Solage® Topical Solution contains mequinol 2% and tretinoin 0.01%, by weight, in a solution base of ethyl alcohol (77.8% v/v), polyethylene glycol 400, butylated hydroxytoluene, ascorbic acid, citric acid, ascorbyl palmitate, edentate disodium and purified water. Mequinol is 4-hydroxyanisole, the monomethyl ether of hydroquinone or 1-hydroxy-4- methoxybenzene. It has the chemical formula, C₇H₈O₂, a molecular weight of 124.14, and the structural formula:

The chemical name for tretinoin, a retinoid, is (all-E)-3,7-dimethyl-9-(2,6,6-trimethyl-1- cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid, also referred to as all-trans-retinoic acid. It has the chemical formula, C₂₀H₂₈O₂, a molecular weight of 300.44, and the structural formula:

Last updated on RxList: 1/14/2008

(To understand fully the indication for this product, please read the entire INDICATIONS section of the labeling).

Solage (mequinol 2%, tretinoin 0.01%) Topical Solution is indicated for the treatment of solar lentigines.

Solage Solution should only be used under medical supervision as an adjunct to a comprehensive skin care and sun avoidance program where the patient should primarily either avoid the sun or use protective clothing.

Neither the safety nor effectiveness of Solage Solution for the prevention or treatment of melasma or postinflammatory hyperpigmentation has been established.

The efficacy of using Solage Solution daily for greater than 24 weeks has not been established.

Patients require detailed instruction to obtain maximal benefits and to understand all the precautions necessary to use this product with greatest safety. The physician should review the Patient Information.

Apply Solage Solution to the solar lentigines using the applicator tip while avoiding application to the surrounding skin. Use twice daily, morning and evening at least 8 hours apart, or as directed by a physician. Patients should not shower or bathe the treatment areas for at least 6 hours after application of Solage Solution. Special caution should be taken when applying Solage

Solution to avoid the eyes, mouth, paranasal creases, and mucous membranes.

Application of Solage Solution may cause transitory stinging, burning or irritation.

Improvement continues gradually through the course of therapy and should be apparent by 24 weeks. Patients should avoid exposure to sunlight (including sunlamps) or wear protective clothing while using Solage Solution. Data are not available to establish how or whether Solage Solution is degraded (either by sunlight or by normal interior lighting) following application to the skin.

With discontinuation of Solage Solution therapy, a majority of patients will experience some repigmentation over time of their lesions.

Applications of larger amounts of medication or more frequently than recommended will not lead to more rapid or better results, and marked redness, peeling, irritation, or hypopigmentation (abnormal lightening) of the skin may occur.

Patients treated with Solage Solution may use cosmetics but should wait 30 minutes before applying.

Solage (mequinol 2%, tretinoin 0.01%) Topical Solution is available in 30 mL plastic bottles with an applicator. NDC 13478-001-01

Storage

The bottle should be protected from light by continuing to store in the carton after opening. Store at 25° C (77° F): excursions permitted to 15-30° C (59-86° F).

Note: FLAMMABLE. Keep away from heat and open flame.

Marketed by: Barrier Therapeutics, Inc. Princeton, New Jersey 08540-6697, USA. Manufactured by: Contract Pharmaceutical Laboratories, Buffalo, 14213 NY, USA. Revised December 2005. FDA Rev date: 4/25/2007

Last updated on RxList: 1/14/2008

In the pivotal clinical trials, adverse reactions were primarily mild to moderate in intensity, occurring in 66% and 30% of patients, respectively. The majority of these events were limited to the skin and 64% had an onset of a skin related adverse reaction early in treatment (by week 8). The most frequent adverse reactions in patients treated with Solage Solution were erythema (49% of patients), burning, stinging, or tingling (26%), desquamation (14%), pruritus (12%), and skin irritation (5%). Some patients experienced temporary hypopigmentation of treated lesions (5%) or of the skin surrounding treated lesions (7%). Ninety-four of 106 patients (89%) had resolution of hypopigmentation upon discontinuation of treatment to the lesion, and/or re-instruction on proper application to the lesion only. Another 8% (9/106) of patients with hypopigmentation events had resolution within 120 days after the end of treatment. Three of the 106 patients (2.8%) had persistence of hypopigmentation beyond 120 days. Approximately 6% of patients discontinued study participation with Solage Solution due to adverse reactions. These discontinuations were due primarily to skin redness (erythema) or related cutaneous adverse reactions. Rare cases of depigmentation at sites distant from the application have been reported in Post Marketing Surveillance.

Adverse Events Occurring in >1% of the Population - All Studies

Body System	Solage Solution (mequinol 2%, tretinoin 0.01%)		Tretinoin, 0.01%		Mequinol, 2%,		Vehicle
Skin and Appendages	N	%	N	%	N	%	N	%
Erythema	613	41.1	261	55.3	13	5.1	8	4.6
Burning/Stinging/ Tingling	270	18.1	173	36.7	26	10.2	20	11.4
Desquamation	171	11.5	93	19.7	7	2.8	2	1.1
Pruritus	148	9.9	66	14.0	12	4.7	3	1.7
Irritation Skin*	90	6.0	25	5.3	1	0.4	1	0.6
Halo Hypopigmentation	96	6.4	16	3.4	2	0.8	2	1.1
Hypopigmentation	62	4.2	8	1.7	2	0.8	0	0.0
Skin Dry	46	3.1	18	3.8	3	1.2	1	0.6
Rash	31	2.0	21	4.4	0	0.0	1	0.6
Crusting	30	2.0	18	3.8	0	0.0	1	0.6
Rash Vesicular Bullae	18	1.2	8	1.7	0	0.0	0	0.0
Dermatitis	29	1.9	0	0.0	0	0.0	0	0.0
Discomfort Skin	52	3.5	0	0.0	0	0.0	0	0.0
Irritant Dermatitis	17	1.1	0	0.0	0	0.0	0	0.0
*In study RD.06.SRE.18091 irritant dermatitis included signs & symptoms of scaling, dryness, stinging/burning and erythema.

Concomitant topical products with a strong skin drying effect, products with high concentrations of alcohol, astringents, spices or lime, medicated soaps or shampoos, permanent wave solutions, electrolysis, hair depilatories or waxes, or other preparations that might dry or irritate the skin should be used with caution in patients being treated with Solage Solution because they may increase irritation when used with Solage Solution.

Solage Solution should not be administered if the patient is also taking drugs known to be photosensitizers (e.g., thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides) because of the possibility of augmented phototoxicity.

Last updated on RxList: 1/14/2008

Solage Solution is a dermal irritant and the results of continued irritation of the skin for greater than 52 weeks in chronic, long-term use are not known. Tretinoin has been reported to cause severe irritation on eczematous skin and should be used only with utmost caution in patients with this condition.

Solage Solution should not be administered if the patient is also taking drugs known to be photosensitizers (e.g., thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides) because of the possibility of augmented phototoxicity. Because of heightened burning susceptibility, exposure to sunlight (including sunlamps) to treated areas should be avoided or minimized during the use of Solage Solution. Patients must be advised to use protective clothing and comply with a comprehensive sun avoidance program when using Solage Solution. Data are not available to establish how or whether Solage Solution is degraded (either by sunlight or by normal interior lighting) following application to the skin. Patients with sunburn should be advised not to use Solage Solution until fully recovered. Patients who may have considerable sun exposure due to their occupation and those patients with inherent sensitivity to sunlight should exercise particular caution when using Solage Solution and ensure that the precautions outlined in the Patient Information are observed.

Solage Solution should be kept out of the eyes, mouth, paranasal creases, and mucous membranes. Solage Solution may cause skin irritation, erythema, burning, stinging or tingling, peeling, and pruritis. If the degree of such local irritation warrants, patients should be directed to use less medication, decrease the frequency of application, discontinue use temporarily, or discontinue use altogether. The efficacy at reduced frequencies of application has not been established.

Solage Solution should be used with caution by patients with a history, or family history, of vitiligo. One patient in the trials, whose brother had vitiligo, experienced hypopigmentation in areas that had not been treated with study medication. Some of these areas continued to worsen for at least one month post treatment with Solage Solution. Six weeks later the severity of the hypopigmentation had decreased from moderate to mild and 106 days post treatment, the patient had resolution of some but not all lesions.

Application of larger amounts of medication than recommended will not lead to more rapid or better results, and marked redness, peeling, discomfort, or hypopigmentation of the skin may occur.

General

For external use only.

Solage Solution should only be used as an adjunct to a comprehensive skin care and sun avoidance program. (See INDICATIONS section).

If a drug sensitivity, chemical irritation, or a systemic adverse reaction develops, use of Solage Solution should be discontinued.

Weather extremes, such as wind or cold, may be more irritating to patients using Solage Solution.

Information for patients

Patients require detailed instruction to obtain maximal benefits and to understand all the precautions necessary to use this product with greatest safety. The Patient Information is attached to this Package Insert.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Although a dermal carcinogenicity study in CD-1 mice indicated that Solage Solution applied topically at daily doses up to 80 and 0.4 mg/kg (240 and 1.2 mg/m² ) of mequinol and tretinoin, respectively, representing approximately 5 times the maximum possible systemic human exposure was not carcinogenic, in a photocarcinogenicity study utilizing Crl:Skh-1(hr/hr BR) hairless albino mice, median time to onset of tumors decreased. Also, the number of tumors increased in all dose groups administered 1.4, 4.3 or 14 µl of Solage Solution/cm² of skin (24 and 0.12, 72 and 0.36, or 240 and 1.2 mg/m² of mequinol and tretinoin, respectively; 0.6, 1.9, or 6.5 times the daily human dose on a mg/m² basis) following chronic topical dosing with intercurrent exposure to ultraviolet radiation for up to 40 weeks. Similar animal studies have shown an increased tumorigenic risk with the use of retinoids when followed by ultraviolet radiation. Although the significance of these studies to human use is not clear, patients using this product should be advised to avoid or minimize exposure to either sunlight or artificial ultraviolet irradiation sources.

Mequinol was non-mutagenic in the Ames/Salmonella assay using strains TA98, TA100, TA1535, and TA1537, all of which are insensitive to mutagenic effects of structurally-related quinones. Solage Solution was non-genotoxic in an in vivo dermal micronucleus assay in rats, but exposure of bone marrow to drug was not demonstrated.

A dermal reproduction study with Solage Solution in Sprague-Dawley rats at a daily dose of 80 and 0.4 mg/kg (480 and 2.4 mg/m²) of mequinol and tretinoin, respectively, approximately 11 times the corresponding maximum possible human exposure, assuming 100% bioavailability following topical application to 5% of the total body surface area, showed no impairment of fertility.

Pregnancy: Teratogenic effects: Pregnancy Category X.

Although the magnitude of the potential for teratogenicity may not be well-defined, Solage Solution is labeled as an "X" because the potential risk of the use of this drug to treat this particular indication (solar lentigines) in a pregnant woman clearly outweighs any possible benefit (see CONTRAINDICATIONS section).

Nursing Mothers: It is not known to what extent mequinol and/or tretinoin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Solage Solution is administered to a nursing woman.

Pediatric Use: The safety and effectiveness of this product have not been established in pediatric patients. Solage Solution should not be used on children.

Geriatric Use: Of the total number of patients in clinical studies of Solage Solution, approximately 43% were 65 and older, while approximately 8% were 75 and over. No overall differences in effectiveness or safety were observed between these patients and younger patients.

Last updated on RxList: 1/14/2008

If Solage Solution is applied excessively, no more rapid or better results will be obtained and marked redness, peeling, discomfort, or hypopigmentation may occur. Oral ingestion of the drug may lead to the same adverse effects as those associated with excessive oral intake of vitamin A (hypervitaminosis A). If oral ingestion occurs, the patient should be monitored, and appropriate supportive measures should be administered as necessary. The maximal no-effect level for oral administration of Solage Solution in rats was 5.0 mL/kg (30 mg/m²). Clinical signs observed were attributed to the high alcohol content (77%) of the drug formulation.

The combination of mequinol and tretinoin may cause fetal harm when administered to a pregnant woman. Due to the known effects of these active ingredients, Solage Topical Solution should not be used in women of childbearing potential.

In a dermal teratology study in New Zealand White rabbits, there were no statistically significant differences among treatment groups in fetal malformation data; however, marked hydrocephaly with visible doming of the head was observed in one mid-dose litter (12 and 0.06 mg/kg or 132 and 0.66 mg/m² of mequinol and tretinoin, respectively) and two fetuses in one high dose litter (40 and 0.2 mg/kg or 440 and 2.2 mg/m² of mequinol and tretinoin, respectively) of Solage Solution, and two high-dose tretinoin (0.2 mg/kg, 2.2 mg/m²) treated litters. These malformations were considered to be treatment related and due to the known effects of tretinoin. This was further supported by coincident appearance of other malformations associated with tretinoin, such as cleft palate and appendicular skeletal defects. No effects attributed to treatment were observed in rabbits in that study treated topically with mequinol alone (dose 40 mg/kg, 440 mg/m²). A no- observed-effect level (NOEL) for teratogenicity in rabbits was established at 4 and 0.02 mg/kg (44 and 0.22 mg/m² mequinol and tretinoin, respectively) for Solage Solution which is approximately the maximum possible human daily dose, based on clinical application to 5% of total body surface area. Plasma tretinoin concentrations were not raised above endogenous levels, even at teratogenic doses. Plasma mequinol concentrations in rabbits at the NOEL at one hour after application were 124 ng/mL or approximately twelve times the mean peak plasma concentrations of that substance seen in human subjects in a clinical pharmacokinetic study. In a repeated study in pregnant rabbits administered the same dose levels as the study described above, additional precautionary measures were taken to prevent ingestion, although there is no evidence to confirm that ingestion occurred in the initial study. Precautionary measures additionally limited transdermal absorption to a six hour exposure period, or approximately one- fourth of the human clinical daily continuous exposure time. This study did not show any significant teratogenic effects at doses up to approximately 13 times the human dose on a mg/m² basis. However, a concurrent tretinoin dose group (0.2 mg/kg/day) did include two litters with limb malformations.

In a published study in albino rats (J. Am. Coll. Toxicology 4(5):31-63, 1985), topical application of 5% of mequinol in a cream vehicle during gestation was embryotoxic and embryolethal. Embryonic loss prior to implantation was noted in that study where animals were treated throughout gestation. Coincidentally, mean preimplantation embryonic loss was increased in the first rabbit study in all mequinol treated groups, relative to control, and in the high dose mequinol/tretinoin and tretinoin only treated groups in the second study. In those studies, dosing began at gestation day 6, when implantation is purported to occur. Increased preimplantation loss was also noted at the high combination dose in a study of early embryonic effects in rats, as was decreased body weight in male pups; these findings are consistent with the published study. Solage Solution was not teratogenic in Sprague-Dawley rats when given in topical doses of 80 and 0.4 mg/kg mequinol and tretinoin, respectively (480 and 2.4 mg/m² or 11 times the maximum human daily dose). The maximum human dose is defined as the amount of solution applied daily to 5% of the total body surface area.

With widespread use of any drug, a small number of birth defect reports associated temporally with the administration of the drug would be expected by chance alone. Thirty cases of temporally-associated congenital malformations have been reported during two decades of clinical use of another formulation of topical tretinoin. Although no definite pattern of teratogenicity and no casual association has been established from these cases, 6 of the reports describe the rare birth defect category holoprosencephaly (defects associated with incomplete midline development of the forebrain). The significance of these spontaneous reports in terms of risk to the fetus is not known.

No adequate or well-controlled trials have been conducted with Solage Solution in pregnant women.

Solage Topical Solution is contraindicated in individuals with a history of sensitivity reactions to any of its ingredients. It should be discontinued if hypersensitivity to any of its ingredients is noted.

Last updated on RxList: 1/14/2008

Solar lentigines are localized, pigmented, macular lesions of the skin on the areas of the body which have been chronically exposed to sunlight.

Biopsy specimens of solar lentigines were collected in a clinical study with Solage Solution at baseline, at the end of a 24 week treatment period and at the end of a subsequent 24 week, no treatment, follow-up period. The end of treatment specimens showed a decrease in melanin pigmentation in both melanocytes and keratinocytes, and an increased lymphocytic infiltration, which may have been the result of irritation or an immunologic reaction. The end of follow-up period specimens showed repigmentation of the melanocytes and keratinocytes to a state similar to the baseline specimens. These results indicate that there is no assurance that any improvement obtained would persist upon discontinuation of drug therapy.

The mechanism of action of mequinol is unknown. Although mequinol is a substrate for the enzyme tyrosinase and acts as a competitive inhibitor of the formation of melanin precursors, the clinical significance of these findings is unknown. The mechanism of action of tretinoin as a depigmenting agent also is unknown.

Pharmacokinetics

The percutaneous absorption of tretinoin and the systemic exposure to tretinoin and mequinol were assessed in healthy subjects (n=8) following two weeks of twice daily topical treatment of Solage Solution. Approximately 0.8 mL of Solage Solution was applied to a 400 cm² area of the back, corresponding to a dose of 37.3 µg/cm² for mequinol and 0.23 µg/cm² for tretinoin. The percutaneous absorption of tretinoin was approximately 4.4%, and systemic concentrations did not increase over endogenous levels. The mean Cmax for mequinol was 9.92 ng/mL (range 4.22 to 23.62 ng/mL) and the Tmax was 2 hours (range 1 to 2 hours).

Clinical Studies

Two adequate and well-controlled trials evaluated changes in treated hyperpigmented lesions on the face, forearms/back of hands in 421 patients treated with Solage Topical Solution, 422 patients treated with tretinoin topical solution, 209 patients treated with mequinol topical solution and 107 patients treated with vehicle for up to 24 weeks. In these studies, patients were to avoid sun exposure and use protective clothing, and use of suncreens was prohibited. Patients were allowed to apply Moisturel® Lotion 30 minutes after application of Solage Solution. Physicians assessed the extent of improvement or worsening of all the treated lesions from the baseline condition on a 7 point scale. The results of these evaluations are shown below.

	Face		Forearms/Back of Hands
	Solage Solution	Vehicle	Solage Solution	Vehicle
Moderate Improvementor greater1	57%	15%	54%	14%
Slight Improvement	28%	36%	26%	33%
No Change2	15%	49%	20%	53%
1 Includes the following grades: Moderate Improvement, Marked Improvement, Almost Clear, Completely Clear. Moderate Improvement or greater was considered clinically meaningful. 2 Includes the following grades: No Change, Worse (less than 1% of patients treated with Solage Solution were rated as worse).

Improvement (lightening) of the solar lentigines occurred gradually over time during the 24 week treatment period. At 24 weeks of treatment, 57% and 54% of patients experienced moderate improvement or greater, and 3% and 1% of patients were completely clear of all treated lesions for the face and forearms/back of hands, respectively. It should be noted that approximately 9% of patients, from both treatment areas in these studies, with moderate improvement or greater also experienced hypopigmentation of the skin surrounding at least one treated lesion. There are no vehicle-controlled effectiveness data on the course of lesions treated beyond 24 weeks. After 24 weeks of treatment, for the forearm/back of hands treatment site, the percentage of patients treated with tretinoin topical solution with moderate improvement or greater, slight improvement, or no change, were 38%, 37%, and 26%, respectively, and for mequinol topical solution were 24%, 40%, and 36%, respectively. For the face treatment site, the percentage of patients treated with tretinoin topical solution with moderate improvement or greater, slight improvement, or no change, were 46%, 33%, and 21%, respectively, and for mequinol topical solution were 33%, 30%, and 37% respectively.

The duration of effect was investigated during a period of up to 24 weeks following the discontinuation of treatment. Results from these studies showed that patients may maintain the level of clinical improvement of their treated lesions from the end of treatment through the 24 week follow-up period. However, some degree of repigmentation of treated lesions was observed over time, demonstrating reversibility of the depigmenting action of Solage Solution. In the pivotal clinical trials of 24 weeks duration, some patients experienced temporary hypopigmentation of treated lesions (5%) or of the skin surrounding treated lesions (7%). Hypopigmentation of the skin surrounding treated lesions occurs even in the setting of proper application of the drug within the lesion border. The majority (94/106 - 89%) resolved upon discontinuation of treatment to the lesion, and/or re-instruction on proper application to the lesion only. Another 8% (9/106) of patients with hypopigmentation events had resolution within 120 days after the end of treatment.

Three of the 106 patients (2.8%) had persistence of hypopigmentation beyond 120 days. This further demonstrates the reversibility of the depigmenting action of Solage Solution. Over 150 patients used Solage Solution twice daily for 52 weeks in an open label clinical study. The safety profile for Solage Solution in this long-term study was similar to that seen in the 24 week studies although burning/stinging/tingling, desquamation, pruritis, and irritation of the skin occurred at lower rates and halo hypopigmentation and hypopigmentation occurred at a slightly greater rate.

Over 90 patients used Solage Solution twice daily and a concomitant sunscreen (PreSun® 29) daily for up to 24 weeks in an open label clinical study. The safety profile for Solage Solution in this study was similar to that seen in studies which prohibited sunscreen use although desquamation, pruritis, and halo hypopigmentation occurred at slightly lower rates. The initial clinical trials for Solage Solution included 1794 individuals of Skin Type I-V, 94.5% of whom were Caucasian. The trials also included 5% of individuals who were Asian/Pacific Islander (1.2%), African-American (0.8%), and Hispanic/Latino (3.5%). An additional open label study was conducted in 259 patients in the Asian (24.3%), Hispanic/Latino (62.2%) and African American (13.5%) ethnic groups with skin types II to V. This number reflects approximately three times as many subjects in this population as were represented in the initial clinical trials. In this study, as in the earlier studies, Solage Solution was used twice daily for a period of 24 weeks. The overall safety profile in this study was generally consistent with the initial clinical trials although erythema, desquamation, and pruritis occurred at lower rates and halo hypopigmentation occurred at a higher rate (7.7% versus 6.2%). The safety of Solage Solution in women of childbearing potential has not been established (see CONTRAINDICATIONS).

Last updated on RxList: 1/14/2008

Solage®
(so-la-jay)
(mequinol 2%, tretinoin 0.01%) Topical Solution

Read the Patient Information that comes with Solage before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking to your doctor about your medical condition or treatment.

What is Solage?

Solage is a prescription medicine used on the skin to treat solar lentigines. Solar lentigines are also called "brown spots", "age spots", or "liver spots". Solar lentigines can happen on areas of skin that have been exposed to too much sunlight over time.

Solage should only be used under medical care along with a skin care and sun avoidance program.

Who should not use Solage Solution?

Do not use Solage if you are:

• a woman who is pregnant, planning to become pregnant, or is able to become pregnant. Solage may harm a fetus (unborn baby).
• allergic to anything in Solage. See the end of this leaflet for a list of ingredients in Solage.

Solage has not been studied in children and should not be used on children.

Solage may not be right for you. Before stating Solage, tell your doctor about all of your health conditions, including, if you:

• have eczema
• have skin irritation
• have vitiligo or a family history of vitiligo. Vitiligo is a condition where color is lost on areas of the skin and white patches appear.
• have a sunburn
• have skin that is sensitive to sunlight
• are exposed to sunlight often because of your job
• are breastfeeding. It is not known if Solage passes into breast milk and to our baby.

Tell your doctor about all of the medicines you take, including prescription and nonprescription medicines, vitamins and herbal supplements. Solage should not be used with other medicines that can make your skin sensitive to sunlight including:

• blood pressure medicines called "thiazides"
• some antibiotic medicines (tetracyclines, fluroquinolones or sulfonamides)
• antipsychotic medicines called "phenothiazines"

Know the medicines you take. Keep a list of your medicines with you to show your doctor. Your doctor will decide if you can use Solage with your other medicines.

Tell your doctor about all of the skin products you use. Your doctor will tell you which skin products you can use with Solage. You must be careful about using skin products that can dry or irritate your skin because dryness and irritation are increased with Solage. Skin products that can dry and irritate your skin include:

• products that contain alcohol, astringents, spices, or lime
• medicated soaps or shampoos
• hair "perms"
• hair removal products such as electrolysis, depilatories, or waxes

How should I use Solage Solution?

• Solage is for skin use only.
• Apply Solage exactly as prescribed and instructed by your doctor. Solage is usually applied twice a day, at least 8 hours apart. Do not use more Solage or use it more often than prescribed.
• Apply Solage to the "spots" to be treated using the applicator tip of the Solage bottle. Be careful and do not apply Solage to "normal" skin.
• Do not use Solage around your eyes, mouth, crease of your nose, or on mucous membranes. Solage can cause severe redness, itching, burning, stinging, and peeling if applied to these areas. If Solage gets in your eyes, rinse them well with water and call your doctor right away. If you get Solage in your mouth or swallow any, get medical treatment right away.
• Do not bathe or shower for at least 6 hours after applying Solage.
• Cosmetics may be applied 30 minutes after using Solage. Talk to your doctor about cosmetics and other skin care products that are okay to use with Solage.
• You must avoid sun exposure (including the use of sunlamps). Always wear protective clothing when you go outside. If your skin gets sunburned, stop Solage until the sunburn has healed.

What are the possible side effects of Solage Solution?

Common side effects of Solage include redness, stinging, burning, tingling, peeling, itching, or irritation on areas of the skin where it is applied.

Solage may cause the treated age spots or surrounding skin to become lighter than your normally colored skin, especially if too much Solage is used or it is used for too long. Call your doctor if your skin becomes lighter than normal. Skin color may return when Solage is stopped.

These are not all of the side effects of Solage Solution. Ask your doctor or pharmacist for more information.

How should I store Solage?

• Store Solage at room temperature, between 59° to 86° F (15° to 30°C). Protect Solage from light by returning the bottle to the carton after each use.

Solage is flammable. Keep away from heat and flames.

• Keep Solage and all medications out of reach of children.

General information about Solage.

Medicines can be prescribed for conditions that are not in patient information leaflets. Use Solage only for what you doctor prescribed. Do not give it to other people, evenif they have the same symptoms you have. It may harm them.

This leaflet gives the most important information about Solage. For more information about Solage, talk with your doctor or pharmacist. For more imformation call 866-440-5508 or visit www.solage.com.

What are the ingredients in Solage?

Active Ingredients: mequinol and tretinoin

Inactive Ingredients: ethyl alcohol (77.8% v/v), polyethylene glycol 400, butylated hydroxytoluene, ascorbic acid, citric acid, ascorbyl palmitate, edetate disodium, and purified water.

Last updated on RxList: 1/14/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

TRETINOIN/MEQUINOL - TOPICAL

(tret-ih-NO-in/MEK-win-all)

COMMON BRAND NAME(S): Solage

USES: This medication is used to treat brown "age" or "liver" spots (solar lentigines).

HOW TO USE: Read the Patient Information Leaflet provided by your pharmacist before you start using this product and each time you get a refill. If you have any questions, consult your doctor or pharmacist.

For external use only. Apply this medication to the affected areas of skin using the applicator tip, usually twice daily at least 8 hours apart, or as directed by your doctor. Temporary lightening of the skin surrounding the treated area (halo hypopigmentation) may occur. Avoid contact with the eyes.

Do not use more than prescribed, apply more often or use for longer than prescribed. Your condition will not clear faster, but risk of side effects may be increased.

Do not shower or bathe the treated skin for at least 6 hours after applying this medication.

Cosmetics may be applied 30 minutes after applying this drug.

SIDE EFFECTS: Temporary stinging, burning, irritation, peeling, redness, itching, or dry skin may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

A serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction include: rash, itching, swelling, dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using this medication, tell your doctor or pharmacist your medical history, especially of: vitiligo, eczema, any allergies.

This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths or sunlamps. Wear protective clothing when outdoors. Other medications (e.g., antibiotics such as ciprofloxacin, sulfamethoxazole, tetracycline) may increase your sun sensitivity. Ask your doctor or pharmacist for more details.

This medication must not be used during pregnancy. If you become pregnant or think you may be pregnant, inform your doctor immediately.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription products you may use, especially of: other skin products.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. This medicine may be harmful if swallowed.

NOTES: Follow a thorough sun protection program, before and after using this medication. Ask your doctor or pharmacist for more details.

Do not share this medication with others.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light, moisture, and open flame. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.