Safety of Doxycycline and Minocycline: A Systematic Review
Kelly S m i t h , MD1; and JamesJ. Leyden, MD 2
1Warner Chilcott Laboratories, Rockaway, New Jersey; and 2Department of Dermatolog6 University of
Pennsylvania, Philadelphia, Pennsylvania
ABSTRACT
Objective: The goal of this review was to summa-
rize the available literature covering the safety profiles
of oral doxycycline and minocycline.
Methods: Scientific literature published between 1966
and August 2003 was searched using the MEDLINE,
EMBASE, and Biosis databases (search terms: mino-
cycline or doxycycline, each paired with adverse reac-
tion, adverse event, and side effect, and doxycycline or
minocycline with the limits English language, human,
and clinical trials). Safety information was collected
from case reports and clinical trials. Adverse event
(AE) rates in the United States were calculated by com-
paring data from the MedWatch AE reporting pro-
gram used by the US Food and Drug Administration
(FDA) with the number of new prescriptions dispensed
for each drug from January 1998 to August 2003.
Results: Between 1966 and 2003, a total of 130
and 333 AEs were published in case reports of doxy-
cycline and minocycline, respectively. In 24 doxycy-
cline clinical trials (n = 3833) and 11 minocycline
trials (n -- 788), the ranges in incidence of AEs were
0% to 61% and 11.7% to 83.3%, respectively. Gas-
trointestinal AEs were most common with doxycy-
cline; central nervous system and gastrointestinal AEs
were most common with minocycline. From January
1998 to August 2003, the FDA MedWatch data con-
tained 628 events for doxycycline and 1099 events for
minocycline reported in the United States. Approxi-
mately 47,630,000 doxycycline and 15,234,000 mino-
cycline new prescriptions were dispensed in the United
States during that period, yielding event rates of 13
per million for doxycycline and 72 per million for
minocycline, based on FDA data.
Conclusions: Between 1998 and 2003, doxycycline
was prescribed 3 times as often as minocycline. The
incidence of AEs with either drug is very low, but
doxycycline had fewer reported AEs. Although more
head-to-head clinical trials are needed for a direct
comparison of AE frequency, these preliminary data
from separate reports suggest the possibility that AEs
may be less likely with doxycycline than minocycline.
(Clin Ther. 2005;27:1329-1342) Copyright © 2005
Excerpta Medica, Inc.
Key words: doxycycline, minocycline, side effect,
adverse reaction, English language.
INTRODUCTION
Tetracycline compounds have been in clinical use
worldwide since 1953, when they were first marketed
by Lederle Laboratories. For many years, tetracycline
was the first choice in the systemic treatment of acne
vulgaris in patients with significant inflammatory le-
sions. Over time, the 4-times-per-day dose schedule and
the need to take tetracycline on an empty stomach
led to the development of synthetic antibiotics in the
tetracycline class, beginning with doxycycline in 1967
and followed by minocycline in 1972.1-3 These 2 drugs
are now the preferred systemic antibiotics used in the
treatment of acne.
Compared with the original tetracycline, the syn-
thetics have easier dose schedules and are more read-
ily absorbed when taken with food. 2 Both doxycycline
and minocycline are effective for the treatment of acne
and both are generally well tolerated. Tetracyclines, as
an antibiotic class, are known to have side effects such
as gastrointestinal symptoms, pediatric tooth discol-
oration, candidiasis, photosensitivity reactions, pig-
mentation changes, and central nervous system effects
(eg, lightheadedness, dizziness). 1,2,4-6 However, within
the class, the adverse event (AE) profiles of doxycy-
cline and minocycline may not appear to be identical,
and physicians may prescribe one antibiotic instead of
the other based on personal perceptions of the safety
profiles.
Accepted for publication August 22, 2005.
doi:l 0.1016/j.clinthera.2005.09.005
0149-2918/05/$19.00
Printed in the USA. Reproduction in whole or part is not permitted.
Copyright © 2005 Excerpta Medica, Inc.
 Before writing a prescription, the clinician must es-
timate the likelihood a given patient will experience a
serious AE with a specific drug. The package labeling
for a drug lists the number of patients who were ex-
posed to it in clinical trials and the number of AEs re-
ported, resulting in a percentage of events. However,
these percentages are not always useful on a practical
basis because the AEs reported in clinical trials can
also include medical events that may be unrelated to
drug exposure. Furthermore, some AEs may not be
recognized until larger numbers of patients are ex-
posed to a drug than usually occurs in preapproval
clinical trials. Additionally, clinical trials that compare
the safety profiles of drugs are rare. Although single
case reports or case series of the AEs associated with
a drug may provide some guidance, they are an unre-
liable way to assess general risk, because the number
of patients exposed to the drug is not known.
The most accurate approach to measuring the risk
of a drug-related AE would be a comparison of the
number of all AEs to the total number of persons ex-
posed to the drug. However, this type of calculation is
virtually impossible because not every event is cap-
tured in a public database, and because patient com-
pliance with prescription regimens may be unreliably
reported. An approximation of this measurement can
be made by comparing AE reports from public safety
databases and journal publications with prescription
database information.
The intent of this review is to summarize the avail-
able literature covering the safety profiles of oral doxy-
cycline and minocycline, comparing the published lit-
erature with US prescription data for a defined period
for these products and providing a profile of the gen-
eral risk of each drug relative to exposure.
METHODS
The MEDLINE, EMBASE, and Biosis databases were
electronically searched for original clinical safety
studies and case reports of AEs with minocycline or
doxycycline. Publications from the earliest year avail-
able on each database (MEDLINE, 1966; EMBASE,
1974; Biosis, 1969) through August 2003 were in-
cluded. Search terms were rninocycline or doxycy-
cline, each combined with adverse reaction, adverse
event, and side effect. Additional search strategies
combined each specific AE identified through case re-
ports with the antibiotic reported to cause the event.
The reference list of each retrieved article was hand-
searched thoroughly to ensure capture of all pertinent
references.
Because these search strategies do not consistently
capture all clinical trials that report adverse events, 7
separate searches of the databases were conducted to
identify all clinical trials involving single-drug therapy
with either doxycycline or minocycline. Two searches
of the databases were conducted using the search
terms doxycycline and minocycIine and the limits
English language, human, and clinical trials. These ar-
ticles were manually reviewed for reports of adverse
events in clinical trials.
Clinical trials and case reports were included if they
were written in English and contained original reports
of AEs reported numerically or as a percentage. In an
effort to minimize the number of AEs caused by unre-
lated drugs, articles were excluded if the use of doxy-
cycline or minocycline in combination with any other
drug was explicitly stated, or if the patients were
being treated for HIV or AIDS. Each report was clas-
sifted based on the method of AE reporting used (ie,
clinical trial or case report).
The total number of AEs was tallied from pub-
lished case reports, and the subset of AEs occurring
only in the United States was also tallied. For the clin-
ical trial data, the percentage (if available) and nature
of AEs in each trial were determined. Information ob-
tained through a Freedom of Information Act request
from the US Food and Drug Administration (FDA)
MedWatch AE reporting program was searched for
reports of AEs associated with doxycycline and
minocycline from January 1, 1998, through August
31, 2003. MedWatch collects both US and foreign
events as voluntarily reported by health care profes-
sionals, consumers, and manufacturers. US drug ex-
posure was approximated by using the number of new
doxycycline and minocycline prescriptions dispensed
from January 1, 1998, through August 31, 2003, as
reported by IMS Health. s International drug exposure
data were not available. The number of US AEs was
tallied and then compared with the US prescription
data for each drug to provide an estimate of the inci-
dence of adverse outcomes for each drug.
RESULTS
Doxycycline
A search of the literature found case reports of a
total of 130 AEs associated with doxycycline published
between 1966 and 2003 (Table I). 9-38 Esophageal ero-
 Table I. Case reports of adverse events with doxycycline, 1966 through August 2003 (N = 130
patients). 9-38
Body System Total
Whole body 130 (100)
Digestive system
Esophageal erosion 72 (5.5)
Skin
Photosensitivity 47 (36)
Photo-onycholysis .5 (4)
Rash 1 (<1)
Central nervous system
Intracranial hypertension 2 (2)
Other
Hypoglycemia 2 (2)
Anosmia 1 (<1)
us = United States.
sion 9-28 and photosensitivity 2°,z9-33 were the most
commonly reported AEs. Overall, few AEs were re-
ported by physicians practicing in the United States.
Twenty-four clinical trials using doxycycline, pub-
lished between 1966 and 2003, met the inclusion cri-
teria; a total of 3833 patients were treated in these
trials. The overall rates of AEs reported in trials
ranged from 0% to 61%, although not all trials spec-
ified which events were considered to be drug related
and which were not. The most common AEs reported
in clinical trials paralleled those of case reports.
All but 3 of the trials reported that gastrointestinal
effects (ie, heartburn, nausea, vomiting, diarrhea, and
gastritis) were the most common AEs; 2 trials report-
ed photosensitivity reactions as most common, 39,4°
and 1 small trial (n = 30) reported no AEs. 41 The re-
ported rate of any type of gastrointestinal event in all
the trials ranged from 0.54% 4 (in a study of 1653 pa-
tients treated with doxycycline 100-200 mg/d for
4-20 days for respiratory tract infection) to 51.7% 42
(in 120 patients given doxycycline 100 mg BID for
10-20 days for the treatment of early Lyme disease)
(Table II). 4,39-61
Skin reaction (ie, rash, pruritus, and photosensitiv-
ity) was the second most common AE. The incidence
of any type of reported skin reaction ranged from
No. (%) of Adverse Events
US Non-US
13 (10) 117 (90)
9 (7) 63 (48)
- 47 (36)
2(2) 3(2)
1 (<1)
2(2)
2(2)
- 1 (<1)
0.42% 4 (in a study of 1653 patients) to 30.5% 40
(among 36 patients with asymptomatic abdominal
aortic aneurysms who were given doxycycline 100 mg
BID for 6 months). In studies that specifically report-
ed the incidence of photosensitivity in doxycycline-
treated patients, the range was 5.8% to 30.5%. 39,40,42
Minocycline
A search of the literature found case reports of a
total of 333 AEs associated with minocycline pub-
lished from 1966 to 2003 (Table III). 26,62-173 Forty
percent of these AEs were reported in the United
States. Early reports of AEs predominantly included
pigmentation of bone, teeth, skin, and thyroid; ner-
vous system effects; and nephritis. 65-113 Beginning in
the 1980s, hepatitis, hypersensitivity, and systemic
immune-mediated reactions (including a lupus-like syn-
drome) were reported with increased frequency in as-
sociation with minocycline. 124-164
Eleven clinical trials of minocycline conducted be-
tween 1966 and 2003, involving 788 patients, met the
inclusion criteria. The overall frequency of AEs
ranged from 11.7% to 83.3%; again, many trials did
not specify which, if any, events were considered to be
drug related. In contrast to the types of AEs published
in case reports, central nervous system effects (ie,
Table II. Frequency o f adverse events reported in clinical trials of doxycycline, 1966 through August 2003
(N = 3833 patients). Values are shown as percentages.

Dose and Time o f Exposure*

Body System/ 200 mg x 1 d then 100-200 mg/d x 100 mg BID x 100 mgTID x 20 d or
Adverse Event 100 mg x 6-13 d 20-21 d 7d 100 mg BID x 3-6 mo

Body as a whole
Head ac h e 2-3 43,44 < 142 1.5 - 5 . 8 45 ,46
InFection 1.3 46
Th ro m bocytopen ia 1.739
Pain 3.344
Somnolence 1.244
Tooth discoloration 8.34°
Digestive system
Gastrointestinal NOS 4-2143,44,47-51t~ 7.4-51.742,52,53 10.6-3745,46,54-59 10-2539,40,60
Heartburn/gastritis 0.94
Nausea/vomiting 0.544 2.461
Skin and appendages
Allergic skin symptoms 0.424
Skin reactions 250 1 253
Pimples/acne 243
Photosensitivity 5.842 1 5-30.539,40
Rash 0.9-243,44,51~ 156
Pruritus 3.1 46
Fixed drug eruption 1.545
Urogenital system
Urogenital NOS 8-12.546,59
Vaginitis 0.5 44 <142
Yeast infection 2.84o
Vaginal dryness 243
Inflamed vulva/
thick white discharge§ 243
Nervous system
CNS-related 347 <159
Dizziness 151~ 2.246
Neuropsychiatric 0.554
immune system
Hypersensitivity 3 47
Respiratory system
Rhinitis 1.247
Special senses
Taste perversion 0.446
Other
Other NOS I-247,50 0.364 2-354-57 539
Minor laboratory
abnormalities 653

NOS = not otherwise specified; CNS = central nervous system.

*In addition to the data shown in the table, Salmi41 reported no adverseevents in a trial of 200 mg x 1 d, then 100 mg/d x 10 d.
tDuration of administration not provided by Freeman et al.49
CData reported as number of events, not percentage of patients, by Stalman et al. sl
§Some patients were treated with other medication in addition to the study drug. 43
Table III, Case reports of adverse events with minocycline, 1966 through August 2003 (N - 324
patients).26,62-173

No. (%) of Adverse Events*

Body System Total US Non-US

Total 333 (100) 133 200
Body system as a whole
Hypersensitivity 15 (5) 4(1) 11 (3)
Serum sickness-like reaction 14(4) 2(<1) 12(4)
Other systemic/cutaneous reaction 4(1) 1 (<1) 3(<1)
Digestive system
Esophageal erosion 5 (2) - 5 (2)
Skin
Hyperpigmentationf 50 (15) 24 (7) 26 (8)
Fixed-drug eruption 2(<1) 1(<1) 1(<1)
Photo-onycholysis 1(<1) 1(<1) -
Rash 2(<1) 1(<1) 1(<1)
Erythema nodosum 1(<1) 1(<1) -
Organ systems
Hepatitis/hepatic dysfunction 31 (9) 14 (4) 17 (5)
Nephritis 4 (1) 1(<1 3 (<1)
Thyroid pigmentation~ 8 (2) 5 (2) 3 (<1)
Central nervous system
Vestibular effects 37 (11) 17 (5) 20 (6)
Intracranial hypertension 8 (2) - 8 (2)
Pseudotumor cerebri 15 (5) 14 (4) 1 (<1)
Immune system
Lupus-like syndrome 93 (28) 35 (11 58(17)
Rheumatologic effects/arthritis 11 (3) 11 (3)
Respiratory system
Pneumonia/pulmonary infiltrates 14 (4) 3 (<1 11 (3)
Pneumonitis 8 (2) 8(2)
Blood
Hemolytic anemia 1(<1) 1 (<1)
Thrombocytopenia 1(<1) 1(<1
Other
Tooth discoloration 5 (2) 5 (2)
Polyarteritis nodosa 2 (<1) 2 (<1
Rhabdomyolysis 1(<1) 1(<1

US = United States.
*Some subjects experienced >I adverse event.
tlncluded hyperpigmentation of skin, nails, and bone.
~Included 3 casesof thyroid pigmentation discovered incidentally postmortem.
Table IV. Frequency o f adverse events reported in clinical trials o f minocycline, 1966 through August 2003 (N
788 patients). Values are shown as percentages.

Dose and Time of Exposure*

100 mg BID x 1 d then

Body System/ 75-100 mg BID x 100 mg/d x 7-9 d or 50 mg BID x 100-200 mg/d x
Adverse Event 5-9 d 100 mg/d x 7-8 d 6 mo 6-9 wk
Body as a whole
Headache 2_401,5,6t 6175
Somnolence 1.5-2 43'178¢
Digestive system
Gastrointestinal NOS 6 it 5.543¢ 817S 6-2560'179
Nausea/vomiting 7-505,6 <1176
Diarrhea 106 2176
Epigastric/abdominal pain 3178 <1 176
Flatulence 1.5178 <1 176
Skin and appendages
Allergic skin symptoms 2175
Pimples/acne 243¢
Rash 3.3-106 243¢ <1176
Pruritus 2175 <1176
Fixed drug eruption 1.5178
Urogenital system
Heavy period 243*
Nervous system
CNS NOS 1760
Dizziness/vertigo 13-331,s,6,174f 3_743,178, <1_6176,179
Lightheadedness 40_535,6,174 53174
Lack of-concentration 24-435, 6
Disassociation 47-506
Loss o f balance 23-275, 6
Vestibular NOS 53-675, 6
Tinnitus 106
Other
Other NOS 33-475,6
Euphoria 10-136
Weakness/Fatigue 236
Oral disturbances (dryness,
altered taste, halitosis, thrush) 1.5-243'178 2176
Visual problem NOS 3.3-106
Chest pain <1176
Increased appetite <1176

NOS = not otherwise specified; CNS = central nervous system.

*Cohen ~76 reported adverse events as number of'events, rather than percentage of patients. A total of 3% of'effects were judged
to be treatment related: gastrointestinal (3 patients), taste perversion (2), rash (1), dry mouth (1), fatigue (1), halitosis (1),
and thrush (1). Grosshans et a1177 did not report numbers or percentages of specific adverse events. However, in all, 4.1% of"
subjects experienced 14 treatment-related effects: nausea, diarrhea, and other gastrointestinal effects were most Frequent;
acne, photosensitivity, ache flare, and eczema flare were also reported. 177
fDuration of'administration not provided by Gallagher and Settle. 1
~ln the trial by Kovacs et al, 43 some patients received medications other than the study drug.
dizziness, lightheadedness, and vertigo) were the most
common AEs in 5 clinical trials, 1,s,6,43,174 and gas-
trointestinal events were most common in 5 oth-
ers. 6°,17sq78 Gastrointestinal events and central ner-
vous system events occurred at an equal rate in I trial. 179
The rate of reported central nervous system effects
in all trials ranged from 3% 178 (in a trial of minocy-
cline 50 mg BID given for 7 days to 68 men with ure-
thritis) to 6 7 % 6 (in a trial of minocycline 100 mg BID
given to healthy women volunteers for 5 days) (Table
IV). 174-179 Among the few studies reporting the sever-
ity of central nervous system effects, the majority of
AEs were mild and transient.l,s,6,174,178 In studies re-
porting discontinuation due to vestibular symptoms,
discontinuation rates ranged from 1.7% to 8 . 8 % . 1,5,6
The incidence of central nervous system effects has
been reported to be significantly higher in women than
in men (P < 0.005). s The occurrence of gastrointesti-
nal AEs ranged from ~1% 176 (in a trial of minocycline
50 mg BID given for 12 weeks to 338 patients with
acne vulgaris) to 50% 6 (in 30 healthy women given
minocycline 100 mg BID).
Results from MedWatch indicated that between
January 1, 1998, and August 31, 2003, a total of
1006 AEs were recorded for doxycycline, of which
628 were reported in the United States. A total of
1557 AEs were reported for minocycline, of which
1099 were reported in the United States. During that
time period, -47,630,000 new prescriptions for doxy-
cycline and -15,234,000 new prescriptions for mino-
cycline were dispensed in the United States. 8 Based on
numbers of prescriptions dispensed during that peri-
od, the overall incidence of AEs in the United States
was calculated to be 13 per million for doxycycline
(2.3 per million per year) and 72 per million for
minocycline (13 per million per year).
DISCUSSION
Between January 1998 and August 2003, more than 3
times as many new prescriptions were dispensed in the
United States for doxycycline than for minocycline.
AE rates for the same time period, based on the FDA's
MedWatch AE reporting program data, were 5 times
greater for minocycline than doxycycline.
Between 1966 and 2003, considerably fewer case
reports of AEs were published for doxycycline than
for minocycline: 130 versus 333. The types of AEs de-
scribed in the case reports differed for the 2 drugs: the
predominant AE for doxycycline was esophageal ero-
sion9-28; for minocycline, hyperpigmentation, 65-71,87-113
hypersensitivity and other systemic reactions, 137-149and
autoimmune effects 132-136,150-164 w e r e m o s t c o m m o n .
Case reports are usually published when they rep-
resent something of clinical interest to the medical com-
munity and, therefore, generally reflect less frequent
and more serious AEs. An individual case report does
not provide significant evidence for an association be-
tween a drug and an event, However, taken collective-
ly, the patterns presented by case reports can suggest
a causal relationship justifying investigation. For ex-
ample, the case reports published in the first decade
after the marketing launch for minocycline did not re-
veal the pattern of autoimmune-related AEs that have
been published over the past decade. This change may
be a result of a greater understanding of the mecha-
nisms involved in an immune response, or possibly
these effects may be noticed only after long-term use,
such as treatment for acne vulgaris.
The use of case reports to identify the frequency
and nature of AEs has several weaknesses. Case re-
ports are not standardized, blinded, or controlled, al-
lowing bias to affect the reporting. In addition, because
physician and patient reporting of AEs for drugs such
as doxycycline and minocycline is voluntary, the actu-
al incidence of AEs may be vastly underreported. This
affects both the published medical literature and the
FDA's MedWatch program. In addition, because FDA
data report AEs in patients taking multiple medica-
tions, the relationship between a given AE and the
drug of interest cannot be definitively determined.
Unlike the case report data, the most frequent AEs
reported in the clinical trials of doxycycline were gas-
trointestinal; in trials of minocycline, central nervous
system and gastrointestinal effects were the most com-
mon. Only a few studies have directly compared
doxycycline and minocycline. 43,6°,18°-184 However,
one of these studies reported only the "most signifi-
cant" AEs, 18° several others did not report numbers or
percentages of specific AEs, 181,183,184 and one used a
lower-than-usual dosage. 182 These studies were, there-
fore, excluded from the tabulation of AEs, although
general AE information from these studies is reported
here. In a prospective, single-blind trial, 103 women
with positive chlamydial cultures were randomized to
receive either minocycline (n = 54) or doxycycline
(n = 49), both given as 100 mg in the morning and
evening on day 1, followed by 100 mg as a single dose
for 9 additional days. 43 AEs were reported by 20%
and 16% of patients receiving minocycline and doxy-
cycline, respectively. Whereas gastrointestinal effects
(ie, gastritis, bloating, and cramps) were most frequent
in the doxycycline group, central nervous system effects
(ie, giddiness and dizziness) were most common in the
minocycline group.
A retrospective analysis evaluated tetracycline,
minocycline, erythromycin, and doxycycline in the
management of inflammatory acne. 6° Ten patients
were treated with doxycycline 100 mg BID and 12 pa-
tients with minocycline 50 to 100 mg BID. In both
groups, gastrointestinal effects were the most common
AE, occurring in 2 (20%) of the doxycycline-treated
patients and 3 (25%) of the minocycline group. In ad-
dition, 2 patients (17%) in the minocycline group ex-
perienced central nervous system effects, compared
with no patients treated with doxycycline.
A randomized, observer-blinded study of 34 patients
given either 50 mg doxycycline QD (n = 15) or 50 mg
minocycline BID (n = 19) for 12 weeks for the treat-
ment of acne vulgaris found that tolerance of the drug
was excellent in 53% of patients receiving doxycycline
and in 37% of patients receiving minocycline.182 Yet
only 1 doxycycline patient and 2 minocycline patients
were reported to have treatment-related AEs (abdominal
pain, and headache and drowsiness, respectively). A
double-blind study assessed 100 mg/d of either doxycy-
cline or minocycline for 3 months in 18 patients with
severe acne. TM Mild, transient, unspecified AEs lasting
no more than 1 week were noted in 4 (19%) doxycy-
cline patients. The small size of these trials limits the ap-
plicability of these data to larger patient populations.
The one larger (n = 237) comparative trial (100 mg
minocycline QD versus 100 mg doxycycline BID for
7 days) reported significantly more gastrointestinal
upset in the doxycycline group compared with the
minocycline group (49/126 [39%] vs 20/111 [18%],
respectively; P < 0.001), as well as significantly more
vomiting alone (9/126 [7%] vs 0; P = 0.004); rates of
dizziness were similar between the 2 groups (11/126
[9%] and 4/111 [4%]). 180
Because these studies were not prospectively de-
signed to evaluate AEs, their results cannot be used to
compare the relative safety of the 2 drugs. Trial-to-
trial comparisons of the frequency of AEs are also not
possible, due to variations in definitions of AEs, dif-
ferences in collection techniques, and disparities in re-
porting. In the absence of a large comparative trial
specifically designed to investigate differences in AEs
between minocycline and doxycycline, a definitive
conclusion as to the differences in relative risks of the
2 antibiotics cannot be accurately made.
In addition, several factors limit the use of clinical
trial data in determining the expected frequency of
AEs relative to drug exposure. Because a small num-
ber of individuals are exposed to a drug in clinical tri-
als, rare AEs may not be identified and the rate of
occurrence of less frequent events may not be accu-
rately reflected. Finally, clinical trials represent a more
controlled patient population compared with the gen-
eral population; therefore, trial results may not be re-
flected in more widespread, general use.
It should be noted that in the few head-to-head
comparison studies of doxycycline and minocycline
published before August 2003, the 2 drugs demon-
strated comparable clinical efficacy in the treatment of
acne vulgaris, 181,182 urethral/cervical infections,43,18°
and respiratory infections in seriously ill hospitalized
patients. 183,184In terms of acne treatment, quantitative
bacteriologic studies demonstrate greater in vivo anti-
microbial activity of minocycline compared with doxy-
cycline and tetracycline against Propionibacterium
aches185,186;however, the limited comparative clinical
trials published before this date were not sufficiently
powered to permit determination of the relative effica-
cy of these agents.
CONCLUSIONS
This review provides a profile of the nature and rates
of AEs related to doxycycline and minocycline use
compared with exposure data. Based on the FDA data
reported here, minocycline was associated with a
higher rate of AEs than was doxycycline in the United
States over the period of 5.5 years from 1998 to
August 2003. This was particularly notable in light of
the 3:1 ratio of doxycycline to minocycline new pre-
scriptions during that time. A search of clinical trials
for the 2 drugs found that gastrointestinal effects were
the most common AE related to doxycycline use, and
central nervous system and gastrointestinal effects
were most common with minocycline. The occurrence
of photosensitivity, although uncommonly reported,
was more frequent with doxycycline than minocy-
cline. For doxycycline, the kinds of AEs in published
case reports were similar to those reported in clinical
trials, whereas those for minocycline were substantial-
ly different, with immunologic events being reported
many years after clinical trials were completed.
 Both doxycycline and minocycline have proven ef-
ficacy and safety profiles for many infectious diseases
and the long-term management of acne vulgaris.
Although more head-to-head clinical trials are needed
for a direct comparison of AE frequency, these prelim-
inary data from separate reports suggest the possibil-
ity that AEs may be less likely with doxycycline than
minocycline.
ACKNOWLEDGM ENTS
This work was supported by a grant from Warner
Chilcott. Editorial assistance was provided by Jo
Applebaum and Lisa Sterling, PharmD.
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infections: A double-blind compar- Laboratories, Rockaway 80 Corporate Center, 100 Enterprise Drive, Suite
ative clinical, microbiological and 280, Rockaway, NJ 07866. E-mail: ksmith@wclabs.com