CABTREO- clindamycin phosphate/benzoyl peroxide/adapalene_gel

Clindamycin: [see Microbiology ( 12. 4 Adapalene: Benzoyl Peroxide: Pharmacodynamics of CABTREO are unknown. Systemic exposure following topical application of CABTREO was evaluated in 28 subjects in an open-label, randomized, pharmacokinetic study. Subjects aged 12 years and older with moderate to severe acne vulgaris applied 2. 4 (mean +/- SD) grams of CABTREO to the entire face (excluding eyes and lips), neck, upper chest, upper back and shoulders once daily for 28 days. Clindamycin phosphate concentrations were measurable in the majority of samples following single and repeated topical administration of CABTREO (LOQ = 0. The mean C max [0-t] max [0-t] Adapalene concentrations were measurable in the majority of samples following single and repeated topical administration of CABTREO (LOQ = 0. The mean C max (0-t) [0-t] Benzoyl peroxide is absorbed by the skin where it is converted to benzoic acid and eliminated in the urine. Drug Interaction Studies In Vitro Studies Erythromycin products: Clindamycin binds to the 50S ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing bacterial protein synthesis. Clindamycin and benzoyl peroxide individually have been shown to have in vitro activity against Cutibacterium acnes (C.

CABTREO 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.

DOSAGE AND ADMINISTRATION
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 [ see Warnings and Precautions ( 5. 3 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. ( 2 Avoid the eyes, mouth, paranasal creases, mucous membranes, and areas of broken, eczematous, or sunburned skin. ( 2 Not for oral, ophthalmic, or intravaginal use.
Instructions for Use
CABTREO registered (clindamycin phosphate, adapalene and benzoyl peroxide) topical gel This Instructions for Use contains information on how to apply CABTREO. Important information: CABTREO is for use on skin only (topical use). CABTREO is not for use in your mouth, eyes, or vagina. Read this Instructions for Use before you start using CABTREO and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or treatment. Apply CABTREO to your face 1 time each day as prescribed. Before you apply CABTREO, wash your face gently with a cleanser, rinse with warm water, and pat your skin dry. Step 1 To apply CABTREO to your face, use the pump to dispense one pea-sized amount of CABTREO onto your fingertip. See Figure 1. Note: One pea-sized amount of CABTREO should be enough to cover your entire face. Figure 1 Step 2 Dot the one pea-sized amount of CABTREO onto six areas of your face (chin, left cheek, right cheek, nose, left forehead, right forehead). See Figure 2. Figure 2 Step 3 Spread the gel over your face and gently rub it in. It is important to spread the gel over your entire face. Step 4 Wash your hands after applying CABTREO. How should I store CABTREO? Store CABTREO at room temperature at or below 77°F (25°C). Do not freeze CABTREO. Keep CABTREO away from heat. Store CABTREO pump upright. Throw away (discard) CABTREO that has passed the expiration date. Keep CABTREO and all medicines out of the reach of children. Distributed by: Manufactured by: Patented. See https://patents. ortho-dermatologics. com for US patent information. CABTREO is a trademark of Bausch Health Companies Inc. or its affiliates. copyright 2025 Bausch Health Companies Inc. or its affiliates This Instructions for Use has been approved by the U. Food and Drug Administration. Revised: 03/2025 90001201 figure-1 figure 2.

The following adverse reactions are discussed in more detail in other sections of the labeling: Hypersensitivity [see Warnings and Precautions ( 5. 1 Colitis [see Warnings and Precautions ( 5. 2 Skin Irritation and Allergic Contact Dermatitis [see Warnings and Precautions ( 5. 4 The most common adverse reactions (occurring in >1% of the CABTREO group and greater than the vehicle group) were application site reactions, pain, erythema, dryness, irritation, exfoliation, and dermatitis. 1 To report SUSPECTED ADVERSE REACTIONS, contact Bausch Health US, LLC at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www. gov/medwatch. 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 [see Clinical Studies ( 14 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 (13. 8) Application site erythema Application site erythema also includes erythema 11 (4. 5) 0 Application site dryness Application site dryness also includes xerosis 10 (4. 8) Application site irritation 5 (2. 1) 0 Application site exfoliation 4 (1. 7) 0 Application site dermatitis 3 (1. 2) 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. 5 Burning 29. 9 Scaling 26. 9 0 Itching 24. 9 0 Stinging 20. 5 Vehicle (N = 121) Erythema 22. 5 0 Burning 2. 9 0 0 Scaling 12. 5 0 0 Itching 11. 8 0 0 Stinging 3. 8 0 0 Local tolerability scores for erythema, scaling, itching, burning, and stinging increased during the first two weeks of treatment and decreased thereafter. 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: [see Contraindications ( 4 Local Adverse Reactions: Gastrointestinal Disorders: Bacterial infections:.

CABTREO is contraindicated in patients with: Known hypersensitivity to clindamycin, adapalene, benzoyl peroxide, any other components of CABTREO, or lincomycin [ see Warnings and Precautions 5. 1 A history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis [ see Warnings and Precautions ( 5. 2 Known hypersensitivity to clindamycin, adapalene, benzoyl peroxide, any components of the formulation, or lincomycin. ( 4 History of regional enteritis, ulcerative colitis, or antibiotic-associated colitis.

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 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. 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 2 No malformations were observed in rats treated with oral adapalene doses of 0. 0 mg/kg/day (up to 13 times the MRHD based on a mg/m 2 2 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 Risk Summary The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for CABTREO and any potential adverse effects on the breastfed child from CABTREO or from the underlying maternal condition. Clindamycin There are no data on the presence of clindamycin in human milk, the effects on the breastfed child, or the effects on milk production following topical administration. However, clindamycin has been reported to be present in human milk in small amounts following oral and parenteral administration. Adapalene There are no data on the presence of topical adapalene gel or its metabolite in human milk, the effects on the breastfed infant, or the effects on milk production. In animal studies, adapalene is present in rat milk with oral administration of the drug. When a drug is present in animal milk, it is likely that the drug will be present in human milk. It is possible that topical administration of large amounts of adapalene could result in sufficient systemic absorption to produce detectable quantities in human milk ( see Clinical Considerations). Benzoyl peroxide There are no data on the presence of topical benzoyl peroxide in human milk, its effects on the breastfed infant, or its effects on milk production. The systemic exposure of benzoyl peroxide is unknown. Based on the published literature, benzoyl peroxide is rapidly metabolized to benzoic acid (an endogenous substance), which is eliminated in the urine. Any amount of benzoyl peroxide excreted into human milk by a nursing mother would be expected to be rapidly metabolized by tissue and stomach esterases. Clinical Considerations To minimize potential exposure to the breastfed infant via breastmilk, use CABTREO on the smallest area of skin and for the shortest duration possible while breastfeeding. To avoid direct infant exposure, advise patients who are breastfeeding not to apply CABTREO directly to the nipple and areola. If applied to the patient’s chest, care should be taken to avoid infant exposure via direct contact with the infant skin. 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 [ see Clinical Studies ( 14 The safety and effectiveness of CABTREO have not been established in pediatric patients younger than 12 years of age. Clinical studies of CABTREO did not include any subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.

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: 7.

NONCLINICAL TOXICOLOGY
No carcinogenicity, genotoxicity, or fertility studies were conducted with CABTREO. Carcinogenicity studies have been conducted with a gel formulation containing 1% clindamycin phosphate and 5% benzoyl peroxide. In a 2-year dermal carcinogenicity study in mice, treatment with the gel formulation at doses up to 15,000 mg/kg/day (up to 24 times the MRHD for clindamycin phosphate and up to 47 times the MRHD for benzoyl peroxide based on a mg/m 2 2 2 Carcinogenicity studies with adapalene were conducted in mice at topical doses of 0.4, 1.3, and 4.0 mg/kg/day of adapalene, and in rats at oral doses of 0.15, 0.5, and 1.5 mg/kg/day of adapalene. The highest dose levels are 5.1 (mice) and 3.8 (rats) times the MRHD based on a mg/m 2 Benzoyl peroxide is a tumor promoter in several animal species. The significance of this finding in humans is unknown. Clindamycin phosphate was not genotoxic in the human lymphocyte chromosome aberration assay. Bacterial mutagenicity assays (Ames test) with benzoyl peroxide provided mixed results; mutagenic potential was observed in a few but not in a majority of investigations. It has been shown to produce single-strand DNA breaks in human bronchial epithelial and mouse epidermal cells, caused DNA-protein cross-links in the human cells, and also induced a dose-dependent increase in sister chromatid exchanges in Chinese hamster ovary cells. Adapalene did not exhibit mutagenic or genotoxic effects in vitro (Ames test, Chinese hamster ovary cell assay, or mouse lymphoma TK assay) or in vivo (mouse micronucleus test). Fertility studies in rats treated orally with up to 300 mg/kg/day of clindamycin phosphate (approximately 96 times the MRHD based on a mg/m 2 In rat oral studies, 20 mg/kg/day adapalene (51 times the MRHD based on a mg/m 2 0 1
CLINICAL STUDIES
The efficacy of CABTREO was evaluated in two multicenter, randomized, double-blind clinical trials (Trial 1 and Trial 2, NCT04214639 and 2 NCT04214652, respectively) in 363 adult and pediatric subjects 10 years of age and older with facial acne vulgaris. While subjects aged 10 to less than 12 years were included in these trials, CABTREO is not approved for use in patients less than 12 years of age. Subjects were randomized 2:1 to receive CABTREO or vehicle applied once daily for 12 weeks. The trial population included 74% White, 15% Black or African American, 7% Asian, 4% Other, and <1% Native Hawaiian or Other Pacific Islander; for ethnicity, 78% identified as non-Hispanic/Latino and 22% identified as Hispanic/Latino. Fifty-eight percent were female and 42% were male. The median age of the trial population was 18 years (range: 10 to 48 years). Enrolled subjects had a score of moderate (3) or severe (4) on the Evaluator’s Global Severity Score (EGSS), 30 to 100 inflammatory lesions (papules, pustules, and nodules), 35 to 150 non-inflammatory lesions (open and closed comedones) and two or fewer facial nodules. At baseline, most subjects (91%) had EGSS scores that equated to moderate acne. The co-primary efficacy endpoints of success on the EGSS, absolute change in noninflammatory lesion count, and absolute change in inflammatory lesion count were assessed at Week 12. Success on the EGSS was defined as at least a 2-grade improvement from baseline and an EGSS score of clear (0) or almost clear (1). Table 3 lists the efficacy results for Trials 1 and 2. Table 3: Efficacy Results at Week 12 Table 3: Efficacy Results at Week 12 in Subjects with Facial Acne Vulgaris in Trials 1 and 2 Trial 1 CABTREO N=122 Vehicle N=61 Treatment Difference (95% Confidence Interval) EGSS Clear or Almost Clear and 2-Grade Reduction from Baseline 49.6% 24.9% 24.7 (10.7, 38.7) Non-Inflammatory Facial Lesions Mean Absolute Reduction 35.4 23.5 11.9 (7.1, 16.6) Mean Percent Reduction 72.7% 47.6% Inflammatory Facial Lesions Mean Absolute Reduction 27.7 21.7 5.9 (3.1, 8.7) Mean Percent Reduction 75.7% 59.6% Trial 2 CABTREO N=120 Vehicle N=60 EGSS Clear or Almost Clear and 2-Grade Reduction from Baseline 50.5% 20.5% 30.0 (16.4, 43.6) Non-Inflammatory Facial Lesions Mean Absolute Reduction 35.2 22.0 13.3 (8.8, 17.7) Mean Percent Reduction 73.3% 49.0% Inflammatory Facial Lesions Mean Absolute Reduction 30.1 20.8 9.3 (6.2, 12.4) Mean Percent Reduction 80.1% 56.2%
Patient Information
CABTREO registered (clindamycin phosphate, adapalene and benzoyl peroxide) topical gel Important information: (topical use) What is CABTREO? CABTREO is a prescription medicine used on the skin (topical) to treat acne vulgaris in adults and children 12 years of age and older. It is not known if CABTREO is safe and effective in children under 12 years of age. Do not use CABTREO if you have: had an allergic reaction to clindamycin, adapalene, benzoyl peroxide, lincomycin, or any of the ingredients in CABTREO. See the end of this Patient Information leaflet for a complete list of ingredients in CABTREO. Crohn''s disease or ulcerative colitis. had inflammation of the colon (colitis), or severe diarrhea with past antibiotic use. Talk with your healthcare provider if you are not sure if you have any of the conditions listed above. Before using CABTREO, tell your healthcare provider about all of your medical conditions, including if you: plan to have surgery. CABTREO may affect how certain medicines work that may be given during surgery. are pregnant or plan to become pregnant. It is not known if CABTREO will harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if CABTREO passes into your breast milk. Clindamycin when taken by mouth or by injection has been reported to appear in breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with CABTREO. If you use CABTREO while breastfeeding: use CABTREO on the smallest area of skin and for the shortest time needed. do not avoid direct skin contact with your baby if CABTREO is applied to your chest. Tell your healthcare provider about all the medicines you take, Especially tell your healthcare provider Especially tell your healthcare provider about any skin products you use. Other skin and topical acne products may increase the irritation of your skin when used with CABTREO. 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 CABTREO? Use CABTREO exactly as your healthcare provider tells you to use it. See the detailed “Instructions for Use” Apply a thin layer of CABTREO to cover the treatment area 1 time each day. Avoid applying CABTREO to the eyes, lips, creases around your nose, your mouth, and areas of your skin with cuts, abrasions, or sunburned skin. Before you apply CABTREO, wash your face gently with a mild or soapless cleanser, rinse with warm water, and pat your skin dry. Wash your hands right away after applying CABTREO. What should I avoid during treatment with CABTREO? Avoid or limit your time in sunlight, including use of tanning beds or sunlamps during treatment with CABTREO. CABTREO 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 wide-brimmed hat and clothes that cover the treated area of your skin if you have to be in sunlight. Cold weather and wind may irritate skin treated with CABTREO. Avoid applying CABTREO to areas with skin problems, including cuts, abrasions, sunburn, or eczema. Avoid skin products that may dry or irritate your skin such as medicated or harsh soaps, astringents, cosmetics that make your skin dry, and products containing high levels of alcohol, spices, or limes. Avoid the use of “waxing” as a hair removal method on skin treated with CABTREO. Avoid getting CABTREO in your hair or on colored fabric. CABTREO may bleach hair or colored fabric. What are the possible side effects of CABTREO? CABTREO may cause serious side effects, including: Allergic reactions. hives, rash, or severe itching swelling of your face, eyes, lips, tongue, or throat trouble breathing or throat tightness feeling faint, dizzy, or lightheaded Inflammation of the colon (colitis). Sensitivity to sunlight. “What should I avoid while using CABTREO?” Skin irritation. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of CABTREO. 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 CABTREO? Store CABTREO at room temperature at or below 77°F (25°C). Do not freeze CABTREO. Keep CABTREO away from heat. Store CABTREO pump upright. Throw away (discard) CABTREO that has passed the expiration date. Keep CABTREO and all medicines out of the reach of children. General information about the safe and effective use of CABTREO. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use CABTREO for a condition for which it was not prescribed. Do not give CABTREO 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 CABTREO that is written for health professionals. What are the ingredients in CABTREO? Active ingredient: Inactive ingredients: Distributed by: Manufactured by: Patented. See https://patents.ortho-dermatologics.com for US patent information. CABTREO is a trademark of Bausch Health Companies Inc. or its affiliates. copyright 2025 Bausch Health Companies Inc. or its affiliates For more information about CABTREO, call 1-800-321-4576. This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 03/2025 90001201

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