SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Gyno-Daktarin 1200mg vaginal capsule

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Each capsule contains 1200 mg miconazole nitrate.

For full list of excipients, see Section 6.1

3    PHARMACEUTICAL FORM

Vaginal capsule, soft.

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

4.    CLINICAL PARTICULARS

4.1.    Therapeutic indications

For the local treatment of vulvovaginal candidosis    and    superinfections due to

Gram-positive bacteria.

4.2    Posology and method of administration

Gyno-Daktarin vaginal capsules are for intravaginal administration.

Adults (aged 18 years and older)

One soft vaginal capsule to be inserted high in the vagina at bedtime, as a single dose. This is best done in the reclining position.

Paediatrics (aged under 18 years)

The safety and efficacy of Gyno-Daktarin vaginal capsule in children and adolescents has not been studied.

4.3 Contraindications

Gyno-Daktarin vaginal capsule is contraindicated in individuals with a known hypersensitivity to miconazole/miconazole nitrate, other imidazole derivatives or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Severe hypersensitivity reactions, including anaphylaxis and angioedema, have been reported during treatment with Gyno-Daktarin vaginal capsule and with other miconazole formulations (see section 4.8). If a reaction suggesting hypersensitivity or irritation should occur, the treatment should be discontinued.

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

Gyno-Daktarin vaginal capsules do 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 vaginal capsules should not be used concurrently with a latex condom or latex diaphragm.

4.5    Interaction with other medicinal products and other forms of interaction

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 the anticoagulant effect should be monitored. The effects and side effects of other drugs metabolized by CYP2C9 (e.g., oral hypoglycemics and phenytoin) and also CYP3A4 (e.g., HMG-CoA reductase inhibitors such as simvastatin and lovastatin and calcium channel blockers such as dihydropyridines and verapamil), when coadministered with miconazole, can be increased and caution should be exercised.

Contact should be avoided between 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).

4.6    Fertility, pregnancy and lactation

Pregnancy

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

Breastfeeding

It is not known whether miconazole nitrate is excreted in human milk. Caution should be exercised when using Gyno-Daktarin vaginal capsules during breastfeeding.

4.7. Effects on ability to drive and use machines

None.

4.8 Undesirable effects

The safety of GYNO-DAKTARIN was evaluated in a total of 537 women with microbiologically confirmed candidiasis and symptoms (e.g., vulvovaginal itching, buming/irritation), or signs of vulvar erythema, edema, excoriation, or vaginal erythema or edema who participated in 2 single-blind clinical trials. Subjects were treated with miconazole intravaginally, randomly assigned to either a single 1,200 mg capsule, or a 7-day application of 2% vaginal cream. Adverse reactions reported by >1% of GYNO-DAKTARIN-treated subjects in these trials are shown in Table 1.

In the table, the frequencies are provided according to the following convention:

Very common	>1/10
Common	>1/100 and < 1/10
Uncommon	>1/1,000 and <1/100
Rare	>1/10,000 and <1/1,000
Very rare	<1/10,000
Table 1. Adverse Reactions Reported by Gyno-Daktarin-treated Subjects in 2 Single Blind Clinical Trials
Body System/Organ Class Frequency Category	Undesirable effects
Skin and Subcutaneous Tissue Disorders Common	Rash
Uncommon	Rash pruritic, urticaria
Reproductive System and Breast Disorders Very common	Genital pruritus female, vaginal burning sensation, vulvovaginal discomfort
Common	Dysmenorrhoea

A range of additional reactions were reported during the clinical trials, such as: vaginal discharge, vaginal haemorrhage, vaginal pain, headache, dysuria, urinary tract infection, abdominal pain, rosacea, swelling of the face and nausea. However due to the design of these studies, a definitive causal relationship could not be established.

Table 2. Adverse Reactions Identified During Postmarketing Experience with Gyno-Daktarin by Frequency Category Estimated from Spontaneous Reporting Rates

Immune System Disorders

Not known    Hypersensitivity including Anaphylactic and Anaphylactoid reactions

Skin and Subcutaneous Tissue Disorders Not known    Angioedema, Pruritus

Reproductive System and Breast Disorders

Not known    Vaginal irritation, pelvic cramps

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

Symptoms

Gyno-Daktarin vaginal capsules are intended for local application and not for oral use. In case of accidental ingestion, no problems are expected.

Treatment

In the event of accidental ingestion of large quantities, use appropriate supportive care.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Pharmacotherapeutic classification:

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

ATC code: G01A F04

Miconazole is a synthetic imidazole antifungal agent with a broad spectrum of activity against pathogenic fungi (including yeasts and dermatophytes) and grampositive bacteria (staphylococcus and streptococcus spp).

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.

In general, miconazole exerts a very rapid effect on pruritus, a symptom that frequently accompanies dermatophyte and yeast infections.

5.2    Pharmacokinetic properties

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 faeces 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 15 to 49 hours in most subjects and likely reflects both absorption from the site of application and metabolism/excretion of the drug.

5.3 Preclinical safety data

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

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Liquid paraffin, white petrolatum and lecithin. The Capsule itself contains gelatin, glycerol, titanium dioxide, sodium ethyl parahydroxybenzoate, sodium propyl parahydroxybenzoate and medium chain triglycerides.

6.2 Incompatibilities

None known

6.3 Shelf life

24 Months

6.4    Special precautions for storage

Do not store above 30°C.

6.5    Nature and contents of container

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

6.6 Special precautions for disposal of a used medicinal product or waste

materials derived from such medicinal product and other handling of the product.

No special requirements

7    MARKETING AUTHORISATION HOLDER

Janssen-Cilag Limited 50-100 Holmers Farm Way High Wycombe Buckinghamshire HP12 4EG UK

8.    MARKETING AUTHORISATION NUMBER

PL 0242/0121

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

August 2001

10 DATE OF REVISION OF THE TEXT

11/12/2015