DAIVONEX Ointment Ref.[50732] Active ingredients: Calcipotriol

In view of the risk of hypercalcaemia secondary to excessive absorption of calcipotriol when there is extensive skin involvement, Daivonex ointment should not be used for severe extensive psoriasis. In children under 6 years, the maximum safe dose has not been established; in children 6 to 12 years, the maximum weekly dose should not exceed 50 g; and in children over 12 years, the maximum weekly dose should not exceed 75 g. In adults, the maximum dosage of 100 g ointment per week should not be exceeded. When using a combination of ointment and cream the total maximum dose should not exceed 100 g per week.

Daivonex ointment is not recommended for use in patients with generalised pustular psoriasis, guttate psoriasis and erythrodermic exfoliative psoriasis.

Daivonex ointment is not recommended for use on the face since it may give rise to itching and erythema of the facial skin. Patients should be instructed to wash their hands after using Daivonex ointment to avoid inadvertent transfer of ointment to the face from other body areas. Should facial dermatitis develop in spite of these precautions, calcipotriol therapy should be discontinued.

Daivonex ointment should be used cautiously in skin folds, where the natural occlusion may give rise to an increase of any irritant effect of calcipotriol. Occlusive dressings should not be used as they may increase absorption of calcipotriol.

Treatment with Daivonex ointment in adults in the recommended amounts up to 100 g/week for 1 year does not generally result in changes in laboratory values. Hypercalcaemia has been reported rarely at the recommended dose (i.e. up to 100 g/week) of Daivonex ointment when used for the approved indication. Serum calcium and renal function should be monitored at 3 monthly intervals during periods of usage of topical calcipotriol. If the serum calcium level is observed to be elevated, treatment with Daivonex ointment should be discontinued and the condition should be treated appropriately. The levels of serum calcium should be measured once weekly until the serum calcium levels return to normal values.

Treatment with Daivonex ointment should be discontinued after satisfactory improvement has occurred and may be restarted if recurrence should develop after discontinuation.

The use of Daivonex ointment for continuous treatment periods exceeding 1 year has not been studied.

The stability of calcipotriol in sunlight and UV light has not been demonstrated. No clinical trials have been conducted with calcipotriol in Australia, where there is a potential to be exposed to high levels of UV radiation. Therefore, treated areas should be protected from sunlight and UV light, particularly where exposure may be considerable for reasons such as occupation. Furthermore, topical calcipotriol should only be used with UV radiation if the physician and patient consider that the potential benefits outweigh the potential risks.

The decision to administer Daivonex ointment in combination with systemic or physical therapy requires careful consideration. Information on the dosages and risks associated with systemic or physical therapies can be found in the Product Information documents for the respective systemic therapies, or in standard texts, which should be consulted. Systemic or physical therapy poses serious risks of toxicity, and such therapy administered in combination with topical Daivonex ointment should be reserved for those adults with refractory psoriasis who are considered suitable for systemic or physical therapy.

For combination therapy with either UVA or UVB there are no safety and efficacy data beyond 10 weeks.

Renal Impairment

Safety has not been established in patients with renal impairment.

Hepatic Impairment

Safety has not been established in patients with hepatic impairment.

Paediatric population

There are no long term efficacy and safety data in children. Daivonex ointment should not be used for more than 8 weeks in children.

Experience of the use of Daivonex ointment in children under 6 years of age is limited. A maximum safe dose has not been established.

In children 6 to 12 years, the maximum weekly dose should not exceed 50 g and in children over 12 years, the maximum weekly dose should not exceed 75 g.

There is no experience of concomitant therapy with other topical antipsoriatic drugs applied to the same skin area.

Daivonex ointment should not be used concurrently with calcium or vitamin D supplements, or with drugs which enhance the systemic availability of calcium.

Pregnancy

Category B1.

Safety for use in pregnancy has not been established. Studies in animals have shown an increase in the incidence of skeletal variations in rats (wavy ribs, extra ribs, incomplete development of skull bones) at oral doses of 18 mg/kg/day and in rabbits (reduced skeletal ossification) at oral doses of 36 mg/kg/day. The significance of these findings for humans is not known. Therefore Daivonex ointment should not be used during pregnancy unless benefits clearly outweigh the risks.

Breastfeeding

It is not known whether calcipotriol is excreted in breast milk, therefore, Daivonex ointment should be used during lactation only if the benefits clearly outweigh the risks.

Daivonex ointment should not be applied to the chest area during breast feeding to avoid possible ingestion by infants.

Fertility

Studies in rats, at doses up to 54 µg/kg/day (318 µg/m²/day) of calcipotriol, demonstrated no impairment of fertility or general reproductive performance.

Not relevant.

Adults

In the clinical trial program conducted for Daivonex ointment, more than 1360 adult patients were evaluated for safety of calcipotriol. Adverse reactions following treatment with Daivonex ointment were reported in 23% of patients and it was necessary to stop calcipotriol therapy in 2% of patients.

The majority of adverse events reported with Daivonex ointment were localised to the skin at the site of application. Lesional/perilesional irritation was reported in 17% of patients, which included irritant contact dermatitis (on and around psoriatic lesions), flaking at the edge of lesions, increased sensitivity, tender psoriatic lesions and vesicles on psoriatic lesions. 2.5% of patients developed face and scalp irritation, including in studies which stipulated that calcipotriol should not be used on the face and scalp, which is likely to be related to inadvertent transfer of the ointment from other body sites. There is also the potential for allergic and hypersensitivity reactions. Photosensitivity reaction and changes in pigmentation have also been reported during therapy with Daivonex ointment.

For comparison, adverse events at the site of application were reported in 9.2% of patients receiving placebo therapy and in 10.8% of patients treated with betamethasone valerate (0.1%) ointment and in 39% of patients treated with dithranol (up to 2%).

One unconfirmed case of Koebner phenomenon has been reported and one unconfirmed case of allergic reaction to Daivonex ointment. Occasionally, hypercalcaemia has been reported, usually related to excessive (greater than 100 g/week) use of the ointment.

Paediatric population

The safety data for topical use of Daivonex ointment in children are based on the study described under Section 5.1 Pharmacodynamic properties – clinical efficacy and safety. The most common adverse event was lesional and perilesional irritation, as was reported in adult patients. Daivonex ointment treatment was discontinued in 2.3% of paediatric patients due to adverse events.

Adverse Events in the vehicle-controlled study (Reported adverse events have been classified using standard WHO terms):

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions https://nzphvc.otage.ac.nz/reporting/

Not applicable.