Clindamycin Phosphate And Tretinoin Gel 1.2%/0.025%

1 INDICATIONS AND USAGE Clindamycin phosphate and tretinoin gel is indicated for the topical treatment of acne vulgaris in patients 12 years or older. Clindamycin phosphate and tretinoin gel is a lincosamide antibiotic and retinoid combination product indicated for the topical treatment of acne vulgaris in patients 12 years or older. (1)

2 DOSAGE AND ADMINISTRATION Clindamycin phosphate and tretinoin gel should be applied once daily in the evening, gently rubbing the medication to lightly cover the entire affected area. Approximately a pea-sized amount will be needed for each application. Avoid the eyes, lips, and mucous membranes. Clindamycin phosphate and tretinoin gel is not for oral, ophthalmic, or intravaginal use. Apply a pea-size amount once daily in the evening lightly covering the entire affected area. Avoid the eyes, lips, and mucous membranes. (2) Not for oral, ophthalmic, or intravaginal use. (2)

6 ADVERSE REACTIONS Observed local treatment-related adverse reactions (≥ 1%) in clinical studies with clindamycin phosphate and tretinoin gel were application site reactions, including dryness, irritation, exfoliation, erythema, pruritus, and dermatitis. Sunburn was also reported. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Encube Ethicals Private Limited at 1-833-285-4151 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Adverse Reactions in Clinical Studies Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared with rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice. The safety data reflect exposure to clindamycin phosphate and tretinoin gel in 1,104 patients with acne vulgaris. Patients were 12 years and older and were treated once daily in the evening for 12 weeks. Adverse reactions that were reported in ≥1% of patients treated with clindamycin phosphate and tretinoin gel are presented in Table 1 . Table 1. Treatment-Related Adverse Reactions Reported by ≥1% of Subjects Clindamycin Phosphate and Tretinoin Gel N = 1,104 n (%) Clindamycin Gel N = 1,091 n (%) Tretinoin Gel N = 1,084 n (%) Vehicle Gel N = 552 n (%) Patients with at least one adverse reaction 140 (13) 38 (3) 141 (13) 17 (3) Application site dryness 64 (6) 12 (1) 62 (6) 3 (1) Application site irritation 50 (5) 4 (<1) 57 (5) 5 (1) Application site exfoliation 50 (5) 2 (<1) 56 (5) 2 (<1) Application site erythema 40 (4) 6 (1) 39 (4) 3 (1) Application site pruritus 26 (2) 7 (1) 23 (2) 6 (1) Sunburn 11 (1) 6 (1) 7 (1) 3 (1) Application site dermatitis 6 (1) 0 (0) 8 (1) 1 (<1) Local skin reactions actively assessed at baseline and end of treatment with a score >0 are presented in Table 2 . Table 2. Clindamycin Phosphate and Tretinoin Gel - Treated Patients with Local Skin Reactions Clindamycin Phosphate and Tretinoin Gel Vehicle Gel Local Reaction Baseline N = 476 (%) End of Treatment N = 409 (%) Baseline N = 219 (%) End of Treatment N = 209 (%) Erythema 24% 21% 31% 35% Scaling 8% 19% 14% 12% Dryness 11% 22% 18% 13% Burning 8% 13% 8% 4% Itching 17% 15% 22% 14% During the 12 weeks of treatment, each local skin reaction peaked at Week 2 and gradually reduced thereafter.

12.3 Pharmacokinetics In an open-label study of 17 patients with moderate-to-severe acne vulgaris, topical administration of approximately 3 grams of clindamycin phosphate and tretinoin gel once daily for 5 days, clindamycin concentrations were quantifiable in all 17 patients starting from 1 hour post-dose. All plasma clindamycin concentrations were ≤5.56 ng/mL on Day 5, with the exception of 1 subject who had a maximum clindamycin concentration of 8.73 ng/mL at 4 hours post-dose. There was no appreciable increase in systemic exposure to tretinoin, as compared with the baseline value. The average tretinoin concentration across all sampling times on Day 5 ranged from 1.19 to 1.23 ng/mL compared with the corresponding baseline mean tretinoin concentration range of 1.16 to 1.30 ng/mL.