DALACIN CREAM 2% - summary of medicine 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.

Excipients of known effect

Dalacin Cream contains 160.5 mg cetostearyl alcohol in each 5 g applicator which is equivalent to 32.1 mg/g.

Dalacin Cream contains 250 mg propylene glycol in each 5 g applicator which

is equivalent to 50 mg/g.

Dalacin Cream contains 50 mg benzyl alcohol in each 5 g applicator which is equivalent to 10 mg/g.

For the full list of excipients, see section 6.1

3 PHARMACEUTICAL FORM

Vaginal 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

Posology

One applicator full intravaginally at bedtime for 7 consecutive days.

In patients for 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 to any of the excipients listed in section 6.1.

Although cross-sensitisation 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 in 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 population

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

Excipient information

Dalacin Cream contains propylene glycol, cetostearyl alcohol and benzyl alcohol (see section 2).

Propylene glycol may cause skin irritation.

Cetostearyl alcohol may cause local skin reactions (e.g. contact dermatitis).

Benzyl alcohol may cause mild local irritation and may also cause hypersensitivity.

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.

4.6 Fertility, pregnancy and lactation

Pregnancy

Use of clindamycin is not recommended during the first trimester, as there are no adequate and well-controlled studies in pregnant women over this period.

In clinical trials, intravaginal use of clindamycin vaginal products in pregnant women during second trimester and systemic use of clindamycin phosphate during the second and third trimester has not been associated with congenital abnormalities.

Clindamycin may be used to treat pregnant women if clearly necessary during the second and third trimester of pregnancy.

Reproduction studies performed in rats and mice using oral and parenteral doses of clindamycin, ranging from 100 to 600 mg/kg/day, have revealed no evidence of harm to the fetus due to clindamycin (see section 5.3). In one mouse strain, cleft palates were observed in species 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. Animal reproduction studies are not always predictive of human response.

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.

Breast-feeding

It is not known if clindamycin is excreted in human breast milk following the use of vaginally administered clindamycin vaginal cream. Clindamycin has been reported to appear in human breast milk in ranges from <0.5 to 3.8 gg/ml following systemic use. Clindamycin has the potential to cause adverse effects on the breastfed infant’s gastro­intestinal flora such as diarrhoea or blood in the stool, or rash. If oral or intravenous clindamycin is required by a nursing mother, it is not a reason to discontinue breastfeeding, but an alternate drug may be preferred. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for clindamycin and any potential adverse effects on the breastfed child from clindamycin or from the underlying maternal condition.

Fertility

Fertility studies in rats treated orally with clindamycin revealed no effects on fertility or mating ability. No animal fertility studies have been performed using the vaginal route of administration.

4.7 Effects on ability to drive and use machines

Clindamycin has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

This section includes adverse reactions reported in clinical trials, clinical safety studies and spontaneous reporting. The frequencies have been assigned using the original marketing authorisation application (MAA) clinical safety summary documentation in the first instance, followed by study reports that did not appear in the original MAA clinical safety summary.

The following convention has been used for the classification of frequency: Very common (>1/10); Common (>1/100 to <1/10); Uncommon (>1/1,000 to <1/100); Not known (frequency cannot be estimated from the available data).

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

There are no reports of overdose with clindamycin. Vaginally applied clindamycin phosphate in the vaginal cream can be absorbed in sufficient amounts to produce systemic effects.

In the event of overdosage, general symptomatic and supportive measures are indicated as required.

Accidental oral intake can lead to effects comparable with those of therapeutic concentrations of orally administered clindamycin.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

General properties

Pharmacotherapeutic group: Gynaecological anti-infectives and antiseptics, ATC Code: G01AA10.

Mechanism of action

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

Pharmacokinetic/Phar­macodynamic (PK/PD) relationship

Similar to other protein synthesis inhibitors, efficacy is associated with the length of time the concentration of clindamycin remains above the MIC of the infecting organism.

Mechanism of resistance

Resistance to clindamycin is most often due to modification of the target site on the ribosome, usually by chemical modification of RNA bases or by point mutations in RNA or occasionally in proteins. Cross resistance has been demonstrated in vitro between lincosamides, macrolides and streptogramins B in some organisms. Cross resistance has been demonstrated between clindamycin and lincomycin.

Breakpoints

Standard methodology for the susceptibility testing of the potential bacterial vaginosis pathogens, Gardnerella vaginalis, and Mobiluncus spp has not been defined. Methods for determining the susceptibility of Bacteroides spp. and Gram-positive anaerobic cocci, as well as Mycoplasma spp. have been described by the Clinical and Laboratory Standards Institute (CLSI) and clindamycin susceptibility breakpoints for Gram-negative and Gram-positive anaerobes have been published by both EUCAST and CLSI. However the breakpoints are intended to guide systemic, rather than localized, antibiotic treatment.

Microbiological susceptibility

Clindamycin is 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.

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

Impairment of fertility:

Fertility studies in rats treated orally with up to 300 mg/kg/day (31 times 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-fetal toxicity was observed at doses that produced maternal toxicity. In rats, maternal death occurred with exposure margins of approximately 400-fold relative to patient exposure. In rabbits, maternal toxicity, including abortions, occurred at exposure margins of 50-fold relative to patient exposure. Embryo-fetal toxicity, including post-implantation loss and decreased viability, occurred in rabbits at exposure margins of 120-fold.

Mutagenesis:

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

Carcinogenesis:

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 (E1520)

Stearic acid

Cetostearyl alcohol

Cetyl palmitate

Liquid paraffin

Benzyl alcohol (E1519)

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.

Not all pack sizes may be marketed.