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Pronunciation
(doks i SYE kleen)
Generic Available (U.S.)
Yes: Excludes capsule (variable release), powder for suspension, syrup
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled 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
Use: Dental
Treatment of periodontitis associated with presence of Actinobacillus actinomycetemcomitans (AA); adjunct to scaling and root planing to promote attachment level gain and to reduce pocket depth in adult periodontitis (systemic levels are subinhibitory against bacteria)
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)
Pregnancy Risk Factor
D
Pregnancy Considerations
Because use during pregnancy may cause fetal harm, doxycycline is classified as pregnancy category D. Exposure to tetracyclines during the second or third trimester may cause permanent discoloration of the teeth. Most reports do not show an increase risk for teratogenicity with the exception of a potential small increased risk for cleft palate or esophageal atresia/stenosis. When considering treatment for life-threatening infection and/or prolonged duration of therapy (such as in anthrax), the potential risk to the fetus must be balanced against the severity of the potential illness.
Lactation
Enters breast milk/not recommended
Breast-Feeding Considerations
Tetracyclines, including doxycycline, are excreted in breast milk and therefore, breast-feeding is not recommended by the manufacturer.
Doxycycline is less bound to the calcium in maternal milk which may lead to increased absorption compared to other tetracyclines. Only minimal amounts of doxycycline are excreted in human milk and the relative amount of tooth staining has been reported to be lower when compared to other tetracycline analogs. Nondose-related effects could include modification of bowel flora.
Contraindications
Hypersensitivity to doxycycline, tetracycline or any component of the formulation; children <8 years of age (except in treatment of anthrax exposure and tickborne rickettsial disease)
Warnings/Precautions
Concerns related to adverse effects:
• Autoimmune syndromes: Have been reported.
• Hepatotoxicity: Rarely occurs; if symptomatic, conduct LFT and discontinue drug.
• Increased BUN: May be associated with increases in BUN secondary to antianabolic effects; use caution in patients with renal impairment.
• Photosensitivity: May cause photosensitivity; discontinue if skin erythema occurs. Use skin protection and avoid prolonged exposure to sunlight; do not use tanning equipment.
• Pseudotumor cerebri: Has been (rarely) reported with tetracycline use; usually resolves with discontinuation.
• 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:
• Pediatrics: May cause tissue hyperpigmentation, 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 (children <8 years of age [product labeling]; use between age 6-7 years has minimal effect [Chapman, 2006]) unless other drugs are not likely to be effective or are contraindicated. Recommended in treatment of anthrax exposure (CDC, 2001) and tickborne rickettsial diseases (CDC, 2006).
• 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®: 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.
Other warnings/precautions:
• 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.
Adverse Reactions
Frequency not defined.
Cardiovascular: Intracranial hypertension, pericarditis
Dermatologic: Angioneurotic edema, erythema multiforme, exfoliative dermatitis (rare), photosensitivity, rash, skin hyperpigmentation, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
Endocrine & metabolic: Brown/black discoloration of thyroid gland (no dysfunction reported), hypoglycemia
Gastrointestinal: Anorexia, diarrhea, dysphagia, enterocolitis, esophagitis (rare), esophageal ulcerations (rare), glossitis, inflammatory lesions in anogenital region, nausea, oral (mucosal) pigmentation, pseudomembranous colitis, tooth discoloration (children), vomiting
Hematologic: Eosinophilia, hemolytic anemia, neutropenia, thrombocytopenia
Hepatic: Hepatotoxicity (rare)
Renal: BUN increased (dose related)
Miscellaneous: Anaphylactoid purpura, anaphylaxis, bulging fontanels (infants), serum sickness, SLE exacerbation
Note: Adverse effects in clinical trials occurring at a frequency more than 1% greater than placebo:
Periostat®: Diarrhea, dyspepsia, joint pain, menstrual cramp, nausea, dyspepsia, pain
Oracea®: Abdominal distention, abdominal pain, anxiety, AST increased, back pain, fungal infection, hyperglycemia, influenza, LDH increased, nasal congestion, nasopharyngitis, pain, sinus headache, sinusitis, xerostomia
Metabolism/Transport Effects
Inhibits CYP3A4 (weak)
Drug Interactions
Antacids: May decrease the absorption of Tetracycline Derivatives. Risk D: Consider therapy modification
ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole systemic exposure/affects with concomitant use of a weak CYP3A4 inhibitor. Decrease aripiprazole dose to 25% of the usual dose in patients receiving both a CYP3A4 and a CYP2D6 inhibitor (regardless of potencies). Risk C: Monitor therapy
Barbiturates: May decrease the serum concentration of Doxycycline. Risk D: Consider therapy modification
BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Bile Acid Sequestrants: May decrease the absorption of Tetracycline Derivatives. Risk D: Consider therapy modification
Bismuth: 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. Risk D: 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 subsalicylate. The need to separate doses during Helicobacter pylori eradication regimens is questionable. Risk D: Consider therapy modification
Calcium Salts: May decrease the serum concentration of Tetracycline Derivatives. Management: If coadministration of oral calcium with oral tetracyclines can not be avoided, consider separating administration of each agent by several hours. Risk D: Consider therapy modification
CarBAMazepine: May decrease the serum concentration of Doxycycline. Risk D: Consider therapy modification
Fosphenytoin: May decrease the serum concentration of Doxycycline. Risk D: Consider therapy modification
Iron Salts: May decrease the absorption of Tetracycline Derivatives. Only a concern with orally administered products. Exceptions: Ferric Gluconate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Risk D: Consider therapy modification
Lanthanum: May decrease the serum concentration of Tetracycline Derivatives. Management: Administer oral tetracycline antibiotics at least two hours before or after lanthanum. Risk D: Consider therapy modification
Magnesium Salts: May decrease the absorption of Tetracycline Derivatives. Only applicable to oral preparations of each agent. Risk D: Consider therapy modification
Neuromuscular-Blocking Agents: Tetracycline Derivatives may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Penicillins: Tetracycline Derivatives may diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Phenytoin: May decrease the serum concentration of Doxycycline. Risk D: Consider therapy modification
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: 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. Risk D: 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; Alitretinoin; Tretinoin (Topical). Risk X: 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. Risk D: 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 24 hours after cessation of antibacterial agents. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Tetracycline Derivatives may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Ethanol/Nutrition/Herb 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).
Storage
Capsule, tablet: Store at controlled room temperature of 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light.
I.V. infusion: Protect from light. Stability varies based on solution.
Reconstitution
I.V. infusion: Following reconstitution with sterile water for injection, dilute to a final concentration of 0.1-1 mg/mL using a compatible solution.
Compatibility
Solutions for I.V. infusion are stable in NS, D5W, Ringer's injection, LR, D5LR.
Y-site administration: Compatible: Acyclovir, amifostine, amiodarone, aztreonam, bivalirudin, cisatracurium, cyclophosphamide, cyclosporine, dexmedetomidine, diltiazem, docetaxel, etoposide phosphate, fenoldopam, filgrastim, fludarabine, gemcitabine, granisetron, hetastarch in lactate electrolyte injection (Hextend®), hydromorphone, linezolid, magnesium sulfate, melphalan, meperidine, morphine, ondansetron, oxytocin, propofol, remifentanil, sargramostim, tacrolimus, telavancin, teniposide, theophylline, thiotepa, vinorelbine. Incompatible: Allopurinol, heparin, pemetrexed, piperacillin/tazobactam. Variable (consult detailed reference): Meropenem.
Compatibility in syringe: Compatible: Doxapram.
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
Periostat® capsules (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.
Pharmacodynamics/Kinetics
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%)
Dosage
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) and Adults: Oral, I.V.: 100-200 mg/day in 1-2 divided doses
Indication-specific dosing:
Children:
Anthrax: Doxycycline should be used in children if antibiotic susceptibility testing, exhaustion of drug supplies, or allergic reaction preclude use of penicillin or ciprofloxacin. For treatment, the consensus recommendation does not include a loading dose for doxycycline.
Inhalational (postexposure prophylaxis) (ACIP, 2010): Oral, I.V. (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 I.V.
Inhalational/gastrointestinal/oropharyngeal (treatment): I.V.: 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
Community-acquired pneumonia (CAP) (IDSA/PIDS, 2011): Oral: Children >7 years: 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): 2-4 mg/kg/day in 2 divided doses (maximum: 200 mg/day)
Cellulitis (purulent) due to community-acquired MRSA (unlabeled use): Oral: Children >8 years and ≤45 kg: 2 mg/kg/dose every 12 hours for 5-10 days (Liu, 2011)
Localized juvenile periodontitis (LJP) (unlabeled use): Oral: 50-100 mg/day
Q fever: Oral, I.V.: 2.2 mg/kg twice/day for 15-21 days (CDC, 2009). Some clinicians may recommend trimethoprim/sulfamethoxazole for children <8 years of age (Hartzell, 2008). Note: Use of tetracyclines should be avoided during tooth development (children ≤8 years of age) unless other drugs are unlikely to be effective or are contraindicated.
Tickborne rickettsial disease: Oral, I.V.: Children ≤8 years: 2.2 mg/kg (maximum dose: 100 mg) every 12 hours for 5-7 days; severe or complicated disease may require longer treatment; human granulocytotropic anaplasmosis (HGA) should be treated for 10-14 days. Note: The American Academy of Pediatrics Committee on Infectious Diseases identifies doxycycline as the drug of choice in children of any age.
Tularemia: I.V. (may transition to oral if clinically indicated) (Dennis, 2001):
Children <45 kg: 2.2 mg/kg every 12 hours for 14-21 days
Children ≥45 kg: 100 mg every 12 hours for 14-21 days
Children ≥8 years:
Lyme disease: 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): 1-2 mg/kg twice daily for 10-21 days (maximum: 100 mg/dose)
Treatment (meningitis and other early neurologic manifestations): 4-8 mg/kg/day in 2 divided doses for 10-28 days (maximum: 200 mg/dose)
Malaria chemoprophylaxis: Oral: 2.2 mg/kg/day (maximum: 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 (CDC, 2012)
Malaria, severe, treatment (unlabeled use): Oral, I.V.:
<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 (unlabeled use): 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).
Children >8 years (and >45 kg) and Adults:
Cellulitis (purulent) due to community-acquired MRSA (unlabeled use): Oral: 100 mg twice daily for 5-10 days (Liu, 2011)
Chlamydial infections, uncomplicated: Oral: 100 mg twice daily for 7 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. Note: The American Academy of Pediatrics Committee on Infectious Diseases identifies doxycycline as the drug of choice in children of any age.
Adults:
Anthrax:
Inhalational (postexposure prophylaxis): Oral, I.V. (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 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; some recommend initial loading dose of 200 mg, followed by 100 mg every 8-12 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
Brucellosis: Oral: 100 mg twice daily for 6 weeks with rifampin or streptomycin
Community-acquired pneumonia, bronchitis: Oral, I.V.: 100 mg twice daily (Ailani, 1999; Mandell, 2007)
Epididymitis: Oral: 100 mg twice daily for 10 days (in combination with ceftriaxone) (CDC, 2010)
Gonococcal infection, uncomplicated (cervix, pharynx, rectum, urethra): Oral: 100 mg twice daily for 7 days (in combination with a cephalosporin) (CDC, 2010)
Alternatively, the manufacturer recommends a single-visit dose in nonanorectal infections in men: 300 mg initially, repeat dose in 1 hour (total dose: 600 mg)
Granuloma inguinale (donovanosis): Oral: 100 mg twice daily for at least 3 weeks (and until lesions have healed) (CDC, 2010)
Lyme disease: 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 10-21 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 (CDC, 2010)
Malaria chemoprophylaxis: Oral: 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
Malaria, severe, treatment (unlabeled use): Oral, I.V.: 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 (unlabeled 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 (CDC, 2010)
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 (CDC, 2010)
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 (CDC, 2010)
Periodontitis: Oral (Periostat®): 20 mg twice daily as an adjunct following scaling and root planing
Periodontitis, refractory (unlabeled use): Oral: 100-200 mg daily (Jolkovsky, 2006)
Proctitis: Oral: 100 mg twice daily for 7 days (in combination with ceftriaxone) (CDC, 2010)
Q fever: Oral: 100 mg every 12 hours for 15-21days (CDC, 2009)
Rosacea (Oracea®): Oral: 40 mg once daily in the morning
Sclerosing agent for pleural effusion (unlabeled use): Intrapleural: 500 mg as a single dose in 100 mL NS (Porcel, 2006); may require a repeat dose (Kvale, 2007)
Syphilis:
Primary/secondary syphilis: Oral: 100 mg twice daily for 14 days (CDC, 2010)
Latent syphilis: Oral: 100 mg twice daily for 28 days (CDC, 2010)
Tularemia: I.V. (may transition to oral if clinically appropriate): Initial: 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, I.V.: 200 mg initially then 100 mg twice daily or 200 mg once daily for 10 days (Daya, 2005; Inglesby, 2000)
Dosing adjustment in renal impairment: No dosage adjustment necessary in renal impairment.
Poorly dialyzed; no supplemental dose or dosage adjustment necessary, including patients on intermittent hemodialysis, peritoneal dialysis, or continuous renal replacement therapy (eg, CVVHD).
Dental Usual Dosing
Adults: Oral: Treatment of periodontitis (refractory): 100-200 mg once daily for 21 days (Jolkovsky, 2006). Note: A specific formulation (Periostat®) containing a subantimicrobial dosage is also available for use as an adjunct to scaling and root planing (see Doxycycline Subantimicrobial monograph). In addition, doxycycline gel (Atridox™) is available for subgingival application (see Doxycycline Hyclate Periodontal Extended-Release Liquid monograph).
Administration: Oral
Oral administration is preferable unless patient has significant nausea and vomiting; I.V. and oral routes are bioequivalent. 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 after taking to reduce the risk of esophageal irritation and ulceration.
Oracea®: Take 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.
Administration: I.V.
Infuse slowly, usually over 1-4 hours. Avoid extravasation. Oral administration is preferable unless patient has significant nausea and vomiting; I.V. and oral routes are bioequivalent.
Administration: Other
Intrapleural (unlabeled route): Add to 100 mL NS and instill into chest tube (Porcel, 2006)
Administration: I.V. Detail
Avoid extravasation. Very irritating to vein; use central line if possible.
pH: 1.8-3.3 (reconstituted solution)
Monitoring Parameters
Perform culture and sensitivity testing prior to initiating therapy. CBC, renal and liver function tests periodically with prolonged therapy.
Test Interactions
False-negative urine glucose using Clinistix®, Tes-Tape®; false-positive urine glucose using Clinitest®; false elevations of urinary catecholamines with fluorescence test
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.
Oracea®: Take on an empty stomach 1 hour before or 2 hours after meals.
Some products may contain sodium.
Patient Education
If administered by infusion, report immediately any acute back pain, difficulty breathing or swallowing, chest tightness, pain, redness, or swelling at infusion site. Oral: Medication may be taken with food if gastric irritation occurs. Avoid alcohol and maintain adequate hydration, unless instructed to restrict fluid intake. Patient may be sensitive to sunlight. May cause nausea, vomiting, or diarrhea. Do not take antidiarrheal medication without instruction from prescriber. Report skin rash or itching; easy bruising or bleeding; yellowing of skin or eyes; pale stool or dark urine; unhealed mouth sores; vaginal itching or discharge; persistent diarrhea; and fever, chills, or unusual cough. Inform prescriber if you think you are pregnant.
Geriatric Considerations
Dose adjustment for renal function is not necessary.
Additional Information
Oracea® capsules are not bioequivalent to other doxycycline products.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Glossitis and tooth discoloration (children). Opportunistic “superinfection” with Candida albicans; tetracyclines are not recommended for use during pregnancy or in children ≤8 years of age since they have been reported to cause enamel hypoplasia and permanent teeth discoloration. The use of tetracyclines should only be used in these patients if other agents are contraindicated or alternative antimicrobials will not eradicate the organism.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Tetracyclines have been reported to cause memory disturbance, mood stabilizing and antidepressant effects
Mental Health: Effects on Psychiatric Treatment
May cause neutropenia; use caution with clozapine and carbamazepine; barbiturates and carbamazepine increase the clearance of doxycycline
Nursing: Physical Assessment/Monitoring
Assess results of culture and sensitivity test and patient's allergy history prior to beginning therapy. I.V.: Infusion site must be closely monitored; extravasation can be very irritating to veins (use of central line is preferable). Teach patient importance of adequate hydration and photosensitivity precautions. Evaluate labs if concerned for hemolytic anemia.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, oral [strength expressed as base]:
Oracea®: 40 mg [30 mg (immediate release) and 10 mg (delayed release)]
Capsule, oral, as hyclate [strength expressed as base]: 50 mg, 100 mg
Ocudox™: 50 mg [kit includes Ocudox™ capsules (60s), Ocusoft® Lid Scrub™ Plus eyelid cleanser pads, and Tears Again® advanced spray]
Oraxyl™: 20 mg
Vibramycin®: 100 mg
Capsule, oral, as monohydrate [strength expressed as base]: 50 mg, 100 mg, 150 mg
Adoxa®: 150 mg
Monodox®: 50 mg, 75 mg, 100 mg
Injection, powder for reconstitution, as hyclate [strength expressed as base]: 100 mg
Doxy 100™: 100 mg
Powder for suspension, oral, as monohydrate [strength expressed as base]:
Vibramycin®: 25 mg/5 mL (60 mL) [raspberry flavor]
Syrup, oral, as calcium [strength expressed as base]:
Vibramycin®: 50 mg/5 mL (473 mL) [contains propylene glycol, sodium metabisulfite; raspberry-apple flavor]
Tablet, oral, as hyclate [strength expressed as base]: 20 mg, 100 mg
Alodox™: 20 mg [kit includes Alodox™ tablets (60s), Ocusoft® Lid Scrub™ pads, eyelid cleanser, and goggles]
Periostat®: 20 mg
Tablet, oral, as monohydrate [strength expressed as base]: 50 mg, 75 mg, 100 mg, 150 mg
Adoxa®: 50 mg [DSC]
Adoxa® Pak™ 1/150: 150 mg [DSC] [scored]
Adoxa® Pak™ 1/75: 75 mg [DSC]
Tablet, delayed release coated beads, oral, as hyclate [strength expressed as base]: 75 mg, 100 mg
Tablet, delayed release coated pellets, oral, as hyclate:
Doryx®: 150 mg [scored; contains sodium 9 mg (0.392 mEq)/tablet]
Tablet, delayed release coated pellets, oral, as hyclate [strength expressed as base]:
Doryx®: 75 mg [DSC] [scored; contains sodium 4.5 mg (0.196 mEq)/tablet]
Doryx®: 100 mg [DSC] [scored; contains sodium 6 mg (0.261 mEq)/tablet]
Doryx®: 150 mg [DSC] [scored; contains sodium 9 mg (0.392 mEq)/tablet]
Pricing: U.S. (www.drugstore.com)
Capsule, delayed release (Oracea)
40 mg (30): $376.98
Capsules (Adoxa)
150 mg (60): $1706.29
Capsules (Doxycycline Hyclate)
50 mg (20): $12.99
100 mg (30): $12.99
Capsules (Doxycycline Monohydrate)
50 mg (30): $42.99
100 mg (30): $69.99
Capsules (Monodox)
75 mg (100): $1402.56
100 mg (50): $675.99
Capsules (Vibramycin)
100 mg (20): $129.99
Suspension (reconstituted) (Vibramycin)
25 mg/5 mL (60): $35.99
Syrup (Vibramycin)
50 mg/5 mL (480): $277.17
Tablet, EC (Doryx)
75 mg (30): $244.72
100 mg (30): $304.28
150 mg (60): $1037.99
Tablets (Adoxa Pak 1/100)
100 mg (31): $305.99
Tablets (Adoxa Pak 1/150)
150 mg (30): $622.83
Tablets (Doxycycline Hyclate)
20 mg (30): $39.99
100 mg (20): $13.99
Tablets (Doxycycline Monohydrate)
100 mg (50): $229.98
150 mg (30): $245.99
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.
U.S. 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
References
Abramowicz M, “Antimicrobial Prophylaxis in Surgery,” Medical Letter on Drugs and Therapeutics, Handbook of Antimicrobial Therapy, 16th ed, New York, NY: Medical Letter, 2002.
Ailani RK, Agastya G, Ailani RK, et al, “Doxycycline is a Cost-Effective Therapy for Hospitalized Patients With Community-Acquired Pneumonia,” Arch Intern Med, 1999, 159(3):266-70.
Böcker R, Mühlberg W, Platt D, et al, “Serum Level, Half-Life and Apparent Volume of Distribution of Doxycycline in Geriatric Patients,” Eur J Clin Pharmacol, 1986, 30(1):105-8.
Bradley JS, Byington CL, Shah SS, et al. “The Management of Community-Acquired Pneumonia in Infants and Children Older Than 3 Months of Age: Clinical Practice Guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America”, Clin Infect Dis, 2011, 53(7):e25-76.
Bryant SG, Fisher S, and Kluge RM, “Increased Frequency of Doxycycline Side Effects,” Pharmacotherapy, 1987, 7(4):125-9.
Center for Disease Control and Prevention (CDC), “Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever, Ehrlichioses, and Anaplasmosis - United States,” MMWR Recomm Rep, 2006 55(RR-4):1-27.
Centers for Disease Control and Prevention (CDC), “Guidelines for Treatment of Malaria in the United States,” Treatment Table Update, September 23, 2011. Available at http://www.cdc.gov/malaria/pdf/treatmenttable.pdf
Centers for Disease Control and Prevention (CDC), “Q Fever," 2009. Available at: http://www.cdc.gov/ncidod/dvrd/qfever/#treatment. Accessed November 29, 2010.
Centers for Disease Control and Prevention (CDC), "Sexually Transmitted Diseases Treatment Guidelines, 2010," MMWR Recomm Rep, 2010, 59(RR-12):1-110.
Centers for Disease Control and Prevention (CDC), "Use of Anthrax Vaccine in the United States. Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009," MMWR, 2010, 59(6):1-30. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5906a1.htm?s_cid=rr5906a1_e
Centers for Disease Control and Prevention, “Update: Investigation of Bioterrorism-Related Anthrax and Interim Guidelines for Exposure Management and Antimicrobial Therapy, October 2001,” MMWR, October 26, 2001, 50(42):909-19. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5042a1.htm
Chow AW, Benninger MS, Brook I, et al, “IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults,” Clin Infect Dis, 2012, 54(8):e72-112.
Daunt N, Brodribb TR, and Dickey JD, “Oesophageal Ulceration Due to Doxycycline,” Br J Radiol, 1985, 58(696):1209-11.
Daya M and Nakamura Y, "Pulmonary Disease From Biological Agents: Anthrax, Plague, Q Fever, and Tularemia," Crit Care Clin, 2005, 21(4):747-63.
Dennis DT, Inglesby TV, Henderson DA, et al, "Tularemia as a Biological Weapon: Medical and Public Health Management," JAMA, 2001, 285(21):2763-73.
Francke EL and Neu HC, “Chloramphenicol and Tetracyclines,” Med Clin North Am, 1987, 71(6):155-68.
Gould FK, Denning DW, Elliott TS, et al, “Guidelines for the Diagnosis and Antibiotic Treatment of Endocarditis in Adults: A Report of the Working Party of the British Society for Antimicrobial Chemotherapy,” J Antimicrob Chemother, 2012, 67(2):269-89.
Halperin JJ, Shapiro ED, Logigian E, et al, “Practice Parameter: Treatment of Nervous System Lyme Disease (an Evidence-Based Review): Report of the Quality Standards Subcommittee of the American Academy of Neurology," Neurology, 2007, 69(1):91-102.
Hartzell JD, Wood-Morris RN, Martinez LJ, et al, "Q Fever: Epidemiology, Diagnosis, and Treatment," Mayo Clin Proc, 2008, 83(5):574-9.
Inglesby TV, Dennis DT, Henderson DA, et al, "Plague as a Biological Weapon: Medical and Public Health Management. Working Group on Civilian Biodefense," JAMA, 2000, 283(17):2281-90.
Jolkovsky DL and Ciancio S, "Chemotherapeutic Agents," Newman MG, Takei HH, Klokkevold PR, et al, eds, Clinical Periodontology, 10th ed, St Louis, MO: Saunders/Elsevier, 2006, 802-3.
Joshi N and Miller DQ, “Doxycycline Revisited,” Arch Intern Med, 1997, 157(13):1421-8.
Kvale PA, Selecky, Prakash BS, et al, “Palliative Care In Lung Cancer: ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition),” Chest, 2007, 132(Suppl 3):268-403.
Liu C, Bayer A, Cosgrove SE, et al, “Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus Aureus Infections in Adults and Children: Executive Summary,” Clin Infect Dis, 2011, 52(3):285-92.
Ljungberg B and Nilsson-Ehle I, “Pharmacokinetics of Antimicrobial Agents in the Elderly,” Rev Infect Dis, 1987, 9(2):250-64.
Mandell LA, Wunderink RG, Anzueto A, et al, “Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines On The Management Of Community-Acquired Pneumonia In Adults,” 2007, Clin Infect Dis, 44(Suppl 2):27-72
Porcel JM, Salud A, Nabal M, et al, “Rapid Pleurodesis With Doxycycline Through a Small-Bore Catheter for the Treatment of Metastatic Malignant Effusions,” Support Care Cancer, 2006, 14(5):475-8.
Rams TE and Slots J, “Antibiotics in Periodontal Therapy: An Update,” Compendium, 1992, 13(12):1130, 1132, 1134.
Ross J, Judlin P, and Nilas L, “European Guideline for the Management of Pelvic Inflammatory Disease, 2008. Available at http://www.iusti.org/regions/europe/PID_v5.pdf. Accessed December 1, 2010.
Saivin S and Hovin G, “Clinical Pharmacokinetics of Doxycycline and Minocycline,” Clin Pharmacokinet, 1985, 15:355-66.
Smilack JD, Wilson WR, and Cockerill FR 3d, “Tetracyclines, Chloramphenicol, Erythromycin, Clindamycin, and Metronidazole,” Mayo Clin Proc, 1991, 66(12):1270-80.
Wilson WR and Cockerill FR 3d, “Tetracyclines, Chloramphenicol, Erythromycin, and Clindamycin,” Mayo Clin Proc, 1987, 62(10):906-15.
Wormser GP, Dattwyler RJ, Shapiro ED, et al, “The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America,” Clin Infect Dis, 2006, 43(9):1089-134.
Wyler DJ, “Malaria: Overview and Update,” Clin Infect Dis, 1993, 16(4):449-56.
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Last full review/revision March 2012
Content last modified March 2012
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