Approved Drug Label (PDF)
6
Adverse Reactions
6.2 Postmarketing Experience
Additions and revisions underlined:
.
. .
Skin: Maculopapular and erythematous rashes,
Stevens-Johnson syndrome, toxic epidermal
necrolysis, exfoliative dermatitis, erythema multiforme,
and fixed drug eruption have been reported.
. . .
Psychiatric: Depression, anxiety,
suicidal ideation, insomnia,
abnormal dreams, hallucination
8
Use in Specific Populations
8.5 Geriatric use
Additions and revisions underlined:
Clinical studies of DORYX did not include sufficient numbers of subjects aged
65 and over to determine whether they respond differently from younger
subjects. Other reported clinical experience
has not identified differences in responses between
the elderly and younger patients.
DORYX 50 mg tablets contain 3 mg
(0.131 mEq) of sodium. DORYX 80 mg tablets contain
4.8 mg (0.209 mEq) of sodium.
. . .
Approved Drug Label (PDF)
8
Use in Specific Populations
8.1 Pregnancy
PLLR
conversion
Risk
Summary
There
are no adequate and well-controlled studies on the use of doxycycline in
pregnant women. The vast majority of reported experience with doxycycline
during human pregnancy is short-term, first trimester exposure. There are no
human data available to assess the effects of long-term therapy of doxycycline
in pregnant women such as that proposed for the treatment of anthrax exposure.
An expert review of published data on experiences with doxycycline use during
pregnancy by TERIS - the Teratogen Information System - concluded that
therapeutic doses during pregnancy are unlikely to pose a substantial
teratogenic risk (the quantity and quality of data were assessed as limited to
fair), but the data are insufficient to state that there is no risk (see Data). 1
In
the US general population the estimated background risk of major birth defects
and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%,
respectively.
Clinical
Considerations
Embryo/Fetal Risk
Results
of animal studies indicate that tetracyclines cross the placenta, are found in
fetal tissues, and can have toxic effects on the developing fetus (often
related to retardation of skeletal development).
Evidence
of embryotoxicity also has been noted in animals treated early in pregnancy. If
any tetracycline is used during pregnancy or if the patient becomes pregnant
while taking these drugs, the patient should be apprised of the potential
hazard to the fetus [see Warnings and
Precautions (5.1, 5.6)].
Data
Human Data
A
case-control study (18,515 mothers of infants with congenital anomalies and
32,804 mothers of infants with no congenital anomalies) shows a weak but
marginally statistically significant association with total malformations and
use of doxycycline anytime during pregnancy. Sixty-three (0.19%) of the
controls and 56 (0.30%) of the cases were treated with doxycycline. This
association was not seen when the analysis was confined to maternal treatment
during the period of organogenesis (that is, in the second and third months of
gestation), with the exception of a marginal
relationship
with neural tube defect based on only two-exposed cases.2
A
small prospective study of 81 pregnancies describes 43 pregnant women treated
for 10 days with doxycycline during early first trimester. All mothers reported
their exposed infants were normal at 1 year of age.3
8.2 Lactation
PLLR conversion
Risk Summary
Tetracyclines are excreted in human milk, however,
the extent of absorption of tetracyclines including doxycycline, by the
breastfed infant is not known. Short-term use by lactating women is not
necessarily contraindicated. The effects of prolonged exposure to doxycycline
in breast milk production and breast fed neonates, infants and children are
unknown4. The developmental and health benefits of breastfeeding
should be considered along with the mother’s clinical need for DORYX and any
potential adverse effects on the breast fed child from DORYX or from the underlying
maternal condition [see Warnings and Precautions
(5.1, 5.6)].
Approved Drug Label (PDF)
5
Warnings and Precautions
Additions and/or
revisions underlined:
5.2 Clostridioides
difficile Associated Diarrhea
‘Clostridioides’
replaces ‘Clostridium’ throughout this subsection.
8
Use in Specific Populations
8.1 Pregnancy
Additions and/or
revisions underlined:
Risk
Summary
There
are no adequate and well-controlled studies on the use of doxycycline in
pregnant women …
Data
Human Data
A
case-control study (18,515 mothers of infants with congenital anomalies and
32,804 mothers of infants with no congenital anomalies) …
8.2 Lactation
Risk
Summary
Tetracyclines
are excreted in human milk …
Approved Drug Label (PDF)
4
Contraindications
Additions
and/or revisions underlined:
The drug is contraindicated in persons who
have shown hypersensitivity to any of the tetracyclines.
5
Warnings and Precautions
Additions
and/or revisions underlined:
5.4
Potential for Microbial Overgrowth
As with other antibacterial preparations,
use of DORYX
may result in overgrowth of non-susceptible organisms, including fungi. If
superinfection occurs, the antibacterial should be discontinued and
appropriate therapy instituted.
Newly
added information:
5.5
Severe Skin Reactions
Severe skin reactions, such as exfoliative
dermatitis erythema multiforme, Stevens-Johnson syndrome, toxic epidermal
necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS)
have been reported in patients receiving doxycycline. If severe skin reactions
occur, doxycycline should be discontinued immediately and appropriate therapy
should be instituted.
Additions
and/or revisions underlined:
5.7
Skeletal Development
Results of animal studies indicate that
tetracyclines cross the placenta, are found in fetal tissues, and can have
toxic effects on the developing fetus (often related to retardation of
skeletal development). Evidence of embryotoxicity also has been noted in
animals treated early in pregnancy. If any tetracycline is used during
pregnancy or if the patient becomes pregnant while taking these drugs, the
patient should be apprised of the potential hazard to the fetus.
6
Adverse Reactions
Newly
added information:
6.1
Clinical Trials Experience
The safety and efficacy of DORYX Tablets,
200 mg as a single daily dose was evaluated in a multicenter, randomized,
double-blind, active-controlled study. DORYX Tablets,
200 mg was given orally once-a-day for 7
days and compared to doxycycline hyclate capsules 100 mg given orally twice
daily for 7 days for the treatment of men and women with uncomplicated
urogenital C. trachomatis infection.
Adverse events in the Safety Population
were reported by 99 (40.2%) subjects in the DORYX Tablets, 200 mg treatment
group and 132 (53.2%) subjects in the doxycycline hyclate capsules reference
treatment group. Most AEs were mild in intensity. The most commonly reported
adverse events in both treatment groups were nausea, vomiting, diarrhea, and
bacterial vaginitis, Table 1.
Table 1: Adverse Reactions Reported in
Greater than or Equal to 2% of Subjects Please refer to label for complete information.
Because clinical trials are conducted
under prescribed conditions, adverse reaction rates observed in the clinical
trial may not always reflect the rates observed in practice.
Additions
and/or revisions underlined:
6.2
Postmarketing Experience
Gastrointestinal: … These
reactions have been caused by both the oral and parenteral administration of
tetracyclines. Superficial
discoloration of the adult permanent dentition, reversible upon drug
discontinuation and professional dental cleaning has been reported. Permanent tooth
discoloration and enamel hypoplasia may occur with drugs of the tetracycline
class when used during tooth development.
Hypersensitivity
reactions:
Urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum
sickness, pericarditis, and exacerbation of systemic lupus erythematosus,
and drug reaction with eosinophilia and systemic symptoms (DRESS).
8
Use in Specific Populations
Additions
and/or revisions underlined:
8.1
Pregnancy
Teratogenic Effects. Pregnancy
Category D:
There are no adequate and
well-controlled studies on the use of doxycycline in pregnant women.
… All mothers reported their exposed
infants were normal at 1 year of age.3
Nonteratogenic effects: [see Warnings and Precautions]
8.3
Nursing Mothers
Tetracyclines are excreted in human milk,
however, the extent of absorption of tetracyclines including doxycycline, by
the breastfed infant is not known. Short-term use by lactating women is not necessarily
contraindicated. The effects of prolonged exposure to doxycycline in breast
milk are unknown4. Because of the potential for
serious adverse
reactions in nursing infants from
doxycycline, a decision should be made whether to discontinue nursing or to
discontinue the drug, taking into account the importance of the drug to the
mother.
8.5
Geriatric Use
… Other reported clinical experience has
not identified differences in responses between the elderly and younger
patients. DORYX 50 mg tablets contain
3 mg (0.131 mEq) of sodium. DORYX 200 mg tablets contain 12 mg (0.522 mEq) of
sodium.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Doxycycline replaces DORYX MPC
throughout section.
Additions
and/or revisions underlined:
All patients taking doxycycline should
be advised:
that
the absorption of tetracyclines is reduced when taken with foods, especially those
that contain calcium. However, the absorption of doxycycline is not markedly
influenced by simultaneous ingestion of food or milk.
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