite sensitivity: Syrup may contain sodium metabisulfite, which may cause allergic reactions in certain individuals (eg, asthmatic patients).
Other warnings/precautions:
• Appropriate use: Acne: The American Academy of Dermatology acne guidelines recommend doxycycline as adjunctive treatment for moderate and severe acne and forms of inflammatory acne that are resistant to topical treatments. Concomitant topical therapy with benzoyl peroxide or a retinoid should be administered with systemic antibiotic therapy (eg, doxycycline) and continued for maintenance after the antibiotic course is completed (AAD [Zaenglein 2016]).
• Limitations of use: Malaria prophylaxis: Doxycycline does not completely suppress asexual blood stages of Plasmodium strains; does not suppress P. falciparum's sexual blood stage gametocytes. Patients completing a regimen may still transmit the infection to mosquitoes outside endemic areas.
Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program
Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination
Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy
Antacids: May decrease the absorption of Tetracyclines. Management: Separate administration of antacids and oral tetracycline derivatives by several hours when possible to minimize the extent of this potential interaction. Monitor for decreased therapeutic effects of tetracyclines. Risk D: Consider therapy modification
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
Barbiturates: May decrease the serum concentration of Doxycycline. Risk C: Monitor therapy
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Tetracyclines. Risk C: Monitor therapy
Bismuth Subcitrate: May decrease the serum concentration of Tetracyclines. Management: Avoid administration of oral tetracyclines within 30 minutes of bismuth subcitrate administration. This is of questionable significance for at least some regimens intended to treat H. pylori infections. Risk D: Consider therapy modification
Bismuth Subsalicylate: May decrease the serum concentration of Tetracyclines. Management: Consider dosing tetracyclines 2 hours before or 6 hours after bismuth. The need to separate doses during Helicobacter pylori eradication regimens is questionable. Risk D: Consider therapy modification
Calcium Salts: May decrease the serum concentration of Tetracyclines. Management: If coadministration of oral calcium with oral tetracyclines cannot be avoided, consider separating administration of each agent by several hours. Risk D: Consider therapy modification
CarBAMazepine: May decrease the serum concentration of Doxycycline. Management: Consider increasing the doxycycline dose, or using another tetracycline derivative due to the potential for reduced doxycycline therapeutic effects when coadministered wth carbamazepine. If combined, monitor for reduced doxycyline efficacy. Risk D: Consider therapy modification
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Fosphenytoin: May decrease the serum concentration of Doxycycline. Management: Consider increasing the dose of doxycycline when initiating phenytoin, or using another tetracycline derivative to avoid this interaction. If coadministered, monitor for decreased therapeutic effects of doxycyline. Risk D: Consider therapy modification
Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Inhibitors of the Proton Pump (PPIs and PCABs): May decrease the bioavailability of Doxycycline. Risk C: Monitor therapy
Iron Preparations: Tetracyclines may decrease the absorption of Iron Preparations. Iron Preparations may decrease the serum concentration of Tetracyclines. Management: Avoid this combination if possible. Administer oral iron preparations at least 2 hours before, or 4 hours after, the dose of the oral tetracycline derivative. Monitor for decreased therapeutic effect of oral tetracycline derivatives. Risk D: Consider therapy modification
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Lanthanum: May decrease the serum concentration of Tetracyclines. Management: Administer oral tetracycline antibiotics at least 2 hours before or after lanthanum. Risk D: Consider therapy modification
Lithium: Tetracyclines may increase the serum concentration of Lithium. Risk C: Monitor therapy
Magnesium Dimecrotate: May interact via an unknown mechanism with Tetracyclines. Risk C: Monitor therapy
Magnesium Salts: May decrease the absorption of Tetracyclines. Only applicable to oral preparations of each agent. Management: Avoid coadministration of oral magnesium salts and oral tetracyclines. If coadministration cannot be avoided, administer oral magnesium at least 2 hours before, or 4 hours after, oral tetracyclines. Monitor for decreased tetracycline therapeutic effects. Risk D: Consider therapy modification
Mecamylamine: Tetracyclines may enhance the neuromuscular-blocking effect of Mecamylamine. Risk X: Avoid combination
Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy
Methoxyflurane: Tetracyclines may enhance the nephrotoxic effect of Methoxyflurane. Risk X: Avoid combination
Mipomersen: Tetracyclines may enhance the hepatotoxic effect of Mipomersen. Risk C: Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Tetracyclines. Management: Avoid this combination if possible. If coadministration cannot be avoided, administer the polyvalent cation-containing multivitamin at least 2 hours before or 4 hours after the tetracycline derivative. Monitor for decreased tetracycline effects. Risk D: Consider therapy modification
Multivitamins/Minerals (with AE, No Iron): May decrease the serum concentration of Tetracyclines. Management: If coadministration of a polyvalent cation-containing multivitamin with oral tetracyclines cannot be avoided, administer the polyvalent cation-containing multivitamin either 2 hours before or 4 hours after the tetracycline product. Risk D: Consider therapy modification
Neuromuscular-Blocking Agents: Tetracyclines may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Penicillins: Tetracyclines may diminish the therapeutic effect of Penicillins. Risk C: Monitor therapy
Phenytoin: May decrease the serum concentration of Doxycycline. Risk C: Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Quinapril: May decrease the serum concentration of Tetracyclines. Risk C: Monitor therapy
Retinoic Acid Derivatives: Tetracyclines may enhance the adverse/toxic effect of Retinoic Acid Derivatives. The development of pseudotumor cerebri is of particular concern. Risk X: Avoid combination
RifAMPin: May decrease the serum concentration of Doxycycline. Risk C: Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Strontium Ranelate: May decrease the serum concentration of Tetracyclines. Management: In order to minimize any potential impact of strontium ranelate on tetracycline antibiotic concentrations, it is recommended that strontium ranelate treatment be interrupted during tetracycline therapy. Risk X: Avoid combination
Sucralfate: May decrease the absorption of Tetracyclines. Management: Administer most tetracycline derivatives at least 2 hours prior to sucralfate in order to minimize the impact of this interaction. Administer oral omadacycline 4 hours prior to sucralfate. Risk D: Consider therapy modification
Sucroferric Oxyhydroxide: May decrease the serum concentration of Tetracyclines. Management: Administer oral/enteral doxycycline at least 1 hour before sucroferric oxyhydroxide. Specific dose separation guidelines for other tetracyclines are not presently available. No interaction is anticipated with parenteral administration of tetracyclines. Risk D: Consider therapy modification
Sulfonylureas: Tetracyclines may enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Tetracyclines may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Ethanol: Chronic ethanol ingestion may reduce the serum concentration of doxycycline.
Food: Doxycycline serum levels may be slightly decreased if taken with high-fat meal or milk. Administration with iron or calcium may decrease doxycycline absorption. May decrease absorption of calcium, iron, magnesium, zinc, and amino acids. Management: Administer Doryx and Doryx MPC without regard to meals. Administer Oracea and doxycycline 20 mg tablet on an empty stomach 1 hour before or 2 hours after meals.
Tetracyclines (in general): Take with food if gastric irritation occurs. While administration with food may decrease GI absorption of doxycycline by up to 20%, administration on an empty stomach is generally not recommended due to GI intolerance. Of currently available tetracyclines, doxycycline has the least affinity for calcium.
Doxycycline 20 mg tablet, Oracea, Apprilon [Canadian product]: Manufacturer states to take on an empty stomach 1 hour before or 2 hours after meals. Take with food if gastric irritation occurs.
Periostat [Canadian product]: Manufacturer states to take at least 1 hour before morning and evening meals. Take with food if gastric irritation occurs.
Some products may contain sodium.
Tetracyclines cross the placenta (Mylonas 2011).
Therapeutic doses of doxycycline during pregnancy are unlikely to produce substantial teratogenic risk, but data are insufficient to say that there is no risk. In general, reports of exposure have been limited to short durations of therapy in the first trimester. Tetracyclines accumulate in developing teeth and long tubular bones (Mylonas 2011). Permanent discoloration of teeth (yellow, gray, brown) can occur following in utero exposure and is more likely to occur following long-term or repeated exposure.
Doxycycline is used for the treatment of Lyme disease. Vertical transmission from mother to fetus is not well documented; it is unclear if infection increases the risk of adverse pregnancy outcomes. A single prophylactic dose of doxycycline can be used in pregnant patients; the use of treatment doses should be individualized (IDSA/AAN/ACR [Lantos 2021]; Lambert 2020; SOGC [Smith 2020]).
Doxycycline is the recommended agent for the treatment of Rocky Mountain spotted fever (RMSF) in pregnant patients (CDC [Biggs 2016]).
Untreated plague (Yersinia pestis) infection in pregnant patients may result in hemorrhage (including postpartum hemorrhage), maternal and fetal death, preterm birth, and stillbirth. Limited data suggest maternal-fetal transmission of Y. pestis can occur if not treated. Pregnant patients should be treated for Y. pestis; parenteral antibiotics are preferred for initial treatment when otherwise appropriate. Doxycycline may be used as an alternative antibiotic for treating pregnant patients with bubonic, pharyngeal, pneumonic, or septicemic plague. Doxycycline may also be used as an alternative antibiotic for pre- and postexposure prophylaxis in pregnant patients exposed to Y. pestis (CDC [Nelson 2021]).
For other indications, many guidelines consider use of doxycycline to be contraindicated during pregnancy, or to be a relative contraindication in pregnant patients if other agents are available and appropriate for use (CDC [Anderson 2013]; CDC 2020; HHS [OI adult] 2022; IDSA [Stevens 2014]). Doxycycline should not be used for the treatment of acne or rosacea in pregnant patients (AAD [Zaenglein 2016]). When systemic antibiotics are needed for dermatologic conditions, other agents are preferred (Kong 2013; Murase 2014). As a class, tetracyclines are generally considered second-line antibiotics in pregnant patients and their use should be avoided (Mylonas 2011).
With long-term use, monitor BUN, hematologic, and hepatic function tests; observe for changes in bowel frequency.
Inhibits protein synthesis by binding with the 30S and possibly the 50S ribosomal subunit(s) of susceptible bacteria; may also cause alterations in the cytoplasmic membrane
20 mg tablets and capsules (Periostat [Canadian product]): Proposed mechanism: Has been shown to inhibit collagenase activity in vitro. Also has been noted to reduce elevated collagenase activity in the gingival crevicular fluid of patients with periodontal disease. Systemic levels do not reach inhibitory concentrations against bacteria.
Absorption: Oral: Almost completely absorbed from the GI tract; average peak plasma concentration may be reduced ~20% (30% for Doryx MPC) by high-fat meal or milk
Distribution: Widely into body tissues and fluids including synovial, pleural, prostatic, seminal fluids, and bronchial secretions; saliva, aqueous humor, and CSF penetration is poor
Protein binding: >90%
Metabolism: Not hepatic; partially inactivated in GI tract by chelate formation
Bioavailability: Reduced at high pH; may be clinically significant in patients with gastrectomy, gastric bypass surgery or who are otherwise deemed achlorhydric
Half-life elimination: 18 to 22 hours; End-stage renal disease: 18 to 25 hours
Time to peak, serum: Oral: Immediate release: 1.5 to 4 hours; delayed release: 2.8 to 3 hours
Excretion: Feces (30%); urine (23% to 40%)
Altered kidney function: Excretion by the kidneys may fall as low as 1% to 5% in 72 hours in patients with CrCl <10 mL/minute.
Anti-infective considerations:
Parameters associated with efficacy: Time and concentration dependent, associated with 24-hour area under the curve (AUC24)/minimum inhibitory concentration (MIC); however, no specific goal AUC24/MIC has been identified (Agwuh 2006; Ambrose 2007; Cunha 2000; Smirnova 2011).
Expected drug exposure in normal renal function: AUC: Adults: Oral: 200 mg once daily for 1 dose, then 100 mg once daily: 12.7 ± 4.9 mg•hour/L (Schreiner 1985).
Postantibiotic effect: 0.7 to 2.8 hours, depending on organism (eg, S. aureus, S. pneumoniae, E. coli) (Cunha 2000).
If a public health emergency is declared and liquid doxycycline is unavailable for the treatment of anthrax, emergency doses may be prepared for children or adults who cannot swallow tablets.
Add 20 mL of water to one 100 mg tablet. Allow tablet to soak in the water for 5 minutes to soften. Crush into a fine powder and stir until well mixed. Appropriate dose should be taken from this mixture. To increase palatability, mix with food or drink. If mixing with drink, add 15 mL of milk, chocolate milk, chocolate pudding, or apple juice to the appropriate dose of mixture. If using apple juice, also add 4 teaspoons of sugar. Doxycycline and water mixture may be stored at room temperature for up to 24 hours.
Capsule, delayed release (Doxycycline Oral)
40 mg (per each): $24.94
Capsule, delayed release (Oracea Oral)
40 mg (per each): $33.16
Capsules (Doxycycline Hyclate Oral)
50 mg (per each): $2.16 - $2.25
100 mg (per each): $0.38 - $9.62
Capsules (Doxycycline Monohydrate Oral)
50 mg (per each): $1.45 - $1.55
75 mg (per each): $16.40 - $16.92
100 mg (per each): $2.13 - $2.56
150 mg (per each): $24.65
Capsules (Mondoxyne NL Oral)
100 mg (per each): $10.52
Capsules (Vibramycin Oral)
100 mg (per each): $1.09
Solution (reconstituted) (Doxy 100 Intravenous)
100 mg (per each): $25.20
Solution (reconstituted) (Doxycycline Hyclate Intravenous)
100 mg (per each): $18.20 - $30.20
Suspension (reconstituted) (Doxycycline Monohydrate Oral)
25 mg/5 mL (per mL): $0.38
Suspension (reconstituted) (Vibramycin Oral)
25 mg/5 mL (per mL): $0.83
Syrup (Vibramycin Oral)
50 mg/5 mL (per mL): $1.29
Tablet, EC (Doryx MPC Oral)
60 mg (per each): $24.00
120 mg (per each): $15.00
Tablet, EC (Doryx Oral)
50 mg (per each): $14.22
80 mg (per each): $44.03
200 mg (per each): $52.64
Tablet, EC (Doxycycline Hyclate Oral)
50 mg (per each): $11.73 - $13.51
75 mg (per each): $10.22
80 mg (per each): $39.58
100 mg (per each): $13.12 - $13.15
150 mg (per each): $17.60
200 mg (per each): $43.42 - $50.01
Tablets (Acticlate Oral)
75 mg (per each): $44.10
150 mg (per each): $44.10
Tablets (Doxycycline Hyclate Oral)
20 mg (per each): $0.74 - $1.30
50 mg (per each): $13.20
75 mg (per each): $31.15 - $31.19
100 mg (per each): $3.28 - $6.15
150 mg (per each): $31.15 - $31.19
Tablets (Doxycycline Monohydrate Oral)
50 mg (per each): $2.89 - $3.36
75 mg (per each): $4.93 - $4.99
100 mg (per each): $4.23 - $4.92
150 mg (per each): $9.14
Tablets (Lymepak Oral)
100 mg (per each): $68.93
Tablets (TargaDOX Oral)
50 mg (per each): $17.86
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