Cabtreo Drug Information

is indicated for the topical treatment of acne vulgaris in adult and pediatric patients 12 years of age and older. CABTREO is a combination of clindamycin phosphate (a lincosamide antibacterial), adapalene (a retinoid), and benzoyl peroxide indicated for the topical treatment of acne vulgaris in adult and pediatric patients 12 years of age and older.

Cleanse the affected area gently. After the skin is dry, apply a thin layer of CABTREO to the affected area once daily. Wash hands thoroughly after application of CABTREO. Avoid the eyes, mouth, paranasal creases, mucous membranes, and areas of broken, eczematous, or sunburned skin.

CABTREO is for topical use only. Not for oral, ophthalmic, or intravaginal use. Apply a thin layer of CABTREO to the affected areas once daily.

Avoid the eyes, mouth, paranasal creases, mucous membranes, and areas of broken, eczematous, or sunburned skin. Not for oral, ophthalmic, or intravaginal use.

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 two multicenter, randomized, double-blind, vehicle-controlled clinical trials (Trial 1 and Trial 2), 363 adult and pediatric subjects 10 years of age and older with facial acne vulgaris were treated with CABTREO or vehicle topically once daily for 12 weeks . Adverse reactions reported by >1% of subjects treated with CABTREO and more frequently than subjects treated with vehicle are summarized in Table 1. These adverse reactions were mild (59%), moderate (36.4%), and severe (4.5%). Overall, 2.5% (6/242) of subjects discontinued CABTREO because of local skin reactions. Table 1: Adverse Reactions Reported by >1% of Subjects with Facial Acne Vulgaris Treated with CABTREO (and More Frequently than Vehicle) in Trials 1 and 2 Adverse Reactions N (%) CABTREO N=242 Vehicle N=121 Application site pain Application site pain also includes application site stinging and burning 33 1 Application site erythema Application site erythema also includes erythema 11 0 Application site dryness Application site dryness also includes xerosis 10 1 Application site irritation 5 0 Application site exfoliation 4 0 Application site dermatitis 3 0 Local tolerability evaluations were conducted at each study visit by assessment of erythema, scaling, itching, burning, and stinging.

Table 2 presents the signs and symptoms of local facial tolerability during the 12 Week treatment period in subjects treated with CABTREO. Table 2: Facial Cutaneous Tolerability Assessment During 12-Week Treatment Period in Subjects with Acne Vulgaris Treated with CABTREO in Trials 1 and 2 Maximum During Treatment The denominators for calculating the percentages were the number of subjects with at least one post-baseline cutaneous tolerability assessment. Week 12 (End of Treatment) The denominators for calculating the percentages were the number of subjects with Week 12 assessment. Mild (%) Mod (%) Severe (%) Mild (%) Mod (%) Severe (%) CABTREO (N = 242) Erythema 34.2 19.7 2.1 22.4 6.5

Burning 29.6 10.7 3.0 4.2 1.4 0.9 Scaling 26.7 3.4 0 7.0

0.9 0 Itching 24.3 3.4 0.4 6.0 0.9 0 Stinging 20.5 5.1 2.6 2.3 0.9

Vehicle (N = 121) Erythema 22.5 21.7 1.7 25.5 5.5 0 Burning

2.5 0.8 0.8 0.9 0 0 Scaling 12.5 0 0 4.5 0 0 Itching 11.6 0.8 0 1.8 0 0 Stinging 3.3 0.8 0 1.8 0 0 Local tolerability scores for erythema, scaling, itching, burning, and stinging increased during the first two weeks of treatment and decreased thereafter.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of products containing clindamycin phosphate, adapalene, and benzoyl peroxide as the active ingredients. Because post-marketing adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune system disorders: anaphylaxis and allergic reactions including eyelid edema, throat tightness, swelling of the face, and eczema. . Local Adverse Reactions: sunburn, blister, pruritis, hyperpigmentation and hypopigmentation.

Gastrointestinal Disorders: abdominal pain and gastrointestinal disturbances. Bacterial infections: gram negative folliculitis

Neuromuscular Blocking Agents Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Use CABTREO with caution in patients receiving such agents. Neuromuscular Blocking Agents: Use CABTREO with caution in patients receiving neuromuscular blocking agents.

Pregnancy Risk Summary Available data with CABTREO use in pregnant women are insufficient to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with CABTREO. Clindamycin In published clinical trials and observational studies with pregnant women, oral or IV administration of clindamycin has not been associated with an increased frequency of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, clindamycin phosphate did not cause malformations or embryofetal development toxicity in pregnant rats and mice when administered during the period of organogenesis at systemic doses up to 192 times the maximum recommended human dose (MRHD) of 2.5 g CABTREO, based on a body surface area (mg/m 2 ) comparison.

Adapalene Available data from clinical trials with adapalene topical gel use in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of adapalene to pregnant rats and rabbits during organogenesis at doses 64 and 128 times, respectively, the MRHD resulted in fetal skeletal and visceral malformations ( see Data). Benzoyl peroxide The systemic exposure of topical benzoyl peroxide is unknown. Based on published literature, benzoyl peroxide is rapidly metabolized to benzoic acid (an endogenous substance), which is eliminated in the urine.

Hence, maternal use is not expected to result in fetal exposure of the drug. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, 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 to 4% and 15 to 20%, respectively. Data Animal Data Animal reproductive/developmental toxicity studies have not been conducted with CABTREO. Clindamycin phosphate administration during the period of organogenesis in pregnant rats and mice at oral doses up to 600 mg/kg/day (192 and 96 times the MRHD, respectively, based on a mg/m 2 comparison) or subcutaneous doses up to 200 mg/kg/day (64 and 32 times the MRHD, respectively, based on a mg/m 2 comparison) did not cause fetal malformations or fetotoxicity. No malformations were observed in rats treated with oral adapalene doses of 0.15 to 5.0 mg/kg/day (up to 13 times the MRHD based on a mg/m 2 comparison). However, malformations were observed in rats and rabbits when treated with oral doses of ≥ 25 mg/kg/day adapalene (64 and 128 times the MRHD, respectively, based on a mg/m 2 comparison). Findings included cleft palate, microphthalmia, encephalocele, and skeletal abnormalities in rats and umbilical hernia, exophthalmos, and kidney and skeletal abnormalities in rabbits.

Dermal adapalene embryofetal development studies in rats and rabbits at doses up to 6.0 mg/kg/day adapalene (up to 15 and 30 times the MRHD, respectively, based on a mg/m 2 comparison) exhibited no fetotoxicity and only minimal increases in skeletal variations (supernumerary ribs in both species and delayed ossification in rabbits).

Pediatric Use The safety and effectiveness of CABTREO for the topical treatment of acne vulgaris have been established in pediatric patients 12 years of age and older. Use of CABTREO for this indication is supported by data from two randomized, double-blind, vehicle-controlled trials. The safety and effectiveness of CABTREO have not been established in pediatric patients younger than 12 years of age.

is contraindicated in patients with: Known hypersensitivity to clindamycin, adapalene, benzoyl peroxide, any other components of CABTREO, or lincomycin. A history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis. Known hypersensitivity to clindamycin, adapalene, benzoyl peroxide, any components of the formulation, or lincomycin.

History of regional enteritis, ulcerative colitis, or antibiotic-associated colitis.