Tri-Luma Use In Pregnancy & Lactation

Pregnancy: Teratogenic Effects: TRI-LUMA Cream contains the teratogen, tretinoin, which may cause embryo-fetal death, altered fetal growth, congenital malformations, and potential neurologic deficits. It is difficult to interpret the animal studies on teratogenicity with TRI-LUMA Cream, because the availability of the dermal applications in these studies cannot be assured, and comparison with clinical dosing is not possible. There are no adequate and well-controlled studies in pregnant women. Orally administered retinoids have been associated with congenital abnormalities. When used in accordance with the prescribing information, topically administered retinoids are generally assumed to result in low systemic exposure due to minimal dermal absorption. However, there could be individual factors (e.g. damaged skin barrier, excessive use) that contribute to an increased systemic exposure. TRI-LUMA is contraindicated in pregnancy, or in women planning a pregnancy. If the product is used during pregnancy, or if the patient becomes pregnant while taking this drug, treatment should be discontinued.
Clinical considerations relevant to actual or potential inadvertent exposure during pregnancy: 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. Thus, safety and efficacy of TRI-LUMA Cream in pregnancy has not been established. 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.
The prescriber should have the following clinical considerations in making prescribing decisions: The potential developmental effects of tretinoin are serious but the risk from topical administration is small.
Exposure during the period for organogenesis in the first trimester is theoretically more likely to produce adverse outcome than in later pregnancy.
The risk to the mother for not treating melasma should be determined by the physician with the patient. Mild forms of melasma may not necessarily require drug treatment. TRI-LUMA Cream is indicated for the treatment of moderate to severe melasma. Melasma may also be managed with other forms of therapy such as topical hydroquinone in the presence of sunlight avoidance, or stopping the use of hormonal birth control methods. If possible, delaying treatment with TRI-LUMA Cream until after delivery should be considered.
There are no adequate and well-controlled studies in pregnant women therefore, the use of TRI-LUMA in pregnant women is not recommended.
Data Discussion: 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.
Human Data: 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, 15 women became pregnant during treatment with TRI-LUMA Cream. Of these pregnancies, 6 resulted in healthy babies, 6 outcomes still unknown, 2 were reported as miscarriages, and 1 case was lost to follow-up.
Epidemiologic studies have not confirmed an increase in birth defects associated with the use of topical tretinoin. However, there may be limitations to the sensitivity of epidemiologic studies in the detection of certain forms of fetal injury, such as subtle neurologic or intelligence deficits.
Animal Data: 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 product.
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 cannot be assured, and comparison with clinical dosing is not possible.
All pregnancies have a risk of birth defect, loss, or other adverse event regardless of drug exposure. Typically, estimates of increased fetal risk from drug exposure rely heavily on animal data. However, animal studies do not always predict effects in humans. Even if human data are available, such data may not be sufficient to determine whether there is an increased risk to the fetus. Drug effects on behavior, cognitive function, and fertility in the offspring are particularly difficult to assess.
Nursing Mothers: Corticosteroids, when 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.