Janssen-Cilag Ltd

Gyno-Daktarin 20 mg/g vaginal cream

Miconazole nitrate 2% w/w

Each gram of cream contains 20 mg miconazole nitrate.

Excipients: Each gram of cream contains 2mg benzoic acid and 5 micrograms of butylated hydroxyanisole.

For full list of excipients, see section 6.1.

Vaginal cream.

The cream is white and homogeneous.

Gyno-Daktarin is for the local treatment of vulvo-vaginal candidosis and superinfection due to susceptible Gram-positive bacteria.

Gyno-Daktarin cream is for vaginal administration.

Recommended dosage:

The contents of two applicators (10 g of cream) inserted high into the vagina at night for 7 days.

Alternatively, the contents of one applicator inserted high into the vagina at night for 14 days.

Continue the full 7 or 14 day course of treatment even after pruritus and leukorrhoea have disappeared or menstruation begins.

Gyno-Daktarin cream is contraindicated in individuals with a known hypersensitivity to miconazole or another ingredient of the formulation.

If local irritation or an allergic reaction occurs, the treatment should be discontinued. Absorption of the antifungal may occur through denuded mucosa. To date there have been no reports of systematic adverse effects following a single dose.

Appropriate therapy is indicated when the sexual partner is also infected.

Gyno-Daktarin cream does not stain skin or clothes.

The concurrent use of latex condoms or diaphragms with vaginal anti-infective preparations may decrease the effectiveness of latex contraceptive agents. Therefore Gyno-Daktarin cream should not be used concurrently with a latex condom or latex diaphragm.

Miconazole administered systemically is known to inhibit CYP3A4/2C9. Due to the limited systemic availability after vaginal application, clinically relevant interactions occur very rarely. In patients on oral anticoagulants, such as warfarin, caution should be exercised and anticoagulant effect should be monitored.

The effects and side effects of some other drugs (e.g., oral hypoglycemics and phenytoin), when co-administered with miconazole, can be increased and caution should be exercised.

Contact should be avoided between certain latex products such as contraceptive diaphragms or condoms and Gyno-Daktarin cream since the constituents of the cream may damage the latex (see Section 4.4, Special warnings and special precautions for use).

Pregnancy

Although intravaginal absorption is limited, Gyno-Daktarin cream should only be used in the first trimester of pregnancy only if, in the judgement of the physician, the potential benefits outweigh the possible risks.

Lactation

It is not known whether miconazole nitrate is excreted in human milk. Caution should be exercised when using Gyno-Daktarin cream during lactation (see Section 4.5, Interactions with other medicinal products and other forms of interaction).

None stated.

Clinical trial data

Adverse events, regardless of causality, reported in 2 Phase 3 clinical trials are shown in Table 1. A total of 537 women with microbiologically confirmed candidiasis and symptoms (e.g. vulvovaginal itching, burning/irritation), or signs of vulvar erythema, edema, excoriation, or vaginal erythema or edema were treated with miconazole intravaginally: randomly assigned to either a single 1,200 mg capsule, or a 7-day application of 2% vaginal cream. There was no placebo reference. Safety was self-assessed daily on a diary card. Included in the table are adverse events reported by 1% of subjects in either treatment group.

Table 1: Adverse events, regardless of causality, reported by 1% of patients in either treatment group in 2 Phase 3 clinical trials

Additional ADRs that occurred in < 1% of Gyno-Daktarin-treated subjects (n=527) in the single-blind clinical datasets are listed in Table 2:

Table 2: Adverse Drug Reactions Reported by < 1% of GYNO-DAKTARIN-treated Subjects in 2 Single-blind clinical Trials

The majority of ADRs reported in clinical trials were mild to moderate in severity.

Postmarketing data

Adverse drug reactions first identified during post-marketing experience with Gyno-Daktarin are included in Table 3. The adverse drug reactions are ranked by frequency according to the following convention:

In Table 3, ADRs are presented byMedRA System organ class and frequency category based on spontaneous rates.

The frequencies provided below reflect reporting rates for adverse drug reactions from spontaneous reports, and do not represent more precise estimates of incidence that might be obtained in clinical or epidemiological studies.

Table3. Postmarketing reports of adverse drug reactions

Symptoms

In case of accidental ingestion, no problems are expected.

Treatment

If in the event of accidental ingestion of large quantities occurs, an appropriate method of gastric emptying may be used if considered appropriate. See also Section 4.5, Interactions with other medicinal products and other forms of interaction.

Pharmacotherapeutic classification:

(Antiinfectives and antiseptics, excl. combinations with corticosteroids, imidazole derivative)

ATC code: G01A F04

Miconazole combines a potent antifungal activity against common dermatophytes and yeasts with an antibacterial activity against certain gram-positive bacilli and cocci.

Miconazole inhibits the biosynthesis of ergosterol in fungi and changes the composition of other lipid components in the membrane, resulting in fungal cell necrosis.

Absorption: Miconazole persists in the vagina for up to 72 hours after a single dose. Systemic absorption of miconazole after intravaginal administration is limited, with a bioavailability of 1 to 2% following intravaginal administration of a 1200 mg dose. Plasma concentrations of miconazole are measurable within 2 hours of administration in some subjects, with maximal levels seen 12 to 24 hours after administration. Plasma concentrations decline slowly thereafter and were still measurable in most subjects 96 hours post-dose. A second dose administered 48 hours later resulted in a plasma profile similar to that of the first dose.

Distribution: Absorbed miconazole is bound to plasma proteins (88.2%) and red blood cells (10.6%).

Metabolism and Excretion: The small amount of miconazole that is absorbed is eliminated predominantly in feces as both unchanged drug and metabolites over a four-day post-administration period. Smaller amounts of unchanged drug and metabolites also appear in urine. The apparent elimination half-life ranges from 20 to 45 hours in most subjects and likely reflects both absorption from the site of application and metabolism/excretion of the drug.

Preclinical data reveal no special hazard for humans based on conventional studies of local irritation, single and repeated dose toxicity, genotoxicity, and toxicity to reproduction.

Macrogol ester

Oleoylmacroglycerides

Liquid paraffin

Benzoic acid (E210)

Butylated hydroxyanisole (E320)

Purified water

Not applicable.

2 years.

Do not store above 25°C.

Tube containing 15 g, 40 g or 78 g of cream*.

The aluminium tube inner is lined with heat polymerised epoxy-phenol resin with a white polypropylene cap.

The cream is supplied with disposable cardboard vaginal applicators.

*Not all pack sizes may be marketed

No special requirements

Janssen-Cilag Ltd

50 100 Holmers Farm Way

High Wycombe

Bucks

HP12 4EG

UK

PA 748/20/1

01 March 2012