EVOCLIN (clindamycin phosphate) aerosol, foam
1 INDICATIONS AND USAGE
EVOCLIN Foam is indicated for topical application in the treatment of acne vulgaris in patients 12 years and older.
EVOCLIN® Foam is a lincosamide product indicated for acne vulgaris in patients 12 years and older. (1)
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
EVOCLIN (clindamycin phosphate) is a white to off-white thermolabile foam. EVOCLIN Foam, 1% contains 10 mg of clindamycin as clindamycin phosphate, USP per gram.
Foam containing 1% clindamycin as clindamycin phosphate. (3)
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).
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). (4)
5 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)
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 therapy 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
The most common adverse reactions (>1%) are headache and application site reactions including burning, pruritus, and dryness. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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.
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 hemorrhagic 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
Risk Summary
There are no available data on EVOCLIN Foam use in pregnant women to inform a drug‑associated risk for adverse developmental outcomes.
Animal reproduction studies have not been conducted with EVOCLIN Foam. No evidence of fetal harm or malformations was observed in pregnant rats and mice administered daily subcutaneous or oral doses of clindamycin salts during organogenesis at doses that produced exposures up to 84 and 42 times, respectively, the maximum recommended human dose (MRHD) of EVOCLIN Foam based on body surface area (BSA) comparisons and assuming 100% absorption [see Data].
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data
Animal Data
Reproduction studies have been conducted in rats and mice using subcutaneous or oral doses of clindamycin phosphate, clindamycin hydrochloride or clindamycin palmitate hydrochloride administered daily during organogenesis at doses up to the equivalent of 432 mg/kg/day clindamycin phosphate. These studies produced no evidence of fetal harm or malformations in rats or mice at exposures 84 or 42 times, respectively, the MRHD of clindamycin phosphate (i.e., 5 milliliters of EVOCLIN Foam) based on BSA comparison and assuming 100% absorption.
8.2 Lactation
Risk Summary
There is no information on the presence of clindamycin in human milk, or the effects on the breast-fed child, or the effects on milk production following use of EVOCLIN Foam. However, orally and parenterally administered clindamycin has been reported to appear in breast milk.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for EVOCLIN Foam and any potential adverse effects on the breast-fed child from EVOCLIN Foam or from the underlying maternal condition.
Clinical Considerations
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, 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.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Mechanism of action of clindamycin 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 topical administration to mice for two years. The topical doses used in this study were approximately 3 and 15 times higher than the MRHD of clindamycin phosphate from EVOCLIN Foam, based on BSA comparison and assuming 100% absorption. No significant increase in tumors was noted in the treated animals.
The genotoxic potential of clindamycin was evaluated in an in vitro Ames assay and in an in vivo rat micronucleus test. Both tests were negative.
Reproduction studies in rats using oral doses of clindamycin hydrochloride or 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.
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
EVOCLIN (clindamycin phosphate) Foam, 1% contains 10 mg of clindamycin as clindamycin phosphate, USP per gram. The white to off-white thermolabile foam is available as follows:
NDC 0378-8134-50
carton of one 50 gram aerosol can
NDC 0378-8134-01
carton of one 100 gram aerosol can
16.2 Storage and Handling
Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]
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).
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.
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 occur.
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.
PATIENT INFORMATION
This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 4/2018
Instructions for Use
EVOCLIN (Ev-o-clin)
(clindamycin phosphate)
Foam, 1%
Important Information: EVOCLIN Foam is for use on the skin only. Do not use EVOCLIN Foam in your eyes, mouth or vagina.
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.
The Instructions for Use has been approved by the U.S. Food and Drug Administration.
EVOCLIN is a registered trademark of Stiefel Laboratories, Inc., a GSK Company, exclusively licensed to the Mylan Companies.
©2018 Delcor Asset Corporation, a Mylan Company
Manufactured for:
Mylan Pharmaceuticals Inc.
Morgantown, WV 26505 U.S.A.
Manufactured by:
DPT Laboratories, Ltd.
San Antonio, TX 78215 U.S.A.
Revised: 4/2018
140944-0418
DPT:CLINPHFO:R2
PRINCIPAL DISPLAY PANEL – 1%
NDC 0378-8134-50
evoclin®
(clindamycin
phosphate)
Foam, 1%
For Topical Use Only
Rx only 50 g
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.
Usual Dosage: Use only as prescribed
by your physician. See accompanying
prescribing information.
Warning: FLAMMABLE. AVOID FIRE,
FLAME, OR SMOKING DURING AND
IMMEDIATELY FOLLOWING
APPLICATION.
Keep this and all medication
out of the 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 20° to 25°C (68° to 77°F).
[See USP Controlled Room
Temperature.]
CFC FREE
Manufactured for:
Mylan Pharmaceuticals Inc.
Morgantown, WV 26505 U.S.A.
Manufactured by:
DPT Laboratories, Ltd.
San Antonio, TX 78215 U.S.A.
For more information, call
Mylan at 1-877-446-3679
(1-877-4-INFO-RX)
or visit www.evoclin.com.
117486-0318
DPT:8134:50:1C:R2
©2018 Delcor Asset Corporation,
a Mylan Company
Evoclin is a registered trademark of Stiefel
Laboratories, Inc., a GSK Company, exclusively
licensed to the Mylan Companies.
Guideline Central and select third party use “cookies” on this website to enhance the user experience.
This technology helps us gather statistical and analytical information to optimize the relevant content for you.
The user also has the option to opt-out which may have an effect on the browsing experience.