Doxycycline

Dosage Forms

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, 100 mg [contains brilliant blue fcf (fd&c blue #1)]

Vibramycin: 100 mg [contains brilliant blue fcf (fd&c blue #1)]

Generic: 50 mg, 100 mg

Capsule, Oral, as monohydrate [strength expressed as base]:

Adoxa: 150 mg [DSC] [contains fd&c red #40, fd&c yellow #6 (sunset yellow)]

Mondoxyne NL: 50 mg [contains fd&c yellow #10 (quinoline yellow)]

Mondoxyne NL: 75 mg [DSC]

Mondoxyne NL: 75 mg, 100 mg [contains fd&c yellow #10 (quinoline yellow)]

Monodox: 75 mg [DSC], 100 mg [DSC]

Okebo: 75 mg, 100 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, 1 x 100 mg, 2 x 100 mg [contains brilliant blue fcf (fd&c blue #1), cetyl alcohol, edetate disodium]

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:

Generic: 25 mg/5 mL (60 mL)

Suspension Reconstituted, Oral, as monohydrate [strength expressed as base]:

Vibramycin: 25 mg/5 mL (60 mL) [contains brilliant blue fcf (fd&c blue #1), 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) [contains butylparaben, propylene glycol, propylparaben, sodium metabisulfite; raspberry-apple flavor]

Tablet, Oral, as hyclate [strength expressed as base]:

Acticlate: 75 mg [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #6 (sunset yellow)]

Acticlate: 150 mg [scored; contains fd&c blue #2 (indigotine)]

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]:

Adoxa: 50 mg [DSC]

Adoxa: 75 mg [DSC] [contains fd&c yellow #10 aluminum lake, fd&c yellow #6 (sunset yellow)]

Adoxa: 100 mg [DSC]

Adoxa Pak 1/100: 100 mg [DSC] [contains fd&c yellow #10 aluminum lake, fd&c yellow #6 (sunset yellow)]

Adoxa Pak 2/100: 100 mg [DSC] [contains fd&c yellow #10 aluminum lake, fd&c yellow #6 (sunset yellow)]

Adoxa Pak 1/150: 150 mg [DSC] [scored; contains fd&c yellow #6 (sunset yellow)]

Avidoxy: 100 mg [contains fd&c yellow #10 aluminum lake, fd&c yellow #6 aluminum lake]

Generic: 50 mg, 75 mg, 100 mg, 150 mg

Tablet Delayed Release, Oral, as hyclate [strength expressed as base]:

Doryx: 50 mg [contains corn starch]

Doryx: 200 mg [DSC]

Doryx: 200 mg [scored; contains corn starch]

Doryx MPC: 120 mg [contains corn starch]

Soloxide: 150 mg [scored]

Generic: 50 mg, 75 mg, 80 mg [DSC], 100 mg, 150 mg, 200 mg

Pharmacology

Mechanism of Action

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.

Pharmacokinetics/Pharmacodynamics

Absorption

Oral: Almost completely from the GI tract; average peak plasma concentration can be reduced by high-fat meal or milk by ~20% (30% for Doryx MPC)

Distribution

Widely distributed into body tissues and fluids including synovial, pleural, prostatic, seminal fluids, and bronchial secretions; saliva, aqueous humor, and CSF penetration is poor

Metabolism

Not hepatic; partially inactivated in GI tract by chelate formation

Excretion

Feces (30%); urine (23% to 40%)

Time to Peak

Serum: Oral: Immediate release: 1.5 to 4 hours; delayed-release tablets: 2.8 to 3 hours

Half-Life Elimination

18 to 22 hours; End-stage renal disease: 18 to 25 hours

Protein Binding

>90%

Use in Specific Populations

Special Populations: Renal Function Impairment

Excretion by the kidneys may fall as low as 1% to 5% in 72 hours in patients with CrCl <10 mL/minute.

Use: Labeled Indications

Acne: Adjunctive therapy in severe acne.

Actinomycosis: Treatment of actinomycosis caused by Actinomyces israelii when penicillin is contraindicated.

Acute intestinal amebiasis: Adjunct to amebicides in acute intestinal amebiasis.

Anthrax, including inhalational anthrax (postexposure): Treatment of anthrax caused by Bacillus anthracis, including inhalational (postexposure) prophylaxis; to reduce the incidence or progression of disease following exposure to aerosolized B. anthracis.

Cholera: Treatment of cholera infections caused by Vibrio cholerae.

Clostridium: Treatment of infections caused by Clostridium spp. when penicillin is contraindicated.

Gram-negative infections: Treatment of infections caused by Escherichia coli, Enterobacter aerogenes, Shigella spp., Acinetobacter spp., Klebsiella spp. (respiratory and urinary infections), and Bacteroides spp.; Neisseria meningitidis (when penicillin is contraindicated).

Gram-positive infections: Treatment of infections caused by Streptococcus spp., when susceptible.

Listeriosis: Treatment of listeriosis due to Listeria monocytogenes when penicillin is contraindicated.

Malaria prophylaxis: Prophylaxis of malaria due to Plasmodium falciparum in short-term travelers (under 4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine-resistant strains.

Mycoplasma pneumoniae: Treatment of infections caused by Mycoplasma pneumoniae.

Ophthalmic infections: Treatment of inclusion conjunctivitis or trachoma caused by Chlamydia trachomatis.

Periodontitis (20 mg tablet and capsule [Periostat (Canadian product)] only): Adjunct to scaling and root planing to promote attachment level gain and to reduce pocket depth in patients with adult periodontitis.

Relapsing fever: Treatment of relapsing fever caused by Borrelia recurrentis.

Respiratory tract infections: Treatment of respiratory infections caused by Haemophilus influenzae, Klebsiella spp., or Mycoplasma pneumoniae; treatment of upper respiratory tract infections caused by Streptococcus pneumoniae; respiratory infections caused by Staphylococcus aureus (doxycycline is not the drug of choice in the treatment of any type of staphylococcal infection).

Rickettsial infections: Treatment of Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, and tick fevers caused by Rickettsiae.

Rosacea (Oracea, Apprilon [Canadian product] only): Treatment of only inflammatory lesions (papules and pustules) of rosacea in adults.

Sexually transmitted infections: Treatment of lymphogranuloma venereum and uncomplicated urethral, endocervical, or rectal infections caused by Chlamydia trachomatis; granuloma inguinale (donovanosis) caused by Klebsiella granulomatis; chancroid caused by Haemophilus ducreyi; nongonococcal urethritis caused by Ureaplasma urealyticum; when penicillin is contraindicated, uncomplicated gonorrhea caused by Neisseria gonorrhea and syphilis caused by Treponema pallidum.

Note: The CDC sexually transmitted disease guidelines recommend dual antimicrobial therapy be used for uncomplicated gonorrhea due to N. gonorrhea resistance concerns; ceftriaxone is the preferred cephalosporin and doxycycline is an alternative option for the second antimicrobial only in cases of azithromycin allergy (CDC [Workowski 2015]).

Skin and skin structure infections (Avidoxy only): Treatment of skin and skin structure infections caused by Staphylococcus aureus (doxycycline is not the drug of choice in the treatment of any type of staphylococcal infection).

Vincent infection: Treatment of Vincent infection caused by Fusobacterium fusiforme when penicillin is contraindicated.

Yaws: Treatment of yaws caused by Treponema pallidum subspecies pertenue when penicillin is contraindicated.

Zoonotic infections: Treatment of psittacosis (ornithosis) caused by Chlamydophila psittaci; plague due to Yersinia pestis; tularemia caused by Francisella tularensis; brucellosis caused by Brucella spp. (in conjunction with streptomycin); bartonellosis caused by Bartonella bacilliformis; infections caused by Campylobacter fetus.

Use: Off Label

Anaplasmosis and ehrlichiosisyes

Based on the IDSA guidelines for the clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis (HGA) and babesiosis and the Centers for Disease Control and Prevention (CDC) guideline for the diagnosis and management of tickborne rickettsial diseases, doxycycline is effective and recommended for the treatment of human anaplasmosis (also known as HGA) and human ehrlichiosis.

Bartonella infections in HIV-infected patientsyes

Based on the US Department of Health and Human Services (HHS) guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents, doxycycline is a recommended and effective agent for treatment of bacillary angiomatosis, peliosis hepatis, bacteremia, osteomyelitis, CNS infections, infective endocarditis, and other severe infections due to Bartonella in adolescent and adult HIV-infected patients.

Bite wound infection (animal or human bite)yes

Based on the IDSA guidelines for the diagnosis and management of SSTIs, doxycycline is an acceptable alternative agent for the prophylaxis and treatment of bite wounds (animal or human).

Cellulitis, mild to moderateyes

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTIs) and the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections, doxycycline is an effective and recommended treatment option for SSTIs caused by MRSA, particularly purulent cellulitis due to community-acquired MRSA (CA-MRSA).

Chronic obstructive pulmonary disease, acute exacerbationb

Data from a randomized, double-blind, placebo-controlled trial support the use of doxycycline in the treatment of acute exacerbation of chronic obstructive pulmonary disease (COPD) Daniels 2010.

Epididymitis, acuteyes

Based on the CDC sexually transmitted diseases treatment guidelines, doxycycline in combination with ceftriaxone is an effective and recommended agent in the treatment acute epididymitis likely caused by sexually transmitted chlamydia and gonorrhea.

Lyme disease (Borrelia spp. infection)byes

Controlled trials support the use of doxycycline in the prevention of development of Lyme disease when administered within 72 hours of the Ixodes scapularis tick bite and also in the management of multiple manifestations of Lyme disease.

Guidelines from the IDSA and American Academy of Neurology (AAN) recommend the use of oral doxycycline as an effective treatment for multiple manifestations of Lyme disease, including more severe neurological manifestations and late Lyme arthritis.

Malaria, treatmentyes

Based on the CDC guidelines for the treatment of malaria in the United States, doxycycline is an effective and recommended treatment option for uncomplicated Plasmodium falciparum or unidentified species in areas with chloroquine-resistance or unknown resistance (in combination with quinine sulfate); Plasmodium vivax in chloroquine-resistant areas (in combination with quinine sulfate and primaquine); and severe malaria (in combination with quinidine gluconate).

Otitis media, acutec

Clinical experience suggests the utility of doxycycline for the management of acute otitis media Limb 2019.

Pelvic inflammatory diseaseyes

Based on the CDC sexually transmitted diseases treatment guidelines, doxycycline, in combination with other appropriate agents, is effective and recommended in the treatment of pelvic inflammatory disease.

Pleurodesis, chemical (sclerosing agent for pleural effusion)cyes

Data from a limited number of patients studied suggest that intrapleural doxycycline may be beneficial in the management of malignant pleural effusions Porcel 2006, Robinson 1993.

Based on the American College of Chest Physicians diagnosis and management of lung cancer clinical practice guidelines, intrapleural doxycycline is effective and recommended in the management of recurrent, symptomatic, malignant pleural effusions.

Proctitis, acute or proctocolitisyes

Based on the CDC sexually transmitted diseases treatment guidelines, doxycycline in combination with ceftriaxone is an effective and recommended agent in the treatment of acute proctitis or proctocolitis.

Prosthetic joint infectionyes

Based on the IDSA guidelines for the management of prosthetic joint infection, doxycycline is an effective and recommended agent for treatment (oral phase) of prosthetic joint infection and for chronic oral antimicrobial suppression of prosthetic joint infection due to staphylococci or Cutibacterium acnes.

Surgical prophylaxis, uterine evacuation (induced abortion or pregnancy loss)yes

Based on the American College of Obstetricians and Gynecologists guidelines for prevention of infection after gynecologic procedures, doxycycline is effective and recommended as antimicrobial prophylaxis for uterine evacuation procedures for induced abortion or pregnancy loss.

Contraindications

Hypersensitivity to doxycycline, other tetracyclines, or any component of the formulation

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

Dosage and Administration

Dosing: Adult

Note: Doxycycline is available as hyclate, monohydrate, and calcium salts. All doses are expressed as doxycycline base.

Usual dosage range:

Oral: Immediate-release and most extended-release formulations: 100 to 200 mg/day in 1 to 2 divided doses. Note: 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 (moderate to severe, inflammatory) (off-label dose): Oral: Note: Use as an adjunct to topical acne therapy (AAD [Zaenglein 2016]).

Immediate release: 50 to 100 mg twice daily or 100 mg once daily (AAD [Zaenglein 2016]; Graber 2019).

Extended release: 100 mg twice daily on day 1, then 100 mg once daily (AAD [Zaenglein 2016]; Graber 2019).

Subantimicrobial dosing: 20 mg twice daily (immediate release) or 40 mg once daily (delayed release) (Moore 2015; Skidmore 2003).

Duration: Use the shortest possible duration to minimize risk of adverse effects and development of bacterial resistance; re-evaluate at 3 to 4 months (AAD [Zaenglein 2016]).

Anaplasmosis and ehrlichiosis (off-label use): Oral, IV: 100 mg twice daily for 10 days (IDSA [Wormser 2006]) or at least 3 days after resolution of fever (CDC [Biggs 2016]).

Anthrax: Note: Consult public health officials for event-specific recommendations.

Inhalational exposure (postexposure prophylaxis): Oral: 100 mg every 12 hours for 60 days (CDC [Hendricks 2014]).

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 (CDC [Hendricks 2014]). 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 (CDC [Hendricks 2014]).

Bartonella spp. infection:

HIV-infected (off-label use): Note: Duration of therapy is at least 3 months; continuation of therapy depends on relapse occurrence and clinical condition (HHS [OI adult 2019]).

Bacillary angiomatosis, peliosis hepatis, bacteremia, and osteomyelitis: Oral, IV: 100 mg every 12 hours (HHS [OI adult 2019]). Note: Some experts recommend concomitant gentamicin for the first 2 weeks of therapy for patients with Bartonella bloodstream infection (Rolain 2004; Spach 2019a).

CNS infections: Oral, IV: 100 mg every 12 hours; may add rifampin therapy (HHS [OI adult 2019]).

Endocarditis: Oral, IV: 100 mg IV every 12 hours in combination with gentamicin for 2 weeks, then continue with doxycycline 100 mg IV or orally every 12 hours (HHS [OI adult 2019]).

Other severe infections: Oral, IV: 100 mg every 12 hours in combination with rifampin (HHS [OI adult 2019]).

HIV-uninfected:

Bacteremia without endocarditis: Oral: 200 mg once daily or 100 mg twice daily for 4 weeks with gentamicin once daily for first 2 weeks (Foucault 2003; Rolain 2004).

Cat-scratch disease, CNS infection, and neuroretinitis: Oral, IV: 100 mg twice daily in combination with rifampin (Rolain 2004).

Endocarditis: Oral: 100 mg every 12 hours for 6 to 12 weeks with gentamicin for first 2 weeks (Rolain 2004; Spach 2019b).

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 (IDSA [Stevens 2014]); duration of treatment for established infection is typically 5 to 14 days (Baddour 2019a; Baddour 2019b). Note: Some experts use in combination with an appropriate agent for anaerobes (Baddour 2019a; Baddour 2019b; IDSA [Stevens 2014]).

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 (Bosilkovski 2019; Jia 2017; Zheng 2018).

Uncomplicated (nonfocal): Oral: 100 mg twice daily for 6 weeks as part of an appropriate combination regimen (Ariza 2007; Hasanjani Roushan 2006; Skalsky 2008).

Spondylitis: Oral: 100 mg twice daily for at least 12 weeks as part of an appropriate combination regimen (Bosilkovski 2019; Colmenero 1994).

Postexposure prophylaxis (high-risk laboratory exposure): Oral: 100 mg twice daily with rifampin for 3 weeks (CDC 2012); for exposure to B. abortus RB51 strains, some experts give doxycycline plus trimethoprim-sulfamethoxazole (Bosilkovski 2019).

Cellulitis, mild to moderate (outpatient treatment; empiric coverage of MRSA) (off-label use): Oral: 100 mg twice daily for 5 to 14 days (IDSA [Liu 2011]; IDSA [Stevens 2014]). Note: For empiric therapy of nonpurulent cellulitis, an additional agent (eg, amoxicillin, cephalexin) for coverage of beta-hemolytic streptococci is needed.

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 (CDC 2015; WHO 2010).

Chronic obstructive pulmonary disease, acute exacerbation: Oral: 200 mg once daily for 5 to 7 days (Daniels 2010; GOLD 2018). Note: Some experts reserve for patients with uncomplicated COPD (eg, age <65 years without major comorbidities, FEV₁ >50% predicted, infrequent exacerbations) (Anzueto 2007; Sethi 2008).

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: Deer tick attached for ≥36 hours, prophylaxis can be given within 72 hours of tick removal, local rate of deer tick infection with Borrelia burgdorferi is ≥20%, and there are no contraindications to doxycycline (Hu 2017; IDSA [Wormser 2006]).

Treatment, early localized disease (single erythema migrans lesion): Oral: 100 mg twice daily for 10 to 21 days (IDSA [Wormser 2006]); some experts prefer a 10-day duration (Sanchez 2016; Wormser 2003).

Treatment, early disseminated disease (multiple erythema migrans lesions): Oral:100 mg twice daily for 14 to 21 days (Hu 2019).

Treatment, early disseminated neurologic disease (isolated facial nerve palsy, meningitis, or radiculoneuropathy): Oral: 100 mg twice daily for 14 days (range: 14 to 28 days) (Hu 2019; IDSA [Wormser 2006]).

Treatment, early disseminated 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 (IDSA [Wormser 2006], although some experts extend the duration up to 28 days in those with serious disease (Hu 2019).

Treatment, arthritis without neurologic involvement: Oral: 100 mg twice daily for 28 days (IDSA [Wormser 2006]).

Malaria:

Chemoprophylaxis in travelers: 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.

Uncomplicated malaria, treatment (chloroquine resistant or unknown resistance; alternative agent) (off-label use): Oral: 100 mg twice daily for 7 days in combination with quinine sulfate (plus primaquine for Plasmodium vivax). Note: Quinine sulfate duration is region specific; consult CDC for current recommendations (CDC 2013).

Severe malaria, treatment (alternative agent) (off-label use): IV, Oral: 100 mg every 12 hours for 7 days in combination with quinidine gluconate. Note: IV therapy should be administered for at least 24 hours or until oral medication tolerated; quinidine gluconate duration is region specific; consult CDC for current recommendations (CDC 2013).

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) (Limb 2019).

Periodontitis, chronic: Subantimicrobial dosing: Oral: 20 mg twice daily (immediate release) for 3 to 9 months as an adjunct to periodontal debridement (Smiley 2015).

Plague (Yersinia pestis) (alternative agent): Oral, IV: 200 mg initially then 100 mg twice daily or 200 mg once daily for 10 to 14 days and at least until 2 days after patient has defervesced (CDC 2015; IDSA [Stevens 2014]; Inglesby 2000; Sexton 2019a).

Pleurodesis, chemical (sclerosing agent for pleural effusion) (off-label use): Intrapleural: 500 mg as a single dose in 30 to 100 mL NS (Porcel 2006; Robinson 1993); may require a repeat dose (Kvale 2007); some experts combine with or administer following instillation of a local anesthetic (eg, lidocaine, 10 mL [100 mg] of 1% solution [Robinson 1993] or mepivacaine 20 mL [400 mg] of 2% solution [Porcel 2006]).

Pneumonia, community-acquired (alternative agent): Outpatients or inpatients (non-ICU): Oral, IV: 100 mg twice daily; for empiric therapy of inpatients, use in combination with another appropriate agent (eg, antipneumococcal beta-lactam). Duration is for a minimum of 5 days; patients should be afebrile for ≥48 hours and clinically stable before discontinuing therapy (IDSA/ATS [Mandell 2007]).

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 (Berbari 2019; IDSA [Osmon 2013]).

Chronic suppression for staphylococci (methicillin resistant) and Cutibacterium acnes (alternative agent for C. acnes): Oral: 100 mg twice daily (IDSA [Osmon 2013]).

Q fever: Oral:

Acute: 100 mg every 12 hours for 14 days (CDC [Anderson 2013]). Note: In patients with valvulopathy/cardiomyopathy, some experts recommend extending treatment to 12 months in combination with hydroxychloroquine to prevent progression to persistent infection (Million 2013; Raoult 2019).

Persistent localized infection (endocarditis, vascular infection): Oral: 100 mg every 12 hours in combination with hydroxychloroquine for ≥18 months depending on site of infection and serologic response (CDC [Anderson 2013]).

Rhinosinusitis, acute bacterial (alternative agent for beta-lactam intolerance): Oral: 200 mg/day in 1 to 2 divided doses for 5 to 7 days (IDSA [Chow 2012]). Note: In uncomplicated acute bacterial rhinosinusitis, initial observation and symptom management without antibiotic therapy is appropriate in most patients (ACP/CDC [Harris 2016]).

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 (CDC [Biggs 2016]). Note: A loading dose of 200 mg IV is recommended for critically ill patients (Sexton 2019b).

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 (Akhyani 2008; Maier 2019).

Subantimicrobial dosing: 40 mg once daily (delayed release; Oracea) or 20 mg twice daily (immediate release) (Sanchez 2005).

Sexually transmitted infections:

Cervicitis or urethritis:

Chlamydia trachomatis: Oral: 100 mg twice daily for 7 days (CDC [Workowski 2015]) or 200 mg delayed release once daily for 7 days (Geisler 2012); consider concurrent treatment for gonorrhea with a single dose of ceftriaxone based on individual risk factors, if local prevalence is elevated (>5%), or if intracellular gram-negative diplococci on Gram stain (CDC [Workowski 2015]; Marrazzo 2017). Note: Directly observed single-dose azithromycin is preferred for the treatment of uncomplicated genital chlamydial infections by some experts (Marrazzo 2017).

Neisseria gonorrhea (alternative agent [due to resistance]; reserve for patients with azithromycin intolerance): Oral: 100 mg twice daily for 7 days in combination with a single dose of ceftriaxone (CDC [Workowski 2015]).

Epididymitis, acute (off-label use): Empiric or pathogen-directed therapy for chlamydia and/or gonorrhea: Oral: 100 mg twice daily for 10 days with single dose of ceftriaxone (CDC [Workowski 2015]). Note: An alternative regimen is recommended in patients who practice insertive anal sex (Eyre 2019; Marrazzo 2017).

Granuloma inguinale (donovanosis) (alternative agent): Oral: 100 mg twice daily for at least 3 weeks and until all lesions have healed. Note: If symptoms do not improve within the first few days of therapy, another agent (eg, aminoglycoside) can be added (CDC [Workowski 2015]).

Lymphogranuloma venereum: Oral: 100 mg twice daily for 21 days (CDC [Workowski 2015]).

Pelvic inflammatory disease (off-label use):

Inpatient (severe PID): IV, Oral: 100 mg every 12 hours in combination with cefoxitin or cefotetan; transition to oral therapy after >24 hours improvement to complete a 14-day total course. If pelvic abscess, anaerobic coverage is warranted (CDC [Workowski 2015]).

Outpatient (mild to moderate PID): Oral: 100 mg every 12 hours for 14 days in combination with a single dose of ceftriaxone (preferred) (Wiesenfeld 2019) or single dose of cefoxitin plus oral probenecid or other third generation cephalosporin; if Trichomonas vaginalis or recent uterine instrumentation, add metronidazole (CDC [Workowski 2015]).

Proctitis, acute or proctocolitis (off-label use): Empiric or pathogen-directed therapy for chlamydia and/or gonorrhea: Oral: 100 mg twice daily for 7 days plus a single dose of ceftriaxone. Note: Provide 21 days of doxycycline if polymerase chain reaction (PCR) for lymphogranuloma venereum (LGV) confirmed or as presumptive therapy for LGV if patient has severe rectal symptoms (eg, bloody discharge, perianal ulcers, or mucosal ulcers), and either a positive rectal chlamydia NAAT or HIV infection. Additional coverage for herpes simplex virus is warranted in patients with perianal or mucosal ulcers (CDC [Workowski 2015]).

Syphilis, penicillin-allergic patients: Note: Limited data support use of alternatives to penicillin and close serologic and clinical follow up is warranted (CDC [Workowski 2015]; Hicks 2019).

Early syphilis (primary, secondary, and early latent): Oral: 100 mg twice daily for 14 days (CDC [Workowski 2015]).

Late syphilis (late latent): Oral: 100 mg twice daily for 28 days (CDC [Workowski 2015]).

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 (ACOG 2018).

Tularemia (Francisella tularensis):

Treatment (mild infection) (alternative agent): Oral: 100 mg twice daily for 14 to 21 days (IDSA [Stevens 2014]; Penn 2019).

Postexposure prophylaxis (nonbioterrorism event, high-risk exposure): Oral: 100 mg twice daily for 14 days (Penn 2019).

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 (Dennis 2001).

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 (Dennis 2001).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

General dosing: Children ≥8 years and Adolescents: Oral, IV: 2.2 mg/kg/dose every 12 hours, maximum daily dose: 200 mg/day.

Anthrax (AAP [Bradley 2014]):

Prophylaxis; post-exposure (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, 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.

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: 1 to 2 mg/kg/dose twice daily for 6 weeks; maximum dose: 100 mg/dose; use in combination with rifampin or an aminoglycoside (Red Book [AAP 2015]).

Chlamydial infections, uncomplicated (sexually transmitted C. trachomatis): Adolescents: Oral: 100 mg twice daily for 7 days (CDC [Workowski 2015]).

Lyme disease: Limited data available:

Prophylaxis, postexposure: Children and Adolescents: Oral: 4.4 mg/kg/dose once as a single dose; maximum dose: 200 mg/dose; initiate within 72 hours of tick removal (CDC 2019).

Treatment:

Early Lyme disease: Note: The American Academy of Pediatrics (AAP) recommends the use of doxycycline in ages <8 years for treatment courses ≤21 days; this recommendation is based upon data in younger children treated for Rocky Mountain spotted fever that suggest short courses of doxycycline are unlikely to cause visible teeth staining or enamel hyperplasia (Red Book [AAP 2018]).

Erythema migrans: Children ≥8 years and Adolescents: Oral: 2 mg/kg/dose twice daily for 10 to 21 days (usual duration: 14 days); maximum dose: 100 mg/dose (IDSA [Wormser 2006]).

Meningitis, neurologic Lyme disease: Children ≥8 years and Adolescents: Oral: 2 to 4 mg/kg/dose twice daily for 10 to 28 days; maximum dose: 200 mg/dose (IDSA [Wormser 2006]).

Borrelial lymphocytoma: Children ≥8 years and Adolescents: Oral: 2 mg/kg/dose twice daily for 10 to 21 days (usual duration: 14 days); maximum dose: 100 mg/dose (IDSA [Wormser 2006]).

Late Lyme disease: Lyme arthritis (no neurologic involvement): Children ≥8 years and Adolescents: Oral: 2 mg/kg/dose twice daily for 28 days; maximum dose: 100 mg/dose (IDSA [Wormser 2006]).

Malaria: Children ≥8 years and Adolescents:

Prophylaxis: 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.

Treatment: Oral, IV: 2.2 mg/kg/dose twice daily for 7 days; maximum dose: 100 mg/dose (CDC 2013); for uncomplicated cases, combination therapy with quinine sulfate is recommended; in severe cases, combination therapy with quinidine gluconate should be used; Note: Duration of either quinine sulfate or quinidine gluconate is region-specific; consult CDC for current recommendations.

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 (IDSA [Bradley 2011]).

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) (CDC [Anderson 2013]).

Skin/soft tissue infections; MRSA or community-acquired cellulitis (purulent) (IDSA [Liu 2011]): 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 (CDC [Biggs 2016]).

Reconstitution

Intravenous: Reconstitute vials with 10 mL of SWFI or compatible IV solution for each 100 mg of doxycycline, to a concentration of 10 mg/mL. Each 100 mg is further diluted with 100 to 1,000 mL of a compatible IV solution (eg, D5W, NS) to a final concentration of 0.1 to 1 mg/mL.

Intrapleural (off-label route): Dilute with 30 to 100 mL NS; may also combine with or administer following a local anesthetic (Porcel 2006; Robinson 1993)

Extemporaneously Prepared

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.

US Food and Drug Administration, Center for Drug Evaluation and Research, “Public Health Emergency Home Preparation Instructions for Doxycycline.” Available at http://www.fda.gov/Drugs/EmergencyPreparedness/BioterrorismandDrugPreparedness/ucm130996.htm

Administration

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 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: May be administered by carefully breaking up the tablet and sprinkling tablet contents on a spoonful of cold applesauce. 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.

Periostat [Canadian product]: Administer 1 hour before breakfast and evening meal.

IV: Infuse IV doxycycline over 1 to 4 hours. Avoid extravasation. 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 (Porcel 2006; Robinson 1993).

Dietary Considerations

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.

Storage

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.

Drug Interactions

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). 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. Consider therapy modification

Barbiturates: May decrease the serum concentration of Doxycycline. Consider therapy modification

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Tetracyclines. Consider therapy modification

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. 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. Consider therapy modification

Calcium Salts: May decrease the serum concentration of Tetracyclines. Management: If coadministration of oral calcium with oral tetracyclines can not be avoided, consider separating administration of each agent by several hours. Consider therapy modification

CarBAMazepine: May decrease the serum concentration of Doxycycline. 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. Avoid combination

Fosphenytoin: May decrease the serum concentration of Doxycycline. Consider therapy modification

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. Exceptions: Ferric Carboxymaltose; Ferric Derisomaltose; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Consider therapy modification

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Lanthanum: May decrease the serum concentration of Tetracyclines. Management: Administer oral tetracycline antibiotics at least two hours before or after lanthanum. Consider therapy modification

Magnesium Dimecrotate: May interact via an unknown mechanism with Tetracyclines. Monitor therapy

Magnesium Salts: May decrease the absorption of Tetracyclines. Only applicable to oral preparations of each agent. Consider therapy modification

Mecamylamine: Tetracyclines may enhance the neuromuscular-blocking effect of Mecamylamine. Avoid combination

Methoxyflurane: Tetracyclines may enhance the nephrotoxic effect of Methoxyflurane. Avoid combination

Mipomersen: Tetracyclines may enhance the hepatotoxic effect of Mipomersen. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Tetracyclines. Management: If coadministration of a polyvalent cation-containing multivitamin with oral tetracyclines can not be avoided, separate administration of each agent by several hours. 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 can not be avoided, separate administration of each agent by several hours. Consider therapy modification

Neuromuscular-Blocking Agents: Tetracyclines may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Penicillins: Tetracyclines may diminish the therapeutic effect of Penicillins. Monitor therapy

Phenytoin: May decrease the serum concentration of Doxycycline. Consider therapy modification

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy

Proton Pump Inhibitors: May decrease the bioavailability of Doxycycline. Monitor therapy

Quinapril: May decrease the serum concentration of Tetracyclines. Management: Separate doses of quinapril and oral tetracycline derivatives by at least 2 hours in order to reduce the risk of interaction. Monitor for reduced efficacy of the tetracycline if these products are used concomitantly. Consider therapy modification

Retinoic Acid Derivatives: Tetracyclines may enhance the adverse/toxic effect of Retinoic Acid Derivatives. The development of pseudotumor cerebri is of particular concern. Exceptions: Adapalene; Bexarotene (Topical); Tretinoin (Topical). Avoid combination

RifAMPin: May decrease the serum concentration of Doxycycline. 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. 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. 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. 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. Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Tetracyclines may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Test Interactions

Injectable tetracycline formulations (if they contain large amounts of ascorbic acid) may result in a false-negative urine glucose using glucose oxidase tests (eg, Clinistix, Diastix, Tes-Tape); false elevations of urinary catecholamines with fluorescence

Adverse Reactions

1% to 10%:

Cardiovascular: Hypertension (3%)

Central nervous system: Anxiety (2%), pain (2%)

Endocrine & metabolic: Increased lactate dehydrogenase (2%), increased serum glucose (1%)

Gastrointestinal: Diarrhea (5%), upper abdominal pain (2%), abdominal distention (1%), abdominal pain (1%), xerostomia (1%)

Hepatic: Increased serum aspartate aminotransferase (2%)

Infection: Fungal infection (2%), influenza (2%)

Neuromuscular & skeletal: Back pain (1%)

Respiratory: Nasopharyngitis (5%), sinusitis (3%), nasal congestion (2%), sinus headache (1%)

Frequency not defined:

Dermatologic: Skin hyperpigmentation

Gastrointestinal: Esophageal ulcer, esophagitis

<1%, postmarketing, and/or case reports: Anaphylactoid reaction, anaphylaxis, angioedema, anorexia, bulging fontanel, Clostridioides difficile associated diarrhea, Clostridioides difficile colitis, dental discoloration, DRESS syndrome, dysphagia, enamel hypoplasia, enterocolitis, eosinophilia, erythema multiforme, erythematous rash, exacerbation of systemic lupus erythematosus, exfoliative dermatitis, glossitis, headache, hemolytic anemia, hepatotoxicity, hypersensitivity reaction, increased blood urea nitrogen, increased serum alanine aminotransferase, inflammatory anogenital lesion, intracranial hypertension, Jarisch-Herxheimer reaction, maculopapular rash, nausea, neutropenia, pancreatitis, pericarditis, serum sickness, skin hyperpigmentation, skin photosensitivity, Stevens-Johnson syndrome, thrombocytopenia, thyroid disease (brown/black discoloration; no dysfunction reported), toxic epidermal necrolysis, urticaria, vomiting

Warnings/Precautions

Concerns related to adverse effects:

• GI inflammation/ulceration: Esophagitis and ulcerations (sometimes severe) may occur; patients with dysphagia and/or retrosternal pain may require assessment for esophageal lesions.
• Hepatotoxicity: Rarely occurs; if symptomatic, assess LFTs and discontinue drug.
• Hypersensitivity syndromes: Severe skin reactions (eg, exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms [DRESS]) have been reported. Discontinue therapy for serious hypersensitivity reactions.
• 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.
• Photosensitivity: May cause photosensitivity; discontinue at first sign of skin erythema. Use skin protection and avoid prolonged exposure to sunlight and ultraviolet light.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
• Tissue hyperpigmentation: May induce hyperpigmentation in many organs, including nails, bone, skin (diffuse pigmentation as well as over sites of scars and injury), eyes, thyroid, visceral tissue, oral cavity (adult teeth, mucosa, alveolar bone), sclerae, and heart valves independently of time or amount of drug administration.

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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pediatric: May cause tissue hyperpigmentation, tooth enamel hypoplasia, or permanent tooth discoloration (more common with long-term use, but observed with repeated, short courses) when used during tooth development (last half of pregnancy, infancy, and childhood ≤8 years of age); 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 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.

Monitoring Parameters

CBC, renal and liver function tests periodically with prolonged therapy. When used as part of alternative treatment for gonococcal infection, test of cure 7 days after dose (CDC [Workowski 2015]).

Patients with no risk factors for chronic Q fever should undergo clinical and serological evaluation 6 months after diagnosis of acute Q fever to identify possible progression to chronic disease. Postpartum women treated during pregnancy for acute Q fever, others who are at high risk for progression to chronic disease or when used as part of treatment for chronic Q fever infection unrelated to endocarditis or vascular infection (eg, osteoarticular infections or chronic hepatitis), assess serologic response at 3, 6, 12, 18, and 24 months after diagnosis of acute Q fever (or after delivery in pregnant women) (CDC 2013).

Pregnancy

Pregnancy Considerations

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 the recommended agent for the treatment of Rocky Mountain spotted fever (RMSF) in pregnant women (CDC [Biggs 2016]). For other indications, many guidelines consider use of doxycycline to be contraindicated during pregnancy, or to be a relative contraindication in pregnant women if other agents are available and appropriate for use (Anderson 2013; CDC 2011; HHS [OI adult 2015]; Stevens 2014; Workowski [CDC 2015]; IDSA [Wormser 2006]). Doxycycline should not be used for the treatment of rosacea in pregnant women. 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 women and their use should be avoided (Mylonas 2011).

Patient Education

What is this drug used for?

• It is used to treat pimples (acne).
• It is used to treat or prevent bacterial infections.
• It is used to prevent malaria.
• It is used to treat swelling of the tissue around the teeth (periodontitis). It is used with scaling and root planing.
• It is used to treat rosacea.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Tooth discoloration
• Nausea
• Vomiting
• Diarrhea
• Lack of appetite

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.
• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting.
• Chest pain
• Not able to pass urine
• Change in amount of urine passed
• Chills
• Sore throat
• Trouble swallowing
• Bruising
• Bleeding
• Joint pain
• Muscle pain
• Fast heartbeat
• Fast breathing
• Throat irritation
• Skin discoloration
• Flushing
• Severe dizziness
• Passing out
• Severe loss of strength and energy
• Swollen gland
• Vaginal itching or discharge
• Headache
• Blurred vision
• Double vision
• Blindness
• Clostridioides (formerly Clostridium) difficile (C. diff)-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools.
• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes.
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.