antibiotic tetracycline has been on the market for over 60 years and is used in
the treatment of many gram negative and gram positive infections as well as
chlamydial, mycoplasmal and rickettsial infections. Unfortunately,
tetracycline is associated with a number of adverse drug events, including
permanent staining of the teeth. The first case report of tooth
discoloration in children occurred in 1956, with many others following.1-4
As a result, tetracycline is not used during the second and third
trimesters of pregnancy or in children up to 8 years of age.2-4 Warning of
this effect also extends to a number of derivatives of tetracycline including
doxycycline (Adoxa Pak 1/150, Doryx, Monodox) and minocycline (Minocin,
Dynacin, Solodyn) to name a few. The development of minocycline was
thought to address this side effect; unfortunately, the staining of teeth
continues to occur.5 In fact, it began to occur in adults but through a different
mechanism. This will be discussed in part 2 of this series (next
staining/discoloration with tetracycline is influenced by the dosage used,
length of treatment or exposure, stage of tooth mineralization (or
calcification) and degree of activity of the mineralization process.6
While staining of the teeth has been seen with all doses of tetracycline, daily
doses greater than 3 grams and longer durations of treatment were determined to
be factors associated with the greatest risk of developing this adverse effect.3 The
discoloration is permanent and can vary from yellow or gray to brown. In
addition, tetracycline (but not minocycline) effected teeth will fluoresce bright
yellow under UV light in a dark room.7,8
How does tetracycline actually cause teeth discoloration?
If the teeth are exposed to tetracycline (whether in utero or through oral
administration) at a time of tooth mineralization or calcification, tetracycline
will bind to calcium ions (calcium orthophosphate) in the teeth. If this
happens prior to the eruption of the teeth through the gingiva (gums), the
tetracycline bound to calcium orthophosphate will cause an initial fluorescent
yellow discoloration.9,10 However, upon eruption of the teeth and
exposure to light, the tetracycline will oxidize causing the discoloration to
change from fluorescent yellow to a nonfluorescent brown over a period of
months to years.7,8 The location of the tooth discoloration
directly correlates to the stage of tooth development at the time of
tetracycline exposure. In addition, permanent teeth tend to show a less
intense but more diffuse discoloration than primary teeth.8 This process
is different for minocycline which will be covered in part 2 of this
is the age limitation from the 2nd and 3rd trimester up to 8 years?
This age range spans the periods of calcification of the teeth. The
calcification of the deciduous teeth may be affected up to the age of 10-14
months, the anterior permanent teeth from 6 months to 6 years and the posterior
permanent teeth up to the age of 8 years.3,8,11 Therefore, tetracycline
exposure during any of these periods of calcification can result in permanent
staining. This is the basis for the manufacturers' of tetracycline warning
against the use of tetracycline in children less than 8 years of age.5
While the risk is highest in children, there has been a case of
tetracycline-induced staining reported in an adult on long-term therapy.12 The
overall prevalence of tetracycline induced staining has been reported to be
3-4% and 3-6% for minocycline.8,13 This adverse drug reaction can
obviously create psychological and esthetic concerns for the patient and should
be taken into consideration.8,14
- Schuster A, Shwachman H. The tetracyclines; applied pharmacology. Pediatr Clin North Am 1956;May: 295-303.
- Wallman IS, Hilton HB. Teeth pigmented by tetracycline. Lancet 1962;1:827-9.
JM, Munroe JD, Anderson DO. The incidence of staining of permanent
teeth by the tetracyclines. Can Med Assoc J 1970;103:351-6.
- Grossman ER. Tetracycline and staining of the teeth. JAMA 1986;255:2442-3.
- Minocycline (Solodyn®) product package insert. Medicis, The Dermatology Company. Scottsdales, AZ. 2008.
- Cohlan SQ. Tetracycline staining of teeth. Teratology 1977;15:127-9.
- van der Bijl P, Pitigoi-Aron G. Tetracyclines and calcified tissues. Ann Dent 1995;54:69-72.
- Sanchez AR, Rogers RS 3rd,
Sheridan PJ. Tetracycline and other tetracycline-derivative staining
of the teeth and oral cavity. Int J Dermatol 2004;43:709-15.
- Good ML, Hussey DL. Minocycline: stain devil? Br J Dermatol 2003;149:237-9.
- Rosen T, Hoffman TJ. Minocycline-induced discoloration of the permanent teeth. J Am Acad Dermatol 1989;21:569.
- Mello HS. The mechanism of tetracycline staining in primary and permanent teeth. J Dent Child 1967;34:478-87.
- Di Benedetto DC. Tetracycline staining in an adult. J Mass Dent Soc 1985;34:183, 217.
- Berger RS, Mandel EB, Hayes TJ et al. Minocycline staining of the oral cavity. J Am Acad Dermatol 1989;21:1300-1.
- Scopp IW, Kazandjian G. Tetracycline-induced staining of teeth. Postgrad Med 1986;79:202-3.
- Tigecycline (Tygacil) product package insert. Wyeth Pharmaceuticals Inc. Philadelphia, PA. February 2009