Rosil

Rating: 5 - 1 review(s)
advertisement
How often in a day do you take medicine? How many times?

Rosil uses

Rosil consists of Clindamycin Hydrochloride, Clindamycin Phosphate.

Clindamycin Hydrochloride:


1 INDICATIONS & USAGE

Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel 1.2% / 0.025% is indicated for the topical treatment of acne vulgaris in patients 12 years or older.

Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel 1.2% / 0.025% 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 & 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. Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel should be kept away from the eyes, the mouth, angles of the nose, and mucous membranes.

Rosil (Clindamycin Hydrochloride) phosphate and tretinoin 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)
  • Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel is not for oral, ophthalmic, or intravaginal use. (2)

3 DOSAGE FORMS & STRENGTHS

Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel, a combination of a lincosamide antibiotic and a retinoid, contains Rosil (Clindamycin Hydrochloride) phosphate, USP 1.2% and tretinoin, USP 0.025%, formulated as a topical gel. Each gram of Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel contains, as dispensed, 10 mg (1%) Rosil (Clindamycin Hydrochloride) as phosphate, USP, and 0.25 mg (0.025%) tretinoin, USP in an aqueous based gel. Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel is available in 30 gram and 60 gram tubes.

Topical gel: Rosil (Clindamycin Hydrochloride) phosphate, USP 1.2% and tretinoin, USP 0.025% gel in 30 and 60 gram tubes. (3)

advertisement

4 CONTRAINDICATIONS

Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel is contraindicated in patients with regional enteritis, ulcerative colitis, or history of antibiotic-associated colitis.

Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel is contraindicated in patients with regional enteritis, ulcerative colitis, or history of antibiotic–associated colitis. (4)

5 WARNINGS AND PRECAUTIONS

  • Colitis: Rosil can cause severe colitis, which may result in death. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of Rosil (Clindamycin Hydrochloride). Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel should be discontinued if significant diarrhea occurs. (5.1)
  • Ultraviolet Light and Environmental Exposures: Avoid exposure to sunlight and sunlamps. Wear sunscreen daily. (5.2)

5.1 Colitis

Systemic absorption of Rosil (Clindamycin Hydrochloride) 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 Rosil (Clindamycin Hydrochloride). When significant diarrhea occurs, Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel should be discontinued.

Severe colitis has occurred following oral or parenteral administration of Rosil (Clindamycin Hydrochloride) 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.

5.2 Ultraviolet Light and Environmental Exposure

Exposure to sunlight, including sunlamps, should be avoided during the use of Rosil (Clindamycin Hydrochloride) phosphate and 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 Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel.

advertisement

6 ADVERSE REACTIONS

Observed local adverse reactions in patients treated with Rosil phosphate and tretinoin gel were skin erythema, scaling, itching, burning, and stinging. Other most commonly reported adverse events (≥ 1% in patients treated with Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel) were nasopharyngitis, pharyngolaryngeal pain, dry skin, cough, and sinusitis. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Actavis at 1-800-432-8534 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 Rosil (Clindamycin Hydrochloride) phosphate and 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 ≥ 1% of patients treated with Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel were compared to adverse reactions in patients treated with Rosil (Clindamycin Hydrochloride) phosphate 1.2% in vehicle gel, tretinoin 0.025% in vehicle gel, and the vehicle gel alone:

Rosil (Clindamycin Hydrochloride)
Phosphate and
Tretinoin Gel Rosil (Clindamycin Hydrochloride) Tretinoin Vehicle
N=1853 N=1428 N=846 N=423
N (%) N (%) N (%) N (%)
Note: Formulations used in all treatment arms were in the Rosil (Clindamycin Hydrochloride) phosphate and tretinoin vehicle gel.
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)

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:

Local Reaction Baseline End of Treatment
N=1835 N=1614
N (%) 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 Rosil (Clindamycin Hydrochloride) phosphate and 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 Rosil (Clindamycin Hydrochloride) phosphate and tretinoin-treated group, decreasing thereafter.

One open-label 12-month safety study for Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel showed a similar adverse reaction profile as seen in the 12-week studies. Eighteen out of 442 subjects (4%) reported gastrointestinal symptoms.

advertisement

7 DRUG INTERACTIONS

  • Concomitant use of topical medications with a strong drying effect can increase skin irritation. Use with caution.
  • Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel should not be used in combination with erythromycin-containing products because of its Rosil (Clindamycin Hydrochloride) 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 Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel, there may be increased skin irritation.

7.2 Erythromycin

Rosil phosphate and tretinoin gel should not be used in combination with erythromycin-containing products due to its Rosil (Clindamycin Hydrochloride) 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

Rosil (Clindamycin Hydrochloride) has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel should be used with caution in patients receiving such agents.

8 USE IN SPECIFIC POPULATIONS

8.1 PREGNANCY

Pregnancy Category C. There are no well-controlled trials in pregnant women treated with Rosil phosphate and tretinoin gel. Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel was tested for maternal and developmental toxicity in New Zealand White Rabbits with topical doses of 60, 180 and 600 mg/kg/day. Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel 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 Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel 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 Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel applied daily to a 60 kg person.

Rosil (Clindamycin Hydrochloride)

Teratology (Segment II) studies using Rosil (Clindamycin Hydrochloride) 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 Rosil (Clindamycin Hydrochloride) in the recommended clinical dose based on a body surface area comparison, respectively) or with subcutaneous doses of Rosil (Clindamycin Hydrochloride) up to 180 mg/kg/day (175 and 88 times the amount of Rosil (Clindamycin Hydrochloride) in the recommended clinical dose based on a body surface area comparison, respectively) revealed no evidence of teratogenicity.

Tretinoin

In 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.

8.3 NURSING MOTHERS

It is not known whether Rosil (Clindamycin Hydrochloride) is excreted in human milk following use of Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel. However, orally and parenterally administered Rosil (Clindamycin Hydrochloride) 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 Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel is administered to a nursing woman.

8.4 PEDIATRIC USE

Safety and effectiveness of Rosil phosphate and tretinoin gel in pediatric patients under the age of 12 have not been established.

Clinical trials of Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel included patients 12 to 17 years of age.

8.5 GERIATRIC USE

Clinical studies of Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

advertisement

11 DESCRIPTION

Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel 1.2% / 0.025%, is an antibiotic and retinoid combination gel product with two active ingredients. Rosil (Clindamycin Hydrochloride) phosphate, USP 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 Rosil (Clindamycin Hydrochloride) phosphate, USP 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 Rosil (Clindamycin Hydrochloride) phosphate, USP is represented below:

Rosil (Clindamycin Hydrochloride) phosphate, USP:

Molecular Formula: C18H34ClN2O8PS Molecular Weight: 504.97

The chemical name for tretinoin, USP 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, USP is represented below:

Tretinoin, USP:

Molecular Formula: C20H28O2 Molecular Weight: 300.44

Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel 1.2% / 0.025% contains the following inactive ingredients: anhydrous citric acid, butylated hydroxytoluene, edetate disodium, hydroxyethyl cellulose, glycerin, methylparaben, polysorbate 80, propylparaben, purified water, tromethamine and xanthan gum.

12f9b5a2-figure-01 12f9b5a2-figure-02

12 CLINICAL PHARMACOLOGY

12.1 MECHANISMS OF ACTION

Rosil

.

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.

12.3 PHARMACOKINETICS

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 Rosil (Clindamycin Hydrochloride) phosphate and 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 Rosil (Clindamycin Hydrochloride) generally did not exceed 3.5 ng/mL, with the exception of one subject whose plasma concentration reached 13.1 ng/mL.

12.4 Microbiology

Rosil (Clindamycin Hydrochloride) 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. Rosil (Clindamycin Hydrochloride) has been shown to have in vitro activity against Propionibacterium acnes, an organism which has been associated with acne vulgaris; however, the clinical significance of this activity against P. acnes was not examined in clinical trials with Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel. P acnes resistance to Rosil (Clindamycin Hydrochloride) has been documented. Resistance to Rosil (Clindamycin Hydrochloride) is often associated with resistance to erythromycin.

13 NONCLINICAL TOXICOLOGY

13.1 CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY

Carcinogenicity, mutagenicity and impairment of fertility testing of Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel have not been performed in any species.

Rosil (Clindamycin Hydrochloride)

The carcinogenicity of a 1% Rosil (Clindamycin Hydrochloride) phosphate gel similar to Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel was evaluated by daily application to mice for two years. The daily doses used in this study were approximately 13 and 72 times higher than the human dose of Rosil (Clindamycin Hydrochloride) phosphate from Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel, assuming complete absorption and based on a body surface area comparison. No significant increase in tumors was noted in the treated animals. For purposes of comparisons of the animal exposure to human exposure, the recommended human topical clinical dose is defined as 1 g of Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel applied daily to a 60 kg person.

Fertility (Segment 1) studies in rats treated orally with up to 300 mg/kg/day of Rosil (Clindamycin Hydrochloride) (approximately 290 times the amount of Rosil (Clindamycin Hydrochloride) delivered from the recommended clinical dose for Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel, based on a body surface area comparison) revealed no effects on fertility or mating ability.

Tretinoin

In two independent studies with long-term topical application of tretinoin in mice, carcinogenicity was not observed. In both studies, tretinoin was administered topically (0.025% or 0.1%) three times per week for up to two years. No carcinogenicity was observed with maximum effects of dermal amyloidosis in the basal layer of the skin.

Tretinoin has been shown to enhance photoco-carcinogenicity in properly performed specific studies, employing concurrent or intercurrent exposure to the drug and UV radiation. The contribution of Rosil (Clindamycin Hydrochloride) to that effect is unknown. Although the significance of these studies to humans is not clear, patients should minimize exposure to sun.

The genotoxic potential of tretinoin was evaluated in an in vitro Ames Salmonella reversion test and an in vitro chromosomal aberration assay in Chinese hamster ovary cells. Both tests were negative.

In oral Segment 1 studies in rats treated with tretinoin, the no-observed-effect-level was 2 mg/kg/day (~78 times the recommended clinical dose assuming 100% absorption and based on body surface area comparison).

14 CLINICAL STUDIES

The safety and efficacy of once daily use of Rosil (Clindamycin Hydrochloride) phosphate and 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 Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel to Rosil (Clindamycin Hydrochloride) 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

  • inflammatory lesion counts,
  • non-inflammatory lesion counts, and
  • total lesion counts

(2) Percent of subjects who cleared or almost cleared at Week 12 as judged by an Evaluator’s Global Severity (EGS) score.

The EGS scoring scale used in all of the clinical trials for Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel is as follows:

Grade Description
Clear Normal, clear skin with no evidence of acne vulgaris
Almost Clear Rare non-inflammatory lesions present, with rare non-inflamed papules (papules must be resolving and may be hyperpigmented, though not pink-red)
Mild Some non-inflammatory lesions are present, with few inflammatory lesions (papules/pustules only; no nodulocystic lesions)
Moderate Non-inflammatory lesions predominate, with multiple inflammatory lesions evident: several to many comedones and papules/pustules, and there may or may not be one small nodulo-cystic lesion
Severe Inflammatory lesions are more apparent many comedones and papules/pustules, there may or may not be a few nodulocystic lesions
Very Severe Highly inflammatory lesions predominate, variable number of comedones, many papules/pustules and many nodulocystic lesions

In Study 1, a total of 1,252 patients were enrolled, and in Study 2, a total of 1,288 patients were enrolled. The combined results are presented in Table 3.

Rosil (Clindamycin Hydrochloride)
Phosphate and Rosil (Clindamycin Hydrochloride) Tretinoin Vehicle
Tretinoin Gel
N=845 N=426 N=846 N=423
* Success was defined as cleared or almost cleared at Week 12
Evaluator’s Global Severity: N (%)
Patients achieving success* 180 (21%) 70 (16%) 122 (14%) 34 (8%)
Inflammatory Lesion Count (% reduction from baseline)
Mean 48% 42% 39% 26%
Non-inflammatory Lesion Count (% reduction from baseline)
Mean 36% 27% 31% 16%
Total Lesion Count (% reduction from baseline)
Mean 41% 34% 34% 20%

In Study 3, Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel was compared to Rosil (Clindamycin Hydrochloride) gel in a total of 2,010 patients with moderate or severe acne vulgaris. 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.

Rosil (Clindamycin Hydrochloride) Phosphate and
Tretinoin Gel Rosil (Clindamycin Hydrochloride)
N = 1008 N = 1002
* Success was defined as at least a 2-grade improvement at Week 12 from baseline.
Evaluator’s Global Severity: N (%)
Patients achieving success* 415 (41%) 345 (34%)
Inflammatory Lesion Count (% reduction from baseline)
Mean 61% 55%
Non-inflammatory Lesion Count (% reduction from baseline)
Mean 50% 41%
Total Lesion Count (% reduction from baseline)
Mean 54% 47%

16 HOW SUPPLIED/STORAGE AND HANDLING

Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel 1.2% / 0.025% is supplied as follows:

30 gram tube NDC 0472-1790-30

60 gram tube NDC 0472-1790-60

Storage and Handling

Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F). Protect from light. Protect from freezing. Keep away from heat.

Keep tube tightly closed.

Keep out of the reach of children.

17 PATIENT COUNSELING INFORMATION

17.1 Instructions for Use

  • At bedtime, the face should be gently washed with a mild soap and warm water. After patting the skin dry, apply Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel as a thin layer over the entire face (excluding the eyes and lips).
  • Patients should be advised not to use more than the recommended pea sized amount and not to apply more often than once daily (at bedtime) as this will not make for faster results and may increase irritation.
  • A sunscreen should be applied every morning and reapplied over the course of the day as needed. Patients should be advised to avoid exposure to sunlight, sunlamp, ultraviolet light, and other medicines that may increase sensitivity to sunlight.

17.2 Skin Irritation

Rosil phosphate and tretinoin gel may cause irritation such as erythema, scaling, itching, burning, or stinging.

17.3 Colitis

In the event a patient treated with Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel experiences severe diarrhea or gastrointestinal discomfort, Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel should be discontinued and a physician should be contacted.

Manufactured by:

G&W laboratories, Inc.

111 Coolidge Street

South Plainfield, NJ 07080 USA

Distributed by:

Actavis Pharma, Inc.

Parsippany, NJ 07054 USA

Revised – September 2015

I600-6210/11 GW 7047

17.4 FDA-Approved Patient Labeling

PATIENT INFORMATION

Rosil (Clindamycin Hydrochloride) Phosphate and Tretinoin (klin-da-MYE-sin FOS-fate and TRET-i-noyn)

Gel 1.2% / 0.025%

IMPORTANT: Not for mouth, eye, or vaginal use.

Read the Patient Information that comes with Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your acne or treatment.

What is Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel?

Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel is an antibiotic and retinoid combination medicine used for the skin treatment of acne in patients 12 years and older.

Who should not use Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel?

Do not use Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel if you:

  • have Crohn’s Disease
  • have Ulcerative Colitis
  • have developed colitis with past antibiotic use

Tell your doctor:

  • if you are pregnant or planning to become pregnant. It is not known if Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel may harm your unborn baby.
  • if you are breastfeeding. Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel may pass through your milk and may harm your baby.
  • about all the medicines and skin products you use:
    • Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel should not be used with erythromycin-containing products.
    • Avoid medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong drying effect, and skin products that contain alcohol, astringents, spices or lime. These products may cause increased skin irritation if used with Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel.

How should I use Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel?

Use Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel exactly as prescribed. It may take some time for you to see improvement of your acne with Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel. Your doctor will tell you how long to use Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel.

At bedtime:

  • Wash your face gently with a mild soap and warm water.
  • Pat the skin dry.
  • Apply a pea-size amount of Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel to your fingertip and spread it over your face. Gently, smooth it into your skin. Do not get Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel in your eyes or mouth, on your lips, on the corners of your nose, or on open wounds.

In the morning:

  • Apply a sunscreen and reapply during the day as needed.
  • Do not apply Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel more than once a day
  • Do not use too much Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel. Too much Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel may irritate your skin.
  • Do not wash your face more than 2 to 3 times a day. Washing your face too often or scrubbing it may make your acne worse.

Avoid:

  • excessive exposure to the sun, cold, and wind. Weather extremes can dry and burn the skin. Always use a sunscreen on Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel treated skin, even on cloudy days. Use other protective clothing such as a hat when you are in the sun.
  • the use of sunlamps and tanning booths

If your face becomes sunburned, stop Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel until your skin has healed.

What are possible side effects with Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel?

  • Skin irritation. Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel may cause skin irritation such as dryness, redness, peeling, burning, or stinging. Stop Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel and call your doctor if your skin becomes very red, swollen, blistered, or crusted.
  • Change in skin color. Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel may cause a temporary skin color change (lighter or darker).
  • Colitis. This occurs rarely. Stop Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel and call your doctor if you develop severe watery diarrhea, or bloody diarrhea.

Talk to your doctor about any side effect that bothers you or that does not go away.

These are not all the side effects with Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel. Ask your doctor or pharmacist for more information.

How should I store Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel?

  • Store Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel at room temperature, 59 to 86°F (15 to 30°C). Do not freeze.
  • Keep Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel away from heat and light.
  • Keep the tube tightly closed.
  • Keep Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel and all medicines out of the reach of children.

General information about Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel

Medicines are sometimes prescribed for purposes other than those listed in patient information leaflet. Do not use Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel for a condition for which it was not prescribed. Do not give Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel to other people, even if they have the same symptoms you have. It may harm them.

This leaflet summarizes the most important information about Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel. If you would like more information, talk with your doctor. You can also ask your pharmacist or doctor for information about Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel that is written for healthcare professionals.

If you have questions about Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel you can also call Actavis at 1-800-432-8534.

What are the ingredients in Rosil (Clindamycin Hydrochloride) phosphate and tretinoin gel?

Active Ingredients: Rosil (Clindamycin Hydrochloride) phosphate, USP 1.2% and tretinoin, USP 0.025%

Inactive Ingredients: anhydrous citric acid, butylated hydroxytoluene, edetate disodium, hydroxyethyl cellulose, glycerin, methylparaben, polysorbate 80, propylparaben, purified water, tromethamine and xanthan gum.

Manufactured by:

G&W laboratories, Inc.

111 Coolidge Street

South Plainfield, NJ 07080 USA

Distributed by:

Actavis Pharma, Inc.

Parsippany, NJ 07054 USA

Revised – September 2015

I600-6210/11 GW 7047

Clindamycin Phosphate:


1 INDICATIONS & USAGE

Rosil (Clindamycin Phosphate) phosphate and tretinoin gel 1.2% / 0.025% is indicated for the topical treatment of acne vulgaris in patients 12 years or older.

Rosil (Clindamycin Phosphate) phosphate and tretinoin gel 1.2% / 0.025% 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 & 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. Rosil (Clindamycin Phosphate) phosphate and tretinoin gel should be kept away from the eyes, the mouth, angles of the nose, and mucous membranes.

Rosil (Clindamycin Phosphate) phosphate and tretinoin 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)
  • Rosil (Clindamycin Phosphate) phosphate and tretinoin gel is not for oral, ophthalmic, or intravaginal use. (2)

3 DOSAGE FORMS & STRENGTHS

Rosil (Clindamycin Phosphate) phosphate and tretinoin gel, a combination of a lincosamide antibiotic and a retinoid, contains Rosil (Clindamycin Phosphate) phosphate, USP 1.2% and tretinoin, USP 0.025%, formulated as a topical gel. Each gram of Rosil (Clindamycin Phosphate) phosphate and tretinoin gel contains, as dispensed, 10 mg (1%) Rosil (Clindamycin Phosphate) as phosphate, USP, and 0.25 mg (0.025%) tretinoin, USP in an aqueous based gel. Rosil (Clindamycin Phosphate) phosphate and tretinoin gel is available in 30 gram and 60 gram tubes.

Topical gel: Rosil (Clindamycin Phosphate) phosphate, USP 1.2% and tretinoin, USP 0.025% gel in 30 and 60 gram tubes. (3)

4 CONTRAINDICATIONS

Rosil (Clindamycin Phosphate) phosphate and tretinoin gel is contraindicated in patients with regional enteritis, ulcerative colitis, or history of antibiotic-associated colitis.

Rosil (Clindamycin Phosphate) phosphate and tretinoin gel is contraindicated in patients with regional enteritis, ulcerative colitis, or history of antibiotic–associated colitis. (4)

5 WARNINGS AND PRECAUTIONS

  • Colitis: Rosil can cause severe colitis, which may result in death. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of Rosil (Clindamycin Phosphate). Rosil (Clindamycin Phosphate) phosphate and tretinoin gel should be discontinued if significant diarrhea occurs. (5.1)
  • Ultraviolet Light and Environmental Exposures: Avoid exposure to sunlight and sunlamps. Wear sunscreen daily. (5.2)

5.1 Colitis

Systemic absorption of Rosil (Clindamycin Phosphate) 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 Rosil (Clindamycin Phosphate). When significant diarrhea occurs, Rosil (Clindamycin Phosphate) phosphate and tretinoin gel should be discontinued.

Severe colitis has occurred following oral or parenteral administration of Rosil (Clindamycin Phosphate) 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.

5.2 Ultraviolet Light and Environmental Exposure

Exposure to sunlight, including sunlamps, should be avoided during the use of Rosil (Clindamycin Phosphate) phosphate and 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 Rosil (Clindamycin Phosphate) phosphate and tretinoin gel.

6 ADVERSE REACTIONS

Observed local adverse reactions in patients treated with Rosil phosphate and tretinoin gel were skin erythema, scaling, itching, burning, and stinging. Other most commonly reported adverse events (≥ 1% in patients treated with Rosil (Clindamycin Phosphate) phosphate and tretinoin gel) were nasopharyngitis, pharyngolaryngeal pain, dry skin, cough, and sinusitis. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Actavis at 1-800-432-8534 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 Rosil (Clindamycin Phosphate) phosphate and 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 ≥ 1% of patients treated with Rosil (Clindamycin Phosphate) phosphate and tretinoin gel were compared to adverse reactions in patients treated with Rosil (Clindamycin Phosphate) phosphate 1.2% in vehicle gel, tretinoin 0.025% in vehicle gel, and the vehicle gel alone:

Rosil (Clindamycin Phosphate)
Phosphate and
Tretinoin Gel Rosil (Clindamycin Phosphate) Tretinoin Vehicle
N=1853 N=1428 N=846 N=423
N (%) N (%) N (%) N (%)
Note: Formulations used in all treatment arms were in the Rosil (Clindamycin Phosphate) phosphate and tretinoin vehicle gel.
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)

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:

Local Reaction Baseline End of Treatment
N=1835 N=1614
N (%) 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 Rosil (Clindamycin Phosphate) phosphate and 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 Rosil (Clindamycin Phosphate) phosphate and tretinoin-treated group, decreasing thereafter.

One open-label 12-month safety study for Rosil (Clindamycin Phosphate) phosphate and tretinoin gel showed a similar adverse reaction profile as seen in the 12-week studies. Eighteen out of 442 subjects (4%) reported gastrointestinal symptoms.

7 DRUG INTERACTIONS

  • Concomitant use of topical medications with a strong drying effect can increase skin irritation. Use with caution.
  • Rosil (Clindamycin Phosphate) phosphate and tretinoin gel should not be used in combination with erythromycin-containing products because of its Rosil (Clindamycin Phosphate) 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 Rosil (Clindamycin Phosphate) phosphate and tretinoin gel, there may be increased skin irritation.

7.2 Erythromycin

Rosil phosphate and tretinoin gel should not be used in combination with erythromycin-containing products due to its Rosil (Clindamycin Phosphate) 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

Rosil (Clindamycin Phosphate) has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, Rosil (Clindamycin Phosphate) phosphate and tretinoin gel should be used with caution in patients receiving such agents.

8 USE IN SPECIFIC POPULATIONS

8.1 PREGNANCY

Pregnancy Category C. There are no well-controlled trials in pregnant women treated with Rosil phosphate and tretinoin gel. Rosil (Clindamycin Phosphate) phosphate and tretinoin gel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Rosil (Clindamycin Phosphate) phosphate and tretinoin gel was tested for maternal and developmental toxicity in New Zealand White Rabbits with topical doses of 60, 180 and 600 mg/kg/day. Rosil (Clindamycin Phosphate) phosphate and tretinoin gel 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 Rosil (Clindamycin Phosphate) phosphate and tretinoin gel 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 Rosil (Clindamycin Phosphate) phosphate and tretinoin gel applied daily to a 60 kg person.

Rosil (Clindamycin Phosphate)

Teratology (Segment II) studies using Rosil (Clindamycin Phosphate) 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 Rosil (Clindamycin Phosphate) in the recommended clinical dose based on a body surface area comparison, respectively) or with subcutaneous doses of Rosil (Clindamycin Phosphate) up to 180 mg/kg/day (175 and 88 times the amount of Rosil (Clindamycin Phosphate) in the recommended clinical dose based on a body surface area comparison, respectively) revealed no evidence of teratogenicity.

Tretinoin

In 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.

8.3 NURSING MOTHERS

It is not known whether Rosil (Clindamycin Phosphate) is excreted in human milk following use of Rosil (Clindamycin Phosphate) phosphate and tretinoin gel. However, orally and parenterally administered Rosil (Clindamycin Phosphate) 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 Rosil (Clindamycin Phosphate) phosphate and tretinoin gel is administered to a nursing woman.

8.4 PEDIATRIC USE

Safety and effectiveness of Rosil phosphate and tretinoin gel in pediatric patients under the age of 12 have not been established.

Clinical trials of Rosil (Clindamycin Phosphate) phosphate and tretinoin gel included patients 12 to 17 years of age.

8.5 GERIATRIC USE

Clinical studies of Rosil (Clindamycin Phosphate) phosphate and tretinoin gel did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

11 DESCRIPTION

Rosil (Clindamycin Phosphate) phosphate and tretinoin gel 1.2% / 0.025%, is an antibiotic and retinoid combination gel product with two active ingredients. Rosil (Clindamycin Phosphate) phosphate, USP 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 Rosil (Clindamycin Phosphate) phosphate, USP 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 Rosil (Clindamycin Phosphate) phosphate, USP is represented below:

Rosil (Clindamycin Phosphate) phosphate, USP:

Molecular Formula: C18H34ClN2O8PS Molecular Weight: 504.97

The chemical name for tretinoin, USP 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, USP is represented below:

Tretinoin, USP:

Molecular Formula: C20H28O2 Molecular Weight: 300.44

Rosil (Clindamycin Phosphate) phosphate and tretinoin gel 1.2% / 0.025% contains the following inactive ingredients: anhydrous citric acid, butylated hydroxytoluene, edetate disodium, hydroxyethyl cellulose, glycerin, methylparaben, polysorbate 80, propylparaben, purified water, tromethamine and xanthan gum.

12f9b5a2-figure-01 12f9b5a2-figure-02

12 CLINICAL PHARMACOLOGY

12.1 MECHANISMS OF ACTION

Rosil

.

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.

12.3 PHARMACOKINETICS

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 Rosil (Clindamycin Phosphate) phosphate and 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 Rosil (Clindamycin Phosphate) generally did not exceed 3.5 ng/mL, with the exception of one subject whose plasma concentration reached 13.1 ng/mL.

12.4 Microbiology

Rosil (Clindamycin Phosphate) 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. Rosil (Clindamycin Phosphate) has been shown to have in vitro activity against Propionibacterium acnes, an organism which has been associated with acne vulgaris; however, the clinical significance of this activity against P. acnes was not examined in clinical trials with Rosil (Clindamycin Phosphate) phosphate and tretinoin gel. P acnes resistance to Rosil (Clindamycin Phosphate) has been documented. Resistance to Rosil (Clindamycin Phosphate) is often associated with resistance to erythromycin.

13 NONCLINICAL TOXICOLOGY

13.1 CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY

Carcinogenicity, mutagenicity and impairment of fertility testing of Rosil (Clindamycin Phosphate) phosphate and tretinoin gel have not been performed in any species.

Rosil (Clindamycin Phosphate)

The carcinogenicity of a 1% Rosil (Clindamycin Phosphate) phosphate gel similar to Rosil (Clindamycin Phosphate) phosphate and tretinoin gel was evaluated by daily application to mice for two years. The daily doses used in this study were approximately 13 and 72 times higher than the human dose of Rosil (Clindamycin Phosphate) phosphate from Rosil (Clindamycin Phosphate) phosphate and tretinoin gel, assuming complete absorption and based on a body surface area comparison. No significant increase in tumors was noted in the treated animals. For purposes of comparisons of the animal exposure to human exposure, the recommended human topical clinical dose is defined as 1 g of Rosil (Clindamycin Phosphate) phosphate and tretinoin gel applied daily to a 60 kg person.

Fertility (Segment 1) studies in rats treated orally with up to 300 mg/kg/day of Rosil (Clindamycin Phosphate) (approximately 290 times the amount of Rosil (Clindamycin Phosphate) delivered from the recommended clinical dose for Rosil (Clindamycin Phosphate) phosphate and tretinoin gel, based on a body surface area comparison) revealed no effects on fertility or mating ability.

Tretinoin

In two independent studies with long-term topical application of tretinoin in mice, carcinogenicity was not observed. In both studies, tretinoin was administered topically (0.025% or 0.1%) three times per week for up to two years. No carcinogenicity was observed with maximum effects of dermal amyloidosis in the basal layer of the skin.

Tretinoin has been shown to enhance photoco-carcinogenicity in properly performed specific studies, employing concurrent or intercurrent exposure to the drug and UV radiation. The contribution of Rosil (Clindamycin Phosphate) to that effect is unknown. Although the significance of these studies to humans is not clear, patients should minimize exposure to sun.

The genotoxic potential of tretinoin was evaluated in an in vitro Ames Salmonella reversion test and an in vitro chromosomal aberration assay in Chinese hamster ovary cells. Both tests were negative.

In oral Segment 1 studies in rats treated with tretinoin, the no-observed-effect-level was 2 mg/kg/day (~78 times the recommended clinical dose assuming 100% absorption and based on body surface area comparison).

14 CLINICAL STUDIES

The safety and efficacy of once daily use of Rosil (Clindamycin Phosphate) phosphate and 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 Rosil (Clindamycin Phosphate) phosphate and tretinoin gel to Rosil (Clindamycin Phosphate) 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

  • inflammatory lesion counts,
  • non-inflammatory lesion counts, and
  • total lesion counts

(2) Percent of subjects who cleared or almost cleared at Week 12 as judged by an Evaluator’s Global Severity (EGS) score.

The EGS scoring scale used in all of the clinical trials for Rosil (Clindamycin Phosphate) phosphate and tretinoin gel is as follows:

Grade Description
Clear Normal, clear skin with no evidence of acne vulgaris
Almost Clear Rare non-inflammatory lesions present, with rare non-inflamed papules (papules must be resolving and may be hyperpigmented, though not pink-red)
Mild Some non-inflammatory lesions are present, with few inflammatory lesions (papules/pustules only; no nodulocystic lesions)
Moderate Non-inflammatory lesions predominate, with multiple inflammatory lesions evident: several to many comedones and papules/pustules, and there may or may not be one small nodulo-cystic lesion
Severe Inflammatory lesions are more apparent many comedones and papules/pustules, there may or may not be a few nodulocystic lesions
Very Severe Highly inflammatory lesions predominate, variable number of comedones, many papules/pustules and many nodulocystic lesions

In Study 1, a total of 1,252 patients were enrolled, and in Study 2, a total of 1,288 patients were enrolled. The combined results are presented in Table 3.

Rosil (Clindamycin Phosphate)
Phosphate and Rosil (Clindamycin Phosphate) Tretinoin Vehicle
Tretinoin Gel
N=845 N=426 N=846 N=423
* Success was defined as cleared or almost cleared at Week 12
Evaluator’s Global Severity: N (%)
Patients achieving success* 180 (21%) 70 (16%) 122 (14%) 34 (8%)
Inflammatory Lesion Count (% reduction from baseline)
Mean 48% 42% 39% 26%
Non-inflammatory Lesion Count (% reduction from baseline)
Mean 36% 27% 31% 16%
Total Lesion Count (% reduction from baseline)
Mean 41% 34% 34% 20%

In Study 3, Rosil (Clindamycin Phosphate) phosphate and tretinoin gel was compared to Rosil (Clindamycin Phosphate) gel in a total of 2,010 patients with moderate or severe acne vulgaris. 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.

Rosil (Clindamycin Phosphate) Phosphate and
Tretinoin Gel Rosil (Clindamycin Phosphate)
N = 1008 N = 1002
* Success was defined as at least a 2-grade improvement at Week 12 from baseline.
Evaluator’s Global Severity: N (%)
Patients achieving success* 415 (41%) 345 (34%)
Inflammatory Lesion Count (% reduction from baseline)
Mean 61% 55%
Non-inflammatory Lesion Count (% reduction from baseline)
Mean 50% 41%
Total Lesion Count (% reduction from baseline)
Mean 54% 47%

16 HOW SUPPLIED/STORAGE AND HANDLING

Rosil (Clindamycin Phosphate) phosphate and tretinoin gel 1.2% / 0.025% is supplied as follows:

30 gram tube NDC 0472-1790-30

60 gram tube NDC 0472-1790-60

Storage and Handling

Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F). Protect from light. Protect from freezing. Keep away from heat.

Keep tube tightly closed.

Keep out of the reach of children.

17 PATIENT COUNSELING INFORMATION

17.1 Instructions for Use

  • At bedtime, the face should be gently washed with a mild soap and warm water. After patting the skin dry, apply Rosil (Clindamycin Phosphate) phosphate and tretinoin gel as a thin layer over the entire face (excluding the eyes and lips).
  • Patients should be advised not to use more than the recommended pea sized amount and not to apply more often than once daily (at bedtime) as this will not make for faster results and may increase irritation.
  • A sunscreen should be applied every morning and reapplied over the course of the day as needed. Patients should be advised to avoid exposure to sunlight, sunlamp, ultraviolet light, and other medicines that may increase sensitivity to sunlight.

17.2 Skin Irritation

Rosil phosphate and tretinoin gel may cause irritation such as erythema, scaling, itching, burning, or stinging.

17.3 Colitis

In the event a patient treated with Rosil (Clindamycin Phosphate) phosphate and tretinoin gel experiences severe diarrhea or gastrointestinal discomfort, Rosil (Clindamycin Phosphate) phosphate and tretinoin gel should be discontinued and a physician should be contacted.

Manufactured by:

G&W laboratories, Inc.

111 Coolidge Street

South Plainfield, NJ 07080 USA

Distributed by:

Actavis Pharma, Inc.

Parsippany, NJ 07054 USA

Revised – September 2015

I600-6210/11 GW 7047

17.4 FDA-Approved Patient Labeling

PATIENT INFORMATION

Rosil (Clindamycin Phosphate) Phosphate and Tretinoin (klin-da-MYE-sin FOS-fate and TRET-i-noyn)

Gel 1.2% / 0.025%

IMPORTANT: Not for mouth, eye, or vaginal use.

Read the Patient Information that comes with Rosil (Clindamycin Phosphate) phosphate and tretinoin gel before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your acne or treatment.

What is Rosil (Clindamycin Phosphate) phosphate and tretinoin gel?

Rosil (Clindamycin Phosphate) phosphate and tretinoin gel is an antibiotic and retinoid combination medicine used for the skin treatment of acne in patients 12 years and older.

Who should not use Rosil (Clindamycin Phosphate) phosphate and tretinoin gel?

Do not use Rosil (Clindamycin Phosphate) phosphate and tretinoin gel if you:

  • have Crohn’s Disease
  • have Ulcerative Colitis
  • have developed colitis with past antibiotic use

Tell your doctor:

  • if you are pregnant or planning to become pregnant. It is not known if Rosil (Clindamycin Phosphate) phosphate and tretinoin gel may harm your unborn baby.
  • if you are breastfeeding. Rosil (Clindamycin Phosphate) phosphate and tretinoin gel may pass through your milk and may harm your baby.
  • about all the medicines and skin products you use:
    • Rosil (Clindamycin Phosphate) phosphate and tretinoin gel should not be used with erythromycin-containing products.
    • Avoid medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong drying effect, and skin products that contain alcohol, astringents, spices or lime. These products may cause increased skin irritation if used with Rosil (Clindamycin Phosphate) phosphate and tretinoin gel.

How should I use Rosil (Clindamycin Phosphate) phosphate and tretinoin gel?

Use Rosil (Clindamycin Phosphate) phosphate and tretinoin gel exactly as prescribed. It may take some time for you to see improvement of your acne with Rosil (Clindamycin Phosphate) phosphate and tretinoin gel. Your doctor will tell you how long to use Rosil (Clindamycin Phosphate) phosphate and tretinoin gel.

At bedtime:

  • Wash your face gently with a mild soap and warm water.
  • Pat the skin dry.
  • Apply a pea-size amount of Rosil (Clindamycin Phosphate) phosphate and tretinoin gel to your fingertip and spread it over your face. Gently, smooth it into your skin. Do not get Rosil (Clindamycin Phosphate) phosphate and tretinoin gel in your eyes or mouth, on your lips, on the corners of your nose, or on open wounds.

In the morning:

  • Apply a sunscreen and reapply during the day as needed.
  • Do not apply Rosil (Clindamycin Phosphate) phosphate and tretinoin gel more than once a day
  • Do not use too much Rosil (Clindamycin Phosphate) phosphate and tretinoin gel. Too much Rosil (Clindamycin Phosphate) phosphate and tretinoin gel may irritate your skin.
  • Do not wash your face more than 2 to 3 times a day. Washing your face too often or scrubbing it may make your acne worse.

Avoid:

  • excessive exposure to the sun, cold, and wind. Weather extremes can dry and burn the skin. Always use a sunscreen on Rosil (Clindamycin Phosphate) phosphate and tretinoin gel treated skin, even on cloudy days. Use other protective clothing such as a hat when you are in the sun.
  • the use of sunlamps and tanning booths

If your face becomes sunburned, stop Rosil (Clindamycin Phosphate) phosphate and tretinoin gel until your skin has healed.

What are possible side effects with Rosil (Clindamycin Phosphate) phosphate and tretinoin gel?

  • Skin irritation. Rosil (Clindamycin Phosphate) phosphate and tretinoin gel may cause skin irritation such as dryness, redness, peeling, burning, or stinging. Stop Rosil (Clindamycin Phosphate) phosphate and tretinoin gel and call your doctor if your skin becomes very red, swollen, blistered, or crusted.
  • Change in skin color. Rosil (Clindamycin Phosphate) phosphate and tretinoin gel may cause a temporary skin color change (lighter or darker).
  • Colitis. This occurs rarely. Stop Rosil (Clindamycin Phosphate) phosphate and tretinoin gel and call your doctor if you develop severe watery diarrhea, or bloody diarrhea.

Talk to your doctor about any side effect that bothers you or that does not go away.

These are not all the side effects with Rosil (Clindamycin Phosphate) phosphate and tretinoin gel. Ask your doctor or pharmacist for more information.

How should I store Rosil (Clindamycin Phosphate) phosphate and tretinoin gel?

  • Store Rosil (Clindamycin Phosphate) phosphate and tretinoin gel at room temperature, 59 to 86°F (15 to 30°C). Do not freeze.
  • Keep Rosil (Clindamycin Phosphate) phosphate and tretinoin gel away from heat and light.
  • Keep the tube tightly closed.
  • Keep Rosil (Clindamycin Phosphate) phosphate and tretinoin gel and all medicines out of the reach of children.

General information about Rosil (Clindamycin Phosphate) phosphate and tretinoin gel

Medicines are sometimes prescribed for purposes other than those listed in patient information leaflet. Do not use Rosil (Clindamycin Phosphate) phosphate and tretinoin gel for a condition for which it was not prescribed. Do not give Rosil (Clindamycin Phosphate) phosphate and tretinoin gel to other people, even if they have the same symptoms you have. It may harm them.

This leaflet summarizes the most important information about Rosil (Clindamycin Phosphate) phosphate and tretinoin gel. If you would like more information, talk with your doctor. You can also ask your pharmacist or doctor for information about Rosil (Clindamycin Phosphate) phosphate and tretinoin gel that is written for healthcare professionals.

If you have questions about Rosil (Clindamycin Phosphate) phosphate and tretinoin gel you can also call Actavis at 1-800-432-8534.

What are the ingredients in Rosil (Clindamycin Phosphate) phosphate and tretinoin gel?

Active Ingredients: Rosil (Clindamycin Phosphate) phosphate, USP 1.2% and tretinoin, USP 0.025%

Inactive Ingredients: anhydrous citric acid, butylated hydroxytoluene, edetate disodium, hydroxyethyl cellulose, glycerin, methylparaben, polysorbate 80, propylparaben, purified water, tromethamine and xanthan gum.

Manufactured by:

G&W laboratories, Inc.

111 Coolidge Street

South Plainfield, NJ 07080 USA

Distributed by:

Actavis Pharma, Inc.

Parsippany, NJ 07054 USA

Revised – September 2015

I600-6210/11 GW 7047

Rosil pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Rosil available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Rosil destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Rosil Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Rosil pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


advertisement

References

  1. Dailymed."CLINDESSE (CLINDAMYCIN PHOSPHATE) CREAM [THER-RX CORPORATION]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."CLINDAMYCIN HYDROCHLORIDE CAPSULE [LANNETT COMPANY, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. "clindamycin". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Rosil?

Depending on the reaction of the Rosil after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Rosil not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Rosil addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

advertisement

Review

sdrugs.com conducted a study on Rosil, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Rosil consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

Visitor reports

Visitor reported useful

No survey data has been collected yet

Visitor reported side effects

No survey data has been collected yet

One visitor reported price estimates

What is your opinion about drug cost? Did you feel the cost is apt, or did you feel it is expensive?
The report given by the sdrugs.com website users shows the following figures about several people who felt the medicine Rosil is expensive, and the medicine is not expensive. The results are mixed. The perception of the cost of the medicine to be expensive or not depends on the brand name of the medicine, country, and place where it is sold, and the affordability of the patient. You can choose a generic drug in the place of the branded drug to save the cost. The efficiency of the medicine will not vary if it is generic or a branded one.
Visitors%
Not expensive1
100.0%

One visitor reported frequency of use

How often in a day do you take the medicine?
Are you taking the Rosil drug as prescribed by the doctor?

Few medications can be taken 3 times in a day more than prescribed when the doctor's advice mentions the medicine can be taken according to frequency or severity of symptoms. Most times, be very careful and clear about the number of times you are taking the medication. The report of sdrugs.com website users about the frequency of taking the drug Rosil is mentioned below.
Visitors%
3 times in a day1
100.0%

Visitor reported doses

No survey data has been collected yet

Visitor reported time for results

No survey data has been collected yet

One visitor reported administration

The drugs are administered in various routes, like oral or injection form. They are administered before food or after food. How are you taking Rosil drug, before food or after food?
Click here to find out how other users of our website are taking it. For any doubts or queries on how and when the medicine is administered, contact your health care provider immediately.
Visitors%
Before food1
100.0%

Visitor reported age

No survey data has been collected yet

Visitor reviews


There are no reviews yet. Be the first to write one!


Your name: 
Email: 
Spam protection:  < Type 16 here

The information was verified by Dr. Arunabha Ray, MD Pharmacology

© 2002 - 2021 "sdrugs.com". All Rights Reserved