|SeeTERMINOLOGY & ABBREVIATIONS|
|Content||Formulation may be available as Gel, clindamycin phosphate 12mg/gram with tretinoin 0.25mg/gram.|
|Indication(s)||Clindamycin-Tretinoin Gel is indicated for the topical treatment ofacne vulgarisin patients 12 years or older.|
|Dosage &Administration||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-Tretinoin Gel should be kept away from the eyes, the mouth, angles of the nose, and mucous membranes.
Clindamycin-Tretinoin Gel is not for oral, ophthalmic, or intravaginal use.
Clindamycin-Tretinoin Gel, 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 Clindamycin-Tretinoin Gel contains, as dispensed, 10 mg (1%) clindamycin as phosphate, and 0.25 mg (0.025%) tretinoin in an aqueous based gel. Clindamycin-Tretinoin Gel is available in 2 gram, 30 gram, and 60 gram tubes.
|Contraindications||Clindamycin-Tretinoin Gel is contraindicated in patients with regional enteritis, ulcerative colitis, or history of antibiotic-associated colitis.|
Systemic 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, Clindamycin-Tretinoin Gel 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 forClostridium difficileand stool assay forC. difficiletoxin may be helpful diagnostically.
Ultraviolet Light and Environmental Exposure
Exposure to sunlight, including sunlamps, should be avoided during the use of Clindamycin-Tretinoin Gel, 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 Clindamycin-Tretinoin Gel.
|Adverse Drug Reactions||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-Tretinoin Gel 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 â‰¥ 1% of patients treated with Clindamycin-Tretinoin 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.
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.
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-Tretinoin Gel 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 Clindamycin-Tretinoin-treated group, decreasing thereafter.
One open-label 12-month safety study for Clindamycin-Tretinoin Gel 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 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-Tretinoin Gel, there may be increased skin irritation.
Clindamycin-Tretinoin Gel should not be used in combination with erythromycin-containing products due to its clindamycin component.In vitrostudies have shown antagonism between these two antimicrobials. The clinical significance of thisin vitroantagonism is not known.
Neuromuscular Blocking Agents
Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, Clindamycin-Tretinoin Gel should be used with caution in patients receiving such agents.
|Pregnancy Category (FDA)& use in specific population||
Mechanisms of Action
Tretinoin: Although the exact mode of action of tretinoin is unknown, current evidence suggests that topical tretinoin decreases cohesiveness of follicular epithelial cells with decreased microcomedo formation.Additionally, tretinoin stimulates mitotic activity and increased turnover of follicular epithelial cells causing extrusion of the comedones.
In an open-label, multiple-dose study treating 12 subjects with moderate to severe acne, the percutaneous absorption of tretinoin following 14 consecutive daily applications of approximately 4 g of Clindamycin-Tretinoin Gel was minimal. Quantifiable tretinoin plasma concentrations ranged from 1.0 to 1.6 ng/mL, with unquantifiable plasma concentrations in 50% to 92% of subjects at any given timepoint following administration. The plasma concentrations of the key tretinoin metabolites, 13- cis -retinoic acid and 4-oxo-13-cis-retinoic acid, ranged from 1.0 to 1.4 ng/mL and from 1.6 to 6.5 ng/mL, respectively. Plasma concentrations for clindamycin generally did not exceed 3.5 ng/mL, with the exception of one subject whose plasma concentration reached 13.1 ng/mL.
Clindamycin binds to the 50S ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing bacterial protein synthesis. Clindamycin has been shown to havein vitroactivity againstPropionibacterium acnes, an organism which has been associated with acne vulgaris; however, the clinical significance of this activity againstP. acneswas not examined in clinical trials with Clindamycin-Tretinoin Gel.P acnesresistance to clindamycin has been documented. Resistance to clindamycin is often associated with resistance to erythromycin.
The safety and efficacy of once daily use of Clindamycin-Tretinoin Gel for treatment of acne vulgaris were assessed in three 12-week prospective, multi-center, randomized, blinded studies in patients 12 years and older. Studies 1 and 2 were of identical design, and compared Clindamycin-Tretinoin Gel to clindamycin in the vehicle gel, tretinoin in the vehicle gel, and the vehicle gel alone. Patients with mild, moderate, or severe acne were enrolled in the studies. The co-primary efficacy variables were:(1) Mean percent change from baseline at Week 12 in
(2) Percent of subjects who cleared or almost cleared at Week 12 as judged by an Evaluator's Global Severity (EGS) score.In Study 3, Clindamycin-Tretinoin Gel was compared to clindamycin gel in a total of 2,010 patients with moderate or severe acne vulgaris (see Table 3) . As with Studies 1 and 2, the co-primary endpoints were mean percent reduction in lesion counts (inflammatory, non-inflammatory and total) and the Evaluator's Global Severity score. In Study 3, success on the EGS score was assessed by the percentage of subjects who had at least 2 grades of improvement from Baseline to Week 12.
|Brand Name||Manufacturer/Marketer||Composition||Dosage Form||Pack Size & Price|
|CLINDAX Plus||Opsonin Pharma Limited||Clindamycin phosphate USP 12mg (1.2%)+ Tretinoin USP 0.25mg (0.025%)||Gel||10gm: 120.00 MRP|
|CLINEX Plus||Aristopharma Ltd.||Clindamycin phosphate USP 12mg (1.2%)+ Tretinoin USP 0.25mg (0.025%)||Gel||15gm: 150.00 MRP|
|CLINFACE GEL||Square Pharmaceuticals Ltd.||Clindamycin + Tretinoin (1.2% + 0.025%)||Gel||15 gm: 151.02 MRP|