1 Name of Medicine
Calcipotriol monohydrate.
Betamethasone dipropionate.
2 Qualitative and Quantitative Composition
Klarvanta contains 50 microgram of calcipotriol (as monohydrate) and 500 microgram of betamethasone (as dipropionate) per gram.
Excipients with known effect. Butylated hydroxytoluene.
For the full list of excipients, see Section 6.1 List of Excipients.
3 Pharmaceutical Form
The foam spray in the can is a white to off-white opalescent liquid.
After spraying, a white to off white foam is formed. The foam has the appearance of non-expanding that gradually collapses after spraying.
4 Clinical Particulars
4.9 Overdose
Usage above the recommended dose may cause elevated serum calcium which subsides when treatment is discontinued. The symptoms of hypercalcaemia include polyuria, constipation, muscle weakness, confusion and coma.
Excessive prolonged use of topical corticosteroids may result in adrenocortical suppression which is usually reversible. Symptomatic treatment may be indicated.
In case of chronic toxicity the corticosteroid treatment must be discontinued gradually.
For information on the management of overdose, contact the Poisons Information Centre on 131 126 (Australia).
5 Pharmacological Properties
5.3 Preclinical Safety Data
Genotoxicity. Calcipotriol was not genotoxic in assays for gene mutations (Ames test and mouse lymphoma TK locus assay) or chromosomal damage (human lymphocyte chromosomal aberration or mouse micronucleus test). Betamethasone dipropionate was not genotoxic in the Ames mutagenicity assay, the mouse lymphoma TK locus assay or in the rat micronucleus test.
Carcinogenicity. A dermal 2-year carcinogenicity study with calcipotriol in mice showed no indications of an increase in tumours at doses up to 30 microgram/kg/day (below the clinical dose on a body surface area basis).
In a 40 week study in which albino hairless mice were exposed to both ultraviolet radiation (UVR) and topically applied calcipotriol, a reduction in the time required for UVR to induce the formation of skin tumours was observed (statistically significant in males only), suggesting that calcipotriol may enhance the effect of UVR to induce skin tumours.
A 2 year oral carcinogenicity study was conducted with calcipotriol in rats at doses up to 15 microgram/kg/day. A treatment-related increase in benign c-cell adenomas was observed in the thyroid of males at 15 microgram/kg/day and females that received ≥ 5 microgram/kg/day. A treatment related increase in benign pheochromocytomas was observed in the adrenal glands of males receiving 15 microgram/kg/day. The relevance of these findings to patients is unknown.
When betamethasone dipropionate was applied topically to mice for up to 24 months at doses up to 8.5 microgram/kg/day in females, and 12.9 microgram/kg/day in males or administered given orally to rats for up to 24 months at doses up to 200 microgram/kg/day (estimated exposures based on AUC of the metabolite betamethasone 17-propionate at least 70 times that expected in patients), no significant changes in tumour incidence were observed when compared to control.
6 Pharmaceutical Particulars
6.7 Physicochemical Properties
Chemical structure. Calcipotriol monohydrate.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSCALMON.gif Calcipotriol monohydrate is (5Z, 7E, 22E, 24S) -24-Cyclopropyl-9,10-secochola- 5,7,10(19),22-tetraene-1α,3β,24-triol monohydrate. The molecular weight of calcipotriol monohydrate is 430.6.
Calcipotriol is a white or almost white crystalline substance. It is freely soluble in ethanol, soluble in chloroform and propylene glycol, particularly insoluble in liquid paraffin. Solubility in water is 0.6 microgram/mL and the melting point is 166 to 168°C. Calcipotriol is a vitamin D derivative and behaves in a similar manner to vitamin D, forming a reversible temperature-dependent equilibrium between calcipotriol and pre-calcipotriol.
Betamethasone dipropionate.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSBETDIP.gif Betamethasone dipropionate is 9-fluoro-11 β, 17, 21-trihydroxy-16 β-methylpregna-1,4- diene-3,20-dione 17,21-dipropionate. The empirical formula is C28H37FO7. The molecular weight of betamethasone dipropionate is 504.6.
Betamethasone dipropionate is a white or almost white, crystalline powder, practically insoluble in water, freely soluble in acetone and in methylene chloride, sparingly soluble in alcohol.
CAS number. Calcipotriol monohydrate. 147657-22-5.
Betamethasone dipropionate. 5593-20-4.
7 Medicine Schedule (Poisons Standard)
Schedule 4 - Prescription only medicine.
Summary Table of Changes
https://stagingapi.mims.com/au/public/v2/images/fulltablegif/KLARVAST.gif