OVERDOSAGE
Excessive topical use of TAZORAC® Gel may
lead to marked redness, peeling, or discomfort (see PRECAUTIONS: General).
TAZORAC® Gels 0.05% and 0.1% are not for oral use.
Oral ingestion of the drug may lead to the same adverse effects as those
associated with excessive oral intake of Vitamin A (hypervitaminosis A) or other
retinoids. If oral ingestion occurs, the patient should be monitored, and
appropriate supportive measures should be administered as necessary.
|
CONTRAINDICATIONS
Retinoids may cause fetal harm when administered to a pregnant
woman.
In rats, tazarotene 0.05% gel, administered topically
during gestation days 6 through 17 at 0.25 mg/kg/day (1.5 mg/m2/day) resulted in reduced fetal body weights and reduced
skeletal ossification. Rabbits dosed topically with
0.25 mg/kg/day (2.75 mg/m2 total body surface area/day)
tazarotene gel during gestation days 6 through 18 were noted with single
incidences of known retinoid malformations, including spina bifida,
hydrocephaly, and heart anomalies. Systemic daily-exposure (AUCde) to tazarotenic acid at topical doses of 0.25 mg/kg/day
tazarotene in a gel formulation in rats and rabbits represented 0.62 and 6.7
times, respectively, the AUC0-24h observed in psoriatic
patients treated with 2 mg/cm2 of tazarotene gel 0.1%
(extrapolated for topical application over 20% body surface area), and 0.78 and
8.4 times, respectively, the maximum AUC0-24h in acne
patients treated with 2 mg/cm2 of tazarotene gel 0.1%
over 15% (targeted) body surface area.
As with other retinoids, when tazarotene was given orally to experimental animals, developmental delays were seen
in rats, and teratogenic effects and post-implantation loss were observed in
rats and rabbits at AUCde values that were 0.55 and 13.2
times, respectively, the AUC0-24h observed in psoriatic
patients treated with 2 mg/cm2 of tazarotene gel 0.1%
(extrapolated for topical application over 20% body surface area), and 0.68 and
16.4 times, respectively, the maximum AUC0-24h in acne
patients treated with 2 mg/cm2 of tazarotene gel 0.1%
over 15% (targeted) body surface area.
In a study of the effect of oral tazarotene on fertility and early embryonic
development in rats, decreased number of implantation sites, decreased litter
size, decreased numbers of live fetuses, and decreased fetal body weights, all
classic developmental effects of retinoids, were observed when female rats were
administered 2 mg/kg/day from 15 days before mating through gestation day 7. A
low incidence of retinoid-related malformations at that dose was reported to be
related to treatment. This dose produced an AUCde that
was 1.7 times the AUC0-24h observed in psoriatic patients
treated with 2 mg/cm2 tazarotene gel 0.1% (extrapolated
for topical application over 20% body surface area) and 2.1 times the maximum
AUC0-24h in acne patients treated with 2 mg/cm2 of tazarotene gel 0.1% over 15% (targeted) body surface
area.
SYSTEMIC EXPOSURE TO TAZAROTENIC ACID IS DEPENDENT UPON THE EXTENT OF THE
BODY SURFACE AREA TREATED. IN PATIENTS TREATED TOPICALLY OVER SUFFICIENT BODY
SURFACE AREA, EXPOSURE COULD BE IN THE SAME ORDER OF MAGNITUDE AS IN THESE
ORALLY TREATED ANIMALS. ALTHOUGH THERE MAY BE LESS SYSTEMIC EXPOSURE IN THE
TREATMENT OF ACNE OF THE FACE ALONE DUE TO LESS SURFACE AREA FOR APPLICATION,
TAZAROTENE IS A TERATOGENIC SUBSTANCE, AND IT IS NOT KNOWN WHAT LEVEL OF
EXPOSURE IS REQUIRED FOR TERATOGENICITY IN HUMANS (SEE CLINICAL PHARMACOLOGY: PHARMACOKINETICS).
There were thirteen reported pregnancies in patients who participated in
clinical trials for topical tazarotene. Nine of the patients were found to have
been treated with topical tazarotene, and the other four had been treated with
vehicle. One of the patients who was treated with tazarotene cream elected to
terminate the pregnancy for non-medical reasons unrelated to treatment. The
other eight pregnant women who were inadvertently exposed to topical tazarotene
during clinical trials subsequently delivered apparently healthy babies. As the
exact timing and extent of exposure in relation to the gestation times are not
certain, the significance of these findings is unknown.
TAZORAC® Gel is contraindicated in women who are or
may become pregnant. If this drug is used during pregnancy, or if the patient
becomes pregnant while taking this drug, treatment should be discontinued and
the patient apprised of the potential hazard to the fetus. Women of
child-bearing potential should be warned of the potential risk and use adequate
birth-control measures when TAZORAC® Gel is used. The
possibility that a woman of childbearing potential is pregnant at the time of
institution of therapy should be considered. A negative result for pregnancy
test having a sensitivity down to at least 50 mIU/mL for human chorionic
gonadotropin (hCG) should be obtained within 2 weeks prior to TAZORAC® Gel therapy, which should begin during a normal menstrual
period (see also PRECAUTIONS: Pregnancy: Teratogenic
Effects).
TAZORAC® Gel is contraindicated in individuals who
have shown hypersensitivity to any of its components.
|