Consumer medicine information

Daivonex Cream

Calcipotriol

BRAND INFORMATION

Brand name

Daivonex Cream

Active ingredient

Calcipotriol

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Daivonex Cream.

What is in this leaflet?

This leaflet answers some common questions about using Daivonex®. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you using Daivonex® against the benefits it is expected to have for you.

If you have any concerns about using Daivonex®, talk to your doctor or pharmacist.

What Daivonex® is used for

Daivonex® is an anti-psoriasis medicine. Daivonex® contains calcipotriol (related to Vitamin D). Daivonex® does not contain steroids.

Daivonex® is used only on skin affected by psoriasis. Psoriasis is a skin disorder in which skin cells are overactive. The calcipotriol in Daivonex® treats the overactive skin cells.

Daivonex® is used in the commonest type of psoriasis, where “plaques” form on the skin. Plaques are raised, rough, reddened areas covered with fine, dry silvery scales.

Daivonex® cream is available only with a doctor’s prescription.

This medicine is not expected to affect your ability to drive a car or operate machinery.

This medicine is not addictive.

Before you use Daivonex®

When you must not use Daivonex®

Do not use Daivonex® if you have an allergy to:

  • any medicine containing calcipotriol
  • any of the ingredients listed at the end of this leaflet (see Product description).

Some of the symptoms of an allergic reaction include shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching or ”hives” on the skin.

Do not use Daivonex® for severe widespread psoriasis, or the types of psoriasis known as guttate, generalised pustular or erythrodermic exfoliative psoriasis.

Your doctor will identify these conditions for you.

Do not use Daivonex® if you

  • have high blood calcium levels.
  • are taking calcium, vitamin D supplements or vitamin D-like medicines, for example calcitriol.

Do not use Daivonex®

  • after the expiry date printed on the pack OR
  • if the packaging is torn, doesn’t look quite right or shows signs of tampering.

If the Daivonex® packaging is damaged or it is past the expiry date, return it to your pharmacist for disposal.

Do not breast-feed if you are using Daivonex® on your breasts.

If you are not sure whether you should start using Daivonex®, talk to your doctor.

Do not use Daivonex® cream in children.

The safety and effectiveness of Daivonex® cream in children under 18 has not been established.

Do not use Daivonex® cream

if you are having or using other treatments for psoriasis unless otherwise advised by your doctor.

Before you start to use it

Tell your doctor if you have a known allergy to Daivonex® or any of the ingredients listed at the end of this leaflet.

Tell your doctor if you

  • have kidney or liver problems
  • are suffering from any other illness.

Tell your doctor if you

  • are pregnant
  • are breast-feeding
  • intend to breast-feed.

If you have not told your doctor about any of the above, tell him/her before you start using this medicine.

Other medicines

Tell your doctor or pharmacist if you are on any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

Your doctor and pharmacist have more information on medicines you should be careful with or avoid whilst using Daivonex®.

How to use Daivonex®

Follow carefully all directions given to you by your doctor or pharmacist.

They may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

How much Daivonex® to use

In one week do not use more than

100 g (no more than three 30 g tubes of Daivonex® cream).

Using combinations of Daivonex® and Daivobet® preparations
You may need to use Daivonex® cream on your body and other products containing calcipotriol (e.g. Daivobet® gel or Daivobet® ointment) on other parts of your body or at different times.

In one week do not use more than

100g (no more than three 30g tubes or bottles) of Daivonex® and Daivobet® NOTE: If you use more than the recommended amount, the levels of calcium in your body may rise, and this can have serious effects.

How to use Daivonex®

NOTE: unlike certain other skin preparations which you use sparingly, use Daivonex® as follows:

  • Apply Daivonex® cream to the psoriasis plaques only. Form a visible coating. If you accidentally get some of the cream on normal skin, wash it off.
  • DO NOT use Daivonex® cream
    - in skin folds,
    - on the genitalia,
    - on the scalp or
    - on the face.

Wash your hands thoroughly after applying it on any part of your body,

unless your hands are being treated.

Take care not to get Daivonex® in your eyes. If this happens, rinse your eyes with clean water and tell your doctor.

If any skin irritation develops,

wash off the Daivonex®.

Do not use Daivonex® on the face.

An itchy red rash may develop.

Do not use Daivonex®

under occlusive dressings (eg. a bandage). The treated area does not need to have a special covering. You may wear your usual clothes.

When to use Daivonex® preparations

Apply Daivonex® twice a day (morning and night).

How long to use it

Continue to use Daivonex® for as long as your doctor tells you.

If you are using Daivonex® for longer than 3 months your doctor may do blood tests to check your calcium levels and kidney function.

Your doctor may decide to stop Daivonex® treatment once your psoriasis has improved.

If you forget to use it

If you forget to use Daivonex®, use it as soon as you remember. Then go on as before.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to use your medicine, ask your doctor or pharmacist for some hints.

If you use too much or use it other than directed. (Overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26 in Australia or 03 474 7000 in New Zealand) for advice, or go to the Emergency Department at the nearest hospital, if you think that you or anyone else may have used too much or swallowed some of this medicine. Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

While you are using Daivonex®

Things you must do

While you are using Daivonex®, protect the treated skin areas from sunlight and Ultra Violet (UV) rays, for example, by wearing protective clothing. This is particularly important if your job or lifestyle means you spend much time outdoors.

If you are going to start any new medicine, tell your doctor and pharmacist that you are using Daivonex®.

If you become pregnant while using Daivonex®, tell your doctor immediately.

Keep all appointments with your doctor so that your progress can be checked.

Your doctor may do some blood tests from time to time.

Things you must not do

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not use Daivonex® with other treatments for psoriasis unless prescribed by your doctor.

Do not use more than the recommended weekly dose (see How to use Daivonex®).

Side effects

As with all medicines, Daivonex® can cause some side effects.

Do not be alarmed by the following list of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist:

  • if you have any unpleasant effects while you are using Daivonex®
    or
  • if you notice any of the following and they worry you:
    - skin irritation (including rashes or peeling)
    - a rash on your face
    - a change in the colour of your skin
    - your skin is more sensitive to light.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

After using Daivonex®

Keep Daivonex® in the box until required.

Storage

Keep your Daivonex® in a cool dry place where the temperature stays below 25°C.

However, do not keep it in the refrigerator as it will not spread easily.

Do not store Daivonex® or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car.

Heat and dampness can destroy some medicines.

Keep Daivonex® where children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop using Daivonex® or the expiry date has passed, ask your pharmacist what to do with any Daivonex® that is left over.

Product description

What it looks like

Daivonex® cream is a soft white cream.

Ingredients

Daivonex® cream contains the active ingredient calcipotriol (50 microgram/gram). It also contains

  • disodium edetate
  • quaternium-15
  • sodium phosphate - dibasic dihydrate
  • cetomacrogol 1000
  • glycerol
  • liquid paraffin
  • cetostearyl alcohol
  • soft white paraffin
  • purified water.

Daivonex® does not contain lactose, sucrose, gluten, tartrazine or any other azo products.

The Australian Registration Number (AUST R) is 57354.

This is not all the information available on Daivonex®. If you have any more questions or are unsure about anything, ask your doctor or pharmacist.

Supplier

LEO Pharma Pty Ltd,
Level 3, Tower 1,
25 Montpelier Road,
Bowen Hills, QLD 4006,
AUSTRALIA
Web: www.leo-pharma.com.au
Australia Toll free no: 1800 991 778

Daivonex® cream is manufactured by: LEO Laboratories Ltd (LEO Pharma), IRELAND

Daivonex, LEO and LEO/lion device are registered trademarks of LEO Pharma A/S, Denmark.

This leaflet was prepared in April 2002 and last modified in July 2012.

LPS-12-031

BRAND INFORMATION

Brand name

Daivonex Cream

Active ingredient

Calcipotriol

Schedule

S4

 

Name of the medicine

Calcipotriol.

Excipients

Cetomacrogol 1000, cetostearyl alcohol, quaternium-15, disodium edetate, dibasic sodium phosphate dihydrate, glycerol, liquid paraffin, soft white paraffin and purified water.

Description

Chemical name: (1S, 3R, 5Z, 7E, 22E, 24S)- 24-cyclopropyl-9, 10-secochola-5,7,10(19), 22-tetraene-1,3,24-triol. CAS: 112965-21-6. Daivonex cream contains the hydrated form of calcipotriol. Calcipotriol is a white or almost white crystalline substance. It is a vitamin D derivative and behaves in a similar manner to vitamin D, forming a reversible temperature dependent equilibrium between calcipotriol and precalcipotriol.

Pharmacology

Calcipotriol is a nonsteroidal antipsoriatic agent, derived from vitamin D. Calcipotriol exhibits a vitamin D like effect by competing for the 1,25(OH)2D3 receptor. Calcipotriol is as potent as 1,25(OH)2D3, the naturally occurring active form of vitamin D, in regulating cell proliferation and cell differentiation, but much less active than 1,25(OH)2D3 in its effect on calcium metabolism. Calcipotriol induces differentiation and suppresses proliferation (without any evidence of a cytotoxic effect) of keratinocytes, thus reversing the abnormal keratinocyte changes in psoriasis. The therapeutic goal envisaged with calcipotriol is thus a normalisation of epidermal growth.

Pharmacokinetics.

Pharmacokinetic studies with 3H-calcipotriol have been performed in rats and minipigs. Oral absorption of calcipotriol was approximately 60% in rats and 40% in minipigs. The half-life of calcipotriol was 12 minutes in rats and 60 minutes in minipigs. The major metabolite of calcipotriol, MC1080, was present in the first plasma sample at five minutes; its half-life was 54 minutes in rats and 1.8 hours in minipigs. Drug related radioactivity was excreted in urine and faeces, and clearance was considered to be almost exclusively metabolic, as less than 5% of the administered radioactivity was excreted at the time of disappearance of all calcipotriol from plasma. Determination of the tissue distribution of calcipotriol was complicated by the appearance of 3H-H2O from the metabolic degradation of 3H-calcipotriol. Autoradiography studies performed in rats, however, established that calcipotriol concentrations were highest in the liver, kidney and intestine. No drug related radioactivity was present 24 hours after administration of 3H-calcipotriol.
Two main metabolites of calcipotriol, MC1046 and MC1080, were present in supernatants from minipigs, rabbit and human liver homogenates and in plasma samples from rats and minipigs. Although the necessity of using very high dosages of calcipotriol precludes the study of calcipotriol metabolism in humans, the present evidence strongly suggests that calcipotriol metabolism is qualitatively similar in rats, minipigs, rabbits and humans.
Bioavailability studies of calcipotriol ointment in psoriatic and healthy patients demonstrated that approximately 2 to 10% of calcipotriol from the applied dose was systemically absorbed. Analogous data are not available for calcipotriol cream, but studies on cadaver skin appear to indicate that the cream is not as well absorbed as the ointment.

Clinical Trials

Clinical trials using calcipotriol cream were of eight weeks duration. Data on local or systemic effects of the cream under conditions of high ultraviolet (UV) exposure such as those existing in Australia are not available. A summary of the trials is presented in Table 1.

Indications

Topical treatment of chronic stable plaque type psoriasis vulgaris in adult patients.

Contraindications

Allergic sensitisation to any constituent of calcipotriol cream.
Known disorders of calcium metabolism.
Not for ophthalmic use.

Precautions

In view of the risk of hypercalcaemia secondary to excessive absorption of calcipotriol when there is extensive skin involvement, calcipotriol cream should not be used for severe extensive psoriasis. The maximum dosage of 100 g cream/week should not be exceeded.
Calcipotriol cream is not recommended for use in patients with generalised pustular psoriasis, guttate psoriasis and erythrodermic exfoliate psoriasis.
Calcipotriol cream 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 calcipotriol to avoid inadvertent transfer to the face from other body areas. Should facial dermatitis develop in spite of these precautions, calcipotriol therapy should be discontinued.
Calcipotriol cream 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 calcipotriol ointment in the recommended amounts up to 100 g/week for one 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 calcipotriol ointment when used for the approved indication. Serum calcium and renal function should be monitored at three monthly intervals during periods of usage of topical calcipotriol. If the serum calcium level is observed to be elevated, calcipotriol treatment 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 topical calcipotriol should be discontinued after satisfactory improvement has occurred and may be restarted if recurrence does occur after discontinuation.
The use of calcipotriol ointment for continuous treatment periods exceeding one year has not been studied.
The effects of calcipotriol when used for long periods during exposure to sunlight and UVA/UVB light have not been extensively studied in patients. The stability of calcipotriol in sunlight and UV light has not been demonstrated. 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 doctor and patient consider that the potential benefits outweigh the potential risks.

Carcinogenicity and mutagenicity

A dermal carcinogenicity study with calcipotriol 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 microgram/kg/day (corresponding to 9, 30 and 90 microgram/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 microgram/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.
In a study where albino hairless mice were repeatedly exposed to both 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 these findings is unknown.
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).

Use in 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, calcipotriol should not be used during pregnancy unless benefits clearly outweigh the risks.

Use in lactation.

It is not known whether calcipotriol is excreted in breast milk, therefore, the drug should be used during lactation only if the benefits clearly outweigh the risks.
Calcipotriol should not be applied to the chest area during breastfeeding to avoid possible ingestion by infants.

Use in children

Daivonex cream should not be used in children.

Renal impairment

Safety has not been established in patients with renal impairment.

Hepatic impairment

Safety has not been established in patients with hepatic impairment.

Interactions

There is no experience of concomitant therapy with other topical antipsoriatic drugs applied to the same skin area or with oral antipsoriatic drugs.
Calcipotriol should not be used concurrently with calcium or vitamin D supplements or with drugs which enhance the systemic availability of calcium.

Adverse Effects

The adverse effects observed in clinical trials conducted for calcipotriol cream are summarised in Table 2.
Photosensitivity reactions, skin discolouration, bullous eruption, skin exfoliation, contact dermatitis and allergic reactions have been reported with topical calcipotriol therapy.
Occasional hypercalcaemia has been reported, usually related to excessive (greater than 100 g/week) use.

Dosage and Administration

Calcipotriol is indicated for topical use only and not for ophthalmic use.

Adults.

Calcipotriol cream should be applied topically to the affected area twice daily (i.e. in the morning and in the evening). Less frequent application may be indicated after the initial period of treatment. After satisfactory improvement has occurred, treatment should be discontinued. If recurrence takes place after discontinuation, the treatment may be reinstituted. Experience is lacking in the use of calcipotriol for periods longer than one year.
The maximum recommended weekly dose of calcipotriol cream is 100 g/week.
It should be noted that there are no long-term clinical studies assessing the safety of using Daivonex cream during exposure to UV and/or sunlight. Therefore, all psoriasis affected areas treated with calcipotriol should be, where possible, protected from direct sunlight and UV light with items of clothing. Furthermore, topical calcipotriol should only be used with UV radiation if the doctor and patient consider that the potential benefits outweigh the potential risks.

Children.

Daivonex cream should not be used in children, as there is inadequate experience with its use.

Overdosage

Hypercalcaemia has been reported rarely at the recommended dose (i.e. up to 100 g/week) of calcipotriol ointment when used for the approved indication. Excessive use, i.e. more than 100 g/week, may cause elevated serum calcium, which rapidly subsides when treatment is discontinued; in such cases, the monitoring of serum calcium levels once weekly or more frequently as required by clinical circumstances until the serum calcium returns to normal levels is recommended.
Contact the Poisons Information Centre on 131 126 for further advice on overdose management.

Presentation

Cream, 50 microgram/g (smooth, white cream base): 30 g, 100 g* (tube, AUST R 57354).
*Not currently marketed in Australia.

Storage

When stored below 25°C the product is stable for two years from the date of manufacture. For ease of application, do not refrigerate.

Poison Schedule

S4.