Arazlo Drug Information

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

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). Use effective sunscreens and wear protective clothing while using ARAZLO.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In 2 multicenter, randomized, double-blind, vehicle-controlled clinical trials, subjects age 9 years and older applied ARAZLO or vehicle once daily for 12 weeks. The majority of subjects were White (74%) and female (66%).

Adverse reactions reported by ≥1% of subjects treated with ARAZLO and more frequently than subjects treated with vehicle are summarized in Table 1. Most adverse reactions were mild to moderate in severity. Severe adverse reactions represented 1.3% of the subjects treated.

Overall, 2.4% (19/779) of subjects discontinued ARAZLO because of local skin reactions. Table 1:Adverse Reactions Reported by ≥1% of the ARAZLO Group and More Frequently than the Vehicle Group 10 0 Skin irritation was evaluated by active assessment of erythema, scaling, itching, burning and stinging, with grades for none, mild, moderate, or severe. The maximum severity generally peaked at Week 2 of therapy and decreased thereafter.

The percentage of subjects with these signs and symptoms at any post-baseline visit are summarized in Table 2. Table 2: Incidence of Local Cutaneous Irritation at any Post-Baseline Visit

Pregnancy Risk Summary ARAZLO is contraindicated in pregnancy. There are no available data on ARAZLO use in pregnant patients to inform a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. 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.

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 skeletal ossification were 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) (see Data).

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) (see Data). 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. Reduced fetal body weights and reduced skeletal ossification occurred at this dose (equivalent to the MRHD based on AUC comparison).

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 loss were observed in rats and rabbits at doses producing 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).

Pediatric Use Safety and effectiveness of ARAZLO for the topical treatment of acne vulgaris have 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. The safety and effectiveness of ARAZLO in pediatric patients below the age of 9 years have not been established.

ARAZLO is contraindicated in pregnancy. ARAZLO may cause fetal harm when administered to a pregnant patient.