A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Panretin Warnings, Precautions, Pregnancy, Nursing, Abuse - Alitretinoin
Panretin Warnings, Precautions, Pregnancy, Nursing, Abuse - Alitretinoin
WARNINGS
Pregnancy
Panretin® gel could cause
fetal harm if significant absorption
were to occur in a pregnant
woman. 9-cis-Retinoic acid has been shown to be teratogenic
in rabbits and mice. An increased
incidence of fused sternebrae and limb
and craniofacial defects
occurred in rabbits given oral
doses of 0.5 mg/kg/day (about five times the estimated daily human topical
dose on a mg/m2 basis,
assuming complete systemic absorption of 9-2 cis-retinoic acid,
when Panretin® gel is administered
as a 60 g t.b. over 1 month in
a 60 kg human) during the period
of organogenesis. Limb and craniofacial
defects also occurred in mice given a single oral dose of 50 mg/kg on
day eleven of gestation
(about 127 times the estimated daily human
topical dose
on a mg/m2 basis). Oral 9-2 cis-retinoic acid was also
embryocidal, as indicated by early resorptions and post-implantation loss
when it was given during the period
of organogenesis to
rabbits at doses of 1.5 mg/kg/day (about 15 times the estimated daily
human topical dose on a mg/m2
basis) and to rats at doses of 5 mg/kg/day (about 25 times the estimated
daily human topical
dose on a mg/m2 basis).
Animal reproduction studies
with topical 9-cis-retinoic
acid have not been conducted.
It is not known whether topical
Panretin® gel can modulate
endogenous 9-cis-retinoic
acid levels in a pregnant
woman nor whether systemic
exposure is increased by
application to ulcerated lesions or by duration
of treatment. There are no adequate
and well-controlled studies in pregnant
women. If Panretin® gel is
used during pregnancy, or if the patient
becomes pregnant while taking
it, the patient should be
apprised of the potential
hazard to the fetus. Women of child-bearing potential should be advised
to avoid becoming pregnant.
PRECAUTIONS
Panretin® gel is indicated
for topical treatment
of Kaposi’s sarcoma. Patients with cutaneous
T-cell lymphoma were less
tolerant of topical
Panretin ® gel; five of seven patients had 6 episodes of treatment-
limiting toxicities— grade 3
dermal irritation— with Panretin® gel
(0.01% or 0.05%).
Photosensitivity
Retinoids as a class have been
associated with photosensitivity. There were no
reports of photosensitivity
associated with the use of Panretin® gel in the clinical
studies. Nonetheless, because in vitro data indicate that 9-cis-retinoic
acid may have a weak
photosensitizing effect, patients should be advised to minimize exposure
of treated areas to sunlight and sunlamps during the use of Panretin®
gel.
Drug Interactions
Patients who are applying Panretin® gel
should not concurrently use products that contain DEET
(N, N-diethyl-m-toluamide), a common component of insect
repellent products. Animal
toxicology studies showed
increased DEET toxicity when
DEET was included as proof of
the formulation. Although there was no
clinical evidence
in the vehicle-controlled studies of drug interactions with systemic
antiretroviral agents,
including protease inhibitors, macrolide antibiotics, and azole antifungals,
the effect of Panretin®
gel on the steady-state concentrations of these drugs is not known. No
drug interaction data are available on concomitant
administration of Panretin®
gel and systemic anti-KS
agents.
Drug/ Laboratory Test Interactions
No interference with
laboratory tests has been
observed.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals to assess the carcinogenic
potential of 9-cis-retinoic
acid have not been conducted.
9-cis-Retinoic acid was not mutagenic in vitro (bacterial assays,
Chinese hamster ovary cell
HGPRT mutation assay) and
was not clastogenic in vitro (chromosome aberration test
in human lymphocytes) nor in
vivo (mouse micronucleus
test).
Pregnancy Category D (see WARNINGS
section)
Nursing Mothers
It is not known whether alitretinoin or its metabolites are excreted
in human milk. Because many
drugs are excreted in human
milk and because of the potential
for adverse reactions from Panretin® gel
in nursing infants, mothers should discontinue nursing
prior to using the drug.
Pediatric Use
Safety and effectiveness
in pediatric patients have
not been established.
Geriatric Use
Inadequate information is available to assess safety and efficacy
in patients age 65 years or older.
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