Acretin C (Clindamycin phosphate and Tretinoin) Gel, 1.2%/0.025% is indicated for the topical
treatment of acne vulgaris in patients 12 years and older.

Posology
Clindamycin Phosphate & Tretinoin Gel should be applied once daily in the evening, gently rubbing
the medication to lightly cover the entire affected area. Approximately a pea-sized amount will be
needed for each application. Avoid the eyes, lips, and mucous membranes.
Clindamycin Phosphate & Tretinoin Gel is not for oral, ophthalmic, or intravaginal use.
Method of administration
 At bedtime, the face should be gently washed with a mild soap and water. After patting the skin
dry, apply Clindamycin Phosphate & Tretinoin Gel as a thin layer over the entire affected area
(excluding the eyes and lips).

 Patients should be advised not to use more than a pea-sized amount to cover the face 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.
 Other topical products with a strong drying effect such as abrasive soaps or cleansers may
cause an increase in skin irritation with Clindamycin Phosphate & Tretinoin Gel.
Skin Irritation
Clindamycin Phosphate & Tretinoin Gel may cause irritation such as erythema, scaling,
itching, burning, or stinging
Colitis
In the event a patient treated with Clindamycin Phosphate & Tretinoin Gel experiences severe
diarrhea or gastrointestinal discomfort, Clindamycin Phosphate & Tretinoin Gel should be
discontinued and a physician should be contacted.

Acretin C is contraindicated: • In patients who have a history of hypersensitivity to the active substances clindamycin and/or tretinoin or to any of the excipients or lincomycin (see also Section 6.1) • In patients with regional enteritis, ulcerative colitis, or history of antibiotic-associated colitis

Colitis
Systemic absorption of clindamycin has been demonstrated following topical use.
Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported
with the use of topical clindamycin. If significant diarrhea occurs, Clindamycin Phosphate &
Tretinoin Gel should be discontinued.
Severe colitis has occurred following oral or parenteral administration of clindamycin with an
onset of up to several weeks following cessation of therapy. Antiperistaltic agents such as opiates
and diphenoxylate with atropine may prolong and/or worsen severe colitis. Severe colitis may result
in death.
Studies indicate a toxin(s) produced by clostridia is one primary cause of antibiotic-associated
colitis. The colitis is usually characterized by severe persistent diarrhea and severe abdominal

cramps and may be associated with the passage of blood and mucus. Stool cultures for Clostridium
difficile and stool assay for C. difficile toxin may be helpful diagnostically.
Ultraviolet Light and Environmental Exposure
Exposure to sunlight, including sunlamps, should be avoided during the use of Clindamycin Phosphate
& Tretinoin Gel.
Patients with sunburn should be advised not to use the product until fully recovered because of
heightened susceptibility to sunlight as a result of the use of tretinoin. Patients who may be required to
have considerable sun exposure due to occupation and those with inherent sensitivity to the sun should
exercise particular caution. Daily use of sunscreen products and protective apparel (e.g., a hat) are
recommended. Weather extremes, such as wind or cold, also may be irritating to patients under treatment
with Clindamycin Phosphate & Tretinoin Gel.

Clindamycin Phosphate & Tretinoin Gel should not be used in combination with erythromycincontaining
products due to possible antagonism to the clindamycin component. In vitro studies have
shown antagonism between these 2 antimicrobials. The clinical significance of this in vitro antagonism
is not known.
Neuromuscular Blocking Agents
Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of
other neuromuscular blocking agents. Therefore, Clindamycin Phosphate & Tretinoin Gel should be
used with caution in patients receiving such agents.

Pregnancy
Pregnancy Category C.
There are no well-controlled studies in pregnant women treated with Clindamycin Phosphate &
Tretinoin gel. Clindamycin Phosphate & Tretinoin Gel should be used during pregnancy only if the
potential benefit justifies the potential risk to the fetus. A limit teratology study performed in Sprague
Dawley rats treated topically with Clindamycin Phosphate & Tretinoin Gel or 0.025% tretinoin gel at a
dose of 2 mL/kg during gestation days 6 to 15 did not result in teratogenic effects. Although no systemic
levels of tretinoin were detected, craniofacial and heart abnormalities were described in drug-treated
groups. These abnormalities are consistent with retinoid effects and occurred at 16 times the

recommended clinical dose assuming 100% absorption and based on body surface area comparison. For
purposes of comparison of the animal exposure to human exposure, the recommended clinical dose is
defined as 1g of Clindamycin Phosphate & Tretinoin Gel applied daily to a 50-kg person.
Clindamycin: Reproductive developmental toxicity studies performed in rats and mice using oral doses
of clindamycin up to 600 mg/kg/day (480 and 240 times the recommended clinical dose based on body
surface area comparison, respectively)
or subcutaneous doses of clindamycin up to 180 mg/kg/day (140 and 70 times the recommended clinical
dose based on body surface area comparison, respectively) revealed no evidence of teratogenicity.
Tretinoin: Oral tretinoin has been shown to be teratogenic in mice, rats, hamsters, rabbits, and primates.
It was teratogenic and fetotoxic in Wistar rats when given orally at doses greater than 1 mg/kg/day (32
times the recommended clinical dose based on body surface area comparison). However, variations in
teratogenic doses among various strains of rats have been reported. In the cynomologous monkey, a
species in which tretinoin metabolism is closer to humans than in other species examined, fetal
malformations were reported at oral doses of 10 mg/kg/day or greater, but none were observed at 5
mg/kg/day (324 times the recommended clinical dose based on body surface area comparison), although
increased skeletal variations were observed at all doses. Dose-related teratogenic effects and increased
abortion rates were reported in pigtail macaques. 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 2 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 fetus is
not known.
Nursing Mothers
It is not known whether clindamycin is excreted in human milk following use of Clindamycin Phosphate
& Tretinoin Gel. 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. It is not known whether tretinoin is excreted in human milk. Because many
drugs are excreted in human milk, caution should be exercised when Clindamycin Phosphate &
Tretinoin Gel is administered to a nursing woman.

Pediatric Use
Safety and effectiveness of Clindamycin Phosphate & Tretinoin Gel in pediatric patients younger than
12 years have not been established.
Clinical trials of Clindamycin Phosphate & Tretinoin Gel included 2,086 subjects aged 12 through 17
years with acne vulgaris. [See Clinical Studies (14).]
Geriatric Use
Clinical trials of Clindamycin Phosphate & Tretinoin Gel did not include sufficient numbers of
subjects aged 65 and older to determine whether they respond differently from younger subjects.

No studies on the effects on the ability to drive and use machines have been performed. It is unlikely
that treatment with Acretin C will have any effect on the ability to drive and use machines.

Adverse Reactions in Clinical Trials
Because clinical trials are conducted under widely varying conditions, adverse reaction rates
observed in clinical trials of a drug cannot be directly compared with rates in the clinical trials
of another drug and may not reflect the rates observed in clinical practice.
The safety data reflect exposure to Clindamycin Phosphate & Tretinoin Gel in 1,104 subjects with
acne vulgaris.
Subjects were 12 years and older and were treated once daily in the evening for 12 weeks.
Adverse reactions that were reported in ≥1% of subjects treated with Clindamycin Phosphate &
Tretinoin Gel are presented in Table 1.

Acretin C Gel is for topical use only. If Acretin C Gel is applied excessively, marked redness, peeling
or discomfort can occur. If excess application occurs accidentally or through over-enthusiastic use,
the face should be gently washed with a mild soap and lukewarm water. Acretin C should be
discontinued for several days before resuming therapy.
In the case of overdosage, topically applied clindamycin phosphate from Acretin C can be absorbed
in sufficient amounts to cause systemic effects. Gastrointestinal side effects including abdominal
pain, nausea, vomiting and diarrhoea may occur (see section 4.4)
In the event of accidental ingestion, treatment should be symptomatic. The same adverse reactions
effects as those expected with clindamycin (i.e. abdominal pain, nausea, vomiting and diarrhoea) and
tretinoin (including teratogenesis in women of childbearing years) are expected. In such cases,
Acretin C Gel should be discontinued and pregnancy testing should be carried out in women of
childbearing potential.

Pharmacotherapeutic group: Anti-Acne Preparations for Topical Use; clindamycin, combinations
ATC code: D10AF51
Acretin C combines two active substances, which act through different mechanisms of action (see
below).
Clindamycin:
Mechanism of Action: Clindamycin binds to the 50S ribosomal subunit of susceptible bacteria and
prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing
proteinsynthesis. 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 trials with Clindamycin Phosphate & Tretinoin
Gel. 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.
Tretinoin:
Although the exact mode of action of tretinoin is unknown, current evidence suggests that topical
tretinoin decreases cohesiveness of folliculare epithelial cells with decreased microcomedone
formation. Additionally, tretinoin stimulates mitotic activity and increased turnover of follicular
epithelial cells causing extrusion of the comedones.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal studies have not been performed to evaluate the carcinogenic potential of Clindamycin
Phosphate & Tretinoin Gel or the effect of Clindamycin Phosphate & Tretinoin gel on fertility.
Clindamycin Phosphate & Tretinoin gel was negative for mutagenic potential when evaluated in an in
vitro ames salmonella reversion assay. Clindamycin Phosphate & Tretinoin Gel was equivocal for
clastogenic potential in the absence of metabolic activation when tested in an in vitro chromosomal
aberration assay.
Clindamycin: Once-daily dermal administration of 1% Clindamycin as Clindamycin phosphate
in the gel vehicle (32 mg/kg/day, 13 times the recommended clinical dose based on body surface area
comparison) to mice for up to 2 years did not produce evidence of tumorigenicity.

Fertility studies in rats treated orally with up to 300 mg/kg/day of clindamycin (240 times the
recommended clinical dose based on body surface area comparison) revealed no effects on fertility or
mating ability.
Tretinoin: In 2 independent mouse studies where tretinoin was administered topically (0.025% or 0.1%)
3 times per week for up to 2 years no carcinogenicity was observed, with maximum effects of dermal
amyloidosis. However, in a dermal carcinogenicity study in mice, tretinoin applied at a dose of 5.1 mcg
(1.4 times the recommended clinical dose based on body surface area comparison) 3 times per week for
20 weeks acted as a weak promoter of skin tumor formation following a single application of
dimethylbenz[α] anthracene (DMBA).
In a study in female SENCAR mice, papillomas were induced by topical exposure to DMBA followed by
promotion with 12-O-tetradecanoylphorbol-13-acetate or mezerein for up to 20 weeks. Topical
application of tretinoin prior to each application of promoting agent resulted in a reduction in the number
of papillomas per mouse. However, papillomas resistant to topical tretinoin suppression were at higher
risk for pre-malignant progression.
Tretinoin has been shown to enhance photocarcinogenicity in properly performed specific studies,
employing concurrent or intercurrent exposure to tretinoin and UV radiation. The photocarcinogenic
potential of the clindamycin tretinoin combination is unknown.
Although the significance of these studies to humans is not clear, patients should avoid 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 fertility studies in rats treated with tretinoin, the no-observed-effect-level was 2 mg/
kg/day (64 times the recommended clinical dose based on body surface area comparison).

In an open-label trial of 17 subjects with moderate-to-severe acne vulgaris, topical administration of
approximately 3 grams of Clindamycin Phosphate & Tretinoin Gel once daily for 5 days, clindamycin
concentrations were quantifiable in all 17 subjects starting from 1 hour post-dose. All plasma clindamycin
concentrations were ≤5.56 ng/mL on Day 5, with the exception of 1 subject who had a maximum
clindamycin concentration of 8.73 ng/mL at 4 hours post-dose. There was no appreciable increase in
systemic exposure to tretinoin, as compared with the baseline value. The average tretinoin concentration
across all sampling times on Day 5 ranged from 1.19 to 1.23 ng/mL compared with the corresponding
baseline mean tretinoin concentration range of 1.16 to 1.30 ng/mL.

The safety and efficacy of Clindamycin Phosphate & Tretinoin Gel, applied once daily for the treatment
of acne vulgaris,
was evaluated in 12-week multi-center, randomized, blinded trials in subjects 12 years
and older.
Treatment response was defined as the percent of subjects who had a 2-grade improvement
from baseline to Week 12 based on the Investigator’s Global Assessment (IGA) and a mean
absolute change from baseline to Week 12 in 2 out of 3 (total, inflammatory, and
non-inflammatory) lesion counts. The IGA scoring scale used in all the clinical trials for
CLINDAMYCIN PHOSPHATE & TRETINOIN Gel.

The safety and efficacy of clindamycin-tretinoin gel was also evaluated in 2 additional 12-week, multicentered,
randomized, blinded trials in subjects 12 years and older. A total of 2,219 subjects with mildto-
moderate acne vulgaris were treated once daily for 12 weeks. Of the 2,219 subjects, 634 subjects were
treated with clindamycin-tretinoin gel. These trials demonstrated consistent outcomes.

 Edetate Disodium (EDTA)
 Butylated Hydroxytoulene
 Citric acid Monohydrate
 Propylene Glycol
 Methyl paraben
 Laureth-4
 Tromethamine (Tris Amino) USP
 Carbopol 980 NF (Carbomer Type-C)
 Purified water

Not applicable

24 months

Do not store above 30°C

Aluminium Collapsible Tubes 30 gm

No special requirements