Daivonex ointment contains 50 μg/g (0.005% w/w) calcipotriol.
Excipients/Inactive Ingredients: Propylene glycol, Liquid paraffin, Macrogol stearyl ether, Disodium phosphate dihydrate, Disodium edetate, all-rac-α-Tocopherol, White soft paraffin.
Pharmacology: Daivonex ointment is a topical formulation of the vitamin D derivative, calcipotriol, which induces differentiation and suppresses proliferation of skin cells (keratinocytes). Daivonex ointment thus normalises abnormal cell proliferation and differentiation in psoriatic skin.
Toxicology: Preclinical safety data: The effect on the calcium metabolism is approximately 100 times less than that of the hormonally active form of vitamin D3. A dermal carcinogenicity study in mice showed no indications of increased carcinogenic risks.
Calcipotriol solution was applied topically for up to 24 months at doses of 3, 10 and 30 μg/kg/day (corresponding to 9, 30 and 90 μg/m2/day). The high-dose was considered to be the Maximum Tolerated Dose for dermal treatment of mice with calcipotriol. Survival was decreased at 10 and 30 μg/kg/day, particularly in the males. The reduced survival was associated with an increased incidence of obstructive uropathy, most probably caused by treatment-related changes in the urinary composition. This is an expected effect of treatment with high doses of calcipotriol or other vitamin D analogues. There were no dermal effects and no dermal or systemic carcinogenicity.
Calcipotriol has shown maternal and fetal toxicity in rats and rabbits when given by the oral route at doses of 54 μg/kg/day and 12 μg/kg/day, respectively. The fetal abnormalities observed with concomitant maternal toxicity included signs indicative of skeletal immaturity (incomplete ossification of the pubic bones and forelimb phalanges and enlarged fontanelles) and an increased incidence of supernumerary ribs.
In a study where albino hairless mice were repeatedly exposed to both ultraviolet (UV) radiation and topically applied calcipotriol for 40 weeks at the same dose levels as in the dermal carcinogenicity study, a reduction in the time required for UV radiation to induce the formation of skin tumours was observed (statistically significant in males only), suggesting that calcipotriol may enhance the effect of UV radiation to induce skin tumours. The clinical relevance of this finding is unknown.
Adults: The ointment should be applied to the affected area once to twice daily. Twice daily application of the ointment is often preferred initially. Application of the ointment can be reduced to once daily when appropriate.
Maximum weekly dose should not exceed 100 g.
Twice daily application of Daivonex in combination with ciclosporin or acitretin and once daily application of Daivonex in combination with corticosteroids (e.g. administration of Daivonex in the morning and steroid in the evening) is effective and well tolerated.
The addition of Daivonex twice daily will enhance the efficacy and reduce the dosage of ciclosporin and acitretin.
Use 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.
Hypersensitivity to the active substance or to any of the excipients.
Due to the content of calcipotriol, Daivonex ointment is contraindicated in patients with known disorders of calcium metabolism (see Precautions).
Effects on calcium metabolism: Due to the content of calcipotriol, hypercalcaemia may occur if the maximum weekly dose is exceeded. Serum calcium is normalised when treatment is discontinued. The risk of hypercalcaemia is minimal when the recommendations relevant to calcipotriol are followed. The maximum weekly dose in adults is 100 g of cream or ointment (equivalent to 5 mg of calcipotriol) or 60 ml of scalp solution (equivalent to 3 mg of calcipotriol). When cream, ointment or cutaneous solution are applied together, the total dose of calcipotriol should not exceed 5 mg per week.
Local adverse reactions: Daivonex ointment should not be applied to the face. The patient must be instructed in correct use of the product to avoid accidental transfer to the face and eyes. Hands must be washed after each application to avoid accidental transfer to these areas.
Daivonex ointment should be used with caution in skin folds as this may increase the risk of developing skin irritation (see Adverse Reactions).
UV exposure: During Daivonex ointment treatment, physicians are recommended to advise patients to limit or avoid excessive exposure to either natural or artificial sunlight. Daivonex ointment should be used with UVR only if the physician and patient consider that the potential benefits outweigh the potential risks.
Unevaluated use: Due to lack of data, Daivonex ointment should be avoided in guttate, erythrodermic, exfoliative and pustular psoriasis.
Due to lack of data, Daivonex should be avoided in patient with severe liver and kidney disease.
Adverse reactions to excipients: Daivonex ointment contains propylene glycol as an excipient which may cause skin irritation.
Effects on the ability to drive and use machines: Daivonex ointment has no or negligible influence on the ability to drive and use machines.
Use in Children: Safety and efficacy in the treatment of children have not yet been established.
Pregnancy: Safety for use of calcipotriol during human pregnancy has not been established. When calcipotriol was administered orally in animals, reproductive toxicity has been shown. Calcipotriol should not be used during pregnancy unless clearly necessary.
Breast-feeding: It is unknown whether calcipotriol is excreted in human milk. Caution should be exercised when prescribing Daivonex ointment to women who breast-feed. The patient should be instructed not to use Daivonex ointment on the breast when breast-feeding.
Fertility: Studies in rats with oral doses of calcipotriol demonstrated no impairment of male and female fertility.
The estimation of the frequency of adverse reactions is based on a pooled analysis of data from clinical studies and spontaneous reporting.
The most frequently reported adverse reactions during treatment are pruritus, skin irritation and erythema.
Systemic reactions (hypercalcaemia and hypercalciuria) have been reported. The risk of developing such reactions increases if the recommended total dose is exceeded (see Precautions).
Adverse reactions are listed by MedDRA SOC and the individual adverse reactions are listed starting with the most frequently reported. Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very rare (<1/10,000). (See table.)
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No interaction studies have been performed with Daivonex.
D05AX02 - calcipotriol ; Belongs to the class of other antipsoriatics for topical use.
Daivonex oint 50 mcg/g
30 g x 1's
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