PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Topical Retinoids for use for Acne

    DEA CLASS

    Rx

    DESCRIPTION

    Combination acne therapy in an alcohol-free hydrogel for topical use; clindamycin is an antibacterial agent and tretinoin (all-trans-retinoic acid or ATRA) is a retinoid and derivative of vitamin A (retinol); tretinoin normalizes desquamation of the follicular epithelium and reduces the number of comedones and inflammatory lesions.

    COMMON BRAND NAMES

    Veltin, Ziana

    HOW SUPPLIED

    Clindamycin Phosphate, Tretinoin/Clindamycin, Tretinoin/Veltin/Ziana Topical Gel: 1.2-0.025%

    DOSAGE & INDICATIONS

    For the treatment of acne vulgaris caused by Propionibacterium acnes.
    Topical dosage (Ziana)
    Adults, Adolescents, and Children 12 years and older

    Apply to affected areas once daily at bedtime.

    Topical dosage (Veltin)
    Adults, Adolescents, and Children 12 years and older

    Apply to the affected area once daily in the evening.

    MAXIMUM DOSAGE

    Adults

    Maximum dosage information not available.

    Elderly

    Maximum dosage information not available.

    Adolescents

    Maximum dosage information not available.

    Children

    >= 12 years: Maximum dosage information not available.
    < 12 years: Not recommended.

    Infants

    Not recommended.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Data are not available for this population; no quantitative recommendations are available.

    Renal Impairment

    Data are not available for this population; no quantitative recommendations are available.

    ADMINISTRATION

    Topical Administration

    Apply topically to the skin. Do not use orally, ophthalmically, or intravaginally.
    Prior to administration, gently wash the skin of the affected areas, rinse with warm water, and pat dry.
    Squeeze a pea-sized amount of the product onto one fingertip, dot onto the chin, cheeks, nose, and forehead, then gently rub over the entire face.
    Keep the product away from the eyes, mucous membranes, and angles of the nose.

    STORAGE

    Veltin:
    - Avoid exposure to heat
    - Protect from freezing
    - Protect from light
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Ziana:
    - Avoid exposure to heat
    - Protect from freezing
    - Protect from light
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Clinical studies for clindamycin; tretinoin did not include sufficient numbers of elderly subjects (aged 65 and over) to determine whether they respond differently from younger subjects.

    Clindamycin hypersensitivity, retinoid hypersensitivity

    Clindamycin; tretinoin products are contraindicated in patients with clindamycin hypersensitivity or retinoid hypersensitivity or hypersensitivity to any other components of the product.

    Colitis, Crohn's disease, diarrhea, gastroenteritis, GI disease, inflammatory bowel disease, pseudomembranous colitis, ulcerative colitis

    Clindamycin; tretinoin is contraindicated in patients with a history of regional gastroenteritis (Crohn's disease), ulcerative colitis, or history of antibiotic-associated colitis (e.g., pseudomembranous colitis). Orally and parenterally administered clindamycin has been associated with severe colitis which may result in patient death. Use of topical clindamycin results in some systemic absorption from the skin (< 1% of the topical dose). Almost all antibacterial agents have been associated with pseudomembranous colitis (antibiotic-associated colitis) which may range in severity from mild to life-threatening. In the colon, overgrowth of Clostridia may exist when normal flora is altered subsequent to antibacterial administration. The toxin produced by Clostridium difficile is a primary cause of pseudomembranous colitis. It is known that systemic use of antibiotics predisposes patients to development of pseudomembranous colitis. Consideration should be given to the diagnosis of pseudomembranous colitis in patients presenting with diarrhea following antibacterial administration. Systemic antibiotics should be prescribed with caution to patients with inflammatory bowel disease such as ulcerative colitis or other GI disease. If diarrhea develops during therapy, the drug should be discontinued. Following diagnosis of pseudomembranous colitis, therapeutic measures should be instituted. In milder cases, the colitis may respond to discontinuation of the offending agent. In moderate to severe cases, fluids and electrolytes, protein supplementation, and treatment with an antibacterial effective against Clostridium difficile may be warranted. Products inhibiting peristalsis are contraindicated in this clinical situation. Practitioners should be aware that antibiotic-associated colitis has been observed to occur over two months or more following discontinuation of systemic antibiotic therapy; a careful medical history should be taken.

    Sunburn, sunlight (UV) exposure

    Patients should limit their sunlight (UV) exposure, including sunlamps, while using clindamycin; tretinoin to decrease the risk for skin irritation. Patients with sunburn should be advised not to use clindamycin; tretinoin until fully recovered because of increased susceptibility to sunlight as a result of the use of tretinoin. Those with inherent photosensitivity or those who may have occupational sun exposure should exercise particular caution; daily use of sunscreen products and protective clothing are recommended.

    Children, infants, neonates

    Safe and effective use of clindamycin; tretinoin in neonates, infants, and  children < 12 years of age has not been established.

    Pregnancy

    Clindamycin; tretinoin combination products are classified FDA pregnancy risk category C. There are no well-controlled studies in pregnant women. Use clindamycin; tretinoin during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal studies have not shown maternal or developmental toxicity and have revealed no evidence of teratogenicity associated with the topical combination. However, teratogenic effects have been temporally associated with another topical formulation containing tretinoin.

    Breast-feeding

    The manufacturer recommends that clindamycin; tretinoin should be used cautiously in women who are breast-feeding. It is not known whether clindamycin or tretinoin are excreted into human milk after topical application. Orally and parenterally administered clindamycin has been reported to appear in breast milk, but minimal systemic absorption occurs after topical administration. Clindamycin is generally considered to be usually compatible with breast-feeding by the American Academy of Pediatrics (AAP). Systemic absorption of tretinoin after topical application is low and therefore it is unlikely that a significant amount of the drug is excreted into breast-milk. Only water-miscible cream products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    ADVERSE REACTIONS

    Moderate

    erythema / Early / 4.0-35.0
    pseudomembranous colitis / Delayed / Incidence not known
    colitis / Delayed / Incidence not known
    superinfection / Delayed / Incidence not known

    Mild

    xerosis / Delayed / 1.0-22.0
    pruritus / Rapid / 2.0-15.0
    skin irritation / Early / 5.0-5.0
    pharyngitis / Delayed / 0-4.0
    diarrhea / Early / 0-1.0
    cough / Delayed / 1.0-1.0
    sinusitis / Delayed / 1.0-1.0
    photosensitivity / Delayed / Incidence not known
    skin hypopigmentation / Delayed / Incidence not known
    skin hyperpigmentation / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acetohexamide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Adapalene; Benzoyl Peroxide: (Moderate) Benzoyl peroxide can potentiate the skin irritation caused by topical tretinoin. Concurrent application of these agents on areas treated with tretinoin should be avoided.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Atenolol; Chlorthalidone: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Azilsartan; Chlorthalidone: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Bendroflumethiazide; Nadolol: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Benzoyl Peroxide: (Moderate) Benzoyl peroxide can potentiate the skin irritation caused by topical tretinoin. Concurrent application of these agents on areas treated with tretinoin should be avoided.
    Benzoyl Peroxide; Clindamycin: (Moderate) Benzoyl peroxide can potentiate the skin irritation caused by topical tretinoin. Concurrent application of these agents on areas treated with tretinoin should be avoided.
    Benzoyl Peroxide; Erythromycin: (Moderate) Benzoyl peroxide can potentiate the skin irritation caused by topical tretinoin. Concurrent application of these agents on areas treated with tretinoin should be avoided.
    Benzoyl Peroxide; Sulfur: (Moderate) Benzoyl peroxide can potentiate the skin irritation caused by topical tretinoin. Concurrent application of these agents on areas treated with tretinoin should be avoided.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Chlorothiazide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Chlorpromazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Chlorpropamide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Chlorthalidone: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Chlorthalidone; Clonidine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Ciprofloxacin: (Moderate) Use tretinoin with caution in patients who are also taking drugs known to be photosensitizers, such as ciprofloxacin, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Fluphenazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Gemifloxacin: (Moderate) Use tretinoin with caution in patients who are also taking drugs known to be photosensitizers, such as gemifloxacin, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Glimepiride: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Glimepiride; Pioglitazone: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Glimepiride; Rosiglitazone: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Glipizide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Glipizide; Metformin: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Glyburide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Glyburide; Metformin: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Hydrochlorothiazide, HCTZ; Irbesartan: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Hydrochlorothiazide, HCTZ; Lisinopril: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Hydrochlorothiazide, HCTZ; Losartan: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Hydrochlorothiazide, HCTZ; Propranolol: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Hydrochlorothiazide, HCTZ; Quinapril: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Hydrochlorothiazide, HCTZ; Spironolactone: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Hydrochlorothiazide, HCTZ; Telmisartan: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Hydrochlorothiazide, HCTZ; Triamterene: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Levofloxacin: (Moderate) Use tretinoin with caution in patients who are also taking drugs known to be photosensitizers, such as levofloxacin, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Mesoridazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Methyclothiazide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Metolazone: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Moxifloxacin: (Moderate) Use tretinoin with caution in patients who are also taking drugs known to be photosensitizers, such as moxifloxacin, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Norfloxacin: (Moderate) Use tretinoin with caution in patients who are also taking drugs known to be photosensitizers, such as norfloxacin, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Ofloxacin: (Moderate) Use tretinoin with caution in patients who are also taking drugs known to be photosensitizers, such as ofloxacin, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Perphenazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Perphenazine; Amitriptyline: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Phenothiazines: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Prochlorperazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Salicylic Acid: (Moderate) When concomitantly prescribed for acne therapy, apply salicylic acid and clindamycin topical solutions separately, at different times of the day to minimize skin irritation, unless directed otherwise by the prescriber. If skin irritation occurs, a decrease in dose or frequency of one or both agents may be necessary.
    Sodium Thiosulfate; Salicylic Acid: (Moderate) When concomitantly prescribed for acne therapy, apply salicylic acid and clindamycin topical solutions separately, at different times of the day to minimize skin irritation, unless directed otherwise by the prescriber. If skin irritation occurs, a decrease in dose or frequency of one or both agents may be necessary.
    Sulfonylureas: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Thiazide diuretics: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Thiethylperazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Thioridazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Tolazamide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Tolbutamide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Trifluoperazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.

    PREGNANCY AND LACTATION

    Pregnancy

    Clindamycin; tretinoin combination products are classified FDA pregnancy risk category C. There are no well-controlled studies in pregnant women. Use clindamycin; tretinoin during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal studies have not shown maternal or developmental toxicity and have revealed no evidence of teratogenicity associated with the topical combination. However, teratogenic effects have been temporally associated with another topical formulation containing tretinoin.

    The manufacturer recommends that clindamycin; tretinoin should be used cautiously in women who are breast-feeding. It is not known whether clindamycin or tretinoin are excreted into human milk after topical application. Orally and parenterally administered clindamycin has been reported to appear in breast milk, but minimal systemic absorption occurs after topical administration. Clindamycin is generally considered to be usually compatible with breast-feeding by the American Academy of Pediatrics (AAP). Systemic absorption of tretinoin after topical application is low and therefore it is unlikely that a significant amount of the drug is excreted into breast-milk. Only water-miscible cream products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    •Clindamycin: Clindamycin antibacterial activity results from inhibition of protein synthesis. The antibiotic binds to the 50 S ribosomal subunits of bacteria, thereby inhibiting protein synthesis. Clindamycin is either bacteriostatic or bactericidal, depending on its concentration at the site of action and on the specific susceptibility of the organism being treated. Clindamycin is active against Propionibacterium acnes, which is part of the normal flora of the skin and is believed to be a primary cause of acne. Propionibacterium acnes metabolizes sebaceous triglycerides, consumes glycerol, and produces free fatty acids. Propionibacterium acnes and the production of fatty acids are believed to stimulate neutrophil chemoattractants, activate compliment, and result in an inflammatory response. Inhibition of P. acnes reduces the concentration of free fatty acids in sebum, which may be the cause of inflammatory lesions associated with acne. Propionibacterium acnes has developed resistance to topical clindamycin, therefore it is recommended to change medication therapy if the patient fails to respond in 4—8 weeks.
     
    •Tretinoin: In treating skin disorders, tretinoin binds to retinoic acid receptors (RARs) which then modifies gene expression, subsequent protein synthesis, and epithelial cell growth and differentiation. It has not been established whether the clinical effects of tretinoin are mediated through activation of RARs, other mechanisms such as irritation, or both. Tretinoin appears to prevent horny cell cohesion and to increase epidermal cell turnover and mitotic activity. Subsequently, in patients with acne, expulsion of existing comedones occurs, and formation of new comedones is prevented through sloughing and expulsion of horny cells from the follicle. Tretinoin reduces the cell layers of the stratum corneum. The bacterium involved in acne, Propionibacterium acnes, and sebum production are unaffected. An additional action of tretinoin may involve keratinization inhibition, which would explain its effectiveness in treating keratinization disorders.

    PHARMACOKINETICS

    Clindamycin phosphate and tretinoin combination products are applied topically to the skin.

    Topical Route

    Clindamycin: Topical clindamycin has been shown to be systemically absorbed, but the amount is minimal. Clindamycin phosphate appears to be less well absorbed through the skin than is the hydrochloride. In an open-label, multiple-dose study (n=12) using clindamycin phosphate; tretinoin gel, clindamycin plasma concentrations generally did not exceed 3.5 ng/mL, with the exception of one subject whose plasma concentration reached 13.1 ng/mL. In another open label, multiple-dose study (n=17), all clindamycin plasma concentrations were <= 5.56 ng/mL on day 5, except for 1 patients with a maximum concentration of 8.3 ng/mL at 4 hours after the dose.
    Tretinoin: Following topical application, a minimal amount of drug is absorbed systemically. In an open-label, multiple-dose study (n=12) using clindamycin phosphate; tretinoin gel, quantifiable tretinoin plasma concentrations ranged from 1 to 1.6 ng/ml; 50—92% of subjects had unquantifiable tretinoin plasma concentrations at any given time point following administration. Key tretinoin metabolites had plasma concentrations ranging from 1 to 1.4 ng/mL for the 13-cis-retinoic acid metabolite and from 1.6 to 6.5 ng/mL for the 4-oxo-13-cis-retinoic acid metabolite. In another open label, multiple-dose study (n=17), there was no appreciable increase in systemic tretinoin exposure as compared to baseline. The average concentration on day 5 ranged from 1.19—1.23 ng/mL as compared to the corresponding baseline of 1.16—1.3 ng/mL.