adapalene/benzoyl peroxide/clindamycin topical (Rx)

>10%

Application site pain (13.6%)

1-10%

Application site erythema (4.5%)

Application site dryness (4.1%)

Application site irritation (2.1%)

Application site exfoliation (1.7%)

Application site dermatitis (1.2%)

Postmarketing Reports

Immune system disorders: Anaphylaxis and allergic reactions, including eyelid edema, throat tightness, facial swelling, and eczema

Local adverse reactions: Sunburn, blister, pruritus, hyperpigmentation, and hypopigmentation

Gastrointestinal disorders: Abdominal pain, GI disturbances

Bacterial infections: Gram-negative folliculitis

Contraindications

Known hypersensitivity to clindamycin, adapalene, benzoyl peroxide, any other components, or lincomycin

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

Cautions

Hypersensitivity reactions, including anaphylaxis, angioedema, and urticaria, reported; discontinue immediately and initiate appropriate therapy if serious hypersensitivity occurs

May increase sensitivity to ultraviolet light; avoid or minimize sun exposure (including use of tanning beds and sun lamps) following application; instruct patients to use sunscreen products and wear protective apparel when exposure to sun cannot be avoided

Skin irritation and allergic contact dermatitis

• Stinging/burning/pain, erythema, dryness, irritation, exfoliation, and dermatitis reported
• These adverse reactions are most likely to occur during the first 4 weeks of treatment
• Irritant and allergic contact dermatitis also reported
• Weather extremes (eg, wind, cold) may be irritating to patients during treatment
• Depending upon severity, instruct patients to use a moisturizer, reduce application frequency adapalene/benzoyl peroxide/clindamycin, or discontinue use
• Avoid applying to areas of broken, eczematous, or sunburned skin
• Avoid use of “waxing” as a depilatory method on skin treated with adapalene/benzoyl peroxide/clindamycin
• Avoid concomitant use of other potentially irritating topical products (eg, peeling, desquamating, or abrasive agents) and products with high concentrations of alcohol, astringents, spices, or limes
• Use with concomitant topical acne therapy has not been evaluated

Colitis

• Diarrhea, bloody diarrhea, and colitis reported with topical and systemic clindamycin
• Severe colitis has occurred with an onset of up to several weeks following cessation of therapy
• Antiperistalsis agents (eg, opiates, diphenoxylate with atropine) may prolong and/or worsen severe colitis
• Severe colitis may result in death
• Discontinue if diarrhea occurs

Drug interaction overview

• Neuromuscular blocking agents

  • Use caution
  • Clindamycin has been shown to have neuromuscular blocking properties that may enhance action of other neuromuscular blocking agents

Pregnancy

Available data regarding use in pregnant females are insufficient to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Adapalene

• Adapalene topical gel use in pregnant females are insufficient to establish a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes

Benzoyl peroxide

• Systemic exposure of topical benzoyl peroxide is unknown
• Benzoyl peroxide is rapidly metabolized to benzoic acid (an endogenous substance), which is eliminated in the urine
• Therefore, maternal use is not expected to result in fetal exposure of the drug

Clindamycin

• Clinical trials and observational studies with pregnant females, 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

Clinical considerations

• To minimize potential exposure to breastfed infants via breastmilk, use on smallest area of skin and for shortest duration possible while breastfeeding
• To avoid direct infant exposure, advise patients who are breastfeeding not to apply directly to the nipple and areola
• If applied to the patient’s chest, care should be taken to avoid exposure via direct contact with the infant’s skin

Lactation

Adapalene

• There are no data on presence of topical adapalene gel or its metabolite in human milk, effects on breastfed infants, or effects on milk production

Benzoyl peroxide

• There are no data on presence of topical benzoyl peroxide in human milk, its effects on breastfed infants, or its effects on milk production

Clindamycin

• There are no data on presence of clindamycin in human milk, effects on breastfed children, or effects on milk production following topical administration
• Clindamycin has been reported to be present in human milk in small amounts following oral and parenteral administration

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Adapalene: Binds to specific retinoic acid nuclear receptors and modulates cellular differentiation, keratinization and inflammatory processes; exact mechanism of action for treatment of acne is unknown

Benzoyl peroxide: Oxidizing agent with bactericidal and keratolytic effects, but the precise mechanism of action is unknown

Clindamycin: Lincosamide antibacterial agent that binds to the 50S ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing protein synthesis; reduces surface fatty acids on skin; exact mechanism of action in treating acne unknown

Absorption

Peak plasma concentration (Days 28-29)

• Adapalene: 0.1 ng/mL
• Clindamycin topical: 2.44 ng/mL

AUC (Days 28-29)

• Adapalene: 2.4 ng⋅h/mL
• Clindamycin topical: 30.7 ng⋅h/mL

Metabolism

Benzoyl peroxide: Converted to benzoic acid

Elimination

Excretion: Benzoyl peroxide is eliminated in the urine after conversion to benzoic acid

Topical Administration

For topical use only; not for oral, ophthalmic, or intravaginal use

Cleanse affected area gently

After the skin is dry, apply a thin layer of gel affected

Wash hands thoroughly after application

Avoid eyes, mouth, paranasal creases, mucous membranes, and areas of broken, eczematous, or sunburned skin

Advise patients that this product may bleach hair and colored fabric

Storage

Before dispensing: Refrigerate at 2-8ºC (36-46ºF) until dispensed to patient; dispense with a 10-week expiration date

After dispensing: Store at room temperature ≤77ºF (25ºC)

Do not freeze

Keep away from heat

Store pump upright