EVOCLIN
HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use EVOCLIN Foam safely and effectively. See full prescribing information for EVOCLIN Foam. EVOCLIN (clindamycin phosphate) Foam, 1%For Topical UseInitial U.S. Approval: 1970INDICATIONS AND USAGEEVOCLIN Foam is a lincosamide product indicated for acne vulgaris in patients 12 years and older. (1)DOSAGE AND ADMINISTRATION •For topical use only; not for oral, ophthalmic, or intravaginal use. (2) •Apply EVOCLIN Foam once daily to affected areas. (2) •Flammable; avoid fire, flame and/or smoking during and immediately following application. (2) DOSAGE FORMS AND STRENGTHSFoam containing 1% clindamycin as clindamycin phosphate. (3)CONTRAINDICATIONSEVOCLIN Foam is contraindicated in individuals with a history of regional enteritis or ulcerative colitis, or a history of antibiotic-associated colitis (including pseudomembranous colitis). (4)WARNINGS AND PRECAUTIONS •Colitis: Clindamycin can cause severe colitis, which may result in death. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of clindamycin. EVOCLIN Foam should be discontinued if significant diarrhea occurs. (5.1) Side EffectsThe most common adverse reactions (>1%) are headache and application site reactions including burning, pruritus, and dryness. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Stiefel Laboratories, Inc. at 1-888-784-3335 (1-888-STIEFEL) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
FULL PRESCRIBING INFORMATION: CONTENTS*
- 1 EVOCLIN INDICATIONS AND USAGE
- 2 EVOCLIN DOSAGE AND ADMINISTRATION
- 3 DOSAGE FORMS AND STRENGTHS
- 4 EVOCLIN CONTRAINDICATIONS
- 5 WARNINGS AND PRECAUTIONS
- 6 EVOCLIN ADVERSE REACTIONS
- 7 DRUG INTERACTIONS
- 8 USE IN SPECIFIC POPULATIONS
- 11 EVOCLIN DESCRIPTION
- 12 CLINICAL PHARMACOLOGY
- 13 NONCLINICAL TOXICOLOGY
- 14 CLINICAL STUDIES
- 16 HOW SUPPLIED/STORAGE AND HANDLING
- 17 PATIENT COUNSELING INFORMATION
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
EVOCLIN Foam is indicated for topical application in the treatment of acne vulgaris in patients 12 years and older.
2 DOSAGE AND ADMINISTRATION
EVOCLIN Foam is for topical use only, and not for oral, ophthalmic, or intravaginal use.
Apply EVOCLIN Foam once daily to affected areas after the skin is washed with mild soap and allowed to fully dry. Use enough to cover the entire affected area.
If there has been no improvement after 6 to 8 weeks or if the condition becomes worse, treatment should be discontinued.
The contents of EVOCLIN Foam are flammable; avoid fire, flame and/or smoking during and immediately following application.
3 DOSAGE FORMS AND STRENGTHS
White to off-white thermolabile foam. Each gram of EVOCLIN Foam contains, as dispensed, 12 mg (1.2%) of clindamycin phosphate, equivalent to 10 mg (1%) of clindamycin.
4 CONTRAINDICATIONS
EVOCLIN Foam is contraindicated in individuals with a history of regional enteritis or ulcerative colitis, or a history of antibiotic-associated colitis (including pseudomembranous colitis).
5 WARNINGS AND PRECAUTIONS
5.1 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. If significant diarrhea occurs, EVOCLIN Foam should be discontinued. [See Adverse Reactions (6.2).]
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.
5.2 Irritation
EVOCLIN Foam can cause irritation. Concomitant topical acne thereapy should be used with caution since a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating, or abrasive agents. If irritation or dermatitis occurs, clindamycin should be discontinued.
Avoid contact of EVOCLIN Foam with eyes, mouth, lips, other mucous membranes or areas of broken skin. If contact occurs, rinse thoroughly with water.
EVOCLIN Foam should be prescribed with caution in atopic individuals.
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
A total of 439 subjects with mild to moderate acne vulgaris were treated once daily for 12 weeks with EVOCLIN Foam.
The incidence of adverse reactions occurring in ≥1% of the subjects in clinical trials comparing EVOCLIN Foam, and its vehicle is presented in Table 1.
|
Adverse Reactions |
Number (%) of Subjects |
|
|
EVOCLIN Foam |
Vehicle Foam |
|
|
N = 439 |
N = 154 |
|
|
Headache |
12 (3%) |
1 (1%) |
|
Application site burning |
27 (6%) |
14 (9%) |
|
Application site pruritus |
5 (1%) |
5 (3%) |
|
Application site dryness |
4 (1%) |
5 (3%) |
|
Application site reaction, not otherwise specified |
3 (1%) |
4 (3%) |
In a contact sensitization study, none of the 203 subjects developed evidence of allergic contact sensitization to EVOCLIN Foam.
6.2 Postmarketing Experience
The following adverse reactions have been identified during post approval use of EVOCLIN Foam: application site pain, application site erythema, diarrhea, urticaria, abdominal pain, hypersensitivity, rash, abdominal discomfort, nausea, seborrhea, application site rash, dizziness, pain of skin, colitis (including pseudomembranous colitis), and hemorraghic diarrhea. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Abdominal pain and gastrointestinal disturbances, as well as gram-negative folliculitis, have also been reported in association with the use of topical formulations of clindamycin. Orally and parenterally administered clindamycin have been associated with severe colitis, which may end fatally.
7 DRUG INTERACTIONS
7.1 Erythromycin
EVOCLIN Foam should not be used in combination with topical or oral erythromycin-containing products due to possible antagonism 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.
7.2 Neuromuscular Blocking Agents
Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, EVOCLIN Foam should be used with caution in patients receiving such agents.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category B: There are no adequate and well-controlled studies in pregnant women treated with EVOCLIN Foam. EVOCLIN Foam should be used during pregnancy only if the potential benefit clearly outweighs the potential risk to the fetus.
Reproduction studies have been performed in rats and mice using subcutaneous and oral doses of clindamycin phosphate, clindamycin hydrochloride and clindamycin palmitate hydrochloride. These studies revealed no evidence of fetal harm. The highest dose used in the rat and mouse teratogenicity studies was equivalent to a clindamycin phosphate dose of 432 mg/kg. For a rat, this dose is 84 fold higher, and for a mouse 42 fold higher, than the anticipated human dose of clindamycin phosphate from EVOCLIN Foam based on a mg/m2 comparison.
8.3 Nursing Mothers
It is not known whether clindamycin is excreted in human milk following use of EVOCLIN Foam. 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.
If used during lactation and EVOCLIN Foam is applied to the chest, care should be taken to avoid accidental ingestion by the infant.
8.4 Pediatric Use
Safety and effectiveness of EVOCLIN Foam in children under the age of 12 have not been studied.
8.5 Geriatric Use
The clinical study with EVOCLIN Foam did not include sufficient numbers of subjects aged 65 and over to determine if they respond differently than younger subjects.
11 DESCRIPTION
EVOCLIN (clindamycin phosphate) Foam contains clindamycin (1%) as clindamycin phosphate.
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:
Molecular Formula: C18H34ClN2O8PS Molecular Weight: 504.97 g/mol
EVOCLIN Foam contains clindamycin (1%) as clindamycin phosphate, at a concentration equivalent to 10 mg clindamycin per gram in a thermolabile hydroethanolic foam vehicle consisting of cetyl alcohol, ethanol (58%), polysorbate 60, potassium hydroxide, propylene glycol, purified water, and stearyl alcohol pressurized with a hydrocarbon (propane/butane) propellant.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Mechanism of action in acne vulgaris is unknown. [See Microbiology (12.4)]
12.2 Pharmacodynamics
Pharmacodynamics of EVOCLIN Foam is unknown.
12.3 Pharmacokinetics
In an open label, parallel group study in 24 subjects with acne vulgaris, 12 subjects (3 male and 9 female) applied 4 grams of EVOCLIN Foam once-daily for five days, and 12 subjects (7 male and 5 female) applied 4 grams of a clindamycin gel, 1%, once daily for five days. On Day 5, the mean Cmax and AUC(0-12) were 23% and 9% lower, respectively, for EVOCLIN Foam than for the clindamycin gel, 1%.
Following multiple applications of EVOCLIN Foam, less than 0.024% of the total dose was excreted unchanged in the urine over 12 hours on Day 5.
12.4 Microbiology
No microbiology studies were conducted in the clinical trials with this product.
Clindamycin binds to the 50S ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing protein synthesis. Clindamycin has been shown to have in vitro activity against Propionibacterium acnes (P. acnes), an organism that has been associated with acne vulgaris; however, the clinical significance of this activity against P. acnes was not examined in clinical studies with EVOCLIN Foam. P. acnes resistance to clindamycin has been documented.
Inducible Clindamycin Resistance
The treatment of acne with antimicrobials is associated with the development of antimicrobial resistance in P. acnes as well as other bacteria (e.g. Staphylococcus aureus, Streptococcus pyogenes). The use of clindamycin may result in developing inducible resistance in these organisms. This resistance is not detected by routine susceptibility testing.
Cross Resistance
Resistance to clindamycin is often associated with resistance to erythromycin.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
The carcinogenicity of a 1.2% clindamycin phosphate gel similar to EVOCLIN Foam was evaluated by daily application to mice for two years. The daily doses used in this study were approximately 3 and 15 times higher than the human dose of clindamycin phosphate from 5 milliliters of EVOCLIN Foam, assuming complete absorption and based on a body surface area comparison. No significant increase in tumors was noted in the treated animals.
A 1.2% clindamycin phosphate gel similar to EVOCLIN Foam caused a statistically significant shortening of the median time to tumor onset in a study in hairless mice in which tumors were induced by exposure to simulated sunlight.
Genotoxicity tests performed included a rat micronucleus test and an Ames Salmonella reversion test. Both tests were negative.
Reproduction studies in rats using oral doses of clindamycin hydrochloride and clindamycin palmitate hydrochloride have revealed no evidence of impaired fertility.
14 CLINICAL STUDIES
In one multicenter, randomized, double-blind, vehicle-controlled clinical trial, subjects with mild to moderate acne vulgaris used EVOCLIN Foam or the vehicle Foam once daily for twelve weeks. Treatment response, defined as the proportion of subjects clear or almost clear, based on the Investigator Static Global Assessment (ISGA), and the mean percent reductions in lesion counts at the end of treatment in this study are shown in Table 2.
|
Efficacy Parameters |
EVOCLIN Foam N=386 |
Vehicle Foam N=127 |
|
Treatment response (ISGA) |
31% |
18% |
|
Percent reduction in lesion counts |
||
|
Inflammatory Lesions |
49% |
35% |
|
Noninflammatory Lesions |
38% |
27% |
|
Total Lesions |
43% |
31% |
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
EVOCLIN Foam containing clindamycin phosphate equivalent to 10 mg clindamycin per gram, is white to off-white in color and thermolabile. It is available in the following sizes:
-
• 100 gram aerosol can - NDC 0145-0061-00 -
• 50 gram aerosol can - NDC 0145-0061-50
16.2 Storage and Handling
Store at controlled room temperature between 68°F to 77°F (20°C to 25°C).
Flammable. Avoid fire, flame or smoking during and immediately following application.
Contents under pressure. Do not puncture or incinerate. Do not expose to heat or store at temperature above 120°F (49°C).
Keep out of reach of children.
17 PATIENT COUNSELING INFORMATION
See FDA-Approved patient labeling (Patient Information).
17.1 Instructions for Use
-
• Patients should be advised to wash their skin with mild soap and allow it to dry before applying EVOCLIN Foam. -
• Patients should use enough EVOCLIN Foam to cover the face and to apply once daily. -
• Patients should dispense EVOCLIN Foam directly into the cap or onto a cool surface. -
• Patients should wash their hands after applying EVOCLIN Foam.
17.2 Skin Irritation
EVOCLIN Foam may cause irritation such as erythema, scaling, itching, burning, or stinging. Patients should be advised to discontinue use if excessive irritancy or dermatitis occurs.
17.3 Colitis
In the event a patient treated with EVOCLIN Foam experiences severe diarrhea or gastrointestinal discomfort, EVOCLIN Foam should be discontinued and a physician should be contacted.
EVC:3PI
Pharmacist-Detach here and Give Instructions to Patient
Patient Information
EVOCLIN (Ev-o-clin)
(clindamycin phosphate) Foam
|
Important: |
For skin use only. Do not use EVOCLIN Foam in your eyes, mouth or vagina. |
Read the Patient Information that comes with EVOCLIN Foam 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 medical condition or treatment.
What is EVOCLIN Foam?
EVOCLIN Foam is a prescription medicine used on the skin (topical) to treat acne in people 12 years and older.
It is not known if EVOCLIN Foam is safe and effective in children under 12 years of age.
Who should not use EVOCLIN Foam?
Do not use EVOCLIN Foam if you:
-
• have Crohn’s disease -
• have ulcerative colitis -
• have had inflammation of the colon (colitis) or severe diarrhea with past antibiotic use
Tell your doctor if you are not sure if you have any of the conditions listed above.
What should I tell my doctor before using EVOCLIN Foam?
Before you use EVOCLIN Foam, tell your doctor if you:
-
• have a history of eczema -
• are planning to have surgery. EVOCLIN Foam may affect how certain medicines work that may be given during surgery. -
• have any other medical conditions -
• are pregnant or planning to become pregnant. It is not known if EVOCLIN Foam may harm your unborn baby. -
• are breastfeeding or plan to breastfeed. It is not known if EVOCLIN Foam passes through your breast milk. You and your doctor should decide if you will use EVOCLIN Foam or breastfeed. If you use EVOCLIN Foam while breastfeeding and EVOCLIN Foam is applied on the chest, take care to avoid getting EVOCLIN Foam into your baby’s mouth.
Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins and herbal supplements. EVOCLIN Foam may affect the way other medicines work and other medicines may affect how EVOCLIN Foam works.
Especially tell your doctor if you take erythromycin or use products on your skin that contain erythromycin.
Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.
How should I use EVOCLIN Foam?
-
• EVOCLIN Foam is for use on the skin only. Do not get EVOCLIN Foam in your eyes, mouth or vagina. -
• Use EVOCLIN Foam exactly as your doctor tells you to use it. See the “Instructions for Applying EVOCLIN Foam” below. -
• Apply EVOCLIN Foam 1 time a day. -
• Wash your skin with mild soap and water and dry before applying EVOCLIN Foam. -
• Do not dispense EVOCLIN Foam directly onto your hands or face, because the foam will begin to melt on contact with warm skin.
Instructions for Applying EVOCLIN Foam.
-
• Remove the clear cap from the EVOCLIN Foam can (See Figure A).
Figure A: Remove clear cap.
-
• Line up the black circle with the nozzle (See Figure B).
Figure B: Line up the black circle with the nozzle.
-
• Hold the can upright and firmly press the nozzle to dispense EVOCLIN Foam (See Figure C).
Figure C: Hold can upright and press nozzle firmly to dispense.
Dispense EVOCLIN Foam into the clear cap or onto a cool surface (see Figure D).
Figure D: Dispense EVOCLIN Foam into clear cap.
-
• Dispense enough EVOCLIN Foam to cover the affected area (see Figure E).
Figure E: Dispense enough EVOCLIN Foam to cover affected area.
-
• If the can seems warm or the foam seems runny, run the can under cold water (See Figure F).
Figure F: If the can seems warm or the foam is runny, run the can under cold water.
-
• Pick up small amounts of EVOCLIN Foam with your fingertips and gently rub the foam into the affected area until the foam disappears (See Figure G).
Figure G: Pick up a small amount of EVOCLIN Foam on your fingertips and gently rub into the affected area until the foam disappears.
-
• Wash your hands after applying EVOCLIN.
Throw away any of the unused medicine that you dispensed out of the can.
What should I avoid while using EVOCLIN Foam?
-
• EVOCLIN Foam is flammable. Avoid fire, flames, or smoking during and right after you apply EVOCLIN Foam to your skin. -
• Avoid getting EVOCLIN Foam in or near your eyes, mouth, lips, or broken skin. If you get EVOCLIN Foam in your eyes, mouth, on lips or broken skin, rinse well with water.
What are possible side effects with EVOCLIN Foam?
EVOCLIN Foam can cause serious side effects including:
-
• Inflammation of the colon (colitis). Clindamycin can cause severe colitis that may lead to death. Stop using EVOCLIN Foam and call your doctor right away if you have severe watery diarrhea, or bloody diarrhea.
The most common side effects of EVOCLIN Foam include:
-
• Skin irritation. EVOCLIN Foam may cause skin irritation such as burning, itching, or dryness. Stop using EVOCLIN Foam and talk with your doctor if you develop any excessive skin irritation. -
• Headache.
Tell your doctor if you have any side effect that bothers you or that does not go away.
These are not all the side effects of EVOCLIN Foam. For more information, ask your doctor or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may report side effects to Stiefel at 1-888-784-3335 (1-888- STIEFEL).
How should I store EVOCLIN Foam?
-
• Store EVOCLIN Foam at room temperature between 68°F to 77°F (20°C to 25°C). -
• Keep EVOCLIN Foam away from heat. Never throw the can into a fire, even if the can is empty. -
• Do not store EVOCLIN Foam at temperatures above 120°F (49°C). -
• Do not break through (puncture) the EVOCLIN Foam can.
Keep EVOCLIN Foam and all medicines out of the reach of children.
General information about the safe and effective use of EVOCLIN Foam:
Medicines are sometimes prescribed for purposes other than those listed in Patient Information. Do not use EVOCLIN Foam for a condition for which it was not prescribed. Do not give EVOCLIN Foam to other people, even if they have the same symptoms you have. It may harm them.
This leaflet summarizes the most important information about EVOCLIN Foam. If you would like more information, talk with your doctor. You can also ask your pharmacist or doctor for information about EVOCLIN Foam that is written for health professionals.
What are the ingredients in EVOCLIN Foam?
Active ingredient: clindamycin phosphate
Inactive ingredients: cetyl alcohol, ethanol (58%), polysorbate 60, potassium hydroxide, propylene glycol, purified water, and stearyl alcohol. The can is pressurized with a hydrocarbon (propane/butane) propellant.
This Patient Information has been approved by the U.S. Food and Drug Administration.
Manufactured for:
Stiefel Laboratories, Inc.
Research Triangle Park, NC 27709
EVC:3PIL
EVOCLIN is a registered trademark of Stiefel Laboratories, Inc.
©2012 Stiefel Laboratories, Inc.
Jan/2012
Principal Display Panel
NDC 0145-0061-50
evoclin ®
(clindamycin phosphate)
Foam, 1%
50 g
Rx only
FOR TOPICAL USE ONLY. NOT FOR OPHTHALMIC, ORAL, OR INTRAVAGINAL USE.
Description: Evoclin® (clindamycin phosphate) Foam 1%, contains clindamycin phosphate, USP, at a concentration equivalent to 10 mg clindamycin per gram in a thermolabile hydroethanolic foam vehicle consisting of cetyl alcohol, ethanol (58%), polysorbate 60, potassium hydroxide, propylene glycol, purified water, and stearyl alcohol pressurized with a hydrocarbon (propane/butane) propellant.
Dosage: Use only as prescribed by your physician. See package insert for full prescribing information.
Warning: FLAMMABLE. AVOID FIRE, FLAME, OR SMOKING DURING AND IMMEDIATELY FOLLOWING APPLICATION.
Keep out of reach of children. Avoid contact with eyes.
Contents under pressure. Do not puncture or incinerate container. Do not expose to heat or store at temperatures above 120°F (49°C).
Store at controlled room temperature, 68°-77°F (20°-25°C).
CFC FREE
Manufactured for
Stiefel Laboratories, Inc.
Research Triangle Park, NC 27709
For additional information:
1-888-784-3335 (1-888-STIEFEL)
or visit www.evoclin.com
111674
©2011 Stiefel Laboratories, Inc.
Evoclin is a registered trademark of Stiefel Laboratories, Inc.
Made in China
10000000090860
EVOCLINclindamycin phosphate AEROSOL, FOAM
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
