Doxycycline

J01A - Tetracyclines ATC J01AA02 Small molecule approved 1967 Oral Narrow therapeutic index

🧬 Cross-allergy: Tetracyclines

JFDA label: DOXYDAR CAPS.

Mechanism of Action

Inhibitor of Matrilysin — Matrix metalloproteinase 7 inhibitor; Inhibitor of Neutrophil collagenase — Matrix metalloproteinase 8 inhibitor; Inhibitor of Collagenase 3 — Matrix metalloproteinase 13 inhibitor; Inhibitor of Interstitial collagenase — Matrix metalloproteinase-1 inhibitor; Inhibitor of Bacterial 70S ribosome — Bacterial 70S ribosome inhibitor

Target	Action	Gene / class
Bacterial 70S ribosome efficacy	INHIBITOR
Collagenase 3 efficacy	INHIBITOR	MMP13
Interstitial collagenase efficacy	INHIBITOR	MMP1
Matrilysin efficacy	INHIBITOR	MMP7
Neutrophil collagenase efficacy	INHIBITOR	MMP8

Indications

Approved

Acne
Actinomycosis
Acute intestinal amebiasis
Anthrax, including inhalational anthrax (postexposure)
Cholera
Clostridium
Gram-negative infections
Gram-positive infections
Listeriosis
Malaria prophylaxis
Mycoplasma pneumoniae
Ophthalmic infections
Periodontitis (20 mg tablet and capsule [Periostat (Canadian product)] only)
Relapsing fever
Respiratory tract infections
Rickettsial infections
Rosacea (Oracea, Apprilon [Canadian product] only)
Sexually transmitted infections
Skin and skin structure infections (Avidoxy only)
Vincent infection
Yaws
Zoonotic infections

Off-label

Anaplasmosis and ehrlichiosis
Bartonella infections in HIV-infected patients (adolescents and adults)
Bite-wound infection (animal and human bites)
Cellulitis, mild to moderate
Epididymitis, acute
Lyme disease (Borrelia spp. infection)
Malaria, treatment
Pelvic inflammatory disease
Pleurodesis, chemical (sclerosing agent for pleural effusion)
Proctitis, acute or proctocolitis
Prosthetic joint infection
Rhinosinusitis, acute bacterial (ABRS)
Surgical prophylaxis, pregnancy termination (dilation and evacuation procedure)

Antimicrobial Spectrum

Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: EUCAST v16 · curated · openfda-label.

Bacteria

Organism	Activity	MIC
Bacillus anthracis	Active	—
Bacteroides fragilis	Active	—
Bacteroides thetaiotaomicron	Active	—
Borrelia burgdorferi	Susceptible	0.5 mg/L
Borrelia recurrentis	Active	—
Campylobacter fetus	Active	—
Chlamydia pneumoniae	Susceptible	1.0 mg/L
Chlamydia trachomatis	Susceptible	1.0 mg/L
Enterobacter aerogenes	Active	—
Enterococcus faecalis	Active	—
Escherichia coli	Active	—
Fusobacterium fusiforme	Active	—
Haemophilus ducreyi	Active	—
Haemophilus influenzae	Susceptible	1.0 mg/L
Haemophilus influenzae	Susceptible	11.0 mg/L
Klebsiella granulomatis	Active	—
Listeria monocytogenes	Active	—
Moraxella catarrhalis	Susceptible	11.0 mg/L
Mycoplasma pneumoniae	Susceptible	1.0 mg/L
Neisseria gonorrhoeae	Active	—
Pasteurella multocida	Susceptible	1.0 mg/L
Plasmodium falciparum	Active	—
Rickettsia spp.	Susceptible	0.5 mg/L
Staphylococcus aureus	Susceptible	1.0 mg/L
Staphylococcus spp.	Susceptible	11.0 mg/L
Streptococcus A/B/C/G	Susceptible	11.0 mg/L
Streptococcus pneumoniae	Susceptible	0.5 mg/L
Streptococcus pneumoniae	Susceptible	11.0 mg/L
Treponema pallidum	Active	—
Treponema pertenue	Active	—
Vibrio cholerae	Susceptible	0.25 mg/L
Vibrio fetus	Active	—
Vibrio spp.	Susceptible	0.5 mg/L
Yersinia pestis	Active	—
Streptococcus pneumoniae	Resistant	1.0 mg/L

Class profile

gramStatus	Both
spectrumBreadth	Broad
atypicalCoverage	Yes
isBactericidal	0
moaCategory	Protein synthesis inhibitor (30S ribosomal)
pdIndex	Time-dependent
postAntibioticEffect	None
mrsaCoverage	0
resistanceMechanisms	Active efflux (Tet pumps),Ribosomal protection proteins

Contraindications

Source: Curated · Lexicomp

Children under 8 years (unless benefits outweigh risks) Absolute
Hypersensitivity to doxycycline, other tetracyclines, or any component of the formulation Periostat, Apprilon [Canadian products]: Additional contraindications: Use in infants and children Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (1)

Common Hypertension

Nervous system disorders (2)

Common Anxiety · pain

Hepatobiliary disorders (1)

Common Increased serum AST

Metabolism and nutrition disorders (2)

Common Increased lactate dehydrogenase · increased serum glucose

Gastrointestinal disorders (7)

Common abdominal distention · abdominal pain · Diarrhea · upper abdominal pain · xerostomia

Not Known Esophageal ulcer · esophagitis

Skin and subcutaneous tissue disorders (1)

Not Known Skin hyperpigmentation

Musculoskeletal and connective tissue disorders (1)

Common Back pain

Infections and infestations (2)

Common Fungal infection · influenza

Respiratory, thoracic and mediastinal disorders (4)

Common nasal congestion · Nasopharyngitis · sinus headache · sinusitis

Dosing

Source: Lexicomp

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 2017) Extended release: 100 mg twice daily on day one, then 100 mg once daily (AAD [Zaenglein 2016]; Graber 2017) 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: 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 2017]). Bacillary angiomatosis, peliosis hepatis, bacteremia, and osteomyelitis: Oral, IV: 100 mg every 12 hours CNS infections: Oral, IV: 100 mg every 12 hours; may add rifampin therapy Endocarditis, confirmed: 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 Other severe infections: Oral, IV: 100 mg every 12 hours in combination with rifampin HIV-uninfected: Bacteremia without endocarditis: Oral: 200 mg once daily or 100 mg twice daily for 4 weeks with gentamicin once daily for fi

(For additional information see "Doxycycline: Pediatric drug information") Usual dosage range: Immediate and delayed-release: Children >8 years and Adolescents (Children >8 years and Adolescents (≥45 kg): Oral, IV: Refer to adult dosing. Anaplasmosis and ehrlichiosis (off-label use): Children Duration of therapy: If co-infection with Lyme disease is not suspected, may treat for at least 3 days after fever subsides and clinical improvement is noted; typical minimum duration of therapy is 5 to 7 days (CDC [Biggs 2016]) If co-infection with Lyme disease is suspected, treat for 10 days (CDC [Biggs 2016]) or, alternatively, treat with a short course of doxycycline (4 to 5 days [ie, ~3 days after resolution of fever]) and start an antimicrobial with efficacy against Borrelia burgdorferi (eg, amoxicillin, cefuroxime) at the end of the doxycycline course to complete 14 days of total treatment (IDSA [Wormser 2006]) Children ≥8 years and Adolescents: Oral, IV: Duration of therapy: 10 days to provide appropriate length of therapy for possible co-infection with Lyme disease (CDC [Biggs 2016]; IDSA [Wormser 2006]) or, alternatively, add another antimicrobial with efficacy against Borrelia burgdorferi (CDC [Biggs 2016]) ≥45 kg: Refer to adult dosing. Bartonella infection: HIV-infected patients (off-label use): Adolescents: Refer to adult dosing. 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]) Lyme disease (Borrelia spp. infection) (off-label use): Children ≥8 years: Oral (Halperin 2007; Wormser 2006): Prophylaxis: 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 in travelers: Children ≥8 years: Oral: 2.2 mg/kg/dose once daily (maximum dose: 100 mg/day) 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 duration of prophylaxis: 4 months (CDC [Arguin 2016]) Severe malaria, treatment (off-label use): Children ≥8 years: Oral, IV: Note: Quinidine gluconate duration is region specific; consult CDC for current recommendations (CDC 2011). ≥45 kg: Refer to adult dosing. Uncomplicated malaria, treatment (chloroquine resistant or unknown resistance) (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). Pneumonia, community-acqu

Refer to adult dosing.

No dosage adjustment necessary. Dialysis: 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).

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

Warnings & Precautions

Source: Lexicomp

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 2006). Recommended in treatment of anthrax exposure (CDC 2001), tickborne rickettsial diseases (CDC 2006), 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.

Pregnancy & Lactation

Pregnancy

FDA category D

Avoid

Avoid in T2/T3. T1: use only if no alternative. Preferred alternatives: amoxicillin, azithromycin (for atypicals)

Lactation

RID 6.14%

Doxycycline is present in breast milk. The relative infant dose (RID) of doxycycline is 6.14% when calculated using the highest average breast milk concentration located and compared to an infant therapeutic dose of 4.4 mg/kg/day. In general, breastfeeding is considered acceptable when the RID is 25% breastfeeding should generally be avoided (Anderson 2016; Ito 2000). Using the highest average milk concentration (1.8 mcg/mL), the estimated daily infant dose via breast milk is 0.27 mg/kg/da

LactMed: monitor the infant.

Monitoring

Efficacy	Culture and susceptibility testing; clinical resolution (temperature, WBC, CRP, procalcitonin)
Toxicity	Renal function (dose adjustment in renal impairment); hepatic function for hepatically cleared agents; signs of C. difficile infection (diarrhoea)
Clinical pearl	Culture results guide de-escalation to narrower-spectrum therapy. Review antibiotic appropriateness at 48–72 h (antimicrobial stewardship).
Counseling	Complete the full course. Report persistent diarrhoea, rash, or lack of improvement after 48–72 h.

Chemistry & Properties

Formula	C22H26N2O9
Molecular weight	462.46 g/mol
IUPAC name	(4S,4aR,5S,5aR,6R,12aR)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4H-tetracene-2-carboxamide
CAS	7164-70-7
PubChem CID	54671203
InChIKey	`XQTWDDCIUJNLTR-CVHRZJFOSA-N`
logP	-0.35 (XLogP -0.7)
Polar surface area	181.62 Å²
H-bond acceptors / donors	9 / 6
Drug-likeness (QED)	0.33
Lipinski violations	1

SMILES

C[C@H]1c2cccc(O)c2C(=O)C2=C(O)[C@]3(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@@H]3[C@@H](O)[C@@H]21.O

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	10.0%
Half-life	6.194 h
Volume of distribution	1.485 L/kg
Protein binding	79.8%
BBB penetrant	No

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OAT1 (Inhibitor)OAT2 (Inhibitor)OAT3 (Inhibitor)OAT4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)OCT1 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)Transporter(unspecified) (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Acitretin	major
Aminolevulinic acid	major
Isotretinoin	major
Lomitapide	major
Methoxyflurane	major
Mipomersen	major
Pexidartinib	major
Tretinoin	major
Typhoid vaccine (live)	major
Vibrio cholerae CVD 103-HgR strain live antigen (live)	major
Vitamin A	major
Activated charcoal	moderate
Aluminum hydroxide	moderate
Aminolevulinic acid (topical)	moderate
Aminophylline	moderate
Amobarbital	moderate
Amoxicillin	moderate
Ampicillin	moderate
Anisindione	moderate
Asparaginase Erwinia chrysanthemi	moderate
Asparaginase Escherichia coli	moderate
Atracurium	moderate
Attapulgite	moderate
Bacampicillin	moderate
Balsalazide	moderate
Bedaquiline	moderate
Benzylpenicillin	moderate
Benzylpenicillin (potassium)	moderate
Benzylpenicillin (sodium)	moderate
Bifidobacterium longum infantis	moderate
Bismuth subcitrate potassium	moderate
Bismuth subgallate	moderate
Bismuth subsalicylate	moderate
Butabarbital	moderate
Butalbital	moderate
Calaspargase pegol	moderate
Calcium Phosphate	moderate
Calcium acetate	moderate
Calcium carbonate	moderate
Calcium chloride	moderate

Showing 40 of 100+.

Registered Products (17)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
DOXYDAR CAPS.	Capsule 100 mg	6 cap pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	1.480
REMYCIN 100 CAPSULES	Capsule 100 mg	10 cap pack varies	JAWEDA INT. DRUD STORE	1.820
Tabocine	Capsule 100 mg	10 cap	Sukhtian Group	1.820
MEDOMYCIN CAP	Capsule 100 mg	10 cap	Khoury Drug Store	1.910
Dumoxin Tabs	Tablet 100 mg	10 tab	Reda Jardaneh Drug Store	1.930
DOXYDAR CAPS.	Capsule 100 mg	8 cap pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	1.980
DOXYDAR CAPS.	Capsule 100 mg	10 cap pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	2.470
Doxymid Capsules	Capsule 100 mg	10 cap pack varies	MIDDLE EAST PHARMA&CHEMICAL IND/JORDAN	2.470
Unidox Capsules	Capsule 100 mg	10 cap pack varies	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	2.470
Unidox F.C Tablets	Film-Coated Tablet 100 mg	10 tab pack varies	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	2.470
Vibramycin Tab	Tablet 100 mg	10 tab	Khoury Drug Store	2.600
DOXYDAR CAPS.	Capsule 100 mg	20 cap pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	4.640
REMYCIN 100 CAPSULES	Capsule 100 mg	100 cap pack varies	JAWEDA INT. DRUD STORE	16.380
DOXYDAR CAPS.	Capsule 100 mg	500 cap pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	79.800
Doxymid Capsules	Capsule 100 mg	500 cap pack varies	MIDDLE EAST PHARMA&CHEMICAL IND/JORDAN	98.800
Unidox Capsules	Capsule 100 mg	1000 cap pack varies	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	197.600
Unidox F.C Tablets	Film-Coated Tablet 100 mg	1000 tab pack varies	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	197.600