Gyno-Daktarin 20mg / g Cream

1. Name Of The Medicinal Product

Gyno-Daktarin 20mg/g cream

2. Qualitative And Quantitative Composition

Miconazole nitrate 2% w/w.

(Each gram of cream contains 20mg miconazole nitrate)

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Vaginal cream.

The cream is white and homogeneous.

4. Clinical Particulars

4.1 Therapeutic Indications

For the treatment of mycotic vulvovaginitis and superinfections due to gram-positive bacteria.

4.2 Posology And Method Of Administration

Gyno-Daktarin cream is for vaginal administration.

Recommended dosage

Administer the contents of one applicator (about 5g of cream) once daily deeply into vagina for 10 – 14 days or twice daily for 7 days. For vulvitis the cream should be applied topically twice daily. Continue the course of treatment even after pruritus and leukorrhoea have disappeared or menstruation begins.

4.3 Contraindications

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

4.4 Special Warnings And Precautions For Use

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

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.

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 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 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).

4.6 Pregnancy And Lactation

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.

4.7 Effects On Ability To Drive And Use Machines

None known.

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, burning/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 Drug Reactions (ADRs) reported by

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

Very common

Common

Uncommon

Rare

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

Table 1. Adverse Drug 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 face and nausea. However due to the design of these studies, a definitive causal relationship could not be established.

Table 2.Adverse Drug 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, Angioedema
Skin and Subcutaneous Tissue Disorders
Not known	Pruritis
Reproductive System and Breast Disorders
Not known	Vaginal irritation, pelvic cramps

4.9 Overdose

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.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic classification:

(Anti-infectives and antiseptics, excl. combinations with corticosteroids, imidazole derivatives)

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 biosynsthesis 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

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 mean apparent elimination half-life is 57 hours.

5.3 Preclinical Safety Data

No relevant information additional to that contained elsewhere in the Summary of Product Characteristics.

6. Pharmaceutical Particulars

6.1 List Of Excipients

PEG-6, PEG-32 and glycol stearate

Oleoyl macroglycerides

Liquid paraffin

Benzoic acid (E210)

Butylated hydroxyanisole (E320)

Purified water

6.2 Incompatibilities

None known.

6.3 Shelf Life

24 months.

6.4 Special Precautions For Storage

Do not store above 25ºC.

6.5 Nature And Contents Of Container

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 are marketed.

6.6 Special Precautions For Disposal And Other Handling

No special requirements.

7. Marketing Authorisation Holder

Janssen-Cilag Ltd

50-100 Holmers Farm Way

High Wycombe

Buckinghamshire

HP12 4EG

UK

8. Marketing Authorisation Number(S)

PL 0242/0015

9. Date Of First Authorisation/Renewal Of The Authorisation

12 December 2008

10. Date Of Revision Of The Text

23^rd July 09