TAZORAC (tazartene) Gel, 0.05% (tazartene) Gel, 0.1% FOR DERMATOLOGIC USE ONLY NOT FOR OPHTHALMIC, ORAL, OR INTRAVAGINAL USE. DESCRIPTION TAZORAC Gel is a translucent, aqueus gel and cntains the cmpund tazartene, a member f the acetylenic class f retinids. It is fr tpical dermatlgic use nly. The active ingredient is represented by the fllwing structural frmula: Frmula: C 21 H 21 NO 2 S Mlecular Weight: 351.46 Chemical Name: Ethyl 6-[(4,4-dimethylthichrman-6-yl)ethynyl]nictinate Cntains: Active: Tazartene 0.05% r 0.1% (w/w) Preservative: Benzyl alchl 1% (w/w) Inactives: Ascrbic acid; butylated hydrxyanisle; butylated hydrxytluene; carbmer hmplymer type B; edetate disdium; hexylene glycl; plxamer 407; plyethylene glycl 400; plysrbate 40; purified water; and trmethamine. CLINICAL PHARMACOLOGY Tazartene is a retinid prdrug which is cnverted t its active frm, the cgnate carbxylic acid f tazartene (AGN 190299), by rapid deesterificatin in animals and man. AGN 190299 ( tazartenic acid ) binds t all three members f the retinic acid receptr (RAR) family: RARα, RARβ, and RARγ but shws relative selectivity fr RARβ, and RARγ and may mdify gene expressin. The clinical significance f these findings is unknwn. Psriasis: The mechanism f tazartene actin in psriasis is nt defined. Tpical tazartene blcks inductin f muse epidermal rnithine decarbxylase (ODC) activity, which is assciated with cell prliferatin and hyperplasia. In cell culture and in vitr mdels f skin, tazartene suppresses expressin f MRP8, a marker f inflammatin present in the epidermis f psriasis patients at high levels. In human keratincyte cultures, it inhibits crnified envelpe frmatin, whse build-up is an element f the psriatic scale. Tazartene als induces the expressin f a gene which may be a grwth suppressr in human keratincytes and which may inhibit epidermal hyperprliferatin in treated plaques. Hwever, the clinical significance f these findings is unknwn. Acne: The mechanism f tazartene actin in acne vulgaris is nt defined. Hwever, the basis f tazartene s therapeutic effect in acne may be due t its anti-hyperprliferative, nrmalizing-f-differentiatin and anti-
inflammatry effects. Tazartene inhibited crnecyte accumulatin in rhin muse skin and crss-linked envelpe frmatin in cultured human keratincytes. The clinical significance f these findings is unknwn. Pharmackinetics: Fllwing tpical applicatin, tazartene underges esterase hydrlysis t frm its active metablite, tazartenic acid. Little parent cmpund culd be detected in the plasma. Tazartenic acid was highly bund t plasma prteins (greater than 99%). Tazartene and tazartenic acid were metablized t sulfxides, sulfnes and ther plar metablites which were eliminated thrugh urinary and fecal pathways. The half-life f tazartenic acid was apprximately 18 hurs, fllwing tpical applicatin f tazartene t nrmal, acne r psriatic skin. The human in viv studies described belw were cnducted with tazartene gel applied tpically at apprximately 2 mg/cm 2 and left n the skin fr 10 t 12 hurs. Bth the peak plasma cncentratin (C max ) and area under the plasma cncentratin time curve (AUC) refer t the active metablite nly. Tw single, tpical dse studies were cnducted using 14 C-tazartene gel. Systemic absrptin, as determined frm radiactivity in the excreta, was less than 1% f the applied dse (withut cclusin) in six psriatic patients and apprximately 5% f the applied dse (under cclusin) in six healthy subjects. One nnradilabeled single-dse study cmparing the 0.05% gel t the 0.1% gel in healthy subjects indicated that the Cmax and AUC were 40% higher fr the 0.1% gel. After 7 days f tpical dsing with measured dses f tazartene 0.1% gel n 20% f the ttal bdy surface withut cclusin in 24 healthy subjects, the Cmax fr tazartenic acid was 0.72 ± 0.58 ng/ml (mean ± SD) ccurring 9 hurs after the last dse, and the AUC 0-24hr fr tazartenic acid was 10.1 ± 7.2 ng hr/ml. Systemic absrptin was 0.91 ± 0.67% f the applied dse. In a 14-day study in five psriatic patients, measured dses f tazartene 0.1% gel were applied daily by nursing staff t invlved skin withut cclusin (8 t 18% f ttal bdy surface area; mean ± SD: 13 ± 5%). The Cmax fr tazartenic acid was 12.0 ± 7.6 ng/ml ccurring 6 hurs after the final dse, and the AUC 0-24hr fr tazartenic acid was 105 ± 55 ng hr/ml. Systemic absrptin was 14.8 ± 7.6% f the applied dse. Extraplatin f these results t represent dsing n 20% f ttal bdy surface yielded estimates fr tazartenic acid with Cmax f 18.9 ± 10.6 ng/ml and AUC 0-24hr f 172 ± 88 ng hr/ml. An in vitr percutaneus absrptin study, using radilabeled drug and freshly excised human skin r human cadaver skin, indicated that apprximately 4 t 5% f the applied dse was in the stratum crneum (tazartene: tazartenic acid = 5:1) and 2 t 4% was in the viable epidermis-dermis layer (tazartene: tazartenic acid = 2:1) 24 hurs after tpical applicatin f the gel. Clinical Studies Psriasis: In tw large vehicle-cntrlled clinical studies, tazartene 0.05% and 0.1% gels applied nce daily fr 12 weeks were significantly mre effective than vehicle in reducing the severity f the clinical signs f stable plaque psriasis cvering up t 20% f bdy surface area. In ne f the studies, patients were fllwed up fr an additinal 12 weeks fllwing cessatin f therapy with TAZORAC Gel. Mean baseline scres and changes frm baseline (reductins) after treatment in these tw studies are shwn in the fllwing table:
Plaque Elevatin, Scaling, and Erythema in Tw Cntrlled Clinical Trials fr Psriasis Plaque Elevatin Scaling Erythema B* C-12* C-24* B* C-12* C-24* B* C-12* C-24* TAZORAC 0.05% Gel TAZORAC 0.1% Gel Vehicle Gel Trunk/Arm/Leg Lesins Knee/Elbw Lesins Trunk/Arm/Leg Lesins Knee/Elbw Lesins Trunk/Arm/Leg Lesins Knee/Elbw Lesins N=108 N=111 N=108 N= 111 N=108 N=112 N=108 N=112 N=108 N=113 N=108 N=113 2.6 2.6 2.6 2.6 2.6 2.6 2.4 2.6 2.6 2.6-1.4-1.3-1.3-1.4-1.4-1.5-1.3-0.7-0.7-0.6-1.2-1.0-0.9-0.7 2.4-0.9 2.4-1.0 2.7 2.2-0.9-0.7 2.6-0.9 2.4-1.3-1.0 2.4-1.0-0.9 Plaque elevatin, scaling, and erythema scred n a 0-4 scale with 0=nne, 1=mild, 2=mderate, 3=severe and 4=very severe. B*=Mean Baseline Severity: C-12*=Mean Change frm Baseline at end f 12 weeks f therapy: C-24*=Mean Change frm Baseline at week 24 (12 weeks after the end f therapy). Glbal imprvement ver baseline at the end f 12 weeks f treatment in these tw studies is shwn in the fllwing table: TAZORAC 0.05% Gel TAZORAC 0.1% Gel Vehicle Gel N=81 N=93 N=79 N=69 N=84 N=91 100% imprvement 2 (2%) 1 (1%) 0 0 1 (1%) 0 75% imprvement 23 (28%) 17 (18%) 30 (38%) 17 (25%) 10 (12%) 9 (10%) 50% imprvement 42 (52%) 39 (42%) 51 (65%) 36 (52%) 28 (33%) 21 (23%) 1-49% imprvement 21 (26%) 32 (34%) 18 (23%) 23 (33%) 27 (32%) 32 (35%) N change r wrse 18 (22%) 22 (24%) 10 (13%) 10 (14%) 29 (35%) 38 (42%) The 0.1% gel was mre effective than the 0.05% gel, but the 0.05% gel was assciated with less lcal irritatin than the 0.1% gel (see ADVERSE REACTIONS sectin). Acne: In tw large vehicle-cntrlled studies, tazartene 0.1% gel applied nce daily was significantly mre effective than vehicle in the treatment f facial acne vulgaris f mild t mderate severity. Percent reductins in lesin cunts after treatment fr 12 weeks in these tw studies are shwn in the fllwing table: Reductin in Lesin Cunts after Twelve Weeks f Treatment in Tw Cntrlled Clinical Trials fr Acne TAZORAC 0.1% Gel Vehicle Gel N=150 N=149 N=148 N=149 Nninflammatry lesins 55% 43% 35% 27% Inflammatry lesins 42% 47% 30% 28% Ttal lesins 52% 45% 33% 27% 2.6-1.3 2.8-1.2 2.3-1.0 2.7-1.2 2.4-0.7 2.3-0.6-0.7 2.6-0.7 2.7-0.5-0.6-0.7 2.2-0.5-0.6 2.7-0.6-0.5
Glbal imprvement ver baseline at the end f 12 weeks f treatment in these tw studies is shwn in the fllwing table: TAZORAC 0.1% Gel Vehicle Gel N=105 N=117 N=117 N=110 100% imprvement 1 (1%) 0 0 0 75% imprvement 40 (38%) 21 (18%) 23 11 (10%) (20%) 50% imprvement 71 (68%) 56 (48%) 47 32 (29%) (40%) 1-49% imprvement 23 (22%) 49 (42%) 48 46 (42%) (41%) N change r wrse 11 (10%) 12 (10%) 22 (19%) 32 (29%) INDICATIONS AND USAGE TAZORAC (tazartene) Gel 0.05% and 0.1% are indicated fr the tpical treatment f patients with stable plaque psriasis f up t 20% bdy surface area invlvement. TAZORAC (tazartene) Gel 0.1% is als indicated fr the tpical treatment f patients with facial acne vulgaris f mild t mderate severity. The efficacy f TAZORAC Gel in the treatment f acne previusly treated with ther retinids r resistant t ral antibitics has nt been established. CONTRAINDICATIONS Retinids may cause fetal harm when administered t a pregnant wman. In rats, tazartene 0.05% gel, administered tpically during gestatin days 6 thrugh 17 at 0.25 mg/kg/day (1.5 mg/m 2 /day) resulted in reduced fetal bdy weights and reduced skeletal ssificatin. Rabbits dsed tpically with 0.25 mg/kg/day (2.75 mg/m 2 ttal bdy surface area/day) tazartene gel during gestatin days 6 thrugh 18 were nted with single incidences f knwn retinid malfrmatins, including spina bifida, hydrcephaly, and heart anmalies. Systemic daily-expsure (AUC de ) t tazartenic acid at tpical dses f 0.25 mg/kg/day tazartene in a gel frmulatin in rats and rabbits represented 0.62 and 6.7 times, respectively, the AUC 0-24h bserved in psriatic patients treated with 2 mg/cm 2 f tazartene gel 0.1% (extraplated fr tpical applicatin ver a 20% bdy surface area), and 0.78 and 8.4 times, respectively, the maximum AUC 0-24h in acne patients treated with 2 mg/cm 2 f tazartene gel 0.1% ver a 15% (targeted) bdy surface area. As with ther retinids, when tazartene was given rally t experimental animals, develpmental delays were seen in rats, and teratgenic effects and pst-implantatin lss were bserved in rats and rabbits at AUC de values that were 0.55 and 13.2 times, respectively, the AUC 0-24h bserved in psriatic patients treated with 2 mg/cm 2 f tazartene gel 0.1% (extraplated fr tpical applicatin ver a 20% bdy surface area), and 0.68 and 16.4 times, respectively, the maximum AUC 0-24h in acne patients treated with 2 mg/cm 2 f tazartene gel 0.1% ver a 15% (targeted) bdy surface area. In a study f the effect f ral tazartene n fertility and early embrynic develpment in rats, decreased number f implantatin sites, decreased litter size, decreased numbers f live fetuses, and decreased fetal bdy weights, all classic develpmental effects f retinids, were bserved when female rats were administered 2 mg/kg/day frm 15 days befre mating thrugh gestatin day 7. A lw incidence f retinid-related
malfrmatins at that dse was reprted t be related t treatment. This dse prduced an AUC de that was 1.7 times the AUC 0-24h bserved in psriatic patients treated with 2 mg/cm 2 tazartene gel 0.1% (extraplated fr tpical applicatin ver a 20% bdy surface area) and 2.1 times the maximum AUC 0-24h in acne patients treated with 2 mg/cm 2 f tazartene gel 0.1% ver a 15% (targeted) bdy surface area. SYSTEMIC EXPOSURE TO TAZAROTENIC ACID IS DEPENDENT UPON THE EXTENT OF THE BODY SURFACE AREA TREATED. IN PATIENTS TREATED TOPICALLY OVER SUFFICIENT BODY SURFACE AREA, EXPOSURE COULD BE IN THE SAME ORDER OF MAGNITUDE AS IN THESE ORALLY TREATED ANIMALS. ALTHOUGH THERE MAY BE LESS SYSTEMIC EXPOSURE IN THE TREATMENT OF ACNE OF THE FACE ALONE DUE TO LESS SURFACE AREA FOR APPLICATION, TAZAROTENE IS A TERATOGENIC SUBSTANCE, AND IT IS NOT KNOWN WHAT LEVEL OF EXPOSURE IS REQUIRED FOR TERATOGENICITY IN HUMANS (SEE CLINICAL PHARMACOLOGY: PHARMACOKINETICS). There were thirteen reprted pregnancies in patients wh participated in clinical trials fr tpical tazartene. Nine f the patients were fund t have been treated with tpical tazartene, and the ther fur had been treated with vehicle. One f the patients wh was treated with tazartene cream elected t terminate the pregnancy fr nn-medical reasns unrelated t treatment. The ther eight pregnant wmen wh were inadvertently expsed t tpical tazartene during clinical trials subsequently delivered apparently healthy babies. As the exact timing and extent f expsure in relatin t the gestatin times are nt certain, the significance f these findings is unknwn. TAZORAC Gel is cntraindicated in wmen wh are r may becme pregnant. If this drug is used during pregnancy, r if the patient becmes pregnant while taking this drug, treatment shuld be discntinued and the patient apprised f the ptential hazard t the fetus. Wmen f child-bearing ptential shuld be warned f the ptential risk and use adequate birth-cntrl measures when TAZORAC Gel is used. The pssibility that a wman f child-bearing ptential is pregnant at the time f institutin f therapy shuld be cnsidered. A negative result fr pregnancy test having a sensitivity dwn t at least 50 miu/ml fr human chrinic gnadtrpin (hcg) shuld be btained within 2 weeks prir t TAZORAC Gel therapy, which shuld begin during a nrmal menstrual perid (see als PRECAUTIONS: Pregnancy: Teratgenic Effects). TAZORAC Gel is cntraindicated in individuals wh have shwn hypersensitivity t any f its cmpnents. WARNINGS See CONTRAINDICATIONS sectin. Wmen f child-bearing ptential shuld be warned f the ptential risk and use adequate birth-cntrl measures when TAZORAC Gel is used. The pssibility that a wman f childbearing ptential is pregnant at the time f institutin f therapy shuld be cnsidered. A negative result fr pregnancy test having a sensitivity dwn t at least 50 miu/ml fr hcg shuld be btained within 2 weeks prir t TAZORAC Gel therapy, which shuld begin during a nrmal menstrual perid. PRECAUTIONS General TAZORAC Gel shuld be applied nly t the affected areas. Fr external use nly. Avid cntact with eyes, eyelids, and muth. If cntact with eyes ccurs, rinse thrughly with water. The safety f use f TAZORAC Gel ver mre than 20% f bdy surface area has nt been established in psriasis r acne. Retinids shuld nt be used n eczematus skin, as they may cause severe irritatin.
Because f heightened burning susceptibility, expsure t sunlight (including sunlamps) shuld be avided unless deemed medically necessary, and in such cases, expsure shuld be minimized during the use f TAZORAC Gel. Patients must be warned t use sunscreens (minimum SPF f 15) and prtective clthing when using TAZORAC Gel. Patients with sunburn shuld be advised nt t use TAZORAC Gel until fully recvered. Patients wh may have cnsiderable sun expsure due t their ccupatin and thse patients with inherent sensitivity t sunlight shuld exercise particular cautin when using TAZORAC Gel and ensure that the precautins utlined in the Infrmatin fr Patients subsectin are bserved. TAZORAC Gel shuld be administered with cautin if the patient is als taking drugs knwn t be phtsensitizers (e.g., thiazides, tetracyclines, flurquinlnes, phenthiazines, sulfnamides) because f the increased pssibility f augmented phtsensitivity. Sme individuals may experience excessive pruritus, burning, skin redness r peeling. If these effects ccur, the medicatin shuld either be discntinued until the integrity f the skin is restred, r the dsing shuld be reduced t an interval the patient can tlerate. Hwever, efficacy at reduced frequency f applicatin has nt been established. Alternatively, patients with psriasis wh are being treated with the 0.1% cncentratin can be switched t the lwer cncentratin. Weather extremes, such as wind r cld, may be mre irritating t patients using TAZORAC Gel. Infrmatin fr Patients See attached Patient Package Insert. Drug Interactins Cncmitant dermatlgic medicatins and csmetics that have a strng drying effect shuld be avided. It is als advisable t "rest" a patient's skin until the effects f such preparatins subside befre use f TAZORAC Gel is begun. In a study f 27 healthy female subjects between the ages f 20 55 years receiving a cmbinatin ral cntraceptive tablet cntaining 1 mg nrethindrne and 35 mcg ethynyl estradil, cncmitant use f tazartene did nt affect the pharmackinetics f nrethindrne and ethynyl estradil ver a cmplete cycle. The impact f tazartene n the pharmackinetics f prgestin nly ral cntraceptives (i.e., minipills) has nt been evaluated. Carcingenesis, Mutagenesis, Impairment f Fertility A lng-term study f tazartene fllwing ral administratin f 0.025, 0.050, and 0.125 mg/kg/day t rats shwed n indicatins f increased carcingenic risks. Based n pharmackinetic data frm a shrter-term study in rats, the highest dse f 0.125 mg/kg/day was anticipated t give systemic expsure (AUC de ) in the rat equivalent t 0.32 times the AUC 0-24h bserved in psriatic patients treated with 2 mg/cm 2 f tazartene gel 0.1% (extraplated fr tpical applicatin ver a 20% bdy surface area), and 0.38 times the maximum AUC 0-24h in acne patients treated with 2 mg/cm 2 f tazartene gel 0.1% ver a 15% (targeted) bdy surface area. In evaluatin f pht c-carcingenicity, median time t nset f tumrs was decreased and the number f tumrs increased in hairless mice fllwing chrnic tpical dsing with intercurrent expsure t ultravilet radiatin at tazartene cncentratins f 0.001%, 0.005%, and 0.01% in a gel frmulatin fr up t 40 weeks. A lng-term tpical applicatin study f up t 0.1% tazartene in a gel frmulatin in mice terminated at 88 weeks shwed that dse levels f 0.05, 0.125, 0.25, and 1 mg/kg/day (reduced t 0.5 mg/kg/day fr males after 41 weeks due t severe dermal irritatin) revealed n apparent carcingenic effects when cmpared t vehicle cntrl animals; untreated cntrl animals were nt cmpletely evaluated. Systemic expsure (AUC 0-12h ) at the
highest dse was 2 times the AUC 0-24h bserved in psriatic patients treated with 2 mg/cm 2 f tazartene gel 0.1% (extraplated fr tpical applicatin ver a 20% bdy surface area), and times the maximum AUC 0-24h in acne patients treated with 2 mg/cm 2 f tazartene gel 0.1% ver a 15% (targeted) bdy surface area. Tazartene was fund t be nn-mutagenic in the Ames assay using Salmnella and E. cli and did nt prduce structural chrmsmal aberratins in a human lymphcyte assay. Tazartene was als nn-mutagenic in the CHO/HGPRT mammalian cell frward gene mutatin assay and was nn-clastgenic in the in viv muse micrnucleus test. N impairment f fertility ccurred in rats when male animals were treated fr 70 days prir t mating and female animals were treated fr 14 days prir t mating and cntinuing thrugh gestatin and lactatin with tpical dses f tazartene gel f up t 0.125 mg/kg/day. Based n data frm anther study, the systemic drug expsure (AUC de ) in the rat wuld be equivalent t 0.31 times the AUC 0-24h bserved in psriatic patients treated with 2 mg/cm 2 f tazartene gel 0.1% (extraplated fr tpical applicatin ver a 20% bdy surface area), and 0.38 times the maximum AUC 0-24h in acne patients treated with 2 mg/cm 2 f tazartene gel 0.1% ver a 15% (targeted) bdy surface area. N impairment f mating perfrmance r fertility was bserved in male rats treated fr 70 days prir t mating with ral dses f up t 1 mg/kg/day tazartene, which prduced an AUC de that was 0.95 times the AUC 0-24h bserved in psriatic patients treated with 2 mg/cm 2 f tazartene gel 0.1% (extraplated fr tpical applicatin ver a 20% bdy surface area), and 1.2 times the maximum AUC 0-24h in acne patients treated with 2 mg/cm 2 f tazartene gel 0.1% ver a 15% (targeted) bdy surface area. N effect n parameters f mating perfrmance r fertility was bserved in female rats treated fr 15 days prir t mating and cntinuing thrugh day 7 f gestatin with ral dses f tazartene up t 2 mg/kg/day. Hwever, there was a significant decrease in the number f estrus stages and an increase in develpmental effects at 2 mg/kg/day (see CONTRAINDICATIONS). This dse prduced an AUC 0-24h which was 1.7 times that bserved in psriatic patients treated with 2 mg/cm 2 f tazartene gel 0.1% (extraplated fr tpical applicatin ver a 20% bdy surface area), and 2.1 times the maximum AUC 0-24h in acne patients treated with 2 mg/cm 2 f tazartene gel 0.1% ver a 15% (targeted) bdy surface area. Reprductive capabilities f F1 animals, including F2 survival and develpment, were nt affected by tpical administratin f tazartene gel t female F0 parental rats frm gestatin day 16 thrugh lactatin day 20 at the maximum tlerated dse f 0.125 mg/kg/day. Based n data frm anther study, the systemic drug expsure (AUC de ) in the rat wuld be equivalent t 0.31 times the AUC 0-24h bserved in psriatic patients treated with 2 mg/cm 2 f tazartene gel 0.1% (extraplated fr tpical applicatin ver a 20% bdy surface area), and 0.38 times the maximum AUC 0-24h in acne patients treated with 2 mg/cm 2 f tazartene gel 0.1% ver a 15% (targeted) bdy surface area. Pregnancy Teratgenic Effects See CONTRAINDICATIONS sectin. Wmen f child-bearing ptential shuld use adequate birth-cntrl measures when TAZORAC Gel is used. The pssibility that a wman f child-bearing ptential is pregnant at the time f institutin f therapy shuld be cnsidered. A negative result fr pregnancy test having a sensitivity dwn t at least 50 miu/ml fr hcg shuld be btained within 2 weeks prir t TAZORAC Gel therapy, which shuld begin during a nrmal menstrual perid. There are n adequate, well-cntrlled studies in pregnant wmen. Althugh there may be less systemic expsure in the treatment f acne f the face alne due t less surface area fr applicatin, tazartene is a teratgenic substance, and it is nt knwn what level f expsure is required fr teratgenicity in humans (see CLINICAL PHARMACOLOGY: Pharmackinetics).
Nursing Mthers After single tpical dses f 14 C-tazartene t the skin f lactating rats, radiactivity was detected in milk, suggesting that there wuld be transfer f drug-related material t the ffspring via milk. It is nt knwn whether this drug is excreted in human milk. Cautin shuld be exercised when tazartene is administered t a nursing wman. Pediatric Use The safety and efficacy f TAZORAC Gel have nt been established in pediatric patients under the age f 12 years. Geriatric Use Of the ttal number f subjects in clinical studies f tazartene gels, 0.05% and 0.1% fr plaque psriasis, 163 were ver the age f 65. Subjects ver 65 years f age experienced mre adverse events and lwer treatment success rates after 12 weeks f use f TAZORAC Gel cmpared with thse 65 years f age and yunger. Currently there is n ther reliable clinical experience n the differences in respnses between the elderly and yunger patients, but greater sensitivity f sme lder individuals can nt be ruled ut. Tazartene gel fr the treatment f acne has nt been clinically evaluated in persns ver the age f 65. ADVERSE REACTIONS In human dermal safety studies, tazartene 0.05% and 0.1% gels did nt induce allergic cntact sensitizatin, phttxicity r phtallergy. Psriasis: The mst frequent adverse events reprted with TAZORAC Gel 0.05% and 0.1% were limited t the skin. Thse ccurring in 10 t 30% f patients, in descending rder, included pruritus, burning/stinging, erythema, wrsening f psriasis, irritatin, and skin pain. Events ccurring in 1 t 10% f patients included rash, desquamatin, irritant cntact dermatitis, skin inflammatin, fissuring, bleeding, and dry skin. Increases in psriasis wrsening and sun-induced erythema were nted in sme patients ver the 4th t 12th mnths as cmpared t the first three mnths f a 1 year study. In general, the incidence f adverse events with TAZORAC Gel 0.05% was 2 t 5% lwer than that seen with TAZORAC Gel 0.1%. Acne: The mst frequent adverse events reprted with TAZORAC Gel 0.1% in the treatment f acne ccurring in 10 t 30% f patients, in descending rder, included desquamatin, burning/stinging, dry skin, erythema and pruritus. Events ccurring in 1 t 10% f patients included irritatin, skin pain, fissuring, lcalized edema and skin disclratin. Pstmarketing Experience The fllwing adverse reactins have been identified during pstapprval use f tazartene. Because these reactins are reprted vluntarily frm a ppulatin f uncertain size, it is nt always pssible t reliably estimate their frequency r establish a causal relatinship t drug expsure. Skin and subcutaneus tissue disrders: blister, dermatitis, urticaria, skin exfliatin, skin disclratin (including skin hyperpigmentatin r skin hyppigmentatin), swelling at r near applicatin sites, and pain. OVERDOSAGE Excessive tpical use f TAZORAC Gel may lead t marked redness, peeling, r discmfrt (see PRECAUTIONS: General). TAZORAC Gels 0.05% and 0.1% are nt fr ral use. Oral ingestin f the drug may lead t the same adverse effects as thse assciated with excessive ral intake f Vitamin A (hypervitaminsis A) r ther
retinids. If ral ingestin ccurs, the patient shuld be mnitred, and apprpriate supprtive measures shuld be administered as necessary. DOSAGE AND ADMINISTRATION General: Applicatin may cause excessive irritatin in the skin f certain sensitive individuals. In cases where it has been necessary t temprarily discntinue therapy, r the dsing has been reduced t a lwer cncentratin (in patients with psriasis) r t an interval the patient can tlerate, therapy can be resumed, r the drug cncentratin r frequency f applicatin can be increased as the patient becmes able t tlerate the treatment. Frequency f applicatin shuld be clsely mnitred by careful bservatin f the clinical therapeutic respnse and skin tlerance [see Precautins]. Tazrac Gel, 0.05% and 0.1%, are fr tpical use nly. Tazrac Gel, 0.05% and 0.1%, are nt fr phthalmic, ral, r intravaginal use. Avid accidental transfer f Tazrac Gel, 0.05% and 0.1%, int eyes, muth, r ther mucus membranes. If cntact with mucus membranes ccurs, rinse thrughly with water [see Precautins]. Efficacy has nt been established fr less than nce daily dsing frequencies. Fr Psriasis: It is recmmended that treatment start with TAZORAC 0.05% Gel, with strength increased t 0.1% if tlerated and medically indicated. Apply TAZORAC Gel nce a day, in the evening, t psriatic lesins, using enugh (2 mg/cm 2 ) t cver nly the lesin with a thin film t n mre than 20% f bdy surface area. If a bath r shwer is taken prir t applicatin, the skin shuld be dry befre applying the gel. If emllients are used, they shuld be applied at least an hur befre applicatin f TAZORAC Gel. Because unaffected skin may be mre susceptible t irritatin, applicatin f tazartene t these areas shuld be carefully avided. TAZORAC Gel was investigated fr up t 12 mnths during clinical trials fr psriasis. Fr Acne: Cleanse the face gently. After the skin is dry, apply a thin film f TAZORAC Gel 0.1% (2 mg/cm 2 ) nce a day, in the evening, t the skin where acne lesins appear. Use enugh t cver the entire affected area. TAZORAC Gel was investigated fr up t 12 weeks during clinical trials fr acne. HOW SUPPLIED TAZORAC (tazartene) Gel is available in cncentratins f 0.05% and 0.1%. It is available in a cllapsible aluminum tube with a tamper-evident aluminum membrane ver the pening and a white prpylene screw cap, in 30 g and 100 g sizes. TAZORAC Gel 0.05% TAZORAC Gel 0.1% 30 g NDC 0023-8335-03 NDC 0023-0042-03 100 g NDC 0023-8335-10 NDC 0023-0042-10 Strage: Stre at 25 C (77 F): excursins permitted t 15-30 C (59-86 F). Revised: 07/2017 2017 Allergan. All rights reserved. All trademarks are the prperty f their respective wners. Irvine, CA 92612 Made in the U.S.A.
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PATIENT INFORMATION TAZORAC (TAZ-r-ac) (tazartene) Gel, 0.05% and 0.1% Imprtant infrmatin: TAZORAC Gel is fr use n skin nly. D nt use TAZORAC Gel in yur eyes, muth, r vagina. What is the mst imprtant infrmatin I shuld knw abut TAZORAC Gel? TAZORAC Gel may cause birth defects if used during pregnancy. Females must nt be pregnant when they start using TAZORAC Gel r becme pregnant during treatment with TAZORAC Gel. Fr females wh are able t get pregnant: Yur dctr will rder a pregnancy test fr yu within 2 weeks befre yu begin treatment with TAZORAC Gel t be sure that yu are nt pregnant. Yur dctr will decide when t d the test. Begin treatment with TAZORAC Gel during a nrmal menstrual perid. Use an effective frm f birth cntrl during treatment with TAZORAC Gel. Talk with yur dctr abut birth cntrl ptins that may be used t prevent pregnancy during treatment with TAZORAC Gel. Stp using TAZORAC Gel and tell yur dctr right away if yu becme pregnant while using TAZORAC Gel. What is TAZORAC Gel? TAZORAC Gel 0.05% and 0.1% is a prescriptin medicine used n the skin (tpical) t treat peple with stable plaque psriasis n up t 20% f yur bdy surface. TAZORAC Gel 0.1% is als used n the skin t treat peple with mild t mderate facial acne vulgaris. It is nt knwn if TAZORAC Gel is: safe and effective fr use in children under 12 years f age. effective fr the treatment f acne in peple wh have been treated with retinid medicines r have acne that des nt respnd t treatment with ral antibitics. effective when used less than 1 time a day. safe if used ver mre than 20% f yur bdy fr the treatment f psriasis r acne. Wh shuld nt use TAZORAC Gel? D nt use TAZORAC Gel if yu: are pregnant r plan t becme pregnant. See What is the mst imprtant infrmatin I shuld knw abut TAZORAC Gel? at the beginning f this leaflet. are allergic t tazartene r any f the ingredients in TAZORAC Gel. See the end f this leaflet fr a cmplete list f ingredients in TAZORAC Gel. What shuld I tell my dctr befre using TAZORAC Gel? Befre yu use TAZORAC Gel, tell yur dctr abut all f yur medical cnditins, including if yu: have eczema r any ther skin prblems are breastfeeding r plan t breastfeed. It is nt knwn if TAZORAC Gel passes int yur breast milk. Talk t yur dctr abut using TAZORAC Gel while breastfeeding. Tell yur dctr abut all the medicines yu take, including prescriptin and ver-the-cunter medicines, vitamins, and herbal supplements. Certain medicines, vitamins, r supplements may make yur skin mre sensitive t sunlight. Als, tell yur dctr abut any csmetics yu use, including misturizers, creams, ltins, r prducts that can dry ut yur skin. Hw shuld I use TAZORAC Gel? Use TAZORAC Gel exactly as yur dctr tells yu t use it. Apply TAZORAC Gel 1 time each day, in the evening. D nt get TAZORAC Gel in yur eyes, n yur eyelids, r in yur muth. If TAZORAC Gel gets in r near yur eyes, rinse them well with water. Call yur dctr r get medical help if yu have eye irritatin that des nt g away.
Wash yur hands after applying TAZORAC Gel. Fllw these instructins fr applying TAZORAC Gel: If yu have psriasis: If yu shwer r bathe befre applying TAZORAC Gel, yur skin shuld be dry befre applying the gel. Yu may use a cream r ltin t sften r misten yur skin at least 1 hur befre yu apply TAZORAC Gel. Apply a thin layer f TAZORAC Gel t cver nly the psriasis lesins. If yu have acne: Gently wash and dry yur face befre applying TAZORAC Gel. Apply a thin layer f TAZORAC Gel t cver nly the acne lesins. If yu swallw TAZORAC Gel, call yur dctr r g t the nearest hspital emergency rm right away. What shuld I avid while using TAZORAC Gel? Avid sunlight, including sunlamps, during treatment with TAZORAC Gel. TAZORAC Gel can make yu mre sensitive t the sun, and the light frm sunlamps and tanning beds. Yu culd get a severe sunburn. Use sunscreen and wear a hat and clthes that cver yur skin if yu have t be in sunlight. Talk t yur dctr if yu get a sunburn during treatment with TAZORAC Gel. If yu get a sunburn, d nt use TAZORAC Gel until yur sunburn is healed. Avid using csmetics r tpical medicines that may make yur skin mre sensitive t sunlight r make yur skin dry. Avid using TAZORAC Gel n unaffected skin r skin with eczema because it may cause severe irritatin. What are the pssible side effects f TAZORAC Gel? TAZORAC Gel may cause serius side effects, including: Skin irritatin. TAZORAC Gel may cause increased skin irritatin. Tell yur dctr if yu develp itching, burning, redness, r peeling f yur skin during treatment with TAZORAC Gel. If yu develp skin irritatin, yur dctr may tell yu t temprarily stp using TAZORAC Gel until yur skin heals, tell yu t use TAZORAC Gel less ften, r if yu are being treated fr psriasis with the 0.1% strength, may change yur TAZORAC Gel dse. Als, wind r cld weather may be mre irritating t yur skin while yu are using TAZORAC Gel. Sensitivity t sunlight and risk f sunburn. See What shuld I avid while using TAZORAC Gel? The mst cmmn side effects f TAZORAC Gel in peple with plaque psriasis include itching, burning, redness wrsening f psriasis, irritatin and skin pain. The mst cmmn side effects f TAZORAC Gel in peple with acne vulgaris include peeling, burning, dry skin, redness and itching. These are nt all the pssible side effects f TAZORAC Gel. Call yur dctr fr medical advice abut side effects. Yu may reprt side effects t FDA at 1-800-FDA-1088. Hw shuld I stre TAZORAC Gel? Stre TAZORAC Gel at 77 F (25 C). Keep TAZORAC Gel and all medicines ut f the reach f children. General infrmatin abut the safe and effective use f TAZORAC Gel. Medicines are smetimes prescribed fr purpses ther than thse listed in a Patient Infrmatin leaflet. D nt use TAZORAC Gel fr a cnditin fr which it was nt prescribed. D nt give TAZORAC Gel t ther peple, even if they have the same symptms yu have. It may harm them. Yu can ask yur dctr r pharmacist fr infrmatin abut TAZORAC Gel that is written fr health prfessinals. What are the ingredients in TAZORAC Gel? Active ingredient: tazartene Inactive ingredients: ascrbic acid, benzyl alchl, butylated hydrxyanisle, butylated hydrxytluene, carbmer hmplymer type B, edetate disdium, hexylene glycl, plxamer 407, plyethylene glycl 400, plysrbate 40, purified water, and trmethamine Manufactured by: Allergan Sales, LLC., Wac, Texas 2017 Allergan. All rights reserved. All trademarks are the prperty f their respective wners. Irvine, CA 92612 Made in the U.S.A.
Fr mre infrmatin, call 1-800-678-1605 r g t www.tazrac.cm This Patient Infrmatin has been apprved by the U.S. Fd and Drug Administratin Revised: July/2017 71722US15