TRI-LUMA (fluocinolone acetonide/tretinoin/hydroquinone)

There are 0 contraindications.

There are 2 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Eczema
Sunburn

There are 1 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Hypothalamic-pituitary insufficiency

There are 21 severe adverse reactions.

More Frequent	Less Frequent
None.	Contact dermatitis Folliculitis Hypersensitivity drug reaction Purpura Skin and skin structure infection Skin atrophy

Rare/Very Rare
Adrenocortical insufficiency Blistering skin Bullous dermatitis Cataracts Central serous chorioretinopathy Dyschromia Glaucoma Hypothalamic-pituitary insufficiency Ocular hypertension Skin crusting Skin hypopigmentation Skin inflammation Skin striae Skin ulcer Urticaria

There are 27 less severe adverse reactions.

More Frequent	Less Frequent
Abnormal desquamation Erythema Skin photosensitivity Stinging of skin	Acute pain at drug application site Blurred vision Headache disorder Paresthesia Pruritus of skin Skin rash Telangiectasia Treatment site sequelae

Rare/Very Rare
Acneiform eruption Alopecia Blistering skin Contact dermatitis Dry skin Dyschromia Edema Glycosuria Hirsutism Hypercortisolism Hyperesthesia Hyperglycemia Miliaria Perioral dermatitis Skin irritation

Reproductive studies in animals have not been performed with topical hydroquinone. It is not known whether hydroquinone can cause fetal harm when used topically by pregnant women. Topical hydroquinone should be used during pregnancy only when clearly needed.

Retinoids (e.g., isotretinoin) have been reported to cause serious fetal harm when administered to pregnant women. (See Cautions: Pregnancy, Fertility, and Lactation, in Isotretinoin 84:36.) Oral tretinoin has been shown to be teratogenic in rats, mice, rabbits, hamsters, and subhuman primates. Tretinoin was teratogenic in Wistar rats when given orally or topically in dosages exceeding 1 mg/kg daily (8 times the maximum human systemic dosage normalized for total body surface area).

In the cynomolgus monkey, which metabolically is closer to humans for tretinoin than other species examined, fetal malformations were reported at oral dosages of 10 mg/kg daily or greater, but none were observed at 5 mg/kg daily (83 times the maximum human systemic dosage normalized for total body surface area), although increased skeletal variations were observed at all dosages. Dose-related increased embryolethality and abortion also were reported. Similar results also have been reported in pigtail macaques.

Topical tretinoin in animal teratogenicity tests has generated equivocal results. There is evidence for teratogenicity (shortened or kinked tail) of topical tretinoin in Wistar rats at dosages exceeding 1 mg/kg daily (8 times the maximum human systemic dosage normalized for total body surface area). Bone anomalies (short (13%) or bent (6%) humerus, incompletely ossified os parietal (14%)) also have been reported in rats when tretinoin 10 mg/kg daily was applied dermally.

Topical tretinoin cream was associated with an increased incidence of cleft palate and hydrocephaly in rabbits when administered in a dosage 91 times the topical human dosage (based on topical application of 1 g of 0.1% tretinoin cream in a 50-kg adult). In New Zealand white rabbits treated with topical tretinoin at dosages 80 times the recommended human topical clinical dosage, an increased incidence of domed head and hydrocephaly was noted in some of the fetuses, typical of retinoid-induced fetal malformations in this species; no abnormalities were observed at dosages 3 times the maximum human systemic dosage of tretinoin after topical administration of 0.1% tretinoin gel (microsphere formulation), normalized for total body surface area.

In addition, topical tretinoin in formulations other than the gel (microsphere formulation) was not teratogenic when given in dosages of 42 or 27 times the maximum human systemic topical dosage in rats or rabbits, respectively. However, delayed ossification of several bones, occurred in rabbits and a dose-dependent incease in supernumerary ribs was observed in rats at these topical dosages. Oral tretinoin was fetotoxic in rats at dosages 21 times the maximum human systemic dosage normalized for total body surface area, resulting in skeletal variations and increased intrauterine death in rats.

Topical tretinoin has been shown to be fetotoxic in rabbits when administered in dosages 8 times the maximum human systemic dosage applied topically and normalized for total body surface area), resulting in fetal resorption and variations in ossification. When given subcutaneously to rabbits, tretinoin was teratogenic at a dosage of 2 mg/kg daily but not at 1 mg/kg daily. These dosages are approximately 400 and 200 times, respectively, the human topical dosage of tretinoin cream (based on topical application of 1 g of 0.025% tretinoin cream in a 50-kg adult).

With widespread use of any drug, a small number of birth defect reports associated with the administration of the drug would be expected by chance alone. During 2 decades of clinical use of one formulation of topical tretinoin (Retin-A(R)), 30 cases of temporally associated congenital malformations have been reported. Although no definite pattern of teratogenicity and no causal associations have been established from these cases, 5 of the reports described the rare birth defect category holoprosencephaly (defects associated with incomplete midline development of the forebrain).

The relevance of these spontaneous reports in terms of risk to the fetus is unknown. To date, there have been no adequate and well-controlled studies performed in pregnant women, and the teratogenic blood level of tretinoin is not known. The manufacturer of some topical tretinoin preparations (e.g., Retin-A(R)) state that topical tretinoin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, while manufacturers of other tretinoin formulations (e.g., Avita(R) cream, Renova(R) emollient cream) state that these products should not be used during pregnancy.

Since it is not known if topical hydroquinone is absorbed or distributed into human milk, the drug should be used with caution in nursing women. It is not known whether topically applied tretinoin is excreted in human milk. Caution should be exercised when topical tretinoin is administered to a nursing woman.

No enhanced Geriatric Use information available for this drug.