MIMS Revision Date: 01 April 2023

1 Name of Medicine

Clotrimazole.

2 Qualitative and Quantitative Composition

Vaginal creams. Canesten Clotrimazole Thrush 6 Day Cream. Contains 10 mg/g (1%) of clotrimazole.
Canesten Clotrimazole Thrush 3 Day Cream. Contains 20 mg/g (2%) of clotrimazole.
Canesten Clotrimazole Thrush 1 Day Cream. Contains 100 mg/g (10%) of clotrimazole.
Vaginal tablets (compressed pessaries). Canesten Clotrimazole Thrush 6 Day Pessary. Contains 100 mg of clotrimazole.
Canesten Clotrimazole Thrush 1 Day Pessary. Contains 500 mg of clotrimazole.
Composite pack: '1 day' compressed pessary plus antifungal cream. Canesten Clotrimazole Thrush 1 Day Pessary + Cream. Includes:
One pessary containing 500 mg of clotrimazole;
One tube of antifungal cream containing 10 mg/g (1%) of clotrimazole.
Excipients with known effect. Vaginal creams. Canesten Clotrimazole Thrush 6 Day Cream. Benzyl alcohol 2% w/w.
Canesten Clotrimazole Thrush 3 Day Cream. Benzyl alcohol 2% w/w.
Canesten Clotrimazole Thrush 1 Day Cream. Benzyl alcohol 1% w/w.
Vaginal tablets (compressed pessaries). Canesten Clotrimazole Thrush 6 Day Pessary. Lactose monohydrate.
Canesten Clotrimazole Thrush 1 Day Pessary. Lactose monohydrate.
Composite pack: '1 day' compressed pessary plus antifungal cream. Canesten Clotrimazole Thrush 1 Day Pessary + Cream. Lactose monohydrate, benzyl alcohol 2% w/w.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Vaginal creams. White cream for vaginal use.
Vaginal tablets (compressed pessaries). Canesten Clotrimazole Thrush 6 Day Pessary. Oblong white vaginal tablet with markings "AD" on one side and "Bayer" on the other.
Canesten Clotrimazole Thrush 1 Day Pessary. Oblong white vaginal tablet with markings "MU" on one side and "Bayer" on the other.
Composite pack: '1 day' compressed pessary plus antifungal cream. Canesten Clotrimazole Thrush 1 Day Pessary + Cream. Oblong white vaginal tablet with markings "MU" on one side and "Bayer" on the other, plus white cream for vaginal use.

4 Clinical Particulars

4.1 Therapeutic Indications

Vaginal creams. Canesten clotrimazole vaginal creams are indicated for the topical treatment of vulvovaginal candidiasis.
Vaginal tablets (compressed pessaries). Canesten clotrimazole vaginal pessaries are indicated for the topical treatment of vaginal candidiasis.
Composite pack: '1 day' compressed pessary plus antifungal cream. Canesten clotrimazole composite pack is indicated for the treatment of candidal infections of the vagina and vulvovagina and sexual partner.

4.2 Dose and Method of Administration

No dosage adjustment is necessary in patients with renal or hepatic impairment due to limited systemic absorption following topical or vaginal application.
Vaginal creams. Canesten Clotrimazole Thrush 6 Day Cream. Once daily, preferably at bedtime for six successive days, one applicator should be filled with cream (approximately 5 g) and inserted as deeply as possible into the vagina with the patient lying on her back with the legs slightly drawn up. The 35 g tube of cream for vaginal use provides for six such doses.
Canesten Clotrimazole Thrush 3 Day Cream. Once daily, preferably at bedtime for three successive days, one applicator should be filled with cream (approximately 5 g) and inserted as deeply as possible into the vagina with the patient lying on her back with the legs slightly drawn up. The 20 g tube of cream for vaginal use provides for three such doses.
Canesten Clotrimazole Thrush 1 Day Cream. The disposable applicator should be filled with the vaginal cream, ensuring the entire contents of the tube are used (approximately 5 g). The cream is then inserted as gently and deeply as possible into the vagina with the patient lying on her back with the legs slightly drawn up. The cream should be used preferably at bedtime as a single dose of treatment.
Canesten clotrimazole vaginal creams may also be used in conjunction with Canesten clotrimazole vaginal pessaries in the management of Candida vulvovaginitis or infection of the peri-anal area while application of the cream to the glans penis of the partner may help prevent re-infection of the female.
Vaginal tablets (compressed pessaries). Canesten Clotrimazole Thrush 6 Day Pessary, Canesten Clotrimazole Thrush 1 Day Pessary. A course of treatment normally consists of either a single 500 mg pessary (1 Day Pessary) or of six 100 mg pessaries (6 Day Pessary). The latter may be given either as two pessaries, inserted one after the other, daily for three days or as one pessary daily for six days. Clinical investigations have shown comparable efficacy from either dosage scheme. Where a first course proved unsuccessful, a second course produced success in 8 of 12 women treated.
Canesten clotrimazole vaginal tablets (pessaries) should be inserted as deeply as possible into the vagina once daily, preferably at bedtime. This is best achieved using the plastic applicator provided and following the directions on the patient instruction sheet. In late pregnancy digital insertion is preferable to use instead of the applicator.
The vaginal tablets need moisture in the vagina to dissolve completely, otherwise undissolved pieces of the vaginal tablet might crumble out of the vagina. To prevent this it is important to insert the pessaries as deeply as possible into the vagina preferably at bedtime. Should the vaginal tablet not dissolve completely within one night the use of a vaginal cream should be considered.
It is suggested that treatment be timed so as to avoid the menstrual period and to be complete before the onset of menstruation.
Composite pack: '1 day' compressed pessary plus antifungal cream. Canesten Clotrimazole Thrush 1 Day Pessary + Cream. The pessary should be inserted gently and as deeply as possible into the vagina, preferably at bedtime. This is best achieved using the plastic applicator provided and following the directions on the instruction leaflet. In late pregnancy digital insertion is preferable to use instead of the applicator. The 500 mg pessary provides therapy for three to four days as it creates high intravaginal concentrations of clotrimazole, however the symptoms may persist for these three to four days.
The antifungal cream may be used in conjunction with the pessary in the management of candidal vulvovaginitis or infection of the peri-anal area while application of the cream to the glans penis of the partner may help prevent reinfection of the female. This should be applied thinly to the affected areas (external genital organs to the anus in the woman; glans and prepuce in men) 2 - 3 times daily and rubbed in.
It is suggested that the treatment be timed so as to avoid the menstrual period and to be complete before the onset of menstruation. If the treatment does coincide with a menstrual period, use sanitary pads not tampons during therapy.

4.3 Contraindications

Known hypersensitivity to clotrimazole, cetostearyl alcohol (only for products containing cetostearyl alcohol), and/or to any other excipients (see Section 6.1 List of Excipients).

4.4 Special Warnings and Precautions for Use

If evidence of local intolerance develops, consider withdrawal of the drug and institution of appropriate therapy.
Canesten clotrimazole vaginal creams and vaginal pessaries are for intravaginal use only and are not to be taken orally. Avoid contact with eyes.
A doctor should be consulted before use in the following instances:
if it is the first occurrence of the problem;
if there have been three or more thrush infections in the previous six months;
if pregnant;
if diabetic;
if under 18 years of age or over the age of 60 years;
if not better in four days.
If the patient has a fever (temperature of 38°C or above), lower abdominal pain, back pain, foul smelling vaginal discharge, nausea, vaginal haemorrhage, and/or associated shoulder pain the patient should consult a doctor.
Only for products containing cetostearyl alcohol (see Section 6.1 List of Excipients): cetostearyl alcohol may cause local skin reactions (e.g. contact dermatitis).
Canesten clotrimazole creams are not intended for ophthalmic use.
If symptoms persist for more than 4 days the patient may have a medical condition that requires treatment by a doctor.
The treatment can be repeated if necessary, however, recurrent infections may indicate an underlying medical cause, including diabetes or HIV infection. Patients should seek medical advice if symptoms return within 2 months.
Since the vagina and vulva are usually both affected, a combination treatment (treatment of both of these areas) should be performed.
lf the labia and adjacent areas are simultaneously infected, local treatment with an external cream should also be given. The sexual partner should also undergo local treatment if symptoms, e.g. pruritus, inflammation, etc. are present.
Treatment during the menstrual period should not be performed. The treatment should be finished before the onset of menstruation.
Do not use tampons, intravaginal douches, spermicides or other vaginal products while using these products.
Avoidance of vaginal intercourse is recommended while using this product because the infection could be transferred to the partner, and the effectiveness and safety of latex products such as condoms and diaphragms may be reduced (see Interactions with latex).
Interactions with latex. Canesten clotrimazole vaginal creams and vaginal pessaries may reduce the effectiveness and safety of latex products, such as condoms and diaphragms. This effect is temporary and occurs only during treatment.
Use in the elderly. No data available.
Paediatric use. No data available.
Effects on laboratory tests. No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Concomitant treatment with vaginal clotrimazole and oral tacrolimus (FK-506, an immunosuppressant) might lead to increased tacrolimus plasma levels. Patients should thus be thoroughly monitored for symptoms of tacrolimus overdosage, if necessary by determination of the respective plasma levels.

4.6 Fertility, Pregnancy and Lactation

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 medicine on fertility.
Use in pregnancy. (Category A)
There is a limited amount of clinical data in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see Section 5.3 Preclinical Safety Data).
Clotrimazole can be used during pregnancy, but only under the direction of a health care professional.
If treatment is carried out during pregnancy, Canesten clotrimazole vaginal pessaries are the preferable choice as they can be inserted without the use of an applicator. Sanitation of the birth canal should be ensured particularly during the last 4-6 weeks of pregnancy.
Use in lactation. Although systemic absorption following topical or vaginal administration is low, caution should be exercised when clotrimazole is administered to nursing mothers as there is no information on whether or not clotrimazole is excreted in breast milk.

4.7 Effects on Ability to Drive and Use Machines

No effects on ability to drive and use machines have been observed.

4.8 Adverse Effects (Undesirable Effects)

The listed adverse drug reactions are based on spontaneous reports, thus, an organisation according to CIOMS III categories of frequency is not possible.
Immune system disorders. Anaphylactic reaction, angioedema, hypersensitivity.
Vascular disorder. Syncope, hypotension.
Respiratory, thoracic and mediastinal disorders. Dyspnoea.
Skin and subcutaneous tissue disorders. Rash, urticaria.
Reproductive system and breast disorders. Vaginal exfoliation, vaginal discharge, vaginal haemorrhage, vulvovaginal erythema, vulvovaginal pruritus, vulvovaginal discomfort, vulvovaginal burning sensation, vulvovaginal pain.
Gastrointestinal disorders. Abdominal pain, nausea.
General disorders and administration site conditions. Application site irritation, oedema, pain.
Eleven (1.6%) of 689 patients treated with Canesten clotrimazole vaginal pessaries complained of possibly drug-related effects. Mild burning occurred in four patients while other complaints such as skin rash and lower abdominal cramps were mentioned. Slight urinary frequency and burning or irritation in the sexual partner occurred rarely. In no case was it necessary to discontinue Canesten clotrimazole vaginal pessaries.
Reporting suspected adverse effects. Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

There have been no reports of overdosage with clotrimazole.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group (ATC code): G01A F02.
Clotrimazole is an imidazole derivative with a broad spectrum antimycotic activity.
Mechanism of action. Clotrimazole acts against fungi by inhibiting ergosterol synthesis. Inhibition of ergosterol synthesis leads to structural and functional impairment of the cytoplasmic membrane.
Clotrimazole has a broad antimycotic spectrum of action in vitro and in vivo, which includes dermatophytes, yeasts, moulds, etc.
Under appropriate test conditions, the minimum inhibitory concentration (MIC) values for these types of fungi are in the region of less than 0.062-8.0 microgram/mL substrate. The mode of action of clotrimazole is primarily fungistatic or fungicidal depending on the concentration of clotrimazole at the site of infection. In vitro activity is limited to proliferating fungal elements; fungal spores are only slightly sensitive.
In addition to its antimycotic action, clotrimazole also acts on Trichomonas vaginalis, gram-positive microorganisms (Streptococci/Staphylococci), and gram-negative microorganisms (Bacteroides/Gardnerella vaginalis).
In vitro clotrimazole inhibits the multiplication of Corynebacteria and gram-positive cocci - with the exception of Enterococci - in concentrations of 0.5-10 microgram/mL substrate and exerts a trichomonacidal action at 100 microgram/mL.
Primarily resistant variants of sensitive fungal species are very rare; the development of secondary resistance by sensitive fungi has so far only been observed in very isolated cases under therapeutic conditions.
Pharmacodynamic effects. A single course of intravaginal Canesten clotrimazole cream has produced mycological cure of vaginal candidiasis as follows:
one 100 mg pessary daily for six days - 80%;
two 100 mg pessary daily for three days - 75%;
one 500 mg pessary - 84%;
5 g of 1% cream daily for six days - approx 75%.
When a first course proved unsuccessful, a second course produced success in 8 of 12 women treated.
Clinical trials. No data available.

5.2 Pharmacokinetic Properties

Absorption and distribution. Studies using ¹⁴C-labelled clotrimazole have shown absorption of about 3% of the administered dose from normal or inflamed human vaginal mucosa (peak serum level of 0.03 microgram/mL) 24 hours after insertion of a 100 mg tablet.
Studies in normal volunteers after vaginal insertion of one 500 mg pessary showed that plasma levels of clotrimazole up to 10 nanogram/mL were reached during the period of assay (up to 72 hours after insertion). Significant concentrations of clotrimazole were present in the vaginal secretion for up to 48 hours after insertion.
Canesten clotrimazole cream containing ¹⁴C-labelled clotrimazole was administered intravaginally to five women (four without gynaecological disorder and one with Candida vaginitis). A maximum serum level of 0.01 microgram/mL was found between 10 and 30 hours after administration.
Six hours after application of labeled topical Canesten clotrimazole cream the concentrations of clotrimazole ranged from 100 microgram/cm³ in the stratum corneum to 0.05-1.0 microgram/cm³ in the stratum reticulare and 0.1 microgram/cm³ in the subcutis.
No measurable radioactivity was found in the serum within 48 hours after application of 0.8 g of the cream.
Pharmacokinetic investigations after dermal application have shown that only a small amount of clotrimazole (< 2% of the dose) is absorbed. The resulting peak plasma concentrations of the active ingredient are < 10 nanogram/mL (i.e. below the detection limit) and do not lead to measurable side effects.
Metabolism and excretion. Studies of urinary excretion have shown that less than 0.5% of dermally applied Canesten clotrimazole cream appears in the urine over a five-day period of observation. Faecal excretion, the route by which most of the absorbed drug is likely to be eliminated, has not been studied in man.

5.3 Preclinical Safety Data

Toxicological studies in rats, dogs and primates given clotrimazole cream or tablet intravaginally showed good vaginal tolerance, and skin applications of clotrimazole cream/lotion were well tolerated in rabbits. Although limited liver toxicity was observed in rats given clotrimazole orally for 18 months; overall, preclinical data reveal no special hazard for humans based on the totality of findings from single- and repeat-dose, genotoxicity, carcinogenicity and reproductive toxicity studies.
Genotoxicity. No mutagenicity has been observed in animal studies.
Carcinogenicity. No carcinogenicity has been observed in animal studies.

6 Pharmaceutical Particulars

6.1 List of Excipients

Vaginal creams. Canesten Clotrimazole Thrush 6 Day Cream. Sorbitan monostearate, polysorbate 60, cetyl palmitate, cetostearyl alcohol, octyldodecanol, benzyl alcohol and purified water.
Canesten Clotrimazole Thrush 3 Day Cream. Sorbitan monostearate, polysorbate 60, cetyl palmitate, cetostearyl alcohol, octyldodecanol, benzyl alcohol and purified water.
Canesten Clotrimazole Thrush 1 Day Cream. Sorbitan monostearate, polysorbate 60, cetyl palmitate, cetostearyl alcohol, isopropyl myristate, benzyl alcohol and purified water.
Vaginal tablets (compressed pessaries). Canesten Clotrimazole Thrush 6 Day Pessary. Lactose monohydrate, maize starch, magnesium stearate, colloidal anhydrous silica, calcium lactate pentahydrate, crospovidone, lactic acid, hypromellose and microcrystalline cellulose.
Canesten Clotrimazole Thrush 1 Day Pessary. Lactose monohydrate, maize starch, magnesium stearate, colloidal anhydrous silica, calcium lactate pentahydrate, crospovidone, lactic acid, hypromellose and microcrystalline cellulose.
Composite pack: '1 day' compressed pessary plus antifungal cream. Canesten Clotrimazole Thrush 1 Day Pessary + Cream. Pessary: lactose monohydrate, maize starch, magnesium stearate, colloidal anhydrous silica, calcium lactate pentahydrate, crospovidone, lactic acid, hypromellose and microcrystalline cellulose.
Cream: sorbitan monostearate, polysorbate 60, cetyl palmitate, cetostearyl alcohol, octyldodecanol, benzyl alcohol and purified water.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Vaginal creams. Canesten Clotrimazole Thrush 6 Day Cream. Store below 25°C.
Canesten Clotrimazole Thrush 3 Day Cream. Store below 25°C.
Canesten Clotrimazole Thrush 1 Day Cream. Store below 25°C.
Vaginal tablets (compressed pessaries). Canesten Clotrimazole Thrush 6 Day Pessary. Store below 30°C.
Canesten Clotrimazole Thrush 1 Day Pessary. Store below 25°C.
Composite pack: '1 day' compressed pessary plus antifungal cream. Canesten Clotrimazole Thrush 1 Day Pessary + Cream. Store below 25°C.

6.5 Nature and Contents of Container

Vaginal creams. Canesten Clotrimazole Thrush 6 Day Cream. Presented in a 35 g tube and packed with six single-use disposable applicators and an instruction leaflet (Consumer Medicine Information).
Canesten Clotrimazole Thrush 3 Day Cream. Presented in a 20 g tube and packed with three single-use disposable applicators and an instruction leaflet (Consumer Medicine Information).
Canesten Clotrimazole Thrush 1 Day Cream. Presented in a 5 g tube and packed with one single-use disposable applicator and an instruction leaflet (Consumer Medicine Information).
Vaginal tablets (compressed pessaries). Canesten Clotrimazole Thrush 6 Day Pessary. Presented in a blister pack of six compressed pessaries, and packed with a plastic applicator and an instruction leaflet (Consumer Medicine Information).
Canesten Clotrimazole Thrush 1 Day Pessary. Presented in a blister pack containing one compressed pessary, and packed with a plastic applicator and an instruction leaflet (Consumer Medicine Information).
Composite pack: '1 day' compressed pessary plus antifungal cream. Canesten Clotrimazole Thrush 1 Day Pessary + Cream. Presented in a carton that includes a blister pack of one Canesten compressed pessary and packed with a plastic applicator. Plus, it includes one 10 g tube of Canesten antifungal cream. An instruction leaflet (Consumer Medicine Information) is also included.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Clotrimazole is a colourless, crystalline, weakly alkaline substance, melting point 141°-145°C, soluble in acetone, chloroform and ethanol and practically insoluble in water. It forms stable salts with both organic and inorganic acids. It is not photosensitive but is slightly hygroscopic, and may be hydrolysed in acid media.
Chemical structure. Chemical name: 1-(o-chloro-α,α-diphenylbenzyl) imidazole.
Structural formula:

Molecular formula: C₂₂H₁₇ClN₂.
Molecular weight: 344.84.
CAS number. 23593-75-1.

7 Medicine Schedule (Poisons Standard)

Pharmacist Only Medicine (S3).

Date of Revision

08 September 2022

Summary Table of Changes