Spinosad

1 INDICATIONS AND USAGE Spinosad Topical Suspension is a pediculicide indicated for the topical treatment of head lice infestations in adult and pediatric patients 6 months of age and older. ( 1.1 ) Spinosad Topical Suspension is a scabicide indicated for the topical treatment of scabies infestations in adult and pediatric patients 4 years of age and older. ( 1.2 ) 1.1 Head Lice Infestations Spinosad Topical Suspension is indicated for the topical treatment of head lice infestations in adult and pediatric patients 6 months of age and older. Adjunctive Measures for Head Lice Infestations Spinosad Topical Suspension should be used in the context of an overall lice management program: Wash in hot water or dry-clean all recently worn clothing, hats, used bedding and towels. Wash personal care items such as combs, brushes and hair clips in hot water. A fine-tooth comb or special nit comb may be used to remove dead lice and nits. 1.2 Scabies Infestations Spinosad Topical Suspension is indicated for the topical treatment of scabies infestations in adult and pediatric patients 4 years of age and older. Adjunctive Measures for Scabies Infestations Wash in hot water or dry-clean any bedding, clothing and towels used by anyone having scabies.

2 DOSAGE AND ADMINISTRATION For topical use only. Not for oral, ophthalmic, or intravaginal use. ( 2 ) Treatment of head lice infestations ( 2.2 ): Shake bottle well Apply a sufficient amount to cover dry scalp, then apply to dry hair Rinse off with warm water after 10 minutes Repeat treatment only if live lice are seen 7 days after first treatment Treatment of scabies infestations ( 2.3 ): Shake bottle well Apply product to skin by rubbing it in to completely cover the body from the neck down to the soles of the feet Patients with balding scalp should also apply product to the scalp, hairline, temples, and forehead Allow to absorb in the skin and dry for 10 minutes before getting dressed Leave on the skin for at least 6 hours before showering or bathing 2.1 Important Administration Instructions For topical use only. Spinosad Topical Suspension is not for oral, ophthalmic, or intravaginal use. Avoid contact with eyes. If Spinosad Topical Suspension gets in or near the eyes, rinse thoroughly with water. 2.2 Treatment of Head Lice Infestations Shake bottle well. Apply a sufficient amount of Spinosad Topical Suspension to cover dry scalp, then apply to dry hair. Depending on hair length, apply up to 120 mL (one bottle) to adequately cover scalp and hair. Leave on for 10 minutes, then thoroughly rinse off with warm water. Wash hands after use. If live lice are seen 7 days after the first treatment, a second treatment should be applied. Apply Spinosad Topical Suspension on pediatric patient only under direct supervision of an adult [see Warnings and Precautions (5.1) ]. 2.3 Treatment of Scabies Infestations Shake bottle well. Apply a sufficient amount of Spinosad Topical Suspension to skin to completely cover the body from the neck to the toes (including the soles of the feet). For patients with balding scalp, also apply product to the scalp, hairline, temples, and forehead. Allow to absorb into the skin and dry for 10 minutes before getting dressed. Leave on the skin for at least 6 hours before showering or bathing. Apply Spinosad Topical Suspension on pediatric patient only under direct supervision of an adult .

5 WARNINGS AND PRECAUTIONS Benzyl Alcohol Toxicity: Not recommended in infants below the age of 6 months; potential for increased systemic absorption. ( 5.1 ) 5.1 Benzyl Alcohol Toxicity Spinosad Topical Suspension contains benzyl alcohol and is not approved for use in neonates and infants below the age of 6 months. Systemic exposure to benzyl alcohol has been associated with serious adverse reactions and death in neonates and low birth-weight infants when administered intravenously [See Use in Specific Populations (8.4) ] .

4 CONTRAINDICATIONS None. None. ( 4 )

8.1 Pregnancy Risk Summary Spinosad, the active ingredient in Spinosad Topical Suspension, is not absorbed systemically following topical application, and maternal use is not expected to result in fetal exposure to the drug. Spinosad Topical Suspension contains benzyl alcohol. Topical benzyl alcohol is unlikely to be absorbed through the skin in clinically relevant amounts; therefore, maternal use is not expected to result in fetal exposure to the drug [ see Clinical Pharmacology (12.3) ]. In animal reproduction studies, no adverse embryofetal effects were seen at oral doses of spinosad up to 200 mg/kg/day in pregnant rats or 50 mg/kg/day in pregnant rabbits administered during the period of organogenesis ( see Data ). The available data do not allow the calculation of relevant comparisons between the systemic exposure of spinosad in animal studies to the systemic exposure that would be expected in humans after topical use of Spinosad Topical Suspension. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk for birth defect, loss, or 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 to 4% and 15 to 20%, respectively. Data Animal Data Systemic embryofetal development studies were conducted in rats and rabbits. Oral doses of 10, 50 and 200 mg/kg/day spinosad were administered during the period of organogenesis (gestational days 6 – 15) to pregnant female rats. No adverse embryofetal effects were noted at any dose. Maternal toxicity occurred at 200 mg/kg/day. Oral doses of 2.5, 10, and 50 mg/kg/day spinosad were administered during the period of organogenesis (gestational days 7 – 19) to pregnant female rabbits. No adverse embryofetal effects were noted at any dose. Maternal toxicity occurred at 50 mg/kg/day. A two-generation dietary reproduction study was conducted in rats. Oral doses of 3, 10, and 100 mg/kg/day spinosad were administered to male and female rats from 10-12 weeks prior to mating and throughout mating, parturition, and lactation. No reproductive/developmental toxicity was noted at doses up to 10 mg/kg/day. In the presence of maternal toxicity, increased dystocia in parturition, decreased gestation survival, decreased litter size, decreased pup body weight, and decreased neonatal survival occurred at a dose of 100 mg/kg/day.

6 ADVERSE REACTIONS Most common adverse events for lice treatment (>1%) were application site erythema and ocular erythema. ( 6.1 ) Most common adverse reactions for scabies treatment (>1%) were application site irritation (pain and burning) and dry skin. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Cipher Pharmaceuticals US LLC at 1-855-628-7622 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice. Head Lice Infestations Spinosad Topical Suspension was studied in two randomized, active-controlled trials (N=552) in subjects with head lice; Table 1 presents selected adverse events, regardless of relationship to Spinosad Topical Suspension, that occurred in at least 1% of subjects. Table 1: Selected Adverse Events Occurring in at least 1% of Subjects with Head Lice Infestation Signs Spinosad (N=552) Permethrin 1% (N=457) Application site erythema 17 (3%) 31(7%) Ocular erythema 12 (2%) 15 (3%) Application site irritation 5 (1%) 7 (2%) Other less common reactions (less than 1% but more than 0.1%) were application site dryness, application site exfoliation, alopecia, and dry skin. Scabies Infestations Spinosad Topical Suspension was studied in three randomized, double-blind, vehicle-controlled trials (Trial 1, Trial 2, and Trial 3) in 592 subjects with scabies infestation, of which 165 were ages 4-17 and 427 were adults. Subjects received a single application of Spinosad Topical Suspension to the skin from the neck to the soles of the feet, which was washed off after a minimum of 6 hours. Table 2 presents adverse reactions related to Spinosad Topical Suspension treatment that occurred in at least 1% of subjects. Table 2: Adverse Reactions Occurring in at least 1% of Subjects with Scabies Infestation (Trials 1, 2 and 3) Signs Spinosad (N=322) Vehicle (N=270) Application site irritation Application site irritation also includes application site pain and burning sensation. 8 (3%) 0 (0%) Dry skin 6 (2%) 0 (0%)