SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Dalacin Cream 2%.

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each gram of cream contains clindamycin phosphate equivalent to 20 mg or 2.0% w/w clindamycin. Each applicator full of 5 grams of vaginal cream contains approximately 100 mg of clindamycin phosphate.

3    PHARMACEUTICAL FORM

Cream

White, semi-solid.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Antibiotic for the treatment of bacterial vaginosis.

4.2 Posology and method of administration

One applicator full intravaginally at bedtime for 7 consecutive days.

In patients in whom a shorter treatment course is desirable, a 3 day regimen has been shown to be effective.

Paediatric population:

Safety and efficacy in paediatric patients have not been established (see Section 4.4).

Elderly:

No clinical studies have been conducted in populations older than 60.

4.3 Contraindications

Dalacin Cream is contra-indicated in patients previously found to be hypersensitive to preparations containing clindamycin or any of the components of the cream base (see "Presentation"). Although crosssensitisation to lincomycin has not been demonstrated, it is recommended that Dalacin Cream should not be used in patients who have demonstrated lincomycin sensitivity. Dalacin Cream 2% is also contraindicated individuals with a history of inflammatory bowel disease or a history of antibiotic-associated colitis.

4.4 Special warnings and precautions for use

The use of clindamycin may result in the overgrowth of non-susceptible organisms, particularly yeasts.

Virtually all antibiotics have been associated with diarrhoea and in some cases pseudomembranous colitis. Therefore, even though only a minimal amount of drug is absorbed, if significant diarrhoea occurs, the drug should be discontinued and appropriate diagnostic procedures and treatment provided as necessary.

Dalacin Cream contains oil-based components. Some of these have been shown to weaken the rubber of condoms and diaphragms and make them less effective as a barrier method of contraception or as protection from sexually transmitted disease, including AIDS. Do not rely on condoms and diaphragms as a form of contraception when using Dalacin Cream.

Paediatric use:

Safety and efficacy in paediatric patients have not been established (see Section 4.2).

4.5 Interaction with other medicinal products and other forms of interaction

Cross resistance has been demonstrated between clindamycin and lincomycin, and erythromycin and clindamycin. Antagonism has been demonstrated between clindamycin and erythromycin in vitro.

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.

No information is available on concomitant use with other intravaginal products, which is not recommended.

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 their first trimester. 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 the first trimester of pregnancy only if clearly needed.

In a clinical trial in pregnant women during the second trimester, Dalacin Cream was effective in treating bacterial vaginosis, and no drug-related medical events were reported in the neonates. However, as with any drug used during pregnancy, a careful risk-benefit assessment should take place beforehand.

Lactation

It is not known if clindamycin is excreted in breast milk following the use of vaginally administered clindamycin phosphate. However, orally and parenterally administered clindamycin has been reported to appear in breast milk. Therefore, a full assessment of benefit-risk should be made when consideration is given to using vaginal clindamycin phosphate in a nursing mother.

4.7 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 following treatment-related adverse events were reported by less than 10% of patients.

In clinical trials medical events judged to be related, probably related, or possibly related to vaginally administered clindamycin phosphate cream were reported for (24%) of patients as indicated below:

Genital tract:    cervicitis/vaginitis (14%); vulvo-vaginal

irritation (6%).

Central nervous system:    dizziness, headache, vertigo.

heartburn, nausea, vomiting, diarrhoea, constipation, abdominal pain.

Dermatological:    rash, exanthema.

Hypersensitivity:    urticaria.

(Events without percentages were reported by less than 1% of the patients.)

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

Vaginally applied clindamycin phosphate vaginal cream 2% 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

Clindamycin inhibits bacterial protein synthesis at the level of the bacterial ribosome. The antibiotic binds preferentially to the 50S ribosomal subunit and affects the process of peptide chain initiation. Although clindamycin phosphate is inactive in vitro, rapid in vivo hydrolysis converts this compound to the antibacterially active clindamycin.

Culture and sensitivity testing of bacteria are not routinely performed to establish the diagnosis of bacterial vaginosis. Standard methodology for the susceptibility testing of the potential bacterial vaginosis pathogens, Gardnerella vaginalis, Mobiluncus spp., or Mycoplasma hominis, has not been defined.

Nonetheless, clindamycin is an antimicrobial agent active in vitro against most strains of the following organisms that have been reported to be associated with bacterial vaginosis:

•    Bacteroides spp.

•    Gardnerella vaginalis

•    Mobiluncus spp.

•    Mycoplasma hominis

• Peptostreptococcus spp.

Cross resistance has been demonstrated between clindamycin and lincomycin.

Antagonism has been demonstrated between clindamycin and erythromycin in vitro. The clinical significance of this interaction is unknown.

5.2 Pharmacokinetic properties

Following a once a day intravaginal dose of 100 mg of clindamycin phosphate vaginal cream 2%, administered to 6 healthy female volunteers for 7 days, approximately 4% (range 0.6% to 11%) of the administered dose was absorbed systemically. The peak serum clindamycin concentration observed on the first day averaged 18 ng/mL (range 4 to 47 ng/mL) and on day 7 it averaged 25 ng/mL (range 6 to 61 ng/mL). These peak concentrations were attained approximately 10 hours post-dosing (range 4-24 hours).

Following a once a day intravaginal dose of 100 mg of clindamycin phosphate vaginal cream 2%, administered for 7 consecutive days to 5 women with bacterial vaginosis, absorption was slower and less variable than that observed in healthy females. Approximately 4% (range 2% to 8%) of the dose was absorbed systemically. The peak serum clindamycin concentration observed on the first day averaged 13 ng/mL (range 6 to 34 ng/mL) and on day 7 it averaged 16 ng/mL (range 7 to 26 ng/mL). These peak concentrations were attained approximately 14 hours post-dosing (range 4-24 hours).

There was little or no systemic accumulation of clindamycin after repeated (7 day) vaginal dosing of clindamycin phosphate vaginal cream 2%. The systemic half-life was 1.5 to 2.6 hours.

Elderly:

Clinical studies for clindamycin phosphate vaginal cream 2% 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

Reproduction studies have been performed in rats and mice using subcutaneous and oral doses of clindamycin ranging from 20 to 600 mg/kg/day and have revealed no evidence of impaired fertility or harm to the fetus due to clindamycin. In one mouse strain, cleft palates were observed in treated fetuses; this response was not produced in other mouse strains or in other species, and is therefore considered to be a strain specific effect.

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

Sorbitan stearate

polysorbate 60 propylene glycol stearic acid cetostearyl alcohol cetyl palmitate liquid paraffin benzyl alcohol water.

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years

6.4 Special precautions for storage

Do not store above 25°C. Do not freeze.

6.5 Nature and contents of container

Laminate tube (consisting of LMDPE and aluminium foil) with polypropylene cap containing 7.8 g, 20 g or 40 g cream, packed in cardboard carton, together with a leaflet.