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Doxycycline

Pronunciation

Pronunciation

(doks i SYE kleen)

Index Terms

  • Doryx MPC
  • Doxycycline Calcium
  • Doxycycline Hyclate
  • Doxycycline Monohydrate

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)]

Oraxyl: 20 mg [DSC]

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 [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

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

Monodox: 75 mg, 100 mg

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]:

Alodox Convenience: 20 mg [DSC]

Morgidox: 1 x 50 MG, 2 x 100 mg, 1 x 100 mg [contains brilliant blue fcf (fd&c blue #1), cetyl alcohol, edetate disodium]

Ocudox: 50 mg [DSC] [contains brilliant blue fcf (fd&c blue #1)]

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

NicAzelDoxy 30: 100 mg [DSC] [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 aluminum lake, fd&c yellow #6 (sunset yellow), fd&c yellow #6 aluminum lake, tartrazine (fd&c yellow #5)]

NicAzelDoxy 60: 100 mg [DSC] [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 aluminum lake, fd&c yellow #6 (sunset yellow), fd&c yellow #6 aluminum lake, tartrazine (fd&c yellow #5)]

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, 100 mg

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

Adoxa: 50 mg

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

Adoxa: 100 mg

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

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

Adoxa Pak 1/150: 150 mg [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

Doryx: 150 mg, 200 mg [scored]

Doryx MPC: 120 mg [contains corn starch]

Generic: 50 mg, 75 mg, 100 mg, 150 mg, 200 mg

Brand Names: U.S.

  • Acticlate
  • Adoxa
  • Adoxa Pak 1/100
  • Adoxa Pak 1/150
  • Adoxa Pak 2/100
  • Alodox Convenience [DSC]
  • Avidoxy
  • Doryx
  • Doryx MPC
  • Doxy 100
  • Mondoxyne NL
  • Monodox
  • Morgidox
  • NicAzelDoxy 30 [DSC]
  • NicAzelDoxy 60 [DSC]
  • Ocudox [DSC]
  • Oracea
  • Oraxyl [DSC]
  • TargaDOX
  • Vibramycin

Pharmacologic Category

  • Antibiotic, Tetracycline Derivative

Pharmacology

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

Periostat capsules [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 from the GI tract; absorption can be reduced by food or milk by 20%

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; Periostat [Canadian product]: ~53-134 L

Metabolism

Not hepatic; partially inactivated in GI tract by chelate formation

Excretion

Feces (30%); urine (23%)

Time to Peak

Serum: 1.5-4 hours

Half-Life Elimination

Single dose: 12-15 hours (usually increases to 22-24 hours with multiple doses); End-stage renal disease: 18-25 hours

Oracea (US labeling), Apprilon (Canadian labeling): Single dose: 21 hours

Periostat [Canadian product]: Single dose: 18 hours

Protein Binding

90%

Special Populations: Renal Function Impairment

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

Use: Labeled Indications

Treatment of infections caused by susceptible Rickettsia, Chlamydia, Chlamydophila, and Mycoplasma spp.; malaria prophylaxis (areas with chloroquine- and/or pyrimethamine-sulfadoxine resistant strains) for short-term travel (<4 months); treatment of lymphogranuloma venereum; treatment of granuloma inguinale (donovanosis) caused by Klebsiella granulomatis; treatment for syphilis in penicillin-allergic patients; uncomplicated urethral, endocervical, or rectal infections caused by Chlamydia trachomatis (oral formulations); Listeria, Actinomyces israelii, and Clostridium infections in penicillin-allergic patients; used for community-acquired pneumonia and other common infections due to susceptible organisms; anthrax due to Bacillus anthracis, including inhalational anthrax (postexposure); treatment of infections caused by uncommon susceptible gram-negative and gram-positive organisms including Borrelia recurrentis, Ureaplasma urealyticum, Haemophilus ducreyi, Yersinia pestis (plague), Francisella tularensis (tularemia due to zoonotic infection), Vibrio cholerae, Campylobacter fetus, Brucella spp, Bartonella bacilliformis, and Klebsiella granulomatis, Q fever; intestinal amebiasis; severe acne; uncomplicated Neisseria gonorrhoeae (excluding anorectal infections in men; oral formulations); nongonococcal urethritis caused by Ureaplasma urealyticum (oral formulations).

Note: The Centers for Disease Control and Prevention (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 alternate option for the second antimicrobial only in cases azithromycin allergy (CDC [Workowski 2015]).

Oracea (US labeling), Apprilon (Canadian labeling): Treatment of inflammatory lesions associated with rosacea

Periostat (Canadian labeling; not available in the US): Adjunctive periodontitis treatment to scaling and root planing to promote attachment level gain and reduce pocket depth

Use: Unlabeled

Sclerosing agent for pleural effusion (injection); vancomycin-resistant enterococci (VRE); alternate treatment for MRSA infections; treatment of periodontitis (refractory); localized juvenile periodontitis (LJP); Lyme disease; treatment of acute bacterial rhinosinusitis (ABRS) (adults); oral phase treatment of prosthetic joint infection; chronic oral antimicrobial suppression of prosthetic joint infection; anorectal gonococcal infections

Contraindications

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

Canadian labeling: Hypersensitivity to doxycycline, tetracycline, or any component of the formulation; myasthenia gravis; concurrent use with isotretinoin

Periostat, Apprilon: Additional contraindications: Use in infants and children <8 years of age or during second or third trimester of pregnancy; breast-feeding

Dosing: Adult

Usual dosage range: Oral, IV: 100 to 200 mg/day in 1 to 2 divided doses

Acute bacterial rhinosinusitis (off-label use): Oral: 200 mg/day in 1 to 2 divided doses for 5 to 7 days (Chow 2012)

Anthrax:

Inhalational (postexposure prophylaxis): Oral, IV (use oral route when possible): 100 mg every 12 hours for 60 days (ACIP 2010)

Cutaneous (treatment): Oral: 100 mg every 12 hours for 60 days. Note: In the presence of systemic involvement, extensive edema, lesions on head/neck, refer to IV dosing for treatment of inhalational/gastrointestinal/oropharyngeal anthrax

Inhalational/gastrointestinal/oropharyngeal (treatment): IV: Initial: 100 mg every 12 hours; switch to oral therapy when clinically appropriate; some recommend initial loading dose of 200 mg, followed by 100 mg every 8 to 12 hours (Franz 1997). Note: Initial treatment should include two or more agents predicted to be effective (CDC 2001). Agents suggested for use in conjunction with doxycycline or ciprofloxacin include rifampin, vancomycin, imipenem, penicillin, ampicillin, chloramphenicol, clindamycin, and clarithromycin. May switch to oral antimicrobial therapy when clinically appropriate. Continue combined therapy for 60 days

Bacillary angiomatosis, cutaneous (off-label use): Oral: 100 mg twice daily. Note: Duration of initial therapy should be for 2 weeks to 2 months, although treatment durations are not standardized (IDSA [Stevens 2014])

Bartonella infection in HIV-infected patients (off-label use; HHS [OI adult 2015]): Note: Duration of therapy is at least 3 months; continuation of therapy depends on relapse occurrence and clinical condition

Bacillary Angiomatosis, Peliosis Hepatis, Bacteremia, and Osteomyelitis: Oral, IV: 100 mg every 12 hours

Infections Involving the CNS: Oral, IV: 100 mg every 12 hours; may add rifampin therapy

Confirmed Bartonella Endocarditis: 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

Other Severe Infections: Oral, IV: 100 mg every 12 hours in combination with rifampin

Bite wounds (animal/human) (off-label use) (IDSA [Stevens 2014]):

Animal bite: Oral, IV: 100 mg twice daily

Human bite: Oral: 100 mg twice daily

Brucellosis: Oral: 100 mg twice daily for 6 weeks with rifampin or streptomycin

Cellulitis (purulent) due to community-acquired MRSA (off-label use): Oral: 100 mg twice daily for 5 to 10 days (Liu 2011)

Cervicitis due to Chlamydia trachomatis (off-label use): Oral: 100 mg twice daily for 7 days; consider concurrent treatment for gonorrhea if patient at risk for contracting or lives in an area with high prevalence of gonorrhea (CDC [Workowski 2015])

Chlamydia trachomatis, uncomplicated urethral, endocervical or rectal infections: Oral:

US labeling: 100 mg twice daily for 7 days; alternatively, for endocervical or urethral infections, may give 200 mg delayed-release tablet once daily for 7 days (CDC [Workowski 2015])

Canadian labeling: 100 mg twice daily for at least 10 days

Community-acquired pneumonia, bronchitis: Oral, IV: 100 mg twice daily (Ailani 1999; Mandell 2007)

Epididymitis (most likely caused by C. trachomatis or N. gonorrhoeae) (off-label use): Oral: 100 mg twice daily for 10 days (in combination with ceftriaxone); sexual partners should also be referred for treatment (CDC [Workowski 2015])

Gonococcal (uncomplicated) infection of the cervix, rectum (off-label use) or urethra: Oral: 100 mg twice daily for 7 days; must be given in combination with ceftriaxone (preferred) or cefixime (only if ceftriaxone is not available) (CDC [Workowski 2015]). Note: Azithromycin is preferred over doxycycline as the second antimicrobial in combination with ceftriaxone in uncomplicated infections due to a high prevalence of tetracycline resistance in isolates and the convenience/compliance advantages of single dose azithromycin therapy; doxycycline should only be used in cases of azithromycin allergy (CDC [Workowski 2015]).

Canadian labeling: Initial: 200 mg in the morning and 100 mg in the evening on day 1 then 100 mg twice daily for 3 days.

Alternatively, the manufacturer’s labeling recommends a single-visit dose in nonanorectal infections in men: 300 mg initially, repeat dose in 1 hour (total dose: 600 mg); of note, this dosing is not mentioned in the CDC STD 2015 treatment guidelines.

Granuloma inguinale (donovanosis) (alternative to preferred therapy): Oral: 100 mg twice daily for at least 3 weeks (and until lesions have healed) (CDC [Workowski 2015]). Note: If symptoms do not improve within the first few days of therapy, the addition of gentamicin may be considered (CDC [Workowski 2015]).

Lyme disease (off-label use): Oral (Halperin 2007; Wormser 2006):

Prevention: Initiate within 72 hours of tick removal: 200 mg administered as a single dose

Treatment (early Lyme disease without neurologic manifestations): 100 mg twice daily for 10 to 21 days

Treatment (meningitis or other early neurologic manifestations): 100 to 200 mg twice daily for 14 days (range: 10 to 28 days)

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

Malaria chemoprophylaxis: Oral: 100 mg/day. Start 1 to 2 days prior to travel to endemic area; continue daily during travel and for 4 weeks after leaving endemic area

Malaria, severe, treatment (off-label use): Oral, IV: 100 mg every 12 hours for 7 days with quinidine gluconate. Note: Quinidine gluconate duration is region specific; consult CDC for current recommendations (CDC 2011).

Malaria, uncomplicated, treatment (off-label use): Oral: 100 mg twice daily for 7 days with quinine sulfate. Note: Quinine sulfate duration is region specific; consult CDC for current recommendations (CDC 2011).

Nongonococcal urethritis: Oral: 100 mg twice daily for 7 days

Pelvic inflammatory disease (off-label use):

Treatment, inpatient: IV: 100 mg twice daily (in combination with cefoxitin [preferred] or cefotetan [preferred] or ampicillin/sulbactam [alternative]); transition from parenteral to oral doxycycline therapy can usually be initiated within 24 to 48 hours of clinical improvement for a total treatment duration of 14 days. If tubo-ovarian abscess is present, oral clindamycin or oral metronidazole in combination with doxycycline is preferred to complete 14 days of therapy (CDC [Workowski 2015])

Treatment, outpatient: Oral: 100 mg twice daily for 14 days (with or without metronidazole); must be preceded by a single IM dose of cefoxitin (plus oral probenecid) or ceftriaxone or other parenteral third-generation cephalosporin (eg, cefotaxime) (CDC [Workowski 2015])

Periodontitis: Oral (Periostat [Canadian product]): 20 mg twice daily as an adjunct following scaling and root planing; may treat for up to 9 months

Periodontitis, refractory (off-label use): Oral: 100 to 200 mg daily (Jolkovsky 2006)

Proctitis, proctocolitis, enteritis (off-label use): Oral: 100 mg twice daily for 7 days (in combination with ceftriaxone) (CDC [Workowski 2015]). Note: Consider 21 days of treatment for presumptive lymphogranuloma venereum in those with HIV infection or positive rectal chlamydial amplification test (NAAT).

Q fever: Oral:

Acute: 100 mg every 12 hours for 14 days (CDC 2013); Note: In patients who have valvular heart disease, consider increasing the duration of therapy to 1 year and adding hydroxychloroquine to the regimen to prevent endocarditis; consultation with an infectious disease expert is recommended (CDC 2002; Fenollar 2001).

Chronic (CDC 2013):

Endocarditis or vascular infection: 100 mg every 12 hours in combination with hydroxychloroquine for ≥18 months

Noncardiac organ disease: 100 mg every 12 hours in combination with hydroxychloroquine (duration based on serologic response; ID consult recommended)

Postpartum with serologic evidence present >12 months after delivery: 100 mg every 12 hours in combination with hydroxychloroquine for 12 months

Rosacea Oral (Oracea [US labeling], Apprilon [Canadian labeling]): 40 mg once daily in the morning

Sclerosing agent for pleural effusion (off-label use): Intrapleural: 500 mg as a single dose in 100 mL NS (Porcel 2006); may require a repeat dose (Kvale 2007)

Skin and soft tissue infections (off-label use) (IDSA [Stevens 2014]):

Due to MSSA or MRSA: Oral: 100 mg twice daily

Necrotizing infection due to Aeromonas hydrophila or Vibrio vulnificus: IV: 100 mg every 12 hours; in combination with ciprofloxacin or ceftriaxone for Aeromonas hydrophila or in combination with ceftriaxone or cefotaxime for Vibrio vulnificus. Continue treatment until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours.

Syphilis, penicillin-allergic patients: Note: Data to support the use of alternatives to penicillin alternatives in primary and secondary syphilis and limited and also are not well documented in the treatment of latent syphilis (CDC [Workowski 2015]).

Primary/secondary syphilis: Oral: 100 mg twice daily for 14 days

Latent syphilis: Oral: 100 mg twice daily for 28 days

Tickborne rickettsial disease: Oral, IV: 100 mg twice daily for 5 to 7 days; severe or complicated disease may require longer treatment; human granulocytotropic anaplasmosis (HGA) should be treated for 10 to 14 days.

Tularemia:

Mild to moderate infections: Oral: 100 mg twice daily for 14 days (IDSA [Stevens 2014])

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 14-21 days (Dennis 2001)

Vibrio cholerae: Oral: 300 mg as a single dose (WHO 2004)

Yersinia pestis (plague): Oral, IV: 200 mg initially then 100 mg twice daily or 200 mg once daily for 10 to 14 days (Daya 2005; Inglesby 2000; IDSA [Stevens 2014])

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Usual dosage range:

Children >8 years and Adolescents (<45 kg): Oral, IV: 2 to 4 mg/kg/day in 1 to 2 divided doses, not to exceed 200 mg/day (AAP [Red Book] 2015)

Children >8 years and Adolescents (≥45 kg): Oral, IV: Refer to adult dosing.

Anthrax:

Inhalational (postexposure prophylaxis) (ACIP 2010): Oral, IV (use oral route when possible):

≤8 years: 2.2 mg/kg every 12 hours for 60 days

>8 years and ≤45 kg: 2.2 mg/kg every 12 hours for 60 days

>8 years and >45 kg: 100 mg every 12 hours for 60 days

Cutaneous (treatment): Oral: See dosing for “Inhalational (postexposure prophylaxis)”

Note: In the presence of systemic involvement, extensive edema, and/or lesions on head/neck, doxycycline should initially be administered IV

Inhalational/gastrointestinal/oropharyngeal (treatment): IV: Refer to dosing for inhalational anthrax (postexposure prophylaxis); switch to oral therapy when clinically appropriate.

Note: Initial treatment should include two or more agents predicted to be effective (CDC 2001). Agents suggested for use in conjunction with doxycycline or ciprofloxacin include rifampin, vancomycin, imipenem, penicillin, ampicillin, chloramphenicol, clindamycin, and clarithromycin. May switch to oral antimicrobial therapy when clinically appropriate. Continue combined therapy for 60 days

Bartonella infection in HIV-infected patients (off-label use): Refer to adult dosing

Community-acquired pneumonia (CAP) (IDSA/PIDS 2011): Children >7 years: Oral: Note: A beta-lactam antibiotic should be added if typical bacterial pneumonia cannot be ruled out.

Presumed atypical, mild atypical (M. pneumoniae, C. pneumoniae, C. trachomatis) infection or step-down therapy (alternative to azithromycin): 2 to 4 mg/kg/day in 2 divided doses (maximum: 200 mg/day)

Cellulitis (purulent) due to community-acquired MRSA (off-label use): Children >8 years and ≤45 kg: Oral: 2 mg/kg/dose every 12 hours for 5 to 10 days; >45 kg: Refer to adult dosing (Liu 2011)

Chlamydial infections, uncomplicated: Children ≥8 years (and >45 kg) and Adolescents: Oral: US labeling: 100 mg twice daily for 7 days; alternatively, for endocervical or urethral infections, may give 200 mg delayed-release tablet once daily for 7 days (CDC [Workowski 2015])

Localized juvenile periodontitis (LJP) (off-label use): Oral: 50 to 100 mg/day

Lyme disease (off-label use): Children ≥8 years: Oral (Halperin 2007; Wormser 2006):

Prevention: 4 mg/kg (maximum: 200 mg) administered as a single dose; Note: Initiate within 72 hours of tick removal

Treatment (early Lyme disease without neurologic manifestations): 1 to 2 mg/kg twice daily for 10 to 21 days (maximum: 100 mg/dose)

Treatment (meningitis and other early neurologic manifestations): 4 to 8 mg/kg/day in 2 divided doses for 10 to 28 days (maximum: 200 mg/dose)

Malaria chemoprophylaxis: Children ≥8 years: Oral:

Manufacturer's labeling: 2 mg/kg/day (maximum: 100 mg daily). Start 1 to 2 days prior to travel to endemic area; continue daily during travel and for 4 weeks after leaving endemic area (CDC 2012)

Alternative recommendation: 2.2 mg/kg/day (maximum: 100 mg daily). Start 1 to 2 days prior to travel to endemic area; continue daily during travel and for 4 weeks after leaving endemic area (CDC 2012)

Malaria, severe, treatment (off-label use): Children ≥8 years: Oral, IV:

<45 kg: 2.2 mg/kg (maximum dose: 100 mg) every 12 hours for 7 days with quinidine gluconate. Note: Quinidine gluconate duration is region specific; consult CDC for current recommendations (CDC 2011).

≥45 kg: 100 mg every 12 hours for 7 days with quinidine gluconate. Note: Quinidine gluconate duration is region specific; consult CDC for current recommendations (CDC 2011).

Malaria, uncomplicated, treatment (off-label use): Children ≥8 years: Oral: 2.2 mg/kg (maximum dose: 100 mg) every 12 hours for 7 days with quinine sulfate. Note: Quinine sulfate duration is region specific, consult CDC for current recommendations (CDC 2011).

Prosthetic joint infection (off-label use): Oral:

Chronic oral antimicrobial suppression:

Propionibacterium spp (alternative to penicillin or amoxicillin): 100 mg twice daily (Osmon 2013)

Staphylococci (oxacillin-resistant): 100 mg twice daily (Osmon 2013)

Staphylococci (oxacillin-sensitive or –resistant) oral phase treatment (after completion of pathogen-specific IV) following 1-stage exchange:

Total ankle, elbow, hip, or shoulder arthroplasty: 100 mg twice daily for 3 months; Note: Must be used in combination with rifampin (Osmon 2013).

Total knee arthroplasty: 100 mg twice daily for 6 months; Note: Must be used in combination with rifampin (Osmon 2013)

Q fever: Oral:

Acute:

Children <8 years with high-risk criteria (eg, hospitalized or have severe illness, with preexisting heart valvulopathy, immunocompromised, or with delayed Q fever diagnosis who have experienced illness for >14 days without resolution of symptoms): 2.2 mg/kg/dose (maximum: 100 mg per dose) twice daily for 14 days (CDC 2013).

Children <8 years with mild or uncomplicated illness: 2.2 mg/kg/dose (maximum: 100 mg per dose) twice daily for 5 days. If patient remains febrile past 5 days of treatment, switch to sulfamethoxazole and trimethoprim (CDC 2013). Note: Some clinicians may recommend initial treatment with sulfamethoxazole and trimethoprim for children <8 years with mild or uncomplicated illness (Hartzell 2008; CDC 2013).

Children ≥8 years and Adolescents: 2.2 mg/kg/dose (maximum: 100 mg per dose) twice daily for 14 days (CDC 2013).

Chronic: ID consult recommended for treatment of chronic Q fever (CDC 2013)

Skin and soft tissue infections due to MSSA or MRSA (off-label use): Children ≥ 8 years: Oral:

≤45 kg: 2 mg/kg every 12 hours (IDSA [Lui 2011])

>45 kg: 100 mg twice daily (IDSA [Lui 2011]; IDSA [Stevens 2014])

Tickborne rickettsial disease (eg, Rocky Mountain spotted fever):

Children and Adolescents <45 kg: Oral, IV: 2.2 mg/kg (maximum dose: 100 mg) every 12 hours for 5 to 7 days; severe or complicated disease may require longer treatment; human granulocytotropic anaplasmosis (HGA) should be treated for 10 to 14 days (CDC 2006)

Children and Adolescents ≥45 kg: Oral, IV: Refer to adult dosing.

Tularemia (when used as a biological weapon) (off-label use) (Dennis 2001):

Mass casualty management or postexposure prophylaxis: Oral:

Children <45 kg: 2.2 mg/kg twice daily for 14 days

Children ≥45 kg: 100 mg twice daily for 14 days

Contained casualty management: IV (may transition to oral if clinically indicated):

Children <45 kg: 2.2 mg/kg twice daily for 14 to 21 days

Children ≥45 kg: 100 mg every 12 hours for 14 to 21 days

Dosing: Renal Impairment

No dosage adjustment necessary.

Poorly dialyzed (0% to 5%); no supplemental dose or dosage adjustment necessary, including patients on intermittent hemodialysis, peritoneal dialysis, or continuous renal replacement therapy (eg, CVVHD).

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Reconstitution

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 to a final concentration of 0.1 to 1 mg/mL.

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: May give with meals to decrease GI upset. Capsule and tablet: Administer with at least 8 ounces of water and have patient sit up for at least 30 minutes (US labeling) or 1 to 2 hours (Canadian labeling) after taking to reduce the risk of esophageal irritation and ulceration.

Oracea (US labeling), Apprilon (Canadian labeling): Administer on an empty stomach 1 hour before or 2 hours after meals.

Doryx: Administer without regard to meals; nausea occurs more frequently when taken on an empty stomach. 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.

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

IV: Infuse IV doxycycline over 1-4 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): Add to 100 mL NS and instill into chest tube (Porcel 2006)

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 not recommended due to GI intolerance. Of currently available tetracyclines, doxycycline has the least affinity for calcium.

Doryx tablets: May be taken without regard to meals; nausea occurs more frequently when taken on an empty stomach.

Oracea (US labeling), Apprilon (Canadian labeling): Take on an empty stomach 1 hour before or 2 hours after meals.

Periostat [Canadian product]: Take at least 1 hour before morning and evening meals.

Some products may contain sodium.

Compatibility

Stable in NS, D5W, Ringer's injection, LR, D5LR.

Y-site administration: Incompatible with allopurinol, heparin, pemetrexed, piperacillin/tazobactam.

Storage

Capsule, tablet: Store at 20°C to 25°C (68°F to 77°F); excursions are 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: Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid. Monitor therapy

Antacids: May decrease the absorption of Tetracycline Derivatives. 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 Tetracycline Derivatives. Consider therapy modification

Bismuth Subcitrate: May decrease the serum concentration of Tetracycline Derivatives. 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 Tetracycline Derivatives. 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 Tetracycline Derivatives. 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. Avoid combination

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

Iron Salts: Tetracycline Derivatives may decrease the absorption of Iron Salts. Iron Salts may decrease the serum concentration of Tetracycline Derivatives. Exceptions: Ferric Carboxymaltose; 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 Tetracycline Derivatives. 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 Tetracycline Derivatives. Monitor therapy

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

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

Mipomersen: Tetracycline Derivatives may enhance the hepatotoxic effect of Mipomersen. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Tetracycline Derivatives. 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 Tetracycline Derivatives. 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: Tetracycline Derivatives may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Penicillins: Tetracycline Derivatives may diminish the therapeutic effect of Penicillins. Consider therapy modification

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

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

Quinapril: May decrease the serum concentration of Tetracycline Derivatives. 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: Tetracycline Derivatives 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 Tetracycline Derivatives. 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 Tetracycline Derivatives. Management: Administer the tetracycline derivative at least 2 hours prior to sucralfate in order to minimize the impact of this interaction. Consider therapy modification

Sucroferric Oxyhydroxide: May decrease the serum concentration of Tetracycline Derivatives. Management: Administer oral/enteral doxycycline at least 1 h 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): Tetracycline Derivatives 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

>10%: Infection: Common cold (22%)

1% to 10%:

Cardiovascular: Hypertension (3%), increased blood pressure (2%)

Central nervous system: Pain (2% to 4%), anxiety (2%)

Dermatologic: Skin rash (4%)

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

Gastrointestinal: Nausea (8%), dyspepsia (6%), diarrhea (5% to 6%), acid indigestion (4%), upper abdominal pain (2%), abdominal distention (1%), abdominal pain (1%), xerostomia (1%)

Genitourinary: Dysmenorrhea (4%)

Hepatic: Increased serum AST (2%)

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

Neuromuscular & skeletal: Arthralgia (6%), back pain (1%)

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

Frequency not defined:

Cardiovascular: Flushing

Dermatologic: Skin hyperpigmentation

Endocrine & metabolic: Thyroid disease (brown/black discoloration; no dysfunction reported)

Gastrointestinal: Anorexia

Genitourinary: Vulvovaginal candidiasis

Hematologic & oncologic: Leukopenia

Immunologic: DRESS syndrome

Neuromuscular & skeletal: Myalgia

Otic: Tinnitus

<1% (Limited to important or life-threatening): Anaphylactoid reaction, bulging fontanel (infants), Clostridium difficile associated diarrhea, decreased appetite, dental discoloration (children), dysphagia, dyspnea, enamel hypoplasia, enterocolitis, eosinophilia, erythema multiforme, erythematous rash, esophageal ulcer, esophagitis, exacerbation of systemic lupus erythematosus, exfoliative dermatitis, glossitis, headache, hemolytic anemia, hepatic dysfunction, hepatotoxicity (rare; including hepatic failure, autoimmune hepatitis, cholestasis), hypersensitivity reaction, hypotension, IgA vasculitis, increased blood urea nitrogen (dose related), increased serum ALT, inflammatory anogenital lesion, intracranial hypertension (adults), maculopapular rash, neutropenia, pericarditis, peripheral edema, permanent vision loss, proctitis, pseudomembranous colitis, serum sickness, skin photosensitivity, Stevens-Johnson syndrome, stomatitis, tachycardia, thrombocytopenia, tinnitus, toxic epidermal necrolysis, vomiting

Warnings/Precautions

Concerns related to adverse effects:

• Gastrointestinal inflammation/ulceration: Esophagitis and ulcerations (sometimes severe) may occur; patients with dysphagia and/or retrosternal pain may require assessment for esophageal lesions; the Canadian labeling recommends discontinuing therapy during assessment period and also recommends avoiding use in patients with obstructive esophageal conditions (eg, stenosis, achalasia).

• Hepatotoxicity: Rarely occurs; if symptomatic, conduct LFT and discontinue drug.

• Hypersensitivity syndromes: Have been reported, including drug rash with eosinophilia and systemic symptoms (DRESS), urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, pericarditis, and systemic lupus erythematosus exacerbation. Discontinue therapy for serious hypersensitivity reactions.

• Increased BUN: May be associated with increases in BUN secondary to antianabolic effects; use caution in patients with renal impairment.

• Intracranial hypertension (eg, pseudotumor cerebri): Intracranial hypertension (headache, blurred vision, diplopia, vision loss, and/or papilledema) has been associated with use. Women of childbearing age who are overweight or have a history of intracranial hypertension are at greater risk. Concomitant use of isotretinoin (known to cause pseudotumor cerebri) and doxycycline should be avoided. 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 patients until they stabilize.

• Photosensitivity: May cause photosensitivity; discontinue if skin erythema occurs. Use skin protection and avoid prolonged exposure to sunlight; do not use tanning equipment.

• 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 (teeth, mucosa, alveolar bone), sclerae, and heart valves independently of time or amount of drug administration.

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); use of tetracyclines should be avoided during tooth development (last half of pregnancy, infancy, and children <8 years of age [product labeling]), unless there are no alternative therapies. Limited use between age 6 to 7 years has minimal effect on the color of permanent incisors (CDC 2006). Recommended in treatment of anthrax exposure (CDC 2001), tickborne rickettsial diseases (CDC 2006), and Q fever (CDC 2013).

• Pregnancy: Do not use during pregnancy. In addition to affecting tooth development, tetracycline use has been associated with retardation of skeletal development and reduced bone growth.

Dosage form specific issues:

• Oracea (US labeling) or Apprilon (Canadian labeling): Should not be used for the treatment or prophylaxis of bacterial infections, since the lower dose of drug per capsule may be subefficacious and promote resistance.

• Syrup: Contains sodium metabisulfite.

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.

Other warnings/precautions:

• Limitations of use: When used for malaria prophylaxis, does not completely suppress asexual blood stages of Plasmodium strains. Doxycycline does not suppress Plasmodium falciparum’s sexual blood stage gametocytes. Patients completing a regimen may still transmit the infection to mosquitoes outside endemic areas.

• Periodontitis: Effectiveness has not been established in patients with coexistent oral candidiasis; use with caution in patients with a history or predisposition to oral candidiasis.

Monitoring Parameters

Perform culture and sensitivity testing prior to initiating therapy. 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 2012).

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 Risk Factor

D

Pregnancy Considerations

Tetracyclines cross the placenta and accumulate in developing teeth and long tubular bones. 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 may discolor fetal teeth following maternal use during pregnancy; the specific teeth involved and the portion of the tooth affected depends on the timing and duration of exposure relative to tooth calcification. As a class, tetracyclines are generally considered second-line antibiotics in pregnant women and their use should be avoided. Tetracycline medications should be used during pregnancy only when other medications are contraindicated or ineffective (Mylonas 2011).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, vomiting, diarrhea, or lack of appetite. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), angina, urinary retention, change in amount of urine passed, chills, pharyngitis, dysphagia, bruising, bleeding, joint pain, severe loss of strength and energy, vaginitis, headache, blurred vision, diplopia, vision loss, signs of Clostridium difficile (C. diff)-associated diarrhea (stomach pain or cramps, very loose or watery stools, or bloody stools) or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating, and advising patients.

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