Each gram of Clotrimazole, vaginal cream 2%, contains:

active ingredient: Clotrimazole – 20 mg;

For a full list of excipients see section List of excipients.

A homogeneous cream with smooth white colour, odourless.

Therapeutic indications

Clotrimazole is indicated for the 3-day treatment of vaginal candidiasis.

The recommended daily dose is one full applicator intravaginally for three consecutive days, preferably at bedtime. Sufficient cream is provided for 3 intravaginal applications.

Dosing Considerations

Vaginal Candidiasis may be accompanied by irritation in the vaginal area. Therefore, concomitant local treatment with Clotrimazole applied to the irritated vaginal area and as far as the anal region twice a day is advisable. Clotrimazole applied on the glans penis may prevent re- infection by the partner.

N.B.: The cream should be inserted deep intravaginally by means of the applicator. The plunger should then be depressed slowly.

Patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the container.

General

Clotrimazole is not for ophthalmic use.

Patients should seek medical advice if they have frequent vaginal infections or if their yeast infection returns in less than 2 months.

Patients should seek medical advice if they suffer from diabetes mellitus, or have underlying immunodeficiency disease (such as HIV-AIDS).

As with all topical agents, skin sensitization may result. Use of Clotrimazole topical preparations should be discontinued should such reactions occur, and appropriate therapy instituted.

Treatment during the menstrual period should not be performed. The treatment should be finished before the onset of menstruation.

While sexual relation may be had during treatment with Clotrimazole, most couples wait until treatment has finished as the partner could become infected.

Before using medical advice must be sought if You are aged under 18.

This product contains cetostearyl alcohol, which may cause local skin reactions (e.g. contact dermatitis).

This medicine contains Propylene glycol. Propylene glycol can cause local irritation.

This medicine contains methylparaben and propylparaben. May cause allergic reactions (possibly delayed).

Concomitant medication with vaginal Clotrimazole and oral tacrolimus/sirolimus (immunosuppressants) might lead to increased tacrolimus/sirolimus plasma levels. Patients should thus be thoroughly monitored for symptoms of tacrolimus/sirolimus overdosage.

Effects on Fertility

No human studies of the effects of Clotrimazole on fertility have been performed; however, animal studies have not demonstrated any effects of the drug on fertility.

Pregnant Women

There are limited amounts of data from the use of clotrimazole in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. Although intravaginal application of clotrimazole has shown negligible absorption from both normal and inflamed human vaginal mucosa, Clotrimazole Vaginal Cream should not be used in the first trimester of pregnancy unless the physician considers it essential to the welfare of the patient. The use of applicators may be undesirable in some pregnant patients and digital insertion of the vaginal tablets may be considered.

Nursing Women

Available pharmacodynamics / toxicological studies in animals have shown excretion of clotrimazole / metabolites in milk. Breast-feeding should be discontinued during treatment with clotrimazole.

The medication has no or negligible influence on the ability to drive or use machinery.

As the listed undesirable effects are based on spontaneous reports, assigning an accurate frequency of occurrence for each is not possible.

Immune system disorders: anaphylactic reaction, angioedema, hypersensitivity.

Vascular disorder: syncope, hypotension.

Respiratory, thoracic and mediastinal disorders: dyspnea. Gastrointestinal disorders: abdominal pain, nausea.

Skin and Subcutaneous Tissue Disorders: rash, urticaria, pruritus.

Reproductive system and breast disorders: vaginal exfoliation, vaginal discharge, vaginal haemorrhage, vulvovaginal discomfort, vulvovaginal erythema, vulvovaginal burning sensation, vulvovaginal pruritus, vulvovaginal pain.

General disorders and administration site conditions: application site irritation, oedema, pain.

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 online to the Scientific Centre of Drug and Medical Technology Expertise after academician E. Gabrielyan of MoH of RA via www.pharm.am (vigilance@pharm.am) or call the hotline numbers: +374 (10) 20 05 05 and +374 (96) 22 05 05.

No risk of acute intoxication is seen as it is unlikely to occur following а single vaginal or dermal application of an overdose (application over а large area under conditions favourable to absorption) or inadvertent oral ingestion. There is no specific antidote.

However, in the event of accidental oral ingestion, routine measures such as gastric lavage should be performed only if clinical symptoms of overdose become apparent (e.g. dizziness, nausea or vomiting). Gastric lavage should be carried out only if the airway can be protected adequately.

Pharmacotherapeutic group: Antifungal

ATC code: G01AF02

Mechanism of Action

Clotrimazole acts primarily by damaging the permeability barrier in the cell membrane of fungi. Clotrimazole brings about inhibition of ergosterol biosynthesis, an essential constituent of fungal cell membranes. If ergosterol synthesis is completely or partially inhibited, the cell is no longer able to construct an intact cell membrane. This leads to death of the fungus.

Exposure of Candida albicans to clotrimazole causes leakage of intracellular phosphorus compounds into the ambient medium with a concomitant breakdown of cellular nucleic acids and potassium efflux. The onset of these events is rapid and extensive after exposure of the organism to the drug, and causes a time-dependent and concentration-dependent inhibition of fungal growth.

Pharmacokinetic investigations after vaginal application have shown that only a small amount of clotrimazole (3-10%) is absorbed. Due to the rapid hepatic metabolization of absorbed clotrimazole into pharmacologically active metabolites, the resulting peak plasma concentrations of clotrimazole after vaginal application of a 500 mg dose were less than 10 ng/ml, suggesting that clotrimazole applied intravaginally is unlikely to lead to measurable systemic effects or side effects.

Metabolism studies performed after oral or intravenous administration have shown that in most species studied, levels of clotrimazole in tissue and serum are low. The majority of the drug is excreted as metabolites in the feces, with small amounts excreted in the urine. Human studies indicate slow excretion following oral administration of 14C-labelled clotrimazole (greater than 6 days). After intraperitoneal and subcutaneous administration, very low levels have been observed in the urine. The absorption and organ distribution of the drug is very poor when administered parenterally.

Intravaginal application in human subjects of 5 mL ¹⁴C-labelled clotrimazole vaginal cream containing 20 mg of active substance has shown that the systemic absorption of clotrimazole from the Vaginal Cream is quantitatively proportional to that from the Vaginal Tablets.

In animal experiments, clotrimazole exerts an in vitro and in vivo, dose-dependent, stimulating effect on certain microsomal enzyme systems which is approximately equal to that of phenobarbital in its inductive potential.

However, this stimulating effect subsides rapidly when treatment is discontinued. The enzyme- inductive effect of clotrimazole has been found to be intact in adrenalectomized animals.

List of excipients:

ceteareth-12

ceteareth-20

paraffin liquid

cetostearyl alcohol

methylparaben

propylparaben

propylene glycol

dimethicone

water purified

Not applicable.

3 years.

Store in a dry and out of the reach of children place, at a temperature not above 25°C.

50 g of cream is filled into aluminum tube (inside package).

The tube packed and inserted with 3 vaginal applicators and leaflet into cardboard box (outer package).

Applicator capacity is 6 g of Clotrimazole 2% vaginal cream.

None.