1 Name of Medicine
Clotrimazole and hydrocortisone cream.
2 Qualitative and Quantitative Composition
CandaDerm contains 1% w/w (10 mg/g) of clotrimazole and 1% w/w (10 mg/g) of hydrocortisone as active ingredients.
Contains chlorocresol as preservative.
For the full list of excipients, see Section 6.1 List of Excipients.
Topical corticosteroid/antifungal. On topical application, corticosteroids (hydrocortisone) produce anti-inflammatory, antipruritic and vasoconstrictor actions. The activity of the drugs is thought to result at least in part from binding with a steroid receptor.
Clotrimazole is a broad-spectrum antifungal agent that is used for the treatment of dermal infections caused by various species of pathogenic dermatophytes, yeast and Pityrosporum orbiculare. The antifungal action appears to be on the cell membrane of the fungi, damaging the permeability barrier.
3 Pharmaceutical Form
CandaDerm cream is an opaque off-white viscous cream.
4.1 Therapeutic Indications
CandaDerm cream is indicated for dermatophyte and yeast infections of the skin when inflammation is prominent. This includes conditions such as fungal infected dermatitis, intertrigo and Candida nappy rash.
4.2 Dose and Method of Administration
Dose.
A small amount of CandaDerm cream should be applied twice daily.
Method of administration.
Apply thinly and evenly with gentle rubbing to the affected area(s). Use only until inflammation, itching and redness have subsided and not for more than 7 days (unless directed by a doctor). Then use an antifungal-only cream such as clotrimazole cream for 14 days after symptoms disappear to avoid recurrence of the infection.4.3 Contraindications
CandaDerm cream is contraindicated in the following cases:
hypersensitivity to the active substances or to any of the excipients listed in Section 6.1 List of Excipients;
on broken skin;
diseases affecting the skin (such as acne, rosacea, perioral dermatitis, lues, tuberculosis, etc.);
in or near the eyes;
viral skin diseases (e.g. herpes simplex, chicken pox, etc.);
dermal vaccination reactions.
4.4 Special Warnings and Precautions for Use
For external use only. Avoid contact with eyes. Do not swallow. Keep this medicine out of the reach of children.
Because of its corticosteroid content, CandaDerm cream should not be applied:
to large areas (more than 10% of the body surface); and/or
under occlusive dressings (such as nappies and bandages) because this may increase absorption.
Cetostearyl alcohol, which is an excipient in this medicine, may cause local skin reactions (e.g. contact dermatitis).
Interactions with latex.
The effectiveness and safety of latex products such as condoms and diaphragms may be reduced by CandaDerm cream when applied on the genital area (women: labia and adjacent area of the vulva; men: prepuce and glans of the penis). The effect is temporary and may occur only during treatment. If an associated infection develops during use and does not respond to therapy, use should be discontinued until the infection is controlled.
Hypothalamic-pituitary axis suppression and atrophic striae.
Long term corticosteroid use may increase the risk of hypothalamic-pituitary axis suppression, especially under occlusion. Use for longer than 4 weeks can cause atrophic striae and prolonged use on flexures and in intertriginous areas is undesirable.
Use in the elderly.
No data available.
Paediatric use.
The risk of systemic absorption, and hence systemic toxicity, is greater in children due to the higher permeation properties of the skin and a larger skin surface to body weight ratio than adults. Do not use on children under 2 years of age except on the advice of a doctor.
Effects on laboratory tests.
No data available.4.5 Interactions with Other Medicines and Other Forms of Interactions
Not known.
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.
No data is available on the effects of topically applied hydrocortisone.
(Category A)
There is a limited amount of data from the use of clotrimazole or hydrocortisone in pregnant women. Animal studies with clotrimazole do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see Section 5.3 Preclinical Safety Data). Studies in animals have shown reproductive effects at high doses of corticosteroids after systemic use (see Section 5.3 Preclinical Safety Data), and there is no animal data on the reproductive effects after topical use. As a precautionary measure, it is recommended not to apply CandaDerm for a long period during pregnancy, particularly in the first three months, and it is preferable to avoid the use of CandaDerm cream during the first trimester of pregnancy.
[Category A: Medicines which have been taken by a large number of pregnant women and women of childbearing age without an increase in the frequency of malformations or other direct or indirect harmful effects on the foetus having been observed.]
Available pharmacodynamic/toxicological data in animals have shown excretion of clotrimazole and/or metabolites in milk after intravenous administration (see Section 5.3 Preclinical Safety Data).
No data on hydrocortisone is available, but topically applied hydrocortisone is unlikely to cause systemic effects due to the low percutaneous penetration. However, cutaneous absorption may be increased under certain circumstances, such as with use of occlusive dressings, the degree of skin damage and the size of the treated area.
Administration of CandaDerm during lactation should only be considered if the expected benefit to the mother outweighs the risk to the infant. If used during lactation, CandaDerm should not be applied to the breasts to avoid accidental ingestion by the infant.4.7 Effects on Ability to Drive and Use Machines
The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.
4.8 Adverse Effects (Undesirable Effects)
The following adverse reactions have been identified during post-approval use of CandaDerm. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency.
Immune system disorders.
Allergic reaction (syncope, hypotension, dyspnoea, urticaria).
Skin and subcutaneous tissue disorders.
Discomfort/pain, oedema, erythema, hypertrichosis, irritation, pruritus, rash, secondary infections and acneiform symptoms, skin atrophy, skin discolouration, skin striae, stinging/burning, telangiectasis.
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
No reports are available on cases of overdosage with CandaDerm cream.
No risk of acute intoxication is seen as it is unlikely to occur following a single dermal application of an overdose (application over a large area under conditions favourable to absorption) or inadvertent oral ingestion. There is no specific antidote.
Excessive chronic exposure results in adverse systemic and dermal effects. In such cases, the use of topical corticosteroid should be discontinued, with consideration given to tapering the dose.
For more information and advice on the management of overdose, contact the Poison Information Centre on 13 11 26 (Australia).
5 Pharmacological Properties
5.1 Pharmacodynamic Properties
Mechanism of action.
Clotrimazole.
Synthetic imidazole derivative with broad spectrum antifungal activity and some antibacterial activity. It exerts its antifungal activity by altering cell membrane permeability by interfering with ergosterol synthesis. The cell membrane is unable to function as a selective barrier, and potassium and other cellular constituents are lost.
In vitro, clotrimazole concentrations of 1 microgram/mL or less inhibit most strains of Trichophyton rubrum, T. mentagrophytes, Epidermophyton floccosum and Microsporum canis. At a concentration of 3 microgram/mL or less, clotrimazole inhibits most other susceptible organisms including Pitysporum orbiculare, Aspergillus fumigatus and a few strains of Proteus vulgaris and Salmonella.
Hydrocortisone.
Corticosteroid in general, decreases inflammation by stabilising leucocyte lysosomal membranes, preventing the release of the destructive contents from leucocytes, inhibiting macrophage accumulation in inflamed areas, reducing leucocyte adhesion to the capillary endothelium, reducing capillary wall permeability and oedema formation, decreasing complement components, antagonising histamine activity and release of kinin from substrates, reducing fibroblast proliferation, collagen deposition, and subsequent scar tissue formation, and possibly by other mechanisms as yet unknown.
Clinical trials.
No data available.
5.2 Pharmacokinetic Properties
Clotrimazole.
Studies of urinary excretion have shown that less than 0.5% of dermally applied clotrimazole 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 humans.
Hydrocortisone.
The rate and extent of hydrocortisone absorption through the skin varies among individual patients.
Absorption is, however, markedly increased when the skin has lost its keratin layer or the rate limiting properties of the stratum corneum. Physical disruption of the stratum corneum, inflammation and/or disease to the epidermal barrier (e.g. psoriasis, eczema) may result in increased absorption.
Hydrocortisone is absorbed to a greater degree from the skin of the ear region (around and behind), scrotum, axilla, eyelid, face and scalp than from the skin of the forearm, knee, elbow, palm and sole. Prolonged absorption persists even after the area of application has been washed, possibly because the drug is retained in the stratum corneum and/or the dermoepidermal layer.
Hydrocortisone is metabolised by the liver and most other tissues to hydrogenated and degraded forms (such as tetrahydrocortisone and tetrahydrocortisol).
The metabolites of hydrocortisone are excreted in urine mainly conjugated as glucoronides, together with a very small proportion of unchanged hydrocortisone. The biological half-life is approximately 100 minutes.
5.3 Preclinical Safety Data
Clotrimazole.
Toxicological studies in different animals with local or intravaginal application showed good local and vaginal tolerability. Preclinical data reveal no special hazard for humans based on conventional studies of single and repeated dose toxicity and toxicity to reproduction.
Hydrocortisone.
As an adrenocortical hormone, hydrocortisone is classified as relatively non-toxic on topical use. So far there is no evidence of any reproduction toxicity for corticoids used topically in accordance with the instructions.
Genotoxicity.
Clotrimazole.
Preclinical data reveal no special hazard for humans based on conventional studies of genotoxicity.
Hydrocortisone.
Teratogenic effects of high doses of glucocorticosteroids such as cleft palate formation, growth retardation, etc. are known after systemic use in animal studies; there are no data on teratogenic damage after dermal use. Years of therapeutic experience in man with topical use of hydrocortisone have not yielded any evidence of teratogenicity.
Carcinogenicity.
No data available.6 Pharmaceutical Particulars
6.1 List of Excipients
Cetomacrogol 1000, cetostearyl alcohol, glycerol, liquid paraffin, propylene glycol, soft white paraffin, purified water, chlorocresol (as preservative).
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.
CandaDerm has a shelf life of 3 months once opened.
6.4 Special Precautions for Storage
Store below 30°C.
6.5 Nature and Contents of Container
CandaDerm filled into aluminium tubes with an inner lacquer and white polyethylene screw cap containing 30 g of cream.
6.6 Special Precautions for Disposal
CandaDerm should not be disposed of via wastewater or household waste. Ask a pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.
6.7 Physicochemical Properties
Chemical structure.
Clotrimazole.
It is a colourless, crystalline, weakly alkaline substance, 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 it is slightly hygroscopic, and may be hydrolysed in acid media.
Chemical name: 1-[(2-chlorophenyl)(diphenyl)methyl]-1H-imidazole.
Molecular formula: C22H17ClN2.
Molecular weight: 344.84.
Melting point: 141 - 145°C.
Hydrocortisone.
Hydrocortisone is an odourless, white or almost white crystalline powder. It is practically insoluble in water, sparingly soluble in acetone and in alcohol, slightly soluble in methylene chloride, very slightly soluble in ether.
Chemical name: (11β)-11,17,21-trihydroxypregn-4-ene-3,20-dione.
Molecular formula: C21H30O5.
Molecular weight: 362.5.
CAS number.
Clotrimazole.
23593-75-1.
Hydrocortisone.
50-23-7.7 Medicine Schedule (Poisons Standard)
Pharmacist Only Medicine (S3).
