Gyno-Mikozal indicated for the local treatment of vulvovaginal candidosis and superinfections due to Gram-positive bacteria.

Gyno-Mikozal ovules are for intravaginal administration.

Adults (aged 18 years and older)

Once daily before bedtime, insert one vaginal ovule deeply into the vagina. This is best done in the reclining position. Repeat this procedure for 3 days.

The treatment can be repeated if necessary. Complete the entire treatment even if symptoms (e.g., pruritus and leukorrhea) have disappeared or menstruation begins.

In case of severe infections it may be advisable to prescribe a 6-day treatment course right from the start.

An entire therapeutic cycle (3 or 6 days) must always be completed, even if the symptoms (itching, redness or discharge) disappear quickly.

Paediatrics (aged under 18 years)

The safety and efficacy of Miconazole nitrate ovules in children and adolescents has not been studied.

Severe hypersensitivity reactions, including anaphylaxis and angioedema, have been reported during treatment with Miconazole nitrate ovules and with other miconazole topical formulations (see section 4.8). If a reaction suggesting hypersensitivity or irritation occur, the treatment should be discontinued.

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

Miconazole nitrate ovules 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 Miconazole nitrate ovules 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 other drugs metabolized by CYP2C9 (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 Miconazole nitrate vaginal ovules since the constituents of the vaginal ovules may damage the latex (see section 4.4)

Pregnancy

Although intravaginal absorption is limited, miconazole nitrate vaginal ovules 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 miconazole nitrate vaginal ovules during breastfeeding.

Not applicable.

The safety of miconazole nitrate 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 vaginal ovule, or a 7-day application of 2% vaginal cream. Adverse reactions reported by ≥1% of miconazole nitrate-treated subjects in these trials are shown in Table 1.

Table 1. Adverse Reactions reported by ≥ 1% of miconazole nitrate treated subjects in 2 single blind clinical trials.

Additional adverse reactions that occurred in < 1% of miconazole nitrate treated subjects (n=537 women) in the single-blind clinical studies are listed in Table 2.

Table 2. Adverse Reactions reported by ≥ 1% of miconazole nitrate treated subjects in 2 single blind clinical trials.

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

Post marketing data

In addition to adverse reactions reported during clinical studies and listed above, the following adverse reactions have been reported during post marketing experience (Table 3).

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

In Table 3, adverse reactions are presented by frequency category based on spontaneous reporting rates.

Healthcare professionals are asked to report any suspected adverse reactions via:

·      Saudi Arabia:

     The National Pharmacovigilance Centre (NPC):

     - SFDA Call Centre: 19999

     - E-mail: npc.drug@sfda.gov.sa

     - Website: https://ade.sfda.gov.sa

· Other GCC States:

     - Please contact the relevant competent authority.

Gyno-Mikozal products are intended for local application and not for oral dose.

Treatment

In the event of accidental ingestion of large quantities of Gyno-Mikozal products, use appropriate supportive care (see also interaction).

Pharmacotherapeutic Properties:

(Anti-infective and antiseptics, excl. combinations with corticosteroids, imidazole derivative)

ATC code: G01A F04

Mechanism of action

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

Pharmacodynamic effects

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

Microbiology                

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

After the vaginal ovule 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 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 studies of local irritation, single and repeated dose toxicity, genotoxicity, and toxicity to reproduction.

Each vaginal ovule contains:

None known

Store below 30°C, protect from heat.

3 ovules in a blister, 1 blister packed in a printed carton along with a leaflet.

Any unused product or waste material should be disposed of in accordance with local requirements.