Cabtreo

Description for Cabtreo

CABTREO (clindamycin phosphate, adapalene, and benzoyl peroxide) topical gel is a white to off-white, opaque gel. Each gram of CABTREO contains 12 mg (1.2%) clindamycin phosphate, equivalent to 10 mg (1%) clindamycin and 1.5 mg (0.15%) adapalene, and 31 mg (3.1%) benzoyl peroxide. Clindamycin phosphate is a water-soluble ester of the semisynthetic antibiotic produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent antibiotic lincomycin. Adapalene, a synthetic retinoid, is a naphthoic acid derivative with retinoid-like properties. Benzoyl peroxide is an oxidizing agent.

The chemical name for clindamycin phosphate is Methyl-7-chloro-6,7,8-trideoxy-6-(1-methyl-trans-4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L-threo-α-D-galacto-octopyranoside 2-(dihydrogen phosphate). The structural formula for clindamycin phosphate is represented below:

Clindamycin Phosphate

Molecular Formula: C₁₈H₃₄ClN₂O₈PS      Molecular Weight: 504.97

The chemical name for adapalene is 6-[3-(1-Adamantyl)-4-methoxyphenyl]-2-naphthoic acid. The structural formula for adapalene is represented below:

Adapalene

Molecular Formula: C₂₈H₂₈O₃      Molecular Weight: 412.52

The chemical name for benzoyl peroxide is dibenzoyl peroxide. The structural formula for benzoyl peroxide is represented below:

Benzoyl Peroxide

Molecular Formula: C₁₄H₁₀O₄      Molecular Weight: 242.23

CABTREO contains the following inactive ingredients: carbomer homopolymer type C (carbomer 980), potassium hydroxide, propylene glycol, and purified water.

ADVERSE REACTIONS

The following adverse reactions are discussed in more detail in other sections of the labeling:

• Hypersensitivity [ see Warnings and Precautions ( 1)]
• Colitis [see Warnings and Precautions ( 2)]
• Skin Irritation and Allergic Contact Dermatitis [see Warnings and Precautions ( 4)]

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 [see Clinical Studies ( 14)] . 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 *	33 (13.6)	1 (0.8)
Application site erythema †	11 (4.5)	0
Application site dryness ‡	10 (4.1)	1 (0.8)
Application site irritation	5 (2.1)	0
Application site exfoliation	4 (1.7)	0
Application site dermatitis	3 (1.2)	0
* Application site pain also includes application site stinging and burning † Application site erythema also includes erythema ‡ Application site dryness also includes xerosis

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 *			Week 12 (End of Treatment) †
	Mild (%)	Mod (%)	Severe (%)	Mild (%)	Mod (%)	Severe (%)
CABTREO (N = 242)
Erythema	34.2	19.7	2.1	22.4	6.5	0.5
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	0.5
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
* The denominators for calculating the percentages were the number of subjects with at least one post-baseline cutaneous tolerability assessment. † The denominators for calculating the percentages were the number of subjects with Week 12 assessment.

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. [see Contraindications ( 4)] .

Local Adverse Reactions:sunburn, blister, pruritis, hyperpigmentation and hypopigmentation.

Gastrointestinal Disorders:abdominal pain and gastrointestinal disturbances.

Bacterial infections:gram negative folliculitis

Drug Interactions for Cabtreo

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.

Warnings for Cabtreo

Included as part of the PRECAUTIONS section.

Precautions for Cabtreo

Hypersensitivity

Hypersensitivity reactions, including anaphylaxis, angioedema, and urticaria, have been reported with use of clindamycin phosphate, benzoyl peroxide, and adapalene [see Adverse Reactions (6.2)]. If a serious hypersensitivity reaction occurs, discontinue CABTREO immediately and initiate appropriate therapy.

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

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

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 (6.1)] .

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.

NONCLINICAL TOXICOLOGY

Carcinogenesis, Mutagenesis, Impairment of Fertility

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 2comparison) did not cause any increase in tumors.

However, in a 2-year dermal carcinogenicity study in rats using a different gel formulation containing 1% clindamycin phosphate and 5% benzoyl peroxide increased the incidence of keratoacanthoma at the treated skin site of male rats treated with 2,000 mg/kg/day (6.4 times the MRHD for clindamycin phosphate and 12.4 times the MRHD for benzoyl peroxide based on a mg/m 2comparison). In an oral (gavage) carcinogenicity study in rats, treatment with the gel formulation at doses up to 3,000 mg/kg/day (up to 10 times the MRHD for clindamycin phosphate and up to 19 times the MRHD for benzoyl peroxide based on a mg/m 2comparison) for up to 97 weeks did not cause any increase in tumors.

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/m² comparison. In the rat study, an increased incidence of benign and malignant pheochromocytomas reported in the adrenal medulla of male rats was observed.

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 2comparison) revealed no effects on fertility or mating ability.

In rat oral studies, 20 mg/kg/day adapalene (51 times the MRHD based on a mg/m 2comparison) did not affect the reproductive performance and fertility of F 0males and females, or the growth, development and reproductive function of F 1 offspring.

Patient Information for Cabtreo

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Administration Instructions

Advise patients to apply CABTREO as a thin layer to affected areas, avoiding the eyes, lips, paranasal creases, mucous membranes, and areas of broken, eczematous, or sunburned skin [see Dosage and Administration (2)] .

Instruct patients to wash hands after application. [see Dosage and Administration (2)] . Advise patients that CABTREO may bleach hair and colored fabric.

Hypersensitivity

Inform patients that hypersensitivity reactions may occur. Advise patients to discontinue use of CABTREO and contact their healthcare provider immediately if symptoms of an allergic reaction, such as severe swelling or shortness of breath, occur [see Warnings and Precautions (5.1), Contraindications (4)] .

Colitis

Advise patients to discontinue use of CABTREO and contact their healthcare provider if diarrhea occurs [ see Warnings and Precautions (5.2)] .

Photosensitivity

Advise patients to minimize or avoid exposure to sunlight or sunlamps, including tanning beds. Instruct patients to use sunscreen and wear protective clothing (e.g., hat) over treated areas when exposure to sun cannot be avoided [see Warnings and Precautions (5.3)] .

Skin Irritation and Allergic Contact Dermatitis

Inform patients that CABTREO may cause irritation, such as erythema, scaling, dryness, itching, stinging or burning. Depending on the severity of the reactions, advise patients to use a moisturizer, reduce the frequency of application, or discontinue use of CABTREO [see Warnings and Precautions (5.4)] .

Lactation

Advise patients to use CABTREO on the smallest area of skin and for the shortest duration possible while breastfeeding. To avoid direct infant exposure, instruct patients who are breastfeeding not to apply CABTREO directly to the nipple and areola. Instruct patients to avoid inadvertent contact of treated areas with infant skin [ see Use in Specific Populations (8.2)].

Distributed by:
Bausch Health US,
LLC Bridgewater,
NJ 08807 USA

Manufactured by:
Bausch Health Companies Inc.
Laval, Quebec H7L 4A8, Canada

Patented. See https://patents.ortho-dermatologics.com for US patent information. CABTREO is a trademark of Bausch Health Companies Inc. or its affiliates.
© 2025 Bausch Health Companies Inc. or its affiliates 90001201

OVERDOSES

No information provided.

Contraindications for Cabtreo

CABTREO is contraindicated in patients with:

• Known hypersensitivity to clindamycin, adapalene, benzoyl peroxide, any other components of CABTREO, or lincomycin [see Warnings and Precautions (1)].
• A history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis [see Warnings and Precautions (2)].

Clinical Pharmacology for Cabtreo

Mechanism Of Action

Clindamycin: Clindamycin is a lincosamide antibacterial [see Microbiology ( 12.4)] .

Adapalene: Adapalene binds to specific retinoic acid nuclear receptors but does not bind to cytosolic receptor protein. Biochemical and pharmacological profile studies have demonstrated that adapalene is a modulator of ce lular differentiation, keratinization and inflammatory processes. However, the significance of these findings with regard to the mechanism of action of adapalene for the treatment of acne is unknown.

Benzoyl Peroxide: Benzoyl peroxide is an oxidizing agent with bactericidal and keratolytic effects but the precise mechanism of action is unknown.

Pharmacodynamics

Pharmacodynamics of CABTREO are unknown.

Pharmacokinetics

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 2.2 ± 0.4 (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 = 0.05 ng/mL). The mean C_max and mean AUC_[0-t] values for clindamycin phosphate were 2.44 ng/mL (range: 0.15 to 6.14 ng/mL) and 30.7 ng•h/mL (range: 1.04 to 87.4 ng•h/mL) on Days 28-29, respectively. Clindamycin (C_max and AUC_[0-t]) accumulated up to approximately 3-fold between Days 1-2 and Days 28-29 following once daily application of CABTREO.

Adapalene concentrations were measurable in the majority of samples following single and repeated topical administration of CABTREO (LOQ = 0.10 ng/mL). The mean C_max and mean AUC_(0-t) values for adapalene were 0.10 ng/mL (range: 0 to 0.27 ng/mL) and 2.40 ng•h/mL (range: 0.56 to 3.87 ng•h/mL) on Days 28-29, respectively.

Adapalene (AUC_[0-t]) accumulated up to approximately 3-fold between Days 1-2 and Days 28-29 for CABTREO.

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:Concurrent use with erythromycin topical or oral products may reduce the efficacy of CABTREO. This finding is based upon the mechanistic understanding of these drugs and published in vitro antagonism between erythromycin and clindamycin. This finding was not confirmed by a dedicated clinical study. While the clinical significance of this finding is unknown, it still warrants consideration given the potential impact on the efficacy of CABTREO.

Microbiology

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. acnes), an organism which has been associated with acne vulgaris. In an in vitro study, the minimum inhibitory concentration (MIC) for benzoyl peroxide against C. acnesis 128 mg/L. The clinical significance of this activity against C. acnesis not known.

C. acnesresistance to clindamycin has been documented. Resistance to clindamycin is often associated with resistance to erythromycin.

INSTRUCTIONS FOR USE

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 refi l. 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.

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. If your healthcare provider tells you to put CABTREO on other areas of your skin with acne, be sure to ask how much you should use.

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:
Bausch Health US, LLC,
Bridgewater, NJ 08807 USA

Manufactured by:
Bausch Health Companies Inc.,
Laval, Quebec H7L 4A8, Canada Patented.

See https://patents.ortho-dermatologics.com for US patent information.
CABTREO is a trademark of Bausch Health Companies Inc. or its affiliates.

© 2025 Bausch Health Companies Inc. or its affiliates.
This Instructions for Use has been approved by the U.S. Food and Drug Administration.
Revised: 03/2025