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THERAPEUTIC TIPS

Clinically Important Considerations with the Use of Oral Doxycycline

James Q. Del Rosso, DO

a,b,c

a
Touro University Nevada, Henderson, NV

b
JDR Dermatology Research, Las Vegas, NV

c
Thomas Dermatology, Las Vegas, NV

Tetracyclines are the most commonly
prescribed antibiotics in dermatology in the
United States (US).

1
These oral agents,

predominantly doxycycline and minocycline,
comprise approximately 75% of all antibiotic
prescriptions written by dermatologists, with
dermatologists accounting for approximately
20% of all tetracyclines prescribed among all
physicians in the US.

1-4
Both doxycycline

and minocycline are highly lipophilic, which
explains their marked skin penetration, with
the reasonable scientific assumption that
high concentrations are achieved within the
lipid-rich pilosebaceous unit.

3
Skin

penetration is important for treatment of both
cutaneous infections and non-infectious
dermatoses, such as acne vulgaris (AV),

rosacea, and other inflammatory
dermatologic disorders that are treated with
tetracycline agents; pilosebaceous unit
penetration is important in acne therapy as
follicular Propionibacterium acnes is one of
the therapeutic targets in AV.

2-8
Both

doxycycline and minocycline exhibit a broad
range of activity against several bacterial
organisms relevant to commonly
encountered skin conditions, such as P
acnes (AV) and Staphylococcus aureus,
including methicillin-resistant strains.

2-5,9

Importantly, tetracyclines also exhibit
multiple biologic effects unrelated to their
antibiotic activity which appear to play
important mechanistic roles in the treatment
of common facial inflammatory dermatoses,

ABSTRACT

Tetracyclines are the most commonly prescribed oral antibiotics in dermatology. They are
used to treat bothcutaneous infections and non-infectious inflammatory disorders, the latter
often with chronic therapy. Doxycycline may be favored by some dermatologists over
minocycline due to a lower risk of certain adverse reactions, especially some with systemic
manifestations. The major adverse events that are more common with doxycycline are
gastrointestinal side effects, including pill esophagitis, and phototoxicity. This article reviews
practical tips when prescribing oral doxycycline, emphasizing suggestions to optimize
therapeutic success and reduce untoward reactions.

INTRODUCTION

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such as AV and rosacea, and less common
diseases such as bullous pemphigoid and
granulomatous disorders.

2,6-8,10,11

It is important to recognize that although
doxycycline and minocycline are within the
same general class of antibiotics, namely
tetracyclines, there are several clinically
relevant differences between these drugs,
especially in their potential adverse reaction
profiles.

2-5,12
This article specifically reviews

clinically relevant considerations when
prescribing oral doxycycline, with emphasis
on four important practical tips to optimize
therapeutic success and avoid adverse
sequelae.

Doxycycline is available as either
doxycycline hyclate or doxycycline
monohydrate, with no clinical evidence of
differences in efficacy or safety between the
two salts of doxycycline when administered
as immediate-release antibiotic-dose
formulations .

2,13,14
Enteric-release

doxycycline and a specific small-tablet brand
doxycycline have been shown to exhibit
similar pharmacokinetic profiles, with both
demonstrating very similar low rates of
potential for gastrointestinal (GI) AEs, such
as nausea, abdominal discomfort/pain,
and/or vomiting, even in the absence of
food.

14
Importantly, however, concurrent

administration with food further decreases
the risk of GI-related AEs.

14
Enteric-coated

doxycycline has been shown to markedly
reduce the risk of GI-related AEs compared
to a standard brand immediate-release
doxycycline formulation.

15
Subantibiotic

dose doxycycline, administered as a specific
modified-release 40 mg capsule once daily
for papulopustular rosacea, was associated
with a marked decrease of GI-related AEs

as compared to immediate-release
doxycycline 100 mg once daily; none of the
study subjects receiving subantibiotic dose
doxycycline experienced nausea, abdominal
discomfort, vomiting, or diarrhea.

Doxycycline is a leading cause of pill
esophagitis, which occurs when patients do
not properly administer the drug; in many
cases this was associated with inadequate
patient education.

2,17,18
Esophageal

inflammation, erosions, and ulcerations have
been described with this entity at all levels
within the esophagus. The most commonly
associated symptoms are odynophagia,
retrosternal pain, and dysphagia.

17,18
In

almost all cases, pill esophagitis occurred in
patients who reported a history of
swallowing their oral doxycycline with only a
small amount of water, and taking the
medication in a recumbent position, or
both.

2,17,18
With proper patient education and

compliance, pill esophagitis can be
prevented. It is important that patients be
instructed to ingest oral doxycycline with a
large glass of water, to be in an upright
position while ingesting the medication, and
to preferably administer during or
immediately after a meal.

2,14,17,18

Although the potential for photoxicity
associated with oral doxycycline use is well-
recognized, a recent systematic review of
phototoxicity of doxycycline identified mostly

Tip #1: Consider the Formulation

When Prescribing Oral Doxycycline

Tip #2: Reduce the Potential for “Pill
Esophagitis” by Optimizing Patient
Education on Proper Administration

of Oral Doxycycline

Tip #3: Consider Potential Dose-
Related Phototoxicity and Employ
Preventative Measures to Reduce

Risk

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case reports and only a few studies that
shed light on this topic.

19
The potential for

phototoxicity is not dependent on gender,
age, or duration of therapy, but rather the
intensity and duration of ultraviolet light (UV)
exposure, with Fitzpatrick skin types I and II
exhibiting an enhanced risk.

19,20
Phototoxic

skin reactions or photo-onycholysis may
occur. The potential for phototoxicity
induced by doxycycline appears to be dose-
related; one series following patients treated
with doxycycline over a 2 year period
(N=106) reported phototoxicity in 42%
(32/76) of those treated with 200 mg/day
and in 20% (6/30) of those treated with 150
mg/day.

21
The reactions did not typically

occur during usual daily sun exposure, but
rather during periods of much greater UV
exposure while on vacation in a sunny
climate.

It is important to recognize that tetracycline-
related phototoxicity is mediated in the long
wavelength of the UVA spectrum (340-400
nm).

19
Sunscreens that absorb UVA light

only in the shorter wavelength end of the
UVA spectrum, such as oxybenzone (340-
360 nm), are inadequate in preventing
doxycycline-induced phototoxic
reactions.

19,22
It is prudent in patients treated

with oral doxycycline to educate them on
principles of photoprotection, including the
use and periodic re-application of a
sunscreen that filters across the entire UVA
spectrum, protective clothing, and avoidance
of intense mid-day sun exposure whenever
possible.

19
Use of oral Polypodium

leucotomos extract (PLE) to further
supplement sunscreen use and other
photoprotection measures may further
reduce the risk of phototoxic effects; this
suggestion is based on theoretical
consideration of data supporting the
ameliorating effects of PLE after UVA or
UVB exposures.

23
For treatment of chronic

inflammatory disorders such as AV, it is

reasonable to suggest to patients to
temporarily discontinue oral doxycycline use
over the short duration of a vacation to be
spent outdoors in a sunny climate or location
of high UV exposure.

The overall safety profile of tetracycline
antibiotics is very favorable.

2,4,5,12
The most

common potential AEs associated with oral
doxycycline use are GI-related AEs,
including pill esophagitis, and
phototoxicity.

2,5,12,18,18
Both are reasonably

preventable as explained above.
Doxycycline use has not been associated
with some of the potential AEs encountered
with utilization of oral minocycline, such as
vestibular AEs (eg vertigo, dizziness),
cutaneous and/or mucosal
hyperpigmentation, and autoimmune
reactions (eg hepatitis, drug-induced lupus-
like syndrome), the latter being rare but with
systemic manifestations; drug
hypersensitivity syndrome (drug reaction
with eosinophilia and systemic symptoms
[DRESS]) has been reported much more
commonly with oral minocycline, and
appears to be very rare and of negligible risk
with oral doxycycline.

2-5,12-14
The rate of

acute vestibular AEs associated with oral
minocycline use has been shown to be less
with use of weight-based dosing (1
mg/kg/day) with a specific extended-release
minocycline tablet formulation.

2
Benign

intracranial hypertension (pseudotumor
cerebri), often presenting with intractable
cephalgia, nausea/vomiting, photophobia,
and/or diplopia, is a rare side effect that may
occur after use of any tetracycline agent, is
diagnosed by the presence of papilledema,
and warrants early detection and

Tip #4: Evaluate the Adverse
Reaction Profile When Prescribing

Oral Doxycycline

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intervention to reduce the risk of vision loss.
2

When treating papulopustular rosacea with
an oral agent, it has been suggested that
subantibiotic dose doxycycline (40 mg MR
capsule once daily or 20 mg twice daily) be
used initially, as there are data
demonstrating efficacy comparable to oral
doxycycline 100 mg daily with fewer GI-
related AEs, and avoidance of antibiotic
resistance due to absence of selection
pressure.

2,16,24

Doxycycline is a commonly prescribed oral
antibiotic in dermatology, used for treatment
of uncomplicated cutaneous infections, such
as those caused by MRSA, and some non-
infectious inflammatory dermatoses, such as
AV, rosacea, and bullous pemphigoid. Pill
esophagitis and phototoxicity are two
preventable AEs that can occur with use of
oral doxycycline. Ingestion with a large glass
of water and food while maintaining an
upright position can prevent pill esophagitis.
Enteric-coated and a special small tablet
formulation of doxycycline are both
associated with a low risk of GI-related AEs.
Prevention of doxycycline-induced
phototoxicity warrants photoprotection
measures that includes use of a sunscreen
that filters out the full UVA spectrum. Oral
doxycycline is essentially devoid of certain
side effects associated with oral minocycline
use, such as vertigo/dizziness, hyper-
pigmentation, drug hypersensitivity
syndrome, and autoimmune reactions.
Subantibiotic dose doxycycline is a preferred
oral therapy choice for papulopustular
rosacea due to low potential for AEs and
avoidance of antibiotic resistance.

Conflict of Interest: none.

Disclosures: Dr. Del Rosso is a consultant,
investigator, and/or speaker for Allergan,
Aqua/Almirall, Bayer, BioPharmX, Celgene, Cipher
(Innocutis), Cutanea, Dermira, Exeltis, Ferndale,
Foamix, Galderma, Genentech, LeoPharma, Novan,
Pfizer (Anacor), Pharmaderm, Promius, Regeneron,
Sanofi/Genzyme, Sebacia, SunPharma, Taro,
Unilever, Valeant (Ortho Dermatologics), and Viamet.
This article was developed and written solely by the
author. The author did not receive any form of
compensation, either directly or indirectly, from any
company or agency related to the development,
authorship, or publication of this article.

Funding: none.

Corresponding Author:
James Q. Del Rosso, DO
JDR Dermatology Research
9080 West Post Road
Suite 100
Las Vegas, Nevada 89148
702-331-4123
jqdelrosso@yahoo.com

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SUMMARY

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