Arazlo

DESCRIPTION

ARAZLO (tazarotene) is a white to off-white lotion containing 0.045% tazarotene by weight for topical administration.

Tazarotene is a member of the acetylenic class of retinoids. The chemical name for tazarotene is 6-[(3,4-Dihydro-4,4- dimethyl-2H-1-benzothiopyran-6-yl)ethynyl]-3-pyridinecarboxylic acid ethyl ester. The structural formula for tazarotene is represented below:

Tazarotene

Each gram of ARAZLO contains 0.45 mg (0.045%) tazarotene in a white to off-white lotion base consisting of carbomer copolymer type B, carbomer homopolymer type A, diethyl sebacate, edetate disodium dihydrate, light mineral oil, methylparaben, propylparaben, purified water, sodium hydroxide, sorbitan monooleate and sorbitol solution, 70%.

INDICATIONS

ARAZLO^®(tazarotene) lotion, 0.045% is indicated for the topical treatment of acne vulgaris in patients 9 years of age and older.

DOSAGE AND ADMINISTRATION

Apply a thin layer of ARAZLO to the affected areas once daily. Avoid the eyes, mouth, paranasal creases, and mucous membranes. If ARAZLO gets in or near eyes, rinse thoroughly with water.

ARAZLO is for topical use only. Not for oral, ophthalmic, or intravaginal use.

Wash hands thoroughly after applying ARAZLO.

Avoid concomitant use with oxidizing agents, such as benzoyl peroxide. If the concomitant use of ARAZLO with oxidizing agents is required, apply each at different times of the day (e.g. one in the morning and the other in the evening) [seeDRUG INTERACTIONS].

Use effective sunscreens and wear protective clothing while using ARAZLO [seeWARNINGS AND PRECAUTIONS].

HOW SUPPLIED

Dosage Forms And Strengths

Lotion, 0.045%

Each gram of ARAZLO contains 0.45 mg (0.045%) tazarotene in a white to off-white topical lotion.

Storage And Handling

ARAZLO (tazarotene) Lotion, 0.045% is a white to off-white lotion supplied in a white aluminum tube as follows:

• 45 g (NDC0187-2098-45)

Storage And Handling Conditions

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from freezing.

Manufactured by: Bausch Health Companies Inc., Laval, Quebec H7L 4A8, Canada. Revised: May 2021

WARNINGS

Included as part of the"PRECAUTIONS"Section

PRECAUTIONS

Embryofetal Toxicity

Based on data from animal reproduction studies, retinoid pharmacology and the potential for systemic absorption, ARAZLO may cause fetal harm when administered to a pregnant patient and is contraindicated during pregnancy. Safety in pregnant patients has not been established. The potential risk to the fetus outweighs the potential benefit to the mother; therefore, discontinue ARAZLO as soon as pregnancy is recognized.

Tazarotene elicits malformations and developmental effects associated with retinoids after topical and oral administration to pregnant rats and rabbits during organogenesis. However, limited case reports of pregnancy in females enrolled in clinical trials for ARAZLO have not reported a clear association with tazarotene and major birth defects or miscarriage risk [seeCONTRAINDICATIONSandUse In Specific Populations].

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 orally treated animals. Tazarotene is a teratogenic substance in animals, and it is not known what level of exposure is required for teratogenicity in humans.

Advise pregnant patients of the potential risk to a fetus. Obtain a pregnancy test within 2 weeks prior to ARAZLO therapy. Initiate ARAZLO therapy during a menstrual period. Advise patients of childbearing potential to use effective contraception during treatment with ARAZLO [seeDOSAGE AND ADMINISTRATIONandUse In Specific Populations].

Skin Irritation

Patients using ARAZLO may experience application site pain, dryness, exfoliation, erythema, and pruritus. Depending upon severity of these adverse reactions, instruct patients to use a moisturizer, reduce the frequency of the application of ARAZLO, or discontinue use. Therapy can be resumed, or the frequency of application can be increased, as the patient becomes able to tolerate treatment.

Avoid use of concomitant medications and cosmetics that have a strong drying effect. It is recommended to postpone treatment with ARAZLO until the drying effects of these products subside.

Avoid application of ARAZLO to eczematous or sunburned skin.

Photosensitivity And Risk For Sunburn

Because of heightened burning susceptibility, minimize unprotected exposure to ultraviolet light including sunlight and sunlamps during the use of ARAZLO. Warn patients who normally experience high levels of sun exposure and those with inherent sensitivity to sun to exercise caution. Use sunscreen products and protective clothing over treated areas when sun exposure cannot be avoided. Patients with sunburn should be advised not to use ARAZLO until fully recovered.

ARAZLO should be administered with caution if the patient is taking drugs known to be photosensitizers (e.g., thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides) because of the increased possibility of augmented photosensitivity. Weather extremes, such as wind or cold, may be more irritating to patients using ARAZLO.

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (PATIENT INFORMATIONS).

Embryofetal Toxicity

Inform patients of childbearing potential of the potential risk to a fetus. To avoid pregnancy, advise these patients to use effective contraception during treatment with ARAZLO.

Advise patients to discontinue the medication if pregnant and to inform their healthcare provider of a known or suspected pregnancy [seeCONTRAINDICATIONS,WARNINGS AND PRECAUTIONSandUse In Specific Populations].

Lactation

Advise patients to use ARAZLO for the shortest duration possible while breastfeeding. Advise breastfeeding patients not to apply ARAZLO directly to the nipple and areola to avoid direct infant exposure [seeUse In Specific Populations].

Skin Irritation

Advise patients to avoid applying ARAZLO to eczematous or sunburned skin. If undue irritation occurs, reduce frequency of application, temporarily interrupt treatment, or discontinue use. Treatment may be resumed once irritation subsides [seeWARNINGS AND PRECAUTIONS].

Photosensitivity And Risk Of Sunburn

Advise patients to minimize exposure to sunlight and sunlamps; recommend the use of sunscreen products and protective apparel (e.g., wide-brimmed hat) when sun exposure cannot be avoided. Advise patients to avoid using ARAZLO if also taking other medicines that may increase sensitivity to sunlight [seeWARNINGS AND PRECAUTIONS].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

A long-term study of tazarotene following oral administration of 0.025, 0.050, and 0.125 mg/kg/day to rats showed no indications of increased carcinogenic risks. Based on pharmacokinetic data from a shorter-term study in rats, the highest dose of 0.125 mg/kg/ day was anticipated to give systemic exposure in the rat equivalent to the MRHD (based on AUC comparison).

A long-term study with topical application of up to 0.1% of tazarotene in a gel formulation in mice terminated at 88 weeks showed that dose levels of 0.05, 0.125, 0.25, and 1 mg/kg/day (reduced to 0.5 mg/kg/day for males after 41 weeks due to severe dermal irritation) revealed no apparent carcinogenic effects when compared to vehicle control animals. Tazarotenic acid systemic exposures at the highest dose was 7 times the MRHD (based on AUC comparison).

Tazarotene was non-mutagenic in the Ames assay and did not produce structural chromosomal aberrations in human lymphocytes. Tazarotene was non-mutagenic in CHO/HGPRT mammalian cell forward gene mutation assay and was non-clastogenic in anin vivomouse micronucleus test.

No impairment of fertility occurred in rats when male animals were treated for 70 days prior to mating and female animals were treated for 14 days prior to mating and continuing through gestation and lactation with topical doses of a tazarotene gel formulation up to 0.125 mg/kg/day. Based on data from another study, the systemic drug exposure in the rat at the highest dose was equivalent to the MRHD (based on AUC comparison).

No impairment of mating performance or fertility was observed in male rats treated for 70 days prior to mating with oral doses of tazarotene up to 1 mg/kg/day which produced a systemic exposure 4 times the MRHD (based on AUC comparison).

No impairment of mating performance or fertility was observed in female rats treated for 15 days prior to mating and continuing through gestation day 7 with oral doses of tazarotene up to 2 mg/kg/day. However, there was a significant decrease in the number of estrous stages and an increase in developmental effects at that dose which produced a systemic exposure 6 times the MRHD (based on AUC comparison).

Use In Specific Populations

Pregnancy

Risk Summary

ARAZLO is contraindicated in pregnancy.

There are no available data on ARAZLO use in pregnant patients to inform a drugassociated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

Based on data from animal reproduction studies,retinoidpharmacology, and the potential for systemic absorption, ARAZLO may cause fetal harm when administered to a pregnant patient and is contraindicated during pregnancy. The potential risk to the fetus outweighs the potential benefit to the mother; therefore, ARAZLO should be discontinued as soon as pregnancy is recognized.

In animal reproduction studies with pregnant rats, reduced fetal body weights and reduced skeletalossificationwere observed after topical administration of a tazarotene gel formulation during the period of organogenesis at a dose equivalent to the maximum recommended human dose (MRHD) (based on AUC comparison). In animal reproduction studies with pregnant rabbits, single incidences of known retinoid malformations, including spina bifida,hydrocephaly, and heart anomalies were observed after topical administration of a tazarotene gel formulation at 15 times the MRHD (based on AUC comparison) (seeData).

In animal reproduction studies with pregnant rats and rabbits, malformations, fetal toxicity, developmental delays, and/or behavioral delays were observed after oral administration of tazarotene during the period of organogenesis at doses 1 and 30 times, respectively, the MRHD (based on AUC comparison). In pregnant rats, decreased litter size, decreased numbers of live fetuses, decreased fetal body weights, and increased malformations were observed after oral administration of tazarotene prior to mating through early gestation at doses 6 times the MRHD (based on AUC comparison) (seeData).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of major birth defects, loss, and other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data

Animal Data

在老鼠embryofetal发展研究,小胡子arotene gel formulation, 0.5% (0.25 mg/ kg/day tazarotene) was topically administered to pregnant rats during gestation days 6 through 17. Reduced fetal body weights and reduced skeletal ossification occurred at this dose (equivalent to the MRHD based on AUC comparison). In an embryofetal development study in rabbits, a tazarotene gel formulation, 0.5% (0.25 mg/kg/day tazarotene) was topically administered to pregnant rabbits during gestation days 6 through 18. Single incidences of known retinoid malformations, including spina bifida, hydrocephaly, and heart anomalies were noted at this dose (15 times the MRHD based on AUC comparison).

When tazarotene was given orally to animals, developmental delays were seen in rats; malformations and post-implantation损失被观察到在老鼠和兔子在剂量公关oducing 1 and 30 times, respectively, the MRHD (based on AUC comparison). In female rats orally administered 2 mg/kg/day of tazarotene from 15 days before mating through gestation day 7, classic developmental effects of retinoids including decreased number of implantation sites, decreased litter size, decreased numbers of live fetuses, and decreased fetal body weights were observed at this dose (6 times the MRHD based on AUC comparison). A low incidence of retinoid-related malformations was observed at this dose.

In a pre- and postnatal development toxicity study, topical administration of a tazarotene gel formulation (0.125 mg/kg/day) to pregnant female rats from gestation day 16 through lactation day 20 reduced pup survival, but did not affect the reproductive capacity of the offspring. Based on data from another study, the systemic drug exposure in the rat at this dose would be equivalent to the MRHD (based on AUC comparison).

Lactation

Risk Summary

There are no data on the presence of tazarotene or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. After single topical doses of a¹⁴C-tazarotene gel formulation to the skin of lactating rats, radioactivity was detected in rat milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ARAZLO and any potential adverse effects on the breastfed child from ARAZLO.

Clinical Considerations

To minimize potential exposure to the breastfed infant via breast milk, use ARAZLO for the shortest duration possible while breastfeeding. Advise breastfeeding patients not to apply ARAZLO directly to thenippleandareolato prevent direct infant exposure.

Females And Males Of Reproductive Potential

Pregnancy Testing

Pregnancy testing is recommended for patients of childbearing potential within 2 weeks prior to initiating ARAZLO therapy which should begin during a menstrual period.

Contraception

Advise patients of childbearing potential to use effective contraception during treatment with ARAZLO.

Pediatric Use

Safety and effectiveness of ARAZLO for the topical treatment ofacne vulgarishave been established in pediatric patients age 9 years and older based on evidence from two multicenter, randomized, double-blind, parallel-group, vehicle-controlled, 12-week clinical trials and an open-label pharmacokinetic study. A total of 300 pediatric subjects aged 9 to less than 17 years received ARAZLO in the clinical studies [seeCLINICAL PHARMACOLOGYandClinical Studies].

The safety and effectiveness of ARAZLO in pediatric patients below the age of 9 years have not been established.

Geriatric Use

的临床试验ARAZLO没有包括sufficient numbers of subjects age 65 years and older to determine whether they respond differently from younger subjects.

OVERDOSE

Oral ingestion of the drug may lead to the same adverse effects as those associated with excessive oral intake ofVitamin A(hypervitaminosis A) or other retinoids. If oral ingestion occurs, monitor the patient closely and administer appropriate supportive measures, as necessary.

CONTRAINDICATIONS

ARAZLO is contraindicated in pregnancy. ARAZLO may cause fetal harm when administered to a pregnant patient [seeWARNINGS AND PRECAUTIONS,Use In Specific Populations].

PATIENT INFORMATION

ARAZLO^®
(ah-RAZ-low)
(tazarotene) lotion, for topical use

Important information:ARAZLO is for use on skin only. Do not use ARAZLO in your eyes, mouth, the corners of your nose, orvagina.

What is the most important information I should know about ARAZLO?

ARAZLO may cause birth defects if used during pregnancy.

You must not be pregnant when you start using ARAZLO or become pregnant during treatment with ARAZLO.

• For people who are able to get pregnant:
  • Your healthcare provider should order a pregnancy test for you within 2 weeks before you begin treatment with ARAZLO to be sure that you are not pregnant. Your healthcare provider will decide when to do the test.
  • Begin treatment with ARAZLO during a normal menstrual period.
  • Use an effective form of birth control (contraception) during treatment with ARAZLO. Talk with your healthcare provider about birth control options that may be used to prevent pregnancy during treatment with ARAZLO.
• Stop using ARAZLO and tell your healthcare provider right away if you become pregnant during treatment with ARAZLO.

What is ARAZLO?

ARAZLO is a prescription medicine used on the skin (topical) to treat people 9 years of age and older with acne vulgaris.

It is not known if ARAZLO is safe and effective in children under 9 years of age.

Do not use ARAZLO if youare pregnant or plan to become pregnant. See, “What is the most important information I should know about ARAZLO?” at the beginning of this leaflet.

Before using ARAZLO, tell your healthcare provider about all your medical conditions, including if you:

• haveeczemaor any other skin problems
• are breastfeeding or plan to breastfeed. It is not known if ARAZLO passes into your breast milk. If you use ARAZLO while breastfeeding, use ARAZLO for the shortest time needed. Do not apply ARAZLO directly to the nipple and the areola to avoid your child being exposed to the medicine.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Certain medicines, vitamins, or supplements may make your skin more sensitive to sunlight. Ask your healthcare provider for a list of medicines if you are not sure.

Especially tell your healthcare providerabout any medicines (such as benzoyl peroxide) used on your skin or cosmetics you use, including moisturizers, creams, lotions, or products that can dry out your skin.

Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine.

How should I use ARAZLO?

• Use ARAZLO exactly as your healthcare provider tells you to use it.
• Apply a thin layer of ARAZLO to cover the affected areas 1 time each day.
• If you use other medicines on your skin such as benzoyl peroxide during treatment with ARAZLO, you should apply one in the morning and one in the evening to separate the application time.
• 在你的眼睛,不要ARAZLO的角落吗r nose, or in your mouth. If ARAZLO gets in your eyes, rinse them well with water. Call your healthcare provider or get medical help if you have eye irritation that does not go away.
• Wash your hands after applying ARAZLO.

What should I avoid during treatment with ARAZLO?

• Avoid sunlight, including sunlamps during treatment with ARAZLO. ARAZLO can make you more sensitive to the sun, and the light from sunlamps and tanning beds. You could get severe sunburn. Use sunscreen and wear a wide-brimmed hat and clothes that cover your skin if you have to be in sunlight.
• Avoid using cosmetics or topical medicines that may make your skin more sensitive to sunlight or make your skin dry.
• Avoid using ARAZLO on skin with eczema or sunburned skin because it may cause severe irritation.

What are the possible side effects of ARAZLO?

ARAZLO may cause serious side effects, including:

• See, “What is the most important information I should know about ARAZLO?”
• Skin irritation.ARAZLO may cause application site skin pain, dryness, flaking or peeling, redness, and itching. Tell your healthcare provider if you develop any skin irritation during treatment with ARAZLO. If you develop any of these symptoms, your healthcare provider may tell you to use a moisturizer, decrease the number of times you apply ARAZLO, or completely stop treatment with ARAZLO. Also, wind or cold weather may be more irritating to your skin during treatment with ARAZLO.
• Sensitivity to sunlight and risk of sunburn. See, “What should I avoid during treatment with ARAZLO?”

The most common side effects of ARAZLO includeskin pain, dryness, peeling, redness, and itching.

These are not all the possible side effects of ARAZLO.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store ARAZLO?

• Store ARAZLO at room temperature between 68°F to 77°F (20°C to 25°C).
• Do not freeze.

Keep ARAZLO and all medicines out of the reach of children.

General information about the safe and effective use of ARAZLO.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use ARAZLO for a condition for which it was not prescribed. Do not give ARAZLO to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about ARAZLO that is written for health professionals.

What are the ingredients in ARAZLO?

活性成分:tazarotene

Inactive ingredients: carbomer copolymer type B, carbomer homopolymer type A, diethyl sebacate, edetate disodium dihydrate, light mineral oil, methylparaben, propylparaben, purified water,sodiumhydroxide, sorbitan monooleate and sorbitol solution, 70%

这个病人已经批准的信息U.S. Food and Drug Administration.