ADERMICA (tretinoin/benzoyl peroxide/clindamycin phosphate/niacinamide)

There are 0 contraindications.

There are 6 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Clostridioides difficile infection
Crohn's disease
Eczema
Exfoliative dermatitis
Sunburn
Ulcerative colitis

There are 2 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Atopic dermatitis
No disease contraindications

There are 22 severe adverse reactions.

More Frequent	Less Frequent
Erythema Pruritus of skin	Skin irritation

Rare/Very Rare
Anaphylaxis Angioedema Blistering skin Bloody diarrhea Clostridioides difficile infection Dermatitis due to topical drug Dyschromia Dyspnea Facial edema Hypersensitivity drug reaction Periorbital edema Pharyngeal edema Pruritus of skin Skin crusting Skin inflammation Skin rash Syncope Throat constriction Urticaria

There are 19 less severe adverse reactions.

More Frequent	Less Frequent
Abnormal desquamation Dry skin Erythema Skin irritation Skin photosensitivity	Abnormal desquamation Dry skin Erythema Headache disorder Oily skin Sensation of warmth Stinging of skin

Rare/Very Rare
Acute abdominal pain Contact dermatitis Diarrhea Dyschromia Edema Gram-negative folliculitis Ocular pain

Retinoids (e.g., isotretinoin) have been reported to cause serious fetal harm when administered to pregnant women. (See Cautions: Pregnancy, Fertility, and Lactation, in Isotretinoin 84:36.) Oral tretinoin has been shown to be teratogenic in rats, mice, rabbits, hamsters, and subhuman primates. Tretinoin was teratogenic in Wistar rats when given orally or topically in dosages exceeding 1 mg/kg daily (8 times the maximum human systemic dosage normalized for total body surface area).

In the cynomolgus monkey, which metabolically is closer to humans for tretinoin than other species examined, fetal malformations were reported at oral dosages of 10 mg/kg daily or greater, but none were observed at 5 mg/kg daily (83 times the maximum human systemic dosage normalized for total body surface area), although increased skeletal variations were observed at all dosages. Dose-related increased embryolethality and abortion also were reported. Similar results also have been reported in pigtail macaques.

Topical tretinoin in animal teratogenicity tests has generated equivocal results. There is evidence for teratogenicity (shortened or kinked tail) of topical tretinoin in Wistar rats at dosages exceeding 1 mg/kg daily (8 times the maximum human systemic dosage normalized for total body surface area). Bone anomalies (short (13%) or bent (6%) humerus, incompletely ossified os parietal (14%)) also have been reported in rats when tretinoin 10 mg/kg daily was applied dermally.

Topical tretinoin cream was associated with an increased incidence of cleft palate and hydrocephaly in rabbits when administered in a dosage 91 times the topical human dosage (based on topical application of 1 g of 0.1% tretinoin cream in a 50-kg adult). In New Zealand white rabbits treated with topical tretinoin at dosages 80 times the recommended human topical clinical dosage, an increased incidence of domed head and hydrocephaly was noted in some of the fetuses, typical of retinoid-induced fetal malformations in this species; no abnormalities were observed at dosages 3 times the maximum human systemic dosage of tretinoin after topical administration of 0.1% tretinoin gel (microsphere formulation), normalized for total body surface area.

In addition, topical tretinoin in formulations other than the gel (microsphere formulation) was not teratogenic when given in dosages of 42 or 27 times the maximum human systemic topical dosage in rats or rabbits, respectively. However, delayed ossification of several bones, occurred in rabbits and a dose-dependent incease in supernumerary ribs was observed in rats at these topical dosages. Oral tretinoin was fetotoxic in rats at dosages 21 times the maximum human systemic dosage normalized for total body surface area, resulting in skeletal variations and increased intrauterine death in rats.

Topical tretinoin has been shown to be fetotoxic in rabbits when administered in dosages 8 times the maximum human systemic dosage applied topically and normalized for total body surface area), resulting in fetal resorption and variations in ossification. When given subcutaneously to rabbits, tretinoin was teratogenic at a dosage of 2 mg/kg daily but not at 1 mg/kg daily. These dosages are approximately 400 and 200 times, respectively, the human topical dosage of tretinoin cream (based on topical application of 1 g of 0.025% tretinoin cream in a 50-kg adult).

With widespread use of any drug, a small number of birth defect reports associated with the administration of the drug would be expected by chance alone. During 2 decades of clinical use of one formulation of topical tretinoin (Retin-A(R)), 30 cases of temporally associated congenital malformations have been reported. Although no definite pattern of teratogenicity and no causal associations have been established from these cases, 5 of the reports described the rare birth defect category holoprosencephaly (defects associated with incomplete midline development of the forebrain).

The relevance of these spontaneous reports in terms of risk to the fetus is unknown. To date, there have been no adequate and well-controlled studies performed in pregnant women, and the teratogenic blood level of tretinoin is not known. The manufacturer of some topical tretinoin preparations (e.g., Retin-A(R)) state that topical tretinoin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, while manufacturers of other tretinoin formulations (e.g., Avita(R) cream, Renova(R) emollient cream) state that these products should not be used during pregnancy.

Reproduction studies in pregnant rats and mice receiving oral and parenteral dosages of clindamycin up to 600 mg/kg daily (62 and 25 times, respectively, the maximum human dosage based on mg/m2) revealed no evidence of harm to the fetus. In one mouse strain, cleft palate was observed in fetuses of pregnant mice treated with clindamycin; this effect was not observed in other mouse strains or in other species. Intravaginal clindamycin has been used to treat bacterial vaginosis in pregnant women during the second and third trimester of pregnancy (for 7 nights of therapy).

In one clinical study of pregnant women receiving clindamycin phosphate vaginal cream or placebo during the second trimester of pregnancy, abnormal labor was reported in about 1.1 or 0.5% of patients, respectively.

Adverse effects have been reported in about 23% of pregnant patients receiving intravaginal clindamycin and have required discontinuance of the drug in about 2% of such patients. Candidal infection (including vaginal and nonvaginal candidiasis; either symptomatic or confirmed by culture) and vaginitis (including vulvovaginitis, vulvovaginal disorder, vaginal discharge, and trichomonal vaginitis) have been reported in about 13.3 and 7.2%

of pregnant patients receiving clindamycin phosphate vaginal cream for 7 days. Vaginal candidiasis and vulvovaginal disorders occurred in 13.3 and 6.7%,

respectively, of pregnant women receiving intravaginal clindamycin for 7 days while each of these adverse effects was reported in 7.1% of pregnant patients receiving placebo. Dysuria, metrorrhagia, vaginal pain, pruritus (at the application site), and trichomonal vaginitis occurred in less than 1% of pregnant patients receiving clindamycin phosphate vaginal cream.

Other adverse effects reported in pregnant patients receiving intravaginal clindamycin include fungal infections and pruritus (in areas other than at the application site) in 1.7 and 1.1%, respectively; these effects were not reported in pregnant women receiving placebo.

Upper respiratory infection and erythema were reported in less than 1% of pregnant women receiving clindamycin phosphate vaginal cream. There are no adequate and controlled studies to date using intravaginal clindamycin cream (Cleocin(R)) during the first trimester of pregnancy or using clindamycin intravaginal suppositories or intravaginal clindamycin cream (Clindesse(R)) during pregnancy; Clindamycin phosphate vaginal cream (Cleocin(R)) should be used during the first trimester of pregnancy only when clearly needed, and intravaginal suppositories and intravaginal clindamycin cream (Clindesse(R)) should be used during pregnancy only when clearly needed. In addition, because there are no adequate and controlled studies to date using topical preparations containing clindamycin phosphate (gel, solution, or lotion) or gels containing clindamycin phosphate in fixed combination with benzoyl peroxide during pregnancy, these preparations should be used during pregnancy only if clearly needed.

Screening and/or treatment for bacterial vaginosis in pregnant women as clinically indicated should be conducted during the first prenatal visit. In one study in women treated with intravaginal clindamycin early in the pregnancy (i.e., before 20 weeks' gestation), administration of clindamycin was associated with a reduction in preterm birth. In other studies, such therapy administered at 16-32 weeks' gestation did not reduce the incidence of adverse pregnancy outcomes.

For the treatment of bacterial vaginosis and reduction in the incidence of adverse pregnancy outcomes associated with bacterial vaginosis (e.g., preterm birth), particularly in pregnant women at high risk for complications of pregnancy, a 7-day regimen of oral metronidazole or a 7-day regimen of oral clindamycin is recommended. CDC states that clindamycin vaginal preparations should only be used during the first half of pregnancy.

It is not known whether topically applied tretinoin is excreted in human milk. Caution should be exercised when topical tretinoin is administered to a nursing woman. Although it is not known whether clindamycin is distributed into milk following topical or intravaginal application, the drug is distributed into milk following systemic administration. Because of the potential for serious adverse reactions to clindamycin in nursing infants, a decision should be made whether to discontinue nursing or to discontinue topical or intravaginal application of the drug, taking into account the importance of the drug to the woman.

No enhanced Geriatric Use information available for this drug.