Doxycycline

Therapeutic Class
Antibiotic, Tetracycline Derivative
Indications

Principally in the treatment of infections caused by susceptible Rickettsia, Chlamydia, and Mycoplasma; alternative to mefloquine for malaria prophylaxis; treatment for syphilis, uncomplicated Neisseria gonorrhoeae, 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, Francisella tularensis, Vibrio cholerae, Campylobacter fetus, Brucella spp, Bartonella bacilliformis, and Klebsiella granulomatis, Q fever, Lyme disease; treatment of inflammatory lesions associated with rosacea; intestinal amebiasis; severe acne; Sclerosing agent for pleural effusion injection; vancomycin-resistant enterococci (VRE); alternate treatment for MRSA infections; treatment of periodontitis (refractory); localized juvenile periodontitis (LIP).

Adult Doses

Usual dosage range: Oral, I.V.: 100-200 mg/day in 1-2 divided doses

Anthrax: (therapy for 60 days)

Inhalational (postexposure prophylaxis) & Cutaneous (treatment): Oral, I.V. (use oral route when possible): 100 mg every 12 hours for 60 days .
Note: In the presence of systemic involvement, extensive edema, lesions on head/neck, refer to I.V. dosing for treatment of inhalational/gastrointestinal/oropharyngeal anthrax

Inhalational/gastrointestinal/oropharyngeal (treatment): I.V.: Initial: 100 mg every 12 hours; switch to oral therapy when clinically appropriate.
Note: Initial treatment should include two or more agents predicted to be effective. Agents suggested for use in conjunction with doxycycline or ciprofloxacin include rifampin, vancomycin, imipenem, penicillin, ampicillin, chloramphenicol, clindamycin, and clarithromycin.Continue combined therapy for 60 days

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

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

Chlamydial infections, uncomplicated: Oral: 100 mg twice daily for ≥7 days

Community-acquired pneumonia, bronchitis: Oral, I.V.: 100 mg twice daily

Epididymitis: Oral: 100 mg twice daily for 10 days (in combination with ceftriaxone)

Gonococcal infection, uncomplicated (cervix, pharynx, rectum, urethra): Oral: 100 mg twice daily for 7 days (in combination with a cephalosporin)

Granuloma inguinale (donovanosis): Oral: 100 mg twice daily for at least 3 weeks (and until lesions have healed) .

Lyme disease: Oral
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 10-21 days
Treatment (meningitis or other early neurologic manifestations): 100-200 mg twice daily for 14 days (range: 10-28 days)

Lymphogranuloma venereum: Oral: 100 mg twice daily for 21 days.

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

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

Pelvic inflammatory disease:
Treatment, inpatient: Oral, I.V.: 100 mg twice daily (in combination with cefoxitin or cefotetan); may transition to oral doxycycline (add clindamycin or metronidazole if tubo-ovarian abscess present) to complete 14 days of treatment
Treatment, outpatient: Oral: 100 mg twice daily for 14 days (with or without metronidazole); preceded by a single I.M. dose of cefoxitin (plus oral probenecid) or ceftriaxone.

Periodontitis: Oral : 20 mg twice daily as an adjunct following scaling and root planing.

Periodontitis, refractory : Oral: 100-200 mg daily

Proctitis: Oral: 100 mg twice daily for 7 days (in combination with ceftriaxone)

Q fever: Oral: 100 mg every 12 hours for 15-21days

Rosacea: Oral: 40 mg once daily in the morning

Sclerosing agent for pleural effusion : Intrapleural: 500 mg as a single dose in 100 mL NS ; may require a repeat dose

Syphilis:
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, I.V.: 100 mg twice daily for 5-7 days; severe or complicated disease may require longer treatment; human granulocytotropic anaplasmosis (HGA) should be treated for 10-14 days.

Tularemia: I.V. (may transition to oral if clinically appropriate): Initial: 100 mg every 12 hours for 14-21 days

Vibrio cholerae: Oral: 300 mg as a single dose

Yersinia pestis (plague): Oral, I.V.: 200 mg initially then 100 mg twice daily or 200 mg once daily for 10 days 

Pediatric Doses

Usual dosage range:

Children >8 years (≤45 kg): Oral, I.V.: 2-5 mg/kg/day in 1-2 divided doses, not to exceed 200 mg/day

Children >8 years (>45 kg): Oral, I.V.: Refer to adult dosing.

Doses in Renal impairment

No dosage adjustment necessary in renal impairment

Contraindications

Children <8 yr; pregnancy, lactation; porphyria; hypersensitivity to tetracyclines; severe hepatic dysfunction; prolonged exposure to sunlight or tanning equipment.

Warnings / Precautions

Impaired hepatic function; history or predisposition to oral candidiasis. Should be taken with at least a glass of water in an upright position to reduce the risk of oesophageal injury.

Adverse Reactions

Permanent staining of teeth; rash, superinfection; nausea, GI upsets, glossitis; dysphagia; photosensitivity, hypersensitivity; haemolytic anaemia, thrombocytopenia, neutropenia and eosinophilia.
Potentially Fatal: Anaphylaxis.

Overdose Reactions

Symptomatic and supportive measures should be used. Dialysis may be of little value.

Drug Interactions

Reduction in absorption and bioavailability when used with antacids, calcium, magnesium and iron. Chronic ethanol ingestion reduces serum concentrations. Metabolism increased by hepatic enzyme inducers such as rifampicin, phenytoin and carbamazepine. May reduce the efficacy of oral contraceptives.
Potentially Fatal: Reduction in absorption and bioavailability when used with antacids, calcium, magnesium and iron. Chronic ethanol ingestion reduces serum concentrations. Metabolism increased by hepatic enzyme inducers such as rifampicin, phenytoin and carbamazepine. May reduce the efficacy of oral contraceptives.

Lab Interactions

False elevations of urine catecholamine levels; false-negative urine-glucose test results

Food Interactions

Ethanol: Chronic ethanol ingestion may reduce the serum concentration of doxycycline.

Food: Doxycycline serum levels may be slightly decreased if taken with food or milk. Administration with iron or calcium may decrease doxycycline absorption. May decrease absorption of calcium, iron, magnesium, zinc, and amino acids.

Herb/Nutraceutical: St John's wort may decrease doxycycline levels. Avoid dong quai, St John's wort (may also cause photosensitization).

Mechanism of Actions

Doxycycline binds to 30S and 50S ribosomal subunits thus causing alterations on the cytoplasmic membrane of susceptible organisms.

Metabolism

Inhibits CYP3A4 (moderate)

Pharmacodynamics

Absorption: Oral: Almost complete

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

Protein binding: 90%

Metabolism: Not hepatic; partially inactivated in GI tract by chelate formation

Bioavailability: Reduced at high pH; may be clinically significant in patients with gastrectomy, gastric bypass surgery or who are otherwise deemed achlorhydric

Half-life elimination: 12-15 hours (usually increases to 22-24 hours with multiple doses); End-stage renal disease: 18-25 hours; Oracea®: 21 hours

Time to peak, serum: 1.5-4 hours

Excretion: Feces (30%); urine (23%)

Monitoring

Perform culture and sensitivity testing prior to initiating therapy. CBC, renal and liver function tests periodically with prolonged therapy.

Administration

May be taken with or without food. Take w/ a full glass of water & remain upright for at least ½ hr. Take w/ food or milk if GI irritation occurs.

Solutions for I.V. infusion are stable in NS, D5W, Ringer's injection, LR, D5LR.

Pregnancy Category

D: Drug Pregnancy Category There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Lactation

Enters breast milk/not recommended

Storage Conditions

Intravenous: Store at 15-30°C. Oral: Store at 15-30°C.

ATC Classification
J01AA02 - doxycycline ; Belongs to the class of tetracyclines. Used in the systemic treatment of infections.
A01AB22 - doxycycline ; Belongs to the class of local antiinfective and antiseptic preparations. Used in the treatment of diseases of the mouth.
GenericPedia Classification
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  • Storage

    Intravenous: Store at 15-30°C. Oral: Store at 15-30°C.

    Available As
  • Doxycycline 10 mg
  • Doxycycline Hydrate 10 mg
  • Doxycycline Monohydrate 100 mg
  • Doxycycline 100 mg
  • Doxycycline Hyclate 100 mg
  • Doxycillin Hyclate 100 mg
  • Doxycycline 100mg
  • Doxycycline Monohydrate 20 mg
  • Doxycycline 200 mg
  • Doxycycline Monohydrate 200 mg
  • Doxycycline Hyclate 200 mg
  • Doxycycline 25 mg
  • Doxycycline 50 mg
  • Doxycycline Hyclate 50 mg
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