Clindasol 1% Lotion is indicated in the treatment of acne vulgaris.

Apply a thin film of Clindasol 1% Lotion twice daily to the affected area.
Shake well before use.

Topical clindamycin is contraindicated in individuals with a history of hypersensitivity to clindamycin, lincomycin or to any of the excipients listed in section 6.1. Clindamycin topical is contraindicated in individuals with a history of inflammatory bowel disease or a history of antibiotic-associated colitis.

Products containing benzoyl peroxide should not be used concurrently with Clindamycin Lotion Oral and parenteral clindamycin, as well as most other antibiotics, have been associated with severe pseudomembranous colitis. Post-marketing studies, however, have indicated a very low incidence of colitis with Clindamycin Lotion The physician should, nonetheless, be alert to the development of antibiotic associated diarrhoea or colitis. If significant or prolonged diarrhoea occurs, the product should be discontinued immediately.
Diarrhoea, colitis, and pseudomembranous colitis have been observed to begin up to several weeks following cessation of oral and parenteral therapy with clindamycin.
Studies indicate a toxin(s) produced by Clostridium difficile is the major cause of antibiotic associated colitis. Colitis is usually characterised by persistent, severe diarrhoea and abdominal cramps. Endoscopic examination may reveal pseudomembranous colitis. Stool culture for C. difficile and/or assay for C. difficile toxin may be helpful to diagnosis. Vancomycin is effective in the treatment of antibiotic-associated colitis produced by C. difficile. The usual dose is 125-500 mg orally every 6 hours for 7-10 days. Additional supportive medical care may be necessary. Mild cases of colitis may respond to discontinuance of clindamycin alone. Colestyramine and
colestipol resins have been shown to bind C. difficile toxin in vitro, and colestyramine has been effective in the treatment of some mild cases of antibiotic-associated colitis. Colestyramine resins have been shown to bind vancomycin; therefore, when both colestyramine and vancomycin are used concurrently, their administration should be separated by at least two hours. Clindamycin Lotion contains an alcohol base which can cause burning and irritation of the eye. In the event of accidental contact with sensitive surfaces (eye, abraded skin, mucous membranes), bathe with copious amounts of cool tap water. The Lotion has an unpleasant taste and caution
should be exercised when applying medication around the mouth. Topical clindamycin should be prescribed with caution to atopic individuals.

Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, it should be used with caution in patients receiving such agents.
Vitamin K antagonists Increased coagulation tests (PT/INR) and/or bleeding have been reported in patients treated with clindamycin in combination with a vitamin K antagonist (e.g. warfarin, acenocoumarol and fluindione). Coagulation tests, therefore, should be frequently monitored in patients treated with vitamin K antagonists.

Pregnancy:
There are no adequate and well-controlled studies in pregnant women during the first trimester. A moderate amount of data from clinical trials in pregnant women (between 300-1000 pregnancy outcomes) during the second and third trimesters indicates systemic administration of clindamycin has not been associated with an increased frequency of congenital abnormalities or feto/neonatal
toxicity. Animal reproductive toxicity studies revealed no evidence of impaired fertility or harm to the foetus due to clindamycin, except at doses that caused maternal toxicity (see section 5.3). Animal reproduction studies are not always predictive of human response.
Clindamycin Solutionshould be used during pregnancy only if clearly needed.

Breast-feeding
It is not known whether clindamycin is excreted in human milk following use of Clindamycin Lotion However, orally and parenterally administered clindamycin has been reported to appear in breast milk. As a general rule, breast-feeding should not be undertaken while a patient is on a drug since many drugs are excreted in human milk.

The effect of clindamycin on the ability to drive or operate machinery has not been systematically evaluated.

The table below lists the adverse reactions identified through clinical trial experience and postmarketing surveillance by system organ class and frequency. The frequency grouping is defined using the following convention: Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very Rare (<1/10,000) and Not known (frequency cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Adverse reactions possibly or probably related to Clindamycin Phosphate Topical Lotionbased on clinical trial experience and post-marketing surveillance:

	Very Common (≥1/10)	Common (≥1/100 to <1/10)	Uncommon ≥1/1,000 to <1/100	Frequency Not Known
Infections and Infestations				Gram-negative folliculitis, Pseudomembranous colitis
Eye Disorders				Stinging of the eye
Gastrointestinal Disorders			Gastrointestinal disturbances	Abdominal pain
Skin and Subcutaneous Tissue Disorders	Skin dryness Skin irritation Urticaria	Skin oiliness		Contact dermatitis

Reporting of suspected adverse reactions
To report any side effect(s):
Saudi Arabia:
The National Pharmacovigilance and Drug Safety Centre (NPC)
Fax: +966-11-205-7662.
Call NPC at +966-11-2038222,
Exts: 2317-2356-2353-2354-2334-2340.
Toll free phone: 8002490000
E-mail: npc.drug@sfda.gov.sa
Website: www.sfda.gov.sa/npc
Other GCC States:
Please contact the relevant competent authority.

Topically applied clindamycin can be absorbed in sufficient amounts to produce systemic effects. In the event of overdosage, general symptomatic and supportive measures are indicated as required.

Pharmacotherapeutic group: Anti-infectives for treatment of acne, ATC Code: DA10AF01.

Mechanism of action
Clindamycin is a lincosamide antibiotic that inhibits bacterial protein synthesis. It binds to the 50S ribosomal subunit and affects both ribosome assembly and the translation process. Although clindamycin phosphate is inactive in vitro, rapid in vivo hydrolysis converts this compound to the antibacterially active clindamycin.
Clindamycin has been shown to have in vitro activity against isolates of the following organisms;
Anaerobic gram positive non spore forming bacilli, including:
Propionibacterium acnes.
Pharmacodynamic effects
Efficacy is related to the time period that the agent level is above the minimum inhibitory concentration (MIC) of the pathogen (%T/MIC).

Resistance
Resistance to clindamycin in Propionibacterium acnes can be caused by mutations at the rRNA antibiotic binding site or by methylation of specific nucleotides in the 23S RNA of the 50S ribosomal subunit. These alterations can determine cross resistance to macrolides and
streptogramins B (MLSB phenotype). Macrolide-resistant isolates should be tested for inducible resistance to clindamycin using the D zone test.
The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable. Particularly in severe infections or therapy failure microbiological diagnosis with verification of the pathogen and its susceptibility to clindamycin is recommended. Resistance is usually defined by susceptibility interpretive criteria (breakpoints) established by EUCAST for systemically administered antibiotics. These breakpoints may be less relevant for topically administered clindamycin. Although clindamycin is not specifically cited, EUCAST has suggested that, for topically applied antimicrobials, resistance might be better defined by epidemiological cut-off values (ECOFFS) rather than the clinical breakpoints determined for systemic administration. However, MIC distributions and ECOFFS have not been published by EUCAST for P. acnes. Based on correlations between clinical results in acne patients and the clindamycin MICs for their P. acnes isolates, values as high as 256 mg/L are considered susceptible for topically administered clindamycin.
A Belgian surveillance study (2011-2012) of anaerobic bacteria included 22 P. acnes isolates;
95.5% were susceptible to clindamycin. An earlier European surveillance study, which included 304 isolates of P. acnes, had reported a resistance rate of 15% to clindamycin. However, this study used a breakpoint of 0.12 mg/L; using the current breakpoint of 4 mg/L, there were no resistant isolates.
Breakpoints
EUCAST breakpoints for Gram-positive anaerobes are listed below. These breakpoints are based on use in systemic infections.
EUCAST Breakpoints for Systemically Administered Clindamycin

 

Pathogen	Susceptible	Resistant
Gram-positive anaerobes (excluding Clostridium difficile)	≤4 mg/L	>4 mg/L

In a U.S. surveillance study, clindamycin MICs were ≤4 mg/L for 97% of P. acnes isolates tested. In some bacterial species, cross resistance has been demonstrated in vitro among lincosamides, macrolides, and streptogramins B.
Clinical efficacy and safety
P. acnes produces an extracellular lipase that hydrolyses sebum triglycerides to glycerol, used by the organism as a growth substrate, and free fatty acids, which have pro-inflammatory and comedogenic properties. A double-blind study had been conducted to examine the effect of topical 1% clindamycin hydrochloride hydrate in a hydroalcoholic vehicle as compared to the effect of the vehicle alone. Fourteen patients applied clindamycin or vehicle alone twice daily for eight weeks. Free fatty acid surface lipid percentages, quantitative bacterial counts, and clinical response were assessed every two weeks. A significant reduction (88%) in the percentage of free fatty acids in the surface lipids was seen in the clindamycin-treated group and not in the vehicle-treated group. Free fatty acids on the skin surface have been decreased from approximately 14% to 2% following application of clindamycin Lotion in a hydroalcoholic base to 9 patients (average age 22.3 years) with acne vulgaris. There was no significant change in the surface microflora. Despite the short duration of treatment, objective clinical improvement was seen in three of nine treated patients, while none was observed in the placebo-treated patients.

 

Following multiple topical applications of clindamycin phosphate at a concentration equivalent to 10 mg clindamycin per mL in an isopropyl alcohol and water lotion, very low levels of clindamycin are present in the serum (0–3 ng/mL) and less than 0.2% of the dose is
recovered in urine as clindamycin.
Clindamycin concentrations have been demonstrated in comedones from acne patients. The mean (±SD) concentration of clindamycin in extracted comedones after application of clindamycin topical lotion for 4 weeks was 0.60 ± 0.11 mcg/mg.

Older people
Clinical studies for topical clindamycin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Impairment of fertility
Fertility studies in rats treated orally with up to 300 mg/kg/day (72-fold the human exposure based on mg/m2) revealed no effects on fertility or mating ability.
Pregnancy
In oral embryo foetal development studies in rats and subcutaneous embryo foetal development studies in rats and rabbits, embryo-foetal toxicity was observed at doses that produced maternal toxicity. In rats, maternal death occurred with an exposure ratio of approximately 3000 relative to patient exposure. In rabbits, maternal toxicity, including abortions, occurred at exposure ratio of approximately 400. Embryo-foetal toxicity, including post-implantation loss and decreased viability, occurred in rabbits at an exposure ratio of 1000.
Carcinogenesis
Long term studies in animals have not been performed with clindamycin to evaluate carcinogenic potential.
Mutagenesis
Genotoxicity tests performed included a rat micronucleus test and an Ames test. Both tests were negative.

Methyl Paraben
Propyl Paraben
Propylene Glycol
Ethanol
Purified Water

Not applicable.

2 years (24 Months).

Do not store above 30°C.
Discard the bottle after one month from opening

Clindasol Lotion is filled in white plastic bottle 60 ml with applicator.

No special requirements.