Tri-Luma (Hydroquinone 4% Cream): Side Effects, Uses, Dosage, Interactions, Warnings (2024)

Description for Tri-Luma

TRI-LUMA (fluocinolone acetonide, hydroquinone, and tretinoin) Cream, 0.01%/4%/0.05% contains fluocinolone acetonide, USP, hydroquinone, USP, and tretinoin, USP, in a light yellow, hydrophilic cream base for topical application.

Fluocinolone acetonide is a synthetic fluorinated corticosteroid. It is a white crystalline powder that is odorless and stable in light.

The chemical name for fluocinolone acetonide is: (6α,11β,16α)-6,9-difluoro-11,21-dihydroxy-16,17-[(1-methylethylidene)bis(oxy)]-pregna-1,-4-diene-3,20dione.

The molecular formula is C₂₄H₃₀F₂O₆ and molecular weight is 452.50.

Fluocinolone acetonide has the following structural formula:

Hydroquinone is a melanin synthesis inhibitor. It is prepared from the reduction of p-benzoquinone with sodium bisulfite. It occurs as fine white needles that darken on exposure to air. The chemical name for hydroquinone is: 1,4-benzenediol.

The molecular formula is C₆H₆O₂ and molecular weight is 110.11.

Hydroquinone has the following structural formula:

Tretinoin, a retinoid, is all-trans-retinoic acid formed from the oxidation of the aldehyde group of retinene to a carboxyl group. It occurs as yellow to light-orange crystals or crystalline powder with a characteristic odor of ensilage. It is highly reactive to light and moisture.

The chemical name for tretinoin is: (all-E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid.

The molecular formula is C₂₀H₂₈O₂ and molecular weight is 300.44.

Tretinoin has the following structural formula:

Each gram of TRI-LUMA Cream contains Active: fluocinolone acetonide 0.01% (0.1 mg), hydroquinone 4% (40 mg), and tretinoin 0.05% (0.5 mg). Inactive: butylated hydroxytoluene, cetyl alcohol, citric acid anhydrous, glycerin, glyceryl stearate, magnesium aluminum silicate, methyl gluceth-10, methylparaben, PEG-100 stearate, propylparaben, purified water, sodium metabisulfite, stearic acid, and stearyl alcohol.

Uses for Tri-Luma

Indication

TRI-LUMA Cream is a combinationof fluocinolone acetonide (a corticosteroid), hydroquinone (a melanin synthesisinhibitor), and tretinoin (a retinoid) that is indicated for the short-termtreatment of moderate to severe melasma of the face, in the presence ofmeasures for sun avoidance, including the use of sunscreens.

Limitations Of Use

TRI-LUMA Cream is NOT indicatedfor the maintenance treatment of melasma. After achieving control with TRI-LUMACream, some patients may be managed with other treatments instead of tripletherapy with TRI-LUMA Cream. Melasma usually recurs upon discontinuation ofTRI-LUMA Cream.

The safety and efficacy ofTRI-LUMA Cream in patients of Fitzpatrick Skin Types V and VI have not beenstudied. Excessive bleaching resulting in undesirable cosmetic effect inpatients with darker skin cannot be excluded.

The safety and efficacy ofTRI-LUMA Cream in the treatment of hyperpigmentation conditions other thanmelasma of the face have not been studied.

Because pregnant and lactatingwomen were excluded from, and women of childbearing potential had to use birthcontrol measures in the clinical trials, the safety and efficacy of TRI-LUMACream in pregnant women and nursing mothers have not been established [see Usein Specific Populations].

Dosage for Tri-Luma

Apply a thin film of TRI-LUMACream to the effected area once daily, at least 30 minutes before bedtime.

Gently wash the face and neckwith a mild cleanser. Rinse and pat the skin dry. Apply TRI-LUMA Cream to thehyperpigmented areas of melasma including about ½ inch of normal appearingskin surrounding each lesion. Rub lightly and uniformly into the skin.

Therapy should be discontinuedwhen control is achieved.

During the day, use a sunscreen of SPF 30, and wear protective clothing. Avoid sunlight exposure. Patients mayuse moisturizers and/or cosmetics during the day. TRI-LUMA Cream is for topicaluse only. It is not for oral, ophthalmic, or intravaginal use.

HOW SUPPLIED

Dosage Forms And Strengths

Cream, 0.01%/4%/0.05%.

Each gram of TRI-LUMA Creamcontains 0.1 mg of fluocinolone acetonide, 40 mg of hydroquinone, and 0.5 mg oftretinoin in a light yellow, hydrophilic cream base.

Storage And Handling

TRI-LUMA Cream is light yellowin color, and supplied in 30 g aluminum tubes, NDC 0299-5950-30.

Storage

Keep tightly closed. Store in a refrigerator, 2°-8° C (36°-46° F). Protect fromfreezing.

Marketed by: Galderma Laboratories, L.P. Fort Worth, TX76177 USA. Manufactured by: Hill Dermaceuticals, Inc. Sanford, FL 32773 USA. Manufacturedby: G Production Inc. Baie d'Urfé, QC, H9X 3S4 Canada. Made in Canada. Revised:March 2014

Side Effects for Tri-Luma

Because clinical trials are conducted under widelyvarying conditions, adverse reaction rates observed in the clinical trials of adrug cannot be directly compared to rates in the clinical trials of anotherdrug and may not reflect the rates observed in clinical practice.

In the controlled clinical trials, adverse events weremonitored in the 161 subjects who used TRI-LUMA Cream once daily during an8-week treatment period. There were 102 (63%) subjects who experienced at leastone treatment-related adverse event during these trials. The most frequentlyreported events were erythema, desquamation, burning, dryness, and pruritus atthe site of application. The majority of these events were mild to moderate inseverity. Adverse events reported by at least 1% of patients and judged by theinvestigators to be reasonably related to treatment with TRI-LUMA Cream fromthe controlled clinical trials are summarized (in decreasing order offrequency) as follows:

Table 1: Incidence and Frequency of Treatment-relatedAdverse Events with TRI-LUMA Cream in at Least 1% or More of Subjects (N=161)

In an open-label trial,subjects who had cumulative treatment of melasma with TRI-LUMA Cream for 6months showed a similar pattern of adverse events as in the 8-week studies.

The following local adversereactions have been reported with topical corticosteroids. They may occur morefrequently with the use of occlusive dressings, especially with higher potencycorticosteroids. These reactions are listed in an approximate decreasing orderof occurrence: burning, itching, irritation, dryness, folliculitis, acneiformeruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis,secondary infection, skin atrophy, striae, and miliaria.

Drug Interactions for Tri-Luma

No information provided.

Warnings for Tri-Luma

Included as part of the PRECAUTIONS section.

Precautions for Tri-Luma

Hypersensitivity

TRI-LUMA Cream contains sodiummetabisulfite, a sulfite that may cause allergic-type reactions includinganaphylactic symptoms and life-threatening asthmatic episodes in susceptibleindividuals. If anaphylaxis, asthma or other clinically significanthypersensitivity reactions occur, institute appropriate therapy and discontinueTRI-LUMA. Allergic contact dermatitis may also occur [see Cutaneous Reactions].

Exogenous Ochronosis

TRI-LUMA Cream containshydroquinone, which may produce exogenous ochronosis, a gradual blue-blackdarkening of the skin, the occurrence of which should prompt discontinuation oftherapy. The majority of patients developing this condition are Black, but itmay also occur in Caucasians and Hispanics.

Effects On Endocrine System

TRI-LUMA Cream contains the corticosteroid fluocinolone acetonide. Systemic absorption of topicalcorticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA)axis suppression with the potential for glucocorticosteroid insufficiency afterwithdrawal of treatment. Manifestations of Cushing's syndrome, hyperglycemia,and glucosuria can also be produced by systemic absorption of topicalcorticosteroid while on treatment. If HPA axis suppression is noted, the use ofTRI-LUMA Cream should be discontinued. Recovery of HPA axis function generallyoccurs upon discontinuation of topical corticosteroids.

The ACTH or cosyntropinstimulation test may be helpful in evaluating patients for HPA axissuppression.

Cutaneous Reactions

Cutaneous hypersensitivity tothe active ingredients of TRI-LUMA Cream has been reported in the literature.In a patch test study to determine sensitization potential in 221 healthyvolunteers, three volunteers developed sensitivity reactions to TRI-LUMA Creamor its components.

TRI-LUMA Cream containshydroquinone and tretinoin that may cause mild to moderate irritation. Localirritation, such as skin reddening, peeling, mild burning sensation, dryness,and pruritus may be expected at the site of application. Transient skinreddening or mild burning sensation does not preclude treatment. If a reactionsuggests hypersensitivity or chemical irritation, the use of the medicationshould be discontinued.

Patients should avoid medicatedor abrasive soaps and cleansers, soaps and cosmetics with drying effects,products with high concentrations of alcohol and astringents, and otherirritants or keratolytic drugs while on TRI-LUMA Cream treatment. Patients arecautioned on concomitant use of medications that are known to bephotosensitizing.

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 washing.
• 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.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, 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 Creamwere applied topically to male and female CD-1 mice for up to 24 months at dosagesapproximating 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 wereobserved.

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 Creamwere applied topically to male and female SD rats for up to 24 months atdosages 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 isletcell adenomas and combined islet cell adenomas and carcinomas of the pancreasin both males and females were observed. The clinical relevance of thesefindings is unknown.

Studies of hydroquinone inanimals have demonstrated some evidence of carcinogenicity. The carcinogenic potential of hydroquinone in humans is unknown.

Studies in hairless albino micesuggest that concurrent exposure to tretinoin may enhance the tumorigenicpotential 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 irradiation sources.

Mutagenicity studies were notconducted with this combination of active ingredients. Published studies havedemonstrated that hydroquinone is a mutagen and a clastogen. Treatment withhydroquinone has resulted in positive findings for genetic toxicity in the Amesassay in bacterial strains sensitive to oxidizing mutagens, in in vitro studiesin mammalian cells, and in the in vivo mouse micronucleus assay. Tretinoin hasbeen shown to be negative for mutagenesis in the Ames assay. Additionalinformation regarding the genetic toxicity potential of tretinoin and offluocinolone acetonide is not available.

A dermal reproductive fertility study was conducted in SDrats using a 10-fold dilution of the clinical formulation. No effect was seenon the traditional parameters used to assess fertility, although prolongationof estrus was observed in some females, and there was a trend towards anincrease in pre-and post-implantation loss that was not statisticallysignificant. No adequate study of fertility and early embryonic toxicity of thefull-strength drug product has been performed. In a six-month study inminipigs, small testes and severe hypospermia were found when males weretreated topically with the full strength drug product.

Use In Specific Populations

Pregnancy

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, andpotential neurologic deficits.

In clinical trials involvingTRI-LUMA Cream in the treatment of facial melasma, women of child-bearingpotential initiated treatment only after having had a negative pregnancy testand used effective birth control measures during therapy. However, 13 womenbecame pregnant during treatment with TRILUMA Cream. Most of the pregnancyoutcomes are unknown. Three women gave birth to apparently healthy babies. Onepregnancy was terminated prematurely, and another ended in miscarriage.

In general, use of drugs shouldbe reduced to a minimum in pregnancy. If a patient has been inadvertentlyexposed to TRI-LUMA Cream in pregnancy, she should be counseled on the risk ofteratogenesis due to this exposure. The risk of teratogenesis due to topicalexposure to TRI-LUMA Cream may be considered low. However, exposure during theperiod of organogenesis in the first trimester is theoretically more likely toproduce adverse outcome than in later pregnancy.

Tretinoin is considered to behighly teratogenic upon systemic administration. Animal reproductive studiesare not available with topical hydroquinone. Corticosteroids have been shown tobe teratogenic in laboratory animals when administered systemically atrelatively low dosage levels. Some corticosteroids have been shown to beteratogenic 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 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 could not be assured, and comparison with clinical dosing is not possible.

Nursing Mothers

Corticosteroids, whensystemically administered, appear in human milk. It is not known whethertopical application of TRI-LUMA Cream could result in sufficient systemicabsorption to produce detectable quantities of fluocinolone acetonide,hydroquinone, or tretinoin in human milk. Because many drugs are secreted inhuman milk, caution should be exercised when TRI-LUMA Cream is administered toa nursing woman. Care should be taken to avoid contact between the infant beingnursed and TRI-LUMA Cream.

Pediatric Use

Safety and effectiveness ofTRI-LUMA Cream in pediatric patients have not been established.

Geriatric Use

Clinical studies of TRI-LUMACream did not include sufficient number of subjects aged 65 and over todetermine whether they respond differently from younger subjects. Otherreported clinical experience has not identified differences in responsesbetween the elderly and younger patients. In general, dose selection for anelderly patient should be cautious, usually starting at the low end of thedosing range, reflecting the greater frequency of decreased hepatic, renal orcardiac function, and of concomitant disease or other drug therapy.

Overdose Information for Tri-Luma

No information provided.

Contraindications for Tri-Luma

TRI-LUMA Cream iscontraindicated in individuals with a history of hypersensitivity to thisproduct or any of its components.

Clinical Pharmacology for Tri-Luma

Mechanism Of Action

The mechanism of action of theactive ingredients in TRI-LUMA Cream in the treatment of melasma is unknown.

Pharmacokinetics

Percutaneous absorption ofunchanged tretinoin, hydroquinone and fluocinolone acetonide into the systemic circulation of two groups of healthy volunteers (Total N=59) was found to beminimal following 8 weeks of daily application of 1g (Group I, n=45) or 6g(Group II, n=14) of TRI-LUMA Cream.

For tretinoin quantifiableplasma concentrations were obtained in 57.78% (26 out of 45) of Group I and57.14% (8 out of 14) of Group II subjects. The exposure to tretinoin asreflected by the C max values ranged from 2.01 to 5.34 ng/mL (Group I) and 2.0to 4.99 ng/mL (Group II). Thus, daily application of TRI-LUMA Cream resulted ina minimal increase of normal endogenous levels of tretinoin. The circulatingtretinoin levels represent only a portion of total tretinoin-associatedretinoids, which would include metabolites of tretinoin and that sequesteredinto peripheral tissues.

For hydroquinone, quantifiableplasma concentrations were obtained in 18% (8 out of 44) Group I subjects. Theexposure to hydroquinone, as reflected by the C max values, ranged from 25.55to 86.52 ng/mL. All Group II subjects (6g dose) had post-dose plasmahydroquinone concentrations below the quantitation limit. For fluocinoloneacetonide, Groups I and II subjects had all post-dose plasma concentrationsbelow quantitation limit.

Clinical Studies

Two adequate and well-controlled efficacy and safetytrials were conducted in 641 subjects between the ages of 21 to 75 years,having Fitzpatrick Skin types I-IV and moderate to severe melasma of the face.TRI-LUMA Cream was compared with 3 possible combinations of 2 of the 3 activeingredients [(1) hydroquinone 4% (HQ) + tretinoin 0.05% (RA); (2) fluocinoloneacetonide 0.01% (FA) + tretinoin 0.05% (RA); (3) fluocinolone acetonide 0.01%(FA) + hydroquinone 4% (HQ)], contained in the same vehicle as TRI-LUMA Cream.Subjects were instructed to apply their study medication each night, afterwashing their face with a mild soapless cleanser, for 8 weeks. Instructionswere given to apply a thin layer of study medication to the hyperpigmented lesion, making sure to cover the entire lesion including the outside bordersextending to the normal pigmented skin. Subjects were provided a mildmoisturizer for use as needed. A sunscreen with SPF 30 was also provided withinstructions for daily use. Protective clothing and avoidance of sunlightexposure to the face was recommended.

Subjects were evaluated for melasma severity at Baselineand at Weeks 1, 2, 4, and 8 of treatment. Primary efficacy was based on theproportion of subjects who had an investigators' assessment of treatmentsuccess, defined as the clearing of melasma at the end of the eight-weektreatment period. The majority of subjects enrolled in the two trials werewhite (approximately 66%) and female (approximately 98%). TRI-LUMA Cream wasdemonstrated to be significantly more effective than any of the othercombinations of the active ingredients.

Primary Efficacy Analysis

Table 2: Investigators' Assessment of Treatment Success*At the End of 8 Weeks of Treatment

In the Investigators'assessment of melasma severity at Day 56 of treatment, the following tableshows the clinical improvement profile for all subjects treated with TRI-LUMACream based on severity of their melasma at the start of treatment.

Table 3: Investigators' Assessment of Change inMelasma Severity from Baseline to Day 56 of Treatment (combined results fromtrials 1 and 2)

Assessment Scale: Cleared(melasma lesions approximately equivalent to surrounding normal skin or withminimal residual hyperpigmentation); Mild (slightly darker than the surroundingnormal skin); Moderate (moderately darker than the surrounding normal skin);Severe (markedly darker than the surrounding normal skin).

Subjects experiencedimprovement of their melasma with the use of TRI-LUMA Cream as early as 4weeks. However, among 7 subjects who had clearing at the end of 4 weeks oftreatment with TRI-LUMA Cream, 4 of them did not maintain the remission afteran additional 4 weeks of treatment.

After 8 weeks of treatment withthe trial drug, subjects entered into an open-label extension period in whichTRI-LUMA Cream was given on an as-needed basis for the treatment of melasma.The remission periods appeared to shorten between progressive courses oftreatment. Additionally, few subjects maintained complete clearing of melasma(approximately 1 to 2%).

Patient Information for Tri-Luma

TRI-LUMA®
(try-LOOM-ah)
(fluocinolone acetonide 0.01%, hydroquinone 4%, andtretinoin 0.05%) Cream

Important information: TRI-LUMA Cream is for use on skinonly. Do not use TRI-LUMA Cream in your mouth, eyes, or vagina.

What is the most important information I should knowabout TRI-LUMA Cream?

TRI-LUMA Cream may cause birth defects or death of thebaby if used during pregnancy. The risk of birth defects or death of thebaby may be greater if TRI-LUMA Cream is used during the first trimester ofpregnancy. Tell your doctor if you are pregnant or plan to become pregnant.

If you become pregnant while using TRI-LUMA Cream,tell your doctor right away.

What is TRI-LUMA Cream?

TRI-LUMA Cream is a prescription medicine used for theshort-term treatment of moderate to severe melasma of the face, in combinationwith sun avoidance and the use of sunscreens.

TRI-LUMA Cream is not for continuous treatment ofmelasma.

It is not known if TRI-LUMA Cream is safe and effectivein children.

It is not known if TRI-LUMA Cream is safe and effectivein people with dark brown to black skin color.

It is not known if TRI-LUMA Cream is safe and effectivein the treatment of dark spots (hyperpigmentation) of the skin caused byconditions other than melasma of the face.

It is not known if TRI-LUMA Cream is safe and effectivein females who are pregnant or who are breastfeeding. See “What is the mostimportant information I should know about TRILUMA Cream?” and “Whatshould I tell my doctor before using TRI-LUMA Cream?”

Who should not use TRI-LUMA Cream?

Do not use TRI-LUMA Cream if you are allergic to it orany of the ingredients in TRI-LUMA Cream. See the end of this leaflet for acomplete list of ingredients in TRI-LUMA Cream.

What should I tell my doctor before using TRI-LUMA Cream?

Before you use TRI-LUMA Cream, tell your doctor ifyou:

• are allergic to sulfites
• have any other medical conditions
• are pregnant or plan to become pregnant. See “What is the most important information I should know about TRI-LUMA Cream?”
• are breastfeeding or plan to breastfeed. It is not known if TRI-LUMA Cream passes into your breast milk. You should avoid skin-to-skin contact between areas treated with TRILUMA Cream and your baby.

Tell your doctor about all the medicines you take,including prescription and over-thecounter medicines, vitamins, herbalsupplements and skin products that you use.

How should I use TRI-LUMA Cream?

• Use TRI-LUMA Cream exactly as your doctor tells you to use it.
• Before you apply TRI-LUMA Cream, gently wash your face with a mild cleanser. Rinse your face and pat your skin dry.
• Apply TRI-LUMA Cream 1 time a day, at least 30 minutes before bedtime.
• Apply a thin layer of TRI-LUMA Cream to the affected skin areas. Include about ½ inch of normal skin surrounding the affected area.
• Gently rub TRI-LUMA Cream evenly into your skin.
• Do not get TRI-LUMA Cream near the corners of your mouth, your nose, your eyes, or open wounds.
• Do not bandage or cover the treated skin after applying TRI-LUMA Cream.
• You may use moisturizers and cosmetics during the day.
• Wash your hands after applying TRI-LUMA Cream.

What should I avoid while using TRI-LUMA Cream?

• You should avoid sunlight, sunlamps, tanning beds, and ultraviolet light during treatment with TRI-LUMA Cream.
  • Use sunscreen with an SPF (sun protection factor) of 30 or more. If you have to be in the sunlight, wear a wide-brimmed hat or other protective clothing to cover the treated areas.
  • Melasma can get worse with even a small amount of sunlight. You should continue to avoid sunlight, use sunscreen, and wear protective clothing after treatment with TRI-LUMA Cream.
• Females should avoid the use of hormonal forms of birth control. Hormonal birth control methods can cause your melasma to become worse. Talk to your doctor about other birth control options.
• Heat and cold weather may irritate skin treated with TRI-LUMA. Talk with your doctor about ways to manage skin irritation.

What are the possible side effects of TRI-LUMA Cream?

TRI-LUMA Cream may cause serious side effects,including:

• allergic reactions. TRI-LUMA Cream may cause allergic reactions that can be life threatening. Stop using TRI-LUMA Cream and call your doctor or get medical help right away if you get any of the following symptoms:
  • swelling of your face, eyes, lips, tongue, or throat
  • trouble breathing
  • severe itching
  • skin rash or hives
• change in skin color. One of the medicines in TRI-LUMA Cream can cause a blue-black darkening of your skin. Stop using TRI-LUMA Cream and tell you doctor if you develop a blue-black darkening of your skin.
• TRI-LUMA Cream can pass through your skin. Too much TRI-LUMA Cream passing through your skin can cause your adrenal glands to stop working. Your doctor may do blood tests to check for adrenal gland problems.
• skin irritation. Stop using TRI-LUMA Cream and call your doctor if you have:
  • blistering or crusting of your skin
  • severe burning
  • swelling of your skin
  • irritation of your eyes, nose, or mouth

The most common side effects of TRI-LUMA Creaminclude:

• redness
• dryness
• peeling
• itching
• burning
• acne

Tell your doctor if you have any side effect that bothersyou or that does not go away.

These are not all the possible side effects of TRI-LUMACream. For more information, ask your doctor or pharmacist. Call your doctorfor medical advice about side effects. You may report side effects to FDA at 1800-FDA-1088.

You may also report side effects to GaldermaLaboratories, L.P. at 1-866-735-4137.

How should I store TRI-LUMA Cream?

• Store TRI-LUMA Cream in a refrigerator, between 36°F to 46°F (2°C to 8 °C).
• Keep TRI-LUMA Cream tube tightly closed.
• Do not freeze TRI-LUMA Cream.

General information about the safe and effective useof TRI-LUMA Cream

Medicines are sometimes prescribed for purposes otherthan those listed in a Patient Information leaflet. Do not use TRI-LUMA Creamfor a condition for which it was not prescribed. Do not give TRI-LUMA Cream toother people, even if they have the same symptoms you have. It may harm them.

If you would like more information, talk with yourdoctor. You can ask your pharmacist or doctor for information about TRI-LUMACream that is written for health professionals.

What are the ingredients in TRI-LUMA Cream?

Active ingredients: fluocinolone acetonide,hydroquinone, and tretinoin

Inactive ingredients: butylated hydroxytoluene,cetyl alcohol, citric acid anhydrous, glycerin, glyceryl stearate, magnesiumaluminum silicate, methyl gluceth-10, methylparaben, PEG-100 stearate,propylparaben, purified water, sodium metabisulfite, stearic acid, and stearylalcohol

This Patient Information has been approved by the U.S.Food and Drug Administration.