Doxycycline versus Tetracycline

Based on "Antibiotic and Chemotherapy"
written by Roger G. Finch

Doxycycline advantages over Tetracycline

  • Doxycycline has more rapid and complete gastrointestinal absorption and higher bioavailability than tetracycline.
  • Less dietary restrictions. Doxycycline can be taken with food because its absorption is not affected by food. Tetracycline absorption is affected by concurrent consumption of dairy products, food or heavy metals.
  • Doxycycline is more lipophilic and as a result achieves higher tissue and intracellular concentrations.
  • Doxycycline does not accumulate in patients with renal impairment.
  • Doxycycline has more convenience of dosage schedule.
  • Doxycycline is potentially less hepatotoxic than tetracycline1.
  • Doxycycline has cytoprotective properties and can protect liver cells from ischemic and hypoxic injury5.

Tetracycline advantages over Doxycycline

  • Reasonable efficacy.
  • Low cost.
  • Tetracycline is available in topical formulations.
  • Tetracycline is less phototoxic.

Difference between Doxycycline and Tetracycline


Table 1. Comparison of Doxycycline and Tetracycline

Doxycycline Tetracycline
Brand names
Vibramycin®, Doryx®, Oracea®, Periostat® Sumycin®, Actisit®
Drug class
Tetracycline antibiotic
Dose formulations
• Capsules
• Capsules, delayed-release
• Injection IV
• Suspension
• Tablets
• Tablets, delayed-release
• Periodontal extended-release liquid
• Capsules
• Tablets
• Topical solution, ointment, cream
Antimicrobial spectrum
Tetracyclines have essentially the same broad antimicrobial activity:
• Wide range of gram-positive and gram-negative bacteria
• Atypical pathogens, including Chlamydia spp, Mycoplasma pneumonia, Rickettsia spp., Borrelia spp., Treponema spp., Vibrio cholerae
• Protozoan parasites
• Doxycycline is more active against staphylococci than tetracycline4
Mechanism of action
Antimicrobial mechanism:
• Tetracyclines are bacteriostatic and work by inhibiting protein synthesis.

Anti-inflammatory mechanism:
• Tetracyclines suppress the synthesis and activity of inflammatory mediators such as metalloproteinases2, prostaglandins, nitric oxide, and cytokines.
• 18 to 22 hours • 6 to 12 hours,
in patients with severe renal impairment up to 30 - 79 hours
Oral bioavailability
• ∼95% (reduced at high gastric pH) • 75%
Metabolism, Elimination
• Doxycycline is eliminated by the gastrointestinal tract and by the kidneys3. It is excreted as unchanged drug in the feces and urine. • Tetracycline is mainly eliminated by the kidneys via glomerular filtration.
• Hypersensitivity to any of tetracycline antibiotics
Side effects
• Hepatotoxicity is rare, occurs more commonly with tetracycline than with doxycycline
• Yellow-gray to brown discoloration of teeth during tooth development, enamel hypoplasia
• Esophagitis and esophageal ulceration
• Abdominal discomfort
• Nausea
• Vomiting
• Dyspepsia
• Diarrhea
• Abdominal discomfort or pain
• Photosensitivity
• Diarrhea
• Nausea
• Epigastric distress
• Vomiting
• Excessive tetracycline accumulation may occur in patients with renal impairment.
Drug interactions
• Antacids - decreased absorption of doxycycline. • Gastrointestinal absorption of tetracycline is reduced by about 50% by food or milk.
• Antacids - decreased absorption of tetracycline.
Pregnancy category


Doxycycline vs Tetracycline for Rosacea

Both tetracycline and doxycycline are considered first-line oral medications for rosacea 6 . However, only doxycycline is FDA approved for rosacea treatment.

Tetracyclines reduce inflammation, capillary vasodilation and leakage, and improve connective tissue integrity. Subantimicrobial dose tetracyclines produce anti-inflammatory action without promoting bacterial resistance.

Both tetracycline and doxycycline are effective for management of ocular rosacea 3.

Results of comparison of doxycycline and tetracycline in ocular rosacea 7 Doxycycline Tetracycline
Regimen 100 mg per day 1000 mg per day
Symptomatic relief after 6 weeks   greater with tetracycline
Symptomatic relief after 3 months
no significant difference
Gastrointestinal tract side effects 12.5%
(2 of 16 patients)
(3 of 8 patients)

Tetracycline dosage for rosacea: 250 mg to 500 mg twice daily for 6 to 12 weeks.

Doxycycline dosage for rosacea: 40 mg to 100 mg once daily for 6 to 12 weeks.

Doxycycline vs Tetracycline for Lyme disease

Tetracycline and doxycycline have excellent activity against spirochete Borrelia burgdorferi8.

Both antibiotics are effective for Lyme disease associated with erythema migrans9. However, doxycycline is preferred to tetracycline, particularly in patients with early disseminated disease. Doxycycline has better microbiologic activity and reaches higher cerebrospinal fluid concentrations. Additionally, doxycycline is effective for human granulocytic ehrlichiosis, which may occur simultaneously with early Lyme disease.

Doxycycline vs Tetracycline for Scrub typhus

Both medications are very effective for the treatment of scrub typhus and prevention of relapses 10.

Results of comparative study 10 Doxycycline Tetracycline
Dosage regimen 100 mg twice daily for 3 days 500 mg 4 times daily for 7 days
Scrub typhus cure rate 93.9% 100%
Relapses No No
Time required for abatement of typhoid fever or for the alleviation of symptoms was similar

Further reading


  • 1. Heaton PC, Fenwick SR, Brewer DE. Association between tetracycline or doxycycline and hepatotoxicity: a population based case-control study.J Clin Pharm Ther. 2007 Oct;32(5):483-7.
  • 2. Bench TJ, Jeremias A, Brown DL. Matrix metalloproteinase inhibition with tetracyclines for the treatment of coronary artery disease. Pharmacol Res. 2011 Dec;64(6):561-6. PubMed
  • 3. Whelton A. Tetracyclines in renal insufficiency: resolution of a therapeutic dilemma. Bull N Y Acad Med. 1978 Feb;54(2):223-36. PubMed
  • 4. Minuth JN, Holmes TM, Musher DM. Activity of tetracycline, doxycycline, and minocycline against methicillin-susceptible and -resistant staphylococci. Antimicrob Agents Chemother. 1974 Oct;6(4):411-4.
  • 5. Schwartz J, Holmuhamedov E, Zhang X, Lovelace GL, Smith CD, Lemasters JJ. Minocycline and doxycycline, but not other tetracycline-derived compounds, protect liver cells from chemical hypoxia and ischemia/reperfusion injury by inhibition of the mitochondrial calcium uniporter.Toxicol Appl Pharmacol. 2013 Nov 15;273(1):172-9. PubMed
  • 6. Goldgar C, Keahey DJ, Houchins J. Treatment options for acne rosacea. Am Fam Physician. 2009 Sep 1;80(5):461-468.
  • 7. Frucht-Pery J, Sagi E, Hemo I, Ever-Hadani P. Efficacy of doxycycline and tetracycline in ocular rosacea. Am J Ophthalmol. 1993 Jul 15;116(1):88-92. PubMed
  • 8. Ates L, Hanssen-Hübner C, Norris DE, Richter D, Kraiczy P, Hunfeld KP. Comparison of in vitro activities of tigecycline, doxycycline, and tetracycline against the spirochete Borrelia burgdorferi. Ticks Tick Borne Dis. 2010 Mar;1(1):30-4. PubMed
  • 9. Nowakowski J, Nadelman RB, Forseter G, McKenna D, Wormser GP. Doxycycline versus tetracycline therapy for Lyme disease associated with erythema migrans. J Am Acad Dermatol. 1995 Feb;32(2 Pt 1):223-7. PubMed
  • 10. Song JH, Lee C, Chang WH, Choi SW, Choi JE, Kim YS, Cho SR, Ryu J, Pai CH. Short-course doxycycline treatment versus conventional tetracycline therapy for scrub typhus. Clin Infect Dis. 1995 Sep;21(3):506-10. PubMed

Published: December 01, 2017
Last updated: December 01, 2017


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