Janssen-Cilag Ltd

Gyno-Daktarin 1200 mg vaginal capsule

Each capsule contains 1200 mg miconazole nitrate

Also contains ethyl parahydroxybenzoate (E125) and sodium propyl parahydroxybenzotae (E217))

For a full list of excipients, see section 6.1.

Vaginal capsule, soft.

White to off white egg shaped soft vaginal capsule containing a white to cream coloured hydrophobic mass.

Adult females only.

For the local treatment of vulvo-vaginal Candida infections, including those with superinfection due to susceptible gram-positive bacteria.

Gyno-Daktarin vaginal capsule is for vaginal administration.

One soft vaginal capsule inserted high into the vagina before retiring at night. This is best done in the reclining position.

Gyno-Daktarin is contraindicated in individuals with a known hypersensitivity to miconazole or another ingredient of the soft vaginal capsule.

Should local sensitisation or an allergic reaction occur, the treatment should be discontinued.

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

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

Gyno-Daktarin vaginal capsule does not stain skin or clothes.

Miconazole administered systemically is known to inhibit CYP3A4/2C9. Due to the limited systemic availability after vaginal application, clinically relevant interactions occur very rarely. However, 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 vaginal capsules since the constituents of the vaginal capsules may damage the latex. (see Section 4.4, Special warnings and special precautions for use).

Pregnancy

Although intravaginal absorption is limited, Gyno-Daktarin vaginal capsule should only be used in the first trimester of pregnancy 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 vaginal capsule during lactation (see Section 4.5, Interactions with other medicinal products and other forms of interaction).

None known.

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 using the following convention:

Very common 1/10

Common 1/100 and < 1/10

Uncommon 1/1,000 and <1/100

Rare 1/10,000, <1/1,000

Very rare <1/10,000, including isolated reports

In Table 3, ADRs are presented by MedRA 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.

Table 3. Postmarketing reports of adverse drug reactions

Symptoms

In case of accidental ingestion, no problems are expected.

Treatment

In the event of accidental ingestion of large quantities, 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.

After the capsule has been inserted into the vagina, the outer covering rapidly disintegrates and the active suspension is almost instantaneously released.

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 mean apparent elimination half-life is 57 hours.

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.

Capsule:

Liquid paraffin

White petrolatum

Lecithin

Capsule shell:

Gelatin

Glycerol

Titanium dioxide (E171)

Sodium ethyl parahydroxybenzoate (E215)

Sodium propyl parahydroxybenzoate (E217)

Medium chain triglycerides

Not applicable.

24 months

Do not store above 30°C. Store in the original package to protect from moisture.

Gyno-Daktarin vaginal capsule is supplied in a blister strip (PVC-LDPE-PVDC/Alu) containing one soft vaginal capsule.

No special requirements.

50-100 Holmers Farm Way

High Wycombe

Buckinghamshire

HP12 4EG

UK

PA 748/20/2

9 June 1989 / 09 June 2009

20 January 2012