Merck Manual

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Brian J. Werth

, PharmD, University of Washington School of Pharmacy

Last full review/revision May 2020| Content last modified May 2020
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Tetracyclines are bacteriostatic antibiotics that bind to the 30S subunit of the ribosome, thus inhibiting bacterial protein synthesis. Specific tetracyclines are

  • Doxycycline

  • Eravacycline (IV only)

  • Minocycline

  • Omadacycline (novel aminomethylcycline)

  • Tetracycline


About 60 to 80% of tetracycline and 90% of doxycycline and minocycline are absorbed after oral use. However, absorption is decreased by metallic cations (eg, aluminum, calcium, magnesium, iron); thus, tetracyclines cannot be taken withpreparations containing these substances (eg, antacids, many vitamin and mineral supplements). Tetracycline and omadacycline should be taken with plenty of water on an empty stomach. Food decreases absorption of other tetracyclines as well, but this effect is less significant for doxycycline and minocycline.

Tetracyclines penetrate into most body tissues and fluids. All are concentrated in unobstructed bile. However, cerebrospinal fluid levels are not reliably therapeutic. Minocycline is the only tetracycline that reaches high concentrations in tears and saliva.

Tetracycline and minocycline are excreted primarily in urine. Doxycycline, eravacycline, and omadacycline are excreted primarily in the intestinal tract.


Tetracyclines are active against infections caused by the following:

About 5 to 10% of pneumococcal strains and many group A beta-hemolytic streptococci, many gram-negative bacillary uropathogens, and penicillinase-producing gonococci are resistant.

Tetracyclines are interchangeable for most indications, although minocycline has been most studied for methicillin-resistant S. aureus infections.

Doxycycline is usually preferred for all of the following because it is better tolerated and can be given twice a day:


Tetracyclines are contraindicated in

  • Patients who have had an allergic reaction to them

  • Children < 8 years (except sometimes for inhalational anthrax or other severe illnesses, such as Rocky Mountain spotted fever, when the benefit outweighs the potential risk of tooth staining)

Use During Pregnancy and Breastfeeding

Tetracyclines cross the placenta, enter fetal circulation, accumulate in fetal bones, and, if used during the 2nd or 3rd trimester, may cause permanent discoloration of the fetus's teeth.

Hepatotoxicity may occur in pregnant women, particularly after IV administration and in those with azotemia or pyelonephritis. Taking high doses during pregnancy can lead to fatty degeneration of the liver, which may be fatal.

Tetracyclines enter breast milk, but usually in small amounts (particularly tetracycline). Use during breastfeeding is usually discouraged.

Adverse Effects

Adverse effects of tetracyclines include

All oral tetracyclines cause nausea, vomiting, and diarrhea and can cause C. difficile–induced diarrhea (pseudomembranous colitis) and candidal superinfections. If not swallowed with water, tetracyclines can cause esophageal erosions.

Photosensitivity due to tetracyclines may manifest as an exaggerated sunburn reaction.

Bone and dental effects include staining of teeth, hypoplasia of dental enamel, and abnormal bone growth in children < 8 years and in fetuses. In infants, tetracyclines may cause idiopathic intracranial hypertension and bulging fontanelles.

Excessive blood levels due to use of high doses or renal insufficiency may lead to fatal acute fatty degeneration of the liver, especially during pregnancy.

Minocycline commonly causes vestibular dysfunction, limiting its use. Use of minocycline has been associated with development of autoimmune disorders such as systemic lupus erythematosus and polyarteritis nodosa, which may be reversible. Minocycline may also cause drug reaction with eosinophilia and systemic symptoms (DRESS), which is characterized by fever, rash, lymphadenopathy, hepatitis, atypical lymphocytosis, eosinophilia, and thrombocytopenia.

Tetracycline can exacerbate azotemia in patients with renal insufficiency.

Expired tetracycline pills can degenerate and, if ingested, cause Fanconi syndrome. Patients should be instructed to discard the drugs when they expire.

Dosing Considerations

Doxycycline, eravacycline, and omadacycline are excreted primarily in the intestinal tract and require no dose reduction in renal insufficiency, whereas tetracycline and minocycline require dose adjustment in patients with reduced kidney function.

Tetracyclines may decrease the effectiveness of oral contraceptives and potentiate the effects of oral anticoagulants.

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