CLINDAMYCIN PHOSPHATE 1.2% AND TRETINOIN 0.025%

Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel is an antibiotic and retinoid combination gel product with two active ingredients. Clindamycin phosphate is a water-soluble ester of the semi-synthetic antibiotic produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent antibiotic lincomycin. The chemical name for clindamycin phosphate is Methyl 7-chloro-6,7,8-trideoxy-6-(1-methyl- trans -4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L- threo -α-D- galacto -octopyranoside 2-(dihydrogen phosphate). The structural formula for clindamycin phosphate is represented below: Clindamycin phosphate: Molecular Formula: C 18 H 34 ClN 2 O 8 PS Molecular Weight: 504.97 The chemical name for tretinoin is 3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8 nonatetraenoic acid (all- trans form). The structural formula for tretinoin is represented below: Tretinoin: Molecular Formula: C 20 H 28 O 2 Molecular Weight: 300.44 Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel contains the following inactive ingredients: butylated hydroxytoluene NF, carbomer 981 NF, citric acid USP, edetate disodium USP, glycerin USP, methylparaben NF, polysorbate 80 NF, propylparaben NF, purified water USP and tromethamine USP. Chemical Structure Chemical Structure

Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel is indicated for the topical treatment of acne vulgaris in patients 12 years or older. Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel is a lincosamide antibiotic and retinoid combination product indicated for the topical treatment of acne vulgaris in patients 12 years or older. ( 1 )

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. Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel should be kept away from the eyes, the mouth, angles of the nose, and mucous membranes. Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel is not for oral, ophthalmic, or intravaginal use. • Apply a pea-sized amount to the entire face once daily at bedtime. Do not apply to eyes, mouth, angles of the nose, or mucous membranes. ( 2 ) • Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel is not for oral, ophthalmic, or intravaginal use. ( 2 )

Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel is contraindicated in patients with regional enteritis, ulcerative colitis, or history of antibiotic-associated colitis. Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel is contraindicated in patients with regional enteritis, ulcerative colitis, or history of antibiotic-associated colitis. ( 4 )

Observed local adverse reactions in patients treated with Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel were skin erythema, scaling, itching, burning, and stinging. Other most commonly reported adverse events (≥1% in patients treated with Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel) were nasopharyngitis, pharyngolaryngeal pain, dry skin, cough, and sinusitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Oceanside Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience 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 Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel in 1853 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 Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel 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 Treated with Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel: 12-Week Studies Clindamycin Phosphate 1.2% and Tretinoin 0.025%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 Clindamycin Phosphate 1.2% and Tretinoin 0.025% 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: Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel-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 Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel and 423 treated with vehicle. Analysis over the 12-week period demonstrated that cutaneous irritation scores for erythema, scaling, itching, burning, and stinging peaked at 2 weeks of therapy, and were slightly higher for the Clindamycin Phosphate 1.2% and Tretinoin 0.025%-treated group, decreasing thereafter. One open-label 12-month safety study for Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel showed a similar adverse reaction profile as seen in the 12-week studies. Eighteen out of 442 subjects (4%) reported gastrointestinal symptoms.

• Concomitant use of topical medications with a strong drying effect can increase skin irritation. Use with caution. ( 7.1 ) • Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel should not be used in combination with erythromycin-containing products because of its clindamycin component. ( 7.2 ) 7.1 Concomitant Topical Medication Concomitant 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 Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel, there may be increased skin irritation. 7.2 Erythromycin Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel 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. 7.3 Neuromuscular Blocking Agents Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel should be used with caution in patients receiving such agents.

Storage and Handling • Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. • Protect from light. • Protect from freezing. • Keep out of the reach of children. • Keep away from heat. • Keep tube tightly closed.