No information provided.
ZIANA Gel (clindamycin phosphate, tretinoin) is contraindicated in patients with regional enteritis, ulcerative colitis, or history of antibiotic-associated colitis.
Because clinical trials are conducted under prescribed conditions, adverse reaction rates observed in the clinical trial may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse reactions that appear to be related to drug use for approximating rates.
The safety data presented in Table 1 (below) reflects exposure to ZIANA Gel (clindamycin phosphate, tretinoin) in 1,853 patients with acne vulgaris. Patients were 12 years and older and were treated once daily for 12 weeks. Adverse reactions that were reported in ≥1% of patients treated with ZIANA Gel (clindamycin phosphate, tretinoin) were compared to adverse reactions in patients treated with clindamycin phosphate 1.2% in vehicle gel, tretinoin 0.025% in vehicle gel, and the vehicle gel alone:
Table 1: Adverse Reactions Reported in at Least 1% of Patients
| ZIANA Gel N=1853 N (%) |
Clindamycin N=1428 N (%) |
Tretinoin N=846 N (%) |
Vehicle N=423 N (%) |
|
| PATIENTS WITH AT LEAST ONE AR | 497 (27) | 342 (24) | 225 (27) | 91 (22) |
| Nasopharyngitis | 65 (4) | 64 (5) | 16 (2) | 5 (1) |
| Pharyngolaryngeal pain | 29 (2) | 18 (1) | 5 (1) | 7 (2) |
| Dry skin | 23 (1) | 7 (1) | 3 (<1) | 0 (0) |
| Cough | 19 (1) | 21 (2) | 9 (1) | 2 (1) |
| Sinusitis | 19 (1) | 19 (1) | 15 (2) | 4 (1) |
| Note: Formulations used in all treatment arms were in the ZIANA vehicle gel. | ||||
Cutaneous safety and tolerance evaluations were conducted at each study visit in all of the clinical trials by assessment of erythema, scaling, itching, burning, and stinging:
Table 2: ZIANA Gel (clindamycin phosphate, tretinoin) -Treated Patients with Local Skin Reactions
| Local Reaction |
Baseline N=1835 N (%) |
End of Treatment N=1614 N (%) |
| Erythema | 636 (35) | 416 (26) |
| Scaling | 237 (13) | 280 (17) |
| Itching | 189 (10) | 70 (4) |
| Burning | 38 (2) | 56 (4) |
| Stinging | 33 (2) | 27 (2) |
At each study visit, application site reactions on a scale of 0 (none), 1 (mild), 2 (moderate), and 3 (severe), and the mean scores were calculated for each of the local skin reactions. In Studies 1 and 2, 1277 subjects enrolled with moderate to severe acne, 854 subjects treated with ZIANA Gel (clindamycin phosphate, tretinoin) and 423 treated with vehicle. Analysis over the twelve week period demonstrated that cutaneous irritation scores for erythema, scaling, itching, burning, and stinging peaked at two weeks of therapy, and were slightly higher for the ZIANA-treated group, decreasing thereafter.
One open-label 12-month safety study for ZIANA Gel (clindamycin phosphate, tretinoin) showed a similar adverse reaction profile as seen in the 12-week studies. Eighteen out of 442 subjects (4%) reported gastrointestinal symptoms.
ZIANA Gel (clindamycin phosphate, tretinoin) is indicated for the topical treatment of acne vulgaris in patients 12 years or older.
Pregnancy Category C. There are no well-controlled trials in pregnant women treated with ZIANA Gel (clindamycin phosphate, tretinoin). ZIANA Gel (clindamycin phosphate, tretinoin) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. ZIANA Gel (clindamycin phosphate, tretinoin) was tested for maternal and developmental toxicity in New Zealand White Rabbits with topical doses of 60, 180 and 600 mg/kg/day. ZIANA Gel (clindamycin phosphate, tretinoin) at 600 mg/kg/day (approximately 12 times the recommended clinical dose assuming 100% absorption and based on body surface area comparison) was considered to be the no-observed-adverse-effect level (NOAEL) for maternal and developmental toxicity following dermal administration of ZIANA Gel (clindamycin phosphate, tretinoin) for two weeks prior to artificial insemination and continuing until gestation day 18, inclusive. For purposes of comparisons of the animal exposure to human exposure, the recommended clinical dose is defined as 1 g of ZIANA Gel (clindamycin phosphate, tretinoin) applied daily to a 60 kg person.
ClindamycinTeratology (Segment II) studies using clindamycin were performed orally in rats (up to 600 mg/kg/day) and mice (up to 100 mg/kg/day) (583 and 49 times amount of clindamycin in the recommended clinical dose based on a body surface area comparison, respectively) or with subcutaneous doses of clindamycin up to 180 mg/kg/day (175 and 88 times the amount of clindamycin in the recommended clinical dose based on a body surface area comparison, respectively) revealed no evidence of teratogenicity.
TretinoinIn oral Segment III studies in rats with tretinoin, decreased survival of neonates and growth retardation were observed at doses in excess of 2 mg/kg/day (~ 78 times the recommended clinical dose assuming 100% absorption and based on body surface area comparison).
With widespread use of any drug, a small number of birth defect reports associated temporally with the administration of the drug would be expected by chance alone. Thirty cases of temporally associated congenital malformations have been reported during two decades of clinical use of another formulation of topical tretinoin. Although no definite pattern of teratogenicity and no causal association have been established from these cases, 5 of the reports describe the rare birth defect category, holoprosencephaly (defects associated with incomplete midline development of the forebrain). The significance of these spontaneous reports in terms of risk to the fetus is not known.
Dermal tretinoin has been shown to be fetotoxic in rabbits when administered in doses 40 times the recommended human clinical dose based on a body surface area comparison. Oral tretinoin has been shown to be fetotoxic in rats when administered in doses 78 times the recommended clinical dose based on a body surface area comparison.
ZIANA (clindamycin phosphate 1.2% and tretinoin 0.025%) Gel is supplied as follows:
| 2 gram tube | NDC 99207-300-02 |
| 30 gram tube | NDC 99207-300-30 |
| 60 gram tube | NDC 99207-300-60 |
See FDA-Approved Patient Labeling.
Instructions for UseZIANA Gel (clindamycin phosphate, tretinoin) may cause irritation such as erythema, scaling, itching, burning, or stinging.
ColitisIn the event a patient treated with ZIANA Gel (clindamycin phosphate, tretinoin) experiences severe diarrhea or gastrointestinal discomfort, ZIANA Gel (clindamycin phosphate, tretinoin) should be discontinued and a physician should be contacted.
Manufactured for: Medicis, The Dermatology Company®
Scottsdale, AZ 85258
By: Contract Pharmaceuticals Limited Niagara
Buffalo, NY 14213
U.S. Patent 5,721,275
U.S. Patent 6,387,383
FDA rev date: 11/7/2006
No information provided. Please see PRECAUTIONS below and SIDE EFFECTS & DRUG INTERACTIONS.
PRECAUTIONS ColitisSystemic absorption of clindamycin has been demonstrated following topical use of this product. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of topical clindamycin. When significant diarrhea occurs, ZIANA Gel (clindamycin phosphate, tretinoin) should be discontinued.
Severe colitis has occurred following oral or parenteral administration of clindamycin 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.
Studies indicate a toxin(s) produced by clostridia is one primary cause of antibiotic-associated colitis. The colitis is usually characterized by severe persistent diarrhea and severe abdominal cramps and may be associated with the passage of blood and mucus. Stool cultures for Clostridium difficile and stool assay for C. difficile toxin may be helpful diagnostically.
Ultraviolet Light and Environmental ExposureExposure to sunlight, including sunlamps, should be avoided during the use of ZIANA Gel (clindamycin phosphate, tretinoin) , and patients with sunburn should be advised not to use the product until fully recovered because of heightened susceptibility to sunlight as a result of the use of tretinoin. Patients who may be required to have considerable sun exposure due to occupation and those with inherent sensitivity to the sun should exercise particular caution. Daily use of sunscreen products and protective apparel (e.g., a hat) are recommended. Weather extremes, such as wind or cold, also may be irritating to patients under treatment with ZIANA Gel (clindamycin phosphate, tretinoin).
USE IN SPECIFIC POPULATIONS PregnancyPregnancy Category C. There are no well-controlled trials in pregnant women treated with ZIANA Gel (clindamycin phosphate, tretinoin). ZIANA Gel (clindamycin phosphate, tretinoin) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. ZIANA Gel (clindamycin phosphate, tretinoin) was tested for maternal and developmental toxicity in New Zealand White Rabbits with topical doses of 60, 180 and 600 mg/kg/day. ZIANA Gel (clindamycin phosphate, tretinoin) at 600 mg/kg/day (approximately 12 times the recommended clinical dose assuming 100% absorption and based on body surface area comparison) was considered to be the no-observed-adverse-effect level (NOAEL) for maternal and developmental toxicity following dermal administration of ZIANA Gel (clindamycin phosphate, tretinoin) for two weeks prior to artificial insemination and continuing until gestation day 18, inclusive. For purposes of comparisons of the animal exposure to human exposure, the recommended clinical dose is defined as 1 g of ZIANA Gel (clindamycin phosphate, tretinoin) applied daily to a 60 kg person.
ClindamycinTeratology (Segment II) studies using clindamycin were performed orally in rats (up to 600 mg/kg/day) and mice (up to 100 mg/kg/day) (583 and 49 times amount of clindamycin in the recommended clinical dose based on a body surface area comparison, respectively) or with subcutaneous doses of clindamycin up to 180 mg/kg/day (175 and 88 times the amount of clindamycin in the recommended clinical dose based on a body surface area comparison, respectively) revealed no evidence of teratogenicity.
TretinoinIn oral Segment III studies in rats with tretinoin, decreased survival of neonates and growth retardation were observed at doses in excess of 2 mg/kg/day (~ 78 times the recommended clinical dose assuming 100% absorption and based on body surface area comparison).
With widespread use of any drug, a small number of birth defect reports associated temporally with the administration of the drug would be expected by chance alone. Thirty cases of temporally associated congenital malformations have been reported during two decades of clinical use of another formulation of topical tretinoin. Although no definite pattern of teratogenicity and no causal association have been established from these cases, 5 of the reports describe the rare birth defect category, holoprosencephaly (defects associated with incomplete midline development of the forebrain). The significance of these spontaneous reports in terms of risk to the fetus is not known.
Dermal tretinoin has been shown to be fetotoxic in rabbits when administered in doses 40 times the recommended human clinical dose based on a body surface area comparison. Oral tretinoin has been shown to be fetotoxic in rats when administered in doses 78 times the recommended clinical dose based on a body surface area comparison.
Nursing MothersIt is not known whether clindamycin is excreted in human milk following use of ZIANA Gel (clindamycin phosphate, tretinoin). However, orally and parenterally administered clindamycin has been reported to appear in breast milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. It is not known whether tretinoin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ZIANA Gel (clindamycin phosphate, tretinoin) is administered to a nursing woman.
Pediatric UseSafety and effectiveness of ZIANA Gel (clindamycin phosphate, tretinoin) in pediatric patients under the age of 12 have not been established.
Clinical trials of ZIANA Gel included patients 12-17 years of age.
Geriatric UseClinical studies of ZIANA Gel (clindamycin phosphate, tretinoin) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
At bedtime, squeeze a pea-sized amount of medication onto one fingertip, dot onto the chin, cheeks, nose, and forehead, then gently rub over the entire face. ZIANA Gel (clindamycin phosphate, tretinoin) should be kept away from the eyes, the mouth, angles of the nose, and mucous membranes. ZIANA Gel (clindamycin phosphate, tretinoin) is not for oral, ophthalmic, or intravaginal use.
DOSAGE FORMS AND STRENGTHSZIANA Gel (clindamycin phosphate, tretinoin) , a combination of a lincosamide antibiotic and a retinoid, contains clindamycin phosphate 1.2% and tretinoin 0.025%, formulated as a topical gel. Each gram of ZIANA Gel (clindamycin phosphate, tretinoin) contains, as dispensed, 10 mg (1%) clindamycin as phosphate, and 0.25 mg (0.025%) tretinoin in an aqueous based gel.
ZIANA Gel (clindamycin phosphate, tretinoin) is available in 2 gram, 30 gram, and 60 gram tubes.
Because clinical trials are conducted under prescribed conditions, adverse reaction rates observed in the clinical trial may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse reactions that appear to be related to drug use for approximating rates.
The safety data presented in Table 1 (below) reflects exposure to ZIANA Gel (clindamycin phosphate, tretinoin) in 1,853 patients with acne vulgaris. Patients were 12 years and older and were treated once daily for 12 weeks. Adverse reactions that were reported in ≥1% of patients treated with ZIANA Gel (clindamycin phosphate, tretinoin) were compared to adverse reactions in patients treated with clindamycin phosphate 1.2% in vehicle gel, tretinoin 0.025% in vehicle gel, and the vehicle gel alone:
Table 1: Adverse Reactions Reported in at Least 1% of Patients
| ZIANA Gel N=1853 N (%) |
Clindamycin N=1428 N (%) |
Tretinoin N=846 N (%) |
Vehicle N=423 N (%) |
|
| PATIENTS WITH AT LEAST ONE AR | 497 (27) | 342 (24) | 225 (27) | 91 (22) |
| Nasopharyngitis | 65 (4) | 64 (5) | 16 (2) | 5 (1) |
| Pharyngolaryngeal pain | 29 (2) | 18 (1) | 5 (1) | 7 (2) |
| Dry skin | 23 (1) | 7 (1) | 3 (<1) | 0 (0) |
| Cough | 19 (1) | 21 (2) | 9 (1) | 2 (1) |
| Sinusitis | 19 (1) | 19 (1) | 15 (2) | 4 (1) |
| Note: Formulations used in all treatment arms were in the ZIANA vehicle gel. | ||||
Cutaneous safety and tolerance evaluations were conducted at each study visit in all of the clinical trials by assessment of erythema, scaling, itching, burning, and stinging:
Table 2: ZIANA Gel (clindamycin phosphate, tretinoin) -Treated Patients with Local Skin Reactions
| Local Reaction |
Baseline N=1835 N (%) |
End of Treatment N=1614 N (%) |
| Erythema | 636 (35) | 416 (26) |
| Scaling | 237 (13) | 280 (17) |
| Itching | 189 (10) | 70 (4) |
| Burning | 38 (2) | 56 (4) |
| Stinging | 33 (2) | 27 (2) |
At each study visit, application site reactions on a scale of 0 (none), 1 (mild), 2 (moderate), and 3 (severe), and the mean scores were calculated for each of the local skin reactions. In Studies 1 and 2, 1277 subjects enrolled with moderate to severe acne, 854 subjects treated with ZIANA Gel (clindamycin phosphate, tretinoin) and 423 treated with vehicle. Analysis over the twelve week period demonstrated that cutaneous irritation scores for erythema, scaling, itching, burning, and stinging peaked at two weeks of therapy, and were slightly higher for the ZIANA-treated group, decreasing thereafter.
One open-label 12-month safety study for ZIANA Gel (clindamycin phosphate, tretinoin) showed a similar adverse reaction profile as seen in the 12-week studies. Eighteen out of 442 subjects (4%) reported gastrointestinal symptoms.
DRUG INTERACTIONS Concomitant Topical MedicationConcomitant topical medication, medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong drying effect, and products with high concentrations of alcohol, astringents, spices or lime should be used with caution. When used with ZIANA Gel (clindamycin phosphate, tretinoin) , there may be increased skin irritation.
ErythromycinZIANA Gel (clindamycin phosphate, tretinoin) should not be used in combination with erythromycin-containing products due to its clindamycin component. In vitro studies have shown antagonism between these two antimicrobials. The clinical significance of this in vitro antagonism is not known.
Neuromuscular Blocking AgentsClindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, ZIANA Gel (clindamycin phosphate, tretinoin) should be used with caution in patients receiving such agents.
