Included as part of the PRECAUTIONS section.
TRI-LUMA Cream contains sodium
metabisulfite, a sulfite that may cause allergic-type reactions including
anaphylactic symptoms and life-threatening asthmatic episodes in susceptible
individuals. If anaphylaxis, asthma or other clinically significant
hypersensitivity reactions occur, institute appropriate therapy and discontinue
TRI-LUMA. Allergic contact dermatitis may also occur [see Cutaneous Reactions].
TRI-LUMA Cream contains
hydroquinone, which may produce exogenous ochronosis, a gradual blue-black
darkening of the skin, the occurrence of which should prompt discontinuation of
therapy. The majority of patients developing this condition are Black, but it
may also occur in Caucasians and Hispanics.
Effects On Endocrine System
TRI-LUMA Cream contains the
corticosteroid fluocinolone acetonide. Systemic absorption of topical
corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA)
axis suppression with the potential for glucocorticosteroid insufficiency after
withdrawal of treatment. Manifestations of Cushing's syndrome, hyperglycemia,
and glucosuria can also be produced by systemic absorption of topical
corticosteroid while on treatment. If HPA axis suppression is noted, the use of
TRI-LUMA Cream should be discontinued. Recovery of HPA axis function generally
occurs upon discontinuation of topical corticosteroids.
The ACTH or cosyntropin
stimulation test may be helpful in evaluating patients for HPA axis
Cutaneous hypersensitivity to
the active ingredients of TRI-LUMA Cream has been reported in the literature.
In a patch test study to determine sensitization potential in 221 healthy
volunteers, three volunteers developed sensitivity reactions to TRI-LUMA Cream
or its components.
TRI-LUMA Cream contains
hydroquinone and tretinoin that may cause mild to moderate irritation. Local
irritation, such as skin reddening, peeling, mild burning sensation, dryness,
and pruritus may be expected at the site of application. Transient skin
reddening or mild burning sensation does not preclude treatment. If a reaction
suggests hypersensitivity or chemical irritation, the use of the medication
should be discontinued.
Patients should avoid medicated
or abrasive soaps and cleansers, soaps and cosmetics with drying effects,
products with high concentrations of alcohol and astringents, and other
irritants or keratolytic drugs while on TRI-LUMA Cream treatment. Patients are
cautioned on concomitant use of medications that are known to be
Patient Counseling Information
See FDA-approved patient labeling (PATIENT INFORMATION)
Inform patients of the following:
- Advise patients to change to non-hormonal forms of birth
control, if hormonal methods are used.
- Use TRI-LUMA Cream as directed by the health care
provider and do not use TRI-LUMA Cream for any disorder other than that for
which it is prescribed.
- Avoid exposure to sunlight, sunlamp, or ultraviolet
light. Patients who are consistently exposed to sunlight or skin irritants
either through their work environment or habits should exercise particular
caution. Use sunscreen and protective covering (such as the use of a hat) over
the treated areas. Sunscreen use is an essential aspect of melasma therapy, as
even minimal sunlight sustains melanocytic activity.
- Weather extremes, such as heat or cold, may be irritating
to patients treated with TRI-LUMA Cream. Because of the drying effect of this
medication, a moisturizer may be applied to the face in the morning after
- Keep TRI-LUMA Cream away from the eyes, nose, angles of
the mouth, or open wounds because these areas are more sensitive to the irritant
effect. If local irritation persists or becomes severe, discontinue application
of the medication and consult your health care provider. Seek medical attention
if you experience allergic contact dermatitis, blistering, crusting, and severe
burning or swelling of the skin and irritation of the mucous membranes of the
eyes, nose, and mouth.
- If the medication is applied excessively, marked redness,
peeling, or discomfort may occur.
- Wash your hands after each application.
Impairment Of Fertility
When fluocinolone acetonide,
hydroquinone, and tretinoin in fixed combinations equivalent to 10%, 50%, 100%,
and 150% of the concentrations in the clinical formulation of TRI-LUMA Cream
were applied topically to male and female CD-1 mice for up to 24 months at dosages
approximating up to 50, 19,000, and 250 μg/kg/day, respectively
(corresponding to dosages of 150, 57,000, and 750 μg/m²/day,
respectively), no statistically significant changes in tumor incidence were
When fluocinolone acetonide,
hydroquinone, and tretinoin in fixed combinations equivalent to 10%, 25%, 50%,
and 100% of the concentrations in the clinical formulation of TRI-LUMA Cream
were applied topically to male and female SD rats for up to 24 months at
dosages approximating up to 10, 4000, and 50 μg/kg/day, respectively
(corresponding to dosages of 60, 24,000, and 300 μg/m²/day,
respectively), statistically significant increases in the incidences of islet
cell adenomas and combined islet cell adenomas and carcinomas of the pancreas
in both males and females were observed. The clinical relevance of these
findings is unknown.
Studies of hydroquinone in
animals have demonstrated some evidence of carcinogenicity. The carcinogenic
potential of hydroquinone in humans is unknown.
Studies in hairless albino mice
suggest that concurrent exposure to tretinoin may enhance the tumorigenic
potential of carcinogenic doses of UVB and UVA light from a solar simulator.
This effect has been confirmed in a later study in pigmented mice, and dark
pigmentation did not overcome the enhancement of photocarcinogenesis by 0.05%
tretinoin. Although the significance of these studies to humans is not clear,
patients should minimize exposure to sunlight or artificial ultraviolet
Mutagenicity studies were not
conducted with this combination of active ingredients. Published studies have
demonstrated that hydroquinone is a mutagen and a clastogen. Treatment with
hydroquinone has resulted in positive findings for genetic toxicity in the Ames
assay in bacterial strains sensitive to oxidizing mutagens, in in vitro studies
in mammalian cells, and in the in vivo mouse micronucleus assay. Tretinoin has
been shown to be negative for mutagenesis in the Ames assay. Additional
information regarding the genetic toxicity potential of tretinoin and of
fluocinolone acetonide is not available.
A dermal reproductive fertility study was conducted in SD
rats using a 10-fold dilution of the clinical formulation. No effect was seen
on the traditional parameters used to assess fertility, although prolongation
of estrus was observed in some females, and there was a trend towards an
increase in pre-and post-implantation loss that was not statistically
significant. No adequate study of fertility and early embryonic toxicity of the
full-strength drug product has been performed. In a six-month study in
minipigs, small testes and severe hypospermia were found when males were
treated topically with the full strength drug product.
Use In Specific Populations
Teratogenic Effects - Pregnancy Category C
There are no adequate and
well-controlled studies in pregnant women. TRI-LUMA Cream should be used during
pregnancy only if the potential benefit justifies the potential risk to the
fetus. TRI-LUMA Cream contains the teratogen, tretinoin, which may cause
embryo-fetal death, altered fetal growth, congenital malformations, and
potential neurologic deficits.
In clinical trials involving
TRI-LUMA Cream in the treatment of facial melasma, women of child-bearing
potential initiated treatment only after having had a negative pregnancy test
and used effective birth control measures during therapy. However, 13 women
became pregnant during treatment with TRILUMA Cream. Most of the pregnancy
outcomes are unknown. Three women gave birth to apparently healthy babies. One
pregnancy was terminated prematurely, and another ended in miscarriage.
In general, use of drugs should
be reduced to a minimum in pregnancy. If a patient has been inadvertently
exposed to TRI-LUMA Cream in pregnancy, she should be counseled on the risk of
teratogenesis due to this exposure. The risk of teratogenesis due to topical
exposure to TRI-LUMA Cream may be considered low. However, exposure during the
period of organogenesis in the first trimester is theoretically more likely to
produce adverse outcome than in later pregnancy.
Tretinoin is considered to be
highly teratogenic upon systemic administration. Animal reproductive studies
are not available with topical hydroquinone. Corticosteroids have been shown to
be teratogenic in laboratory animals when administered systemically at
relatively low dosage levels. Some corticosteroids have been shown to be
teratogenic after dermal application in laboratory animals.
- In a dermal application study using TRI-LUMA Cream in
pregnant rabbits, there was an increase in the number of in utero deaths and a
decrease in fetal weights in litters from dams treated topically with the drug
- In a dermal application study in pregnant rats treated
with TRI-LUMA Cream during organogenesis there was evidence of teratogenicity
of the type expected with tretinoin. These morphological alterations included
cleft palate, protruding tongue, open eyes, umbilical hernia, and retinal
folding or dysplasia.
- In a dermal application study on the gestational and
postnatal effects of a 10-fold dilution of TRI-LUMA Cream in rats, an increase
in the number of stillborn pups, lower pup body weights, and delay in preputial
separation were observed. An increase in overall activity was seen in some
treated litters at postnatal day 22 and in all treated litters at five weeks, a
pattern consistent with effects previously noted in animals exposed in utero with
retinoic acids. No adequate study of the late gestational and postnatal effects
of the full-strength TRI-LUMA Cream has been performed.
- It is difficult to interpret these animal studies on
teratogenicity with TRI-LUMA Cream, because the availability of the dermal
applications in these studies could not be assured, and comparison with
clinical dosing is not possible.
systemically administered, appear in human milk. It is not known whether
topical application of TRI-LUMA Cream could result in sufficient systemic
absorption to produce detectable quantities of fluocinolone acetonide,
hydroquinone, or tretinoin in human milk. Because many drugs are secreted in
human milk, caution should be exercised when TRI-LUMA Cream is administered to
a nursing woman. Care should be taken to avoid contact between the infant being
nursed and TRI-LUMA Cream.
Safety and effectiveness of
TRI-LUMA Cream in pediatric patients have not been established.
Clinical studies of TRI-LUMA
Cream did not include sufficient number 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. In general, dose selection for an
elderly patient should be cautious, usually starting at the low end of the
dosing range, reflecting the greater frequency of decreased hepatic, renal or
cardiac function, and of concomitant disease or other drug therapy.