Cabtreo

CABTREO is 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.

Topical gel: 1.2% clindamycin phosphate, 0.15% adapalene, and 3.1% benzoyl peroxide as a white to off-white, opaque gel.

CABTREO is supplied in 20-gram and 50-gram pumps.

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.

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.

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 (

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.

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
²comparison) or subcutaneous doses up to 200 mg/kg/day (64 and 32 times the MRHD, respectively, based on a mg/m
²comparison) 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
²comparison). 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
²comparison). 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
²comparison) exhibited no fetotoxicity and only minimal increases in skeletal variations (supernumerary ribs in both species and delayed ossification in rabbits).

• Hypersensitivity
  : If a serious hypersensitivity reaction occurs, discontinue CABTREO immediately and initiate appropriate therapy. (
  
  
  5.1 Hypersensitivity

  Hypersensitivity reactions, including anaphylaxis, angioedema, and urticaria, have been reported with use of clindamycin phosphate, benzoyl peroxide, and adapalene

  [see Adverse Reactions ].

  If a serious hypersensitivity reaction occurs, discontinue CABTREO immediately and initiate appropriate therapy.
  )
  
• Colitis
  : Clindamycin can cause severe colitis, which may result in death. Discontinue CABTREO if diarrhea occurs. (
  
  
  5.2 Colitis

  Diarrhea, bloody diarrhea, and colitis have been reported with the use of topical and systemic clindamycin. Severe colitis has occurred with an onset of up to several weeks following cessation of therapy. Antiperistaltic agents such as opiates and diphenoxylate with atropine may prolong and/or worsen severe colitis. Severe colitis may result in death. Discontinue CABTREO if diarrhea occurs.
  )
  
• Photosensitivity
  : Avoid or minimize exposure to sunlight and sunlamps. Wear sunscreen and protective clothing when sun exposure cannot be avoided. (
  
  
  5.3 Photosensitivity

  CABTREO may increase sensitivity to ultraviolet light. Avoid or minimize sun exposure (including use of tanning beds, and sun lamps) following CABTREO application. Instruct patients to use sunscreen products and wear protective apparel (e.g., hat) when exposure to sun cannot be avoided.
  )
  
• Skin Irritation and Allergic Contact Dermatitis
  : Erythema, scaling, dryness, stinging/burning, irritant and allergic contact dermatitis may occur with use of CABTREO and may necessitate discontinuation (
  
  
  5.4 Skin Irritation and Allergic Contact Dermatitis

  Stinging/burning/pain, erythema, dryness, irritation, exfoliation, and dermatitis have been reported with use of CABTREO. These application site adverse reactions occurred at a greater frequency in CABTREO-treated subjects than in vehicle-treated subjects. These adverse reactions are most likely to occur during the first four weeks of treatment [

  see Adverse Reactions ]

  .

  Irritant and allergic contact dermatitis have been reported with use of CABTREO.

  Weather extremes, such as wind or cold, may be irritating to patients under treatment with CABTREO.

  Depending upon the severity of these adverse reactions, instruct patients to use a moisturizer, reduce the frequency of the application of CABTREO, or discontinue use. Avoid applying CABTREO to areas of broken, eczematous, or sunburned skin. Avoid use of “waxing” as a depilatory method on skin treated with CABTREO.

  Avoid concomitant use of other potentially irritating topical products such as peeling, desquamating, or abrasive agents and products with high concentrations of alcohol, astringents, spices, or limes.

  Use of CABTREO with concomitant topical acne therapy has not been evaluated.
  )