SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Dalacin® T Topical Solution

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

One ml of Dalacin T Topical Solution contains the equivalent of 10 mg Clindamycin.

Excipients with known effect:

Propylene glycol 50 mg/ml.

For the full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Topical solution.

Colourless aqueous solution.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Dalacin T Topical Solution is indicated in the treatment of acne vulgaris

4.2    Posology and method of administration

Apply a thin film of Dalacin T Topical Solution twice daily to the affected area.

Shake well before use.

4.3 Contraindications

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.

4.4 Special warnings and precautions for use

Products containing benzoyl peroxide should not be used concurrently with Dalacin T Topical Solution.

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 Dalacin T Topical Solution. 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.

Dalacin T Topical Solution 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 solution 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.

4.5 Interaction with other medicinal products and other forms of interaction

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.

4.6 Fertility, Pregnancy and lactation

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 fetus due to clindamycin, except at doses that caused maternal toxicity (see section 5.3). Animal reproduction studies are not always predictive of human response.

Dalacin T Topical Solution should be used during pregnancy only if clearly needed.

Breast-feeding

It is not known whether clindamycin is excreted in human milk following use of Dalacin T Topical Solution. 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.

Effects on ability to drive and use machines

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

4.8 Undesirable effects

The table below lists the adverse reactions identified through clinical trial experience and post-marketing 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 Solution based 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
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

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any

suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

4.9 Overdose

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.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

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

Microbiology

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 nonsporeforming bacilli, including:

•    Propionibacterium acnes.

EUCAST has established susceptibility interpretive criteria for gram-negative and gram-positive anaerobes (with the exception of C. difficile): susceptible, <4 mg/L; resistant, >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 solution 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.

5.2 Pharmacokinetic properties

Following multiple topical applications of clindamycin phosphate at a concentration equivalent to 10 mg clindamycin per mL in an isopropyl alcohol and water solution, very low levels of clindamycin are present in the serum (03 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 solution 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.

5.3 Preclinical safety data

Embryo fetal development studies using oral doses in rats and subcutaneous doses in rats and rabbits, revealed no evidence of developmental toxicity except at doses that produced maternal toxicity. In reproductive studies in rats there was no evidence of impaired fertility.

Clindamycin was not genotoxic when evaluated in the in vivo rat micronucleus test and the Ames test.

Long-term studies in animals to evaluate carcinogenic potential have not been performed with clindamycin.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Isopropyl alcohol Propylene glycol Purified water Hydrochloric acid (10%)

Sodium hydroxide (10%)

6.2    Incompatibilities

Not applicable.

6.3    Shelf life

24 months.

6.4    Special precautions for storage

Do not store above 25°C.

6.5    Nature and contents of container

Bottle - White high density polyethylene bottle containing 30 ml, 50 ml or 60 ml.

Cap - Polypropylene, linerless screw caps or polypropylene screw caps lined with laminated films consisting of polyethylene, polyvinylidene chloride (PVdc) and polyethylene.