Dalacin® T Topical Solution

Clindamycin Phosphate Topical Solution.

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

For excipients see Section 6.1 ('List of excipients').

Topical solution.

Clear colourless aqueous solution.

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

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

Topical clindamycin is contraindicated in individuals with a history of hypersensitivity to clindamycin or lincomycin. 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 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.

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.

Pregnancy:

There are no adequate and well-controlled studies in pregnant women. Animal reproductive toxicity studies revealed no evidence of impaired fertility or harm to the fetus due to clindamycin (see section 5.3). Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Lactation:

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, breastfeeding 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.

Skin dryness is the most common adverse reaction seen with the solution. In addition, thefollowing adverse effects have been reported with the use of topical clindamycin

Eye disorders: stinging of the eye

Gastrointestinal disorders: abdominal pain, gastrointestinal disturbances

Infections and infestations: gram-negative folliculitis

Skin and subcutaneous skin disorders: skin irritation, contact dermatitis, skin oiliness, urticaria

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.

Anti-infectives for treatment of acne.           D10A F

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.

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 (0–3 ng/mL) and less than 0.2% of the dose is recovered in urine as clindamycin.

Clindamycin concentrations has 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.

Geriatric Use

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.

Reproduction studies performed in rats and mice using subcutaneous and oral doses of clindamycin revealed no evidence of impaired fertility or harm to the fetus due to clindamycin.

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.

Isopropyl alcohol

Propylene glycol

Purified water

Hydrochloric acid (10%)

Sodium hydroxide (10%)

Not applicable.

24 months.

Store below 25°C

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

Cap – Prolypropylene, linerless screw caps

Or Polypropylene screw caps lined with laminated films consisting of polyethylene, polyvinylidene chloride (PVdc) and polyethylene

Applicator – Low-density polyethylene applicator made by Dab-O-Matic

None.

Pharmacia Limited

Ramsgate Road

Sandwich Kent

CT13 9NJ

United Kingdom

PL 0032/0135

Date of first authorisation: 18 January 1988

Date of renewal of authorisation: 22^nd May 2001

Date of renewal of authorisation: 7^th August 2009

05/2012

Ref: DA8_1

POM