New Zealand - English - Medsafe (Medicines Safety Authority)
Consumer Medicine Information
ointment, cream and
Please read this leaflet carefully before you start your treatment.
Keep this leaflet. You may want to read it again.
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
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
overactive skin cells.
DAIVONEX is used in the commonest type of psoriasis, where "plaques" form in the
skin. Plaques are raised, rough, reddened areas covered with fine, dry silvery scales.
Plaques are usually a centimetre or two across.
DAIVONEX preparations are available as ointment, cream and scalp solution.
DAIVONEX preparations are available only with a doctor's prescription.
This medicine is not expected to affect your ability to drive a car or operate
This medicine is not addictive.
Before you use DAIVONEX
When you must not use DAIVONEX (All Preparations)
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
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
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
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
When you must not use DAIVONEX Cream or Scalp Solution
Do not use DAIVONEX cream or scalp solution in children.
Safety and effectiveness of these forms of DAIVONEX in children have not
DAIVONEX ointment may be used in children (see How to use DAIVONEX).
Do not use DAIVONEX cream or scalp solution if you are having other
treatments for psoriasis.
DAIVONEX ointment may be used with some other treatments for psoriasis. Talk to
your doctor to find out if this applies to you.
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
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.
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 of each DAIVONEX preparation to use
DAIVONEX ointment only
over 12 years old
- Do not use more than 75 g in one week.
6 - 12 years old
- Do not use more than 50 g in one week.
under 6 years old
- Follow your doctor's instructions.
DAIVONEX cream and ointment:
- Do not use more than 100 g in one
week. For example, no more than
3 tubes of 30 g or
1 tube of 100 g.
DAIVONEX scalp solution:
- Do not use more than 60 mL in one week.
For example, no more than
1 bottle containing 60 mL or
2 bottles containing 30 mL.
Using combinations of DAIVONEX preparations
IMPORTANT: You may need to use a combination of DAIVONEX
preparations to treat your psoriasis. For example, you may use scalp solution
on your head and ointment or cream on other parts of your body.
- In one week do not use more than
60 mL of DAIVONEX scalp
solution plus one 30 g tube of
DAIVONEX cream or ointment
30 mL of DAIVONEX scalp solution plus two 30 g tubes of DAIVONEX
cream or ointment.
- In one week do not use more than
one 30 g tube of DAIVONEX cream and two 30 g tubes
of DAIVONEX ointment
two 30 g tubes of DAIVONEX cream and one 30 g tube
of DAIVONEX ointment.
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 preparations
NOTE: unlike certain other skin preparations which you use sparingly, use
DAIVONEX as follows:
DAIVONEX cream and ointment:
Apply DAIVONEX cream or ointment to the psoriasis plaques only.
Form a visible coating. If you accidentally get some of the cream or
ointment on normal skin, wash it off.
DO NOT use DAIVONEX cream or ointment
in skin folds,
on the genitalia,
on the scalp or
on the face.
DAIVONEX scalp solution:
Use DAIVONEX scalp solution ONLY on the scalp.
Apply DAIVONEX scalp solution, drop by drop, only to the areas of your
scalp that have psoriasis.
If any accidentally gets on your face, wash it off immediately.
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.
Avoid getting DAIVONEX on your face accidentally.
If any skin irritation develops, wash off the DAIVONEX preparation.
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
Do not use DAIVONEX ointment for more than 8 weeks.
Continue to use DAIVONEX for as long as your doctor tells you.
If you are using DAIVONEX for longer than 3 months your doctor will probably
do blood tests to check your calcium levels and kidney function.
Your doctor may decide to stop DAIVONEX treatment once your psoriasis has
If you forget to use it
If you forget to use DAIVONEX, use it as soon as you remember. Then go on as
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 (0800
764 766 / 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 out-of-doors. [An
exception is if your doctor has advised combination treatment with DAIVONEX
ointment and UV therapy.]
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 cream or scalp solution with other treatments for
Your doctor will tell you if you can use DAIVONEX ointment with other psoriasis
Do not use more than the recommended weekly dose (see How to use
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 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.
Keep your DAIVONEX ointment or cream or scalp solution in a cool dry place
where the temperature stays below 25°C. However, do not keep DAIVONEX
cream or ointment in the refrigerator as the cream or ointment will not spread easily.
Also, keep your DAIVONEX scalp solution away from fire or flames because it
may catch fire.
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.
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.
Ointment and Daivonex
Cream 6 months after opening.
scalp solution 3 months after opening.
What it looks like
DAIVONEX ointment is a white to yellowish ointment.
DAIVONEX cream is a soft white cream.
DAIVONEX scalp solution is a colourless, non-runny solution.
DAIVONEX ointment contains the active ingredient calcipotriol (50 microgram/g). It
sodium phosphate - dibasic dihydrate
soft white paraffin.
DAIVONEX cream contains the active ingredient calcipotriol (50
microgram/g). It also contains
sodium phosphate - dibasic dihydrate
soft white paraffin
DAIVONEX scalp solution contains the active ingredient
calcipotriol (50 microgram/mL).
It also contains
DAIVONEX does not contain lactose, sucrose, gluten, tartrazine or any
other azo products.
This is not all the information available on DAIVONEX. If you have any
more questions or are unsure about anything, ask your doctor or
DAIVONEX is supplied in New Zealand by:
LEO Pharma Ltd
Level 31, Vero Centre,48 Shortland Street,
Auckland 1010,New Zealand
DAIVONEX is manufactured by:
Leo Pharma A/S
Proprietor of the registered trademark LEO, LION Device
Date of Preparation: This leaflet was prepared in January 2016
NEW ZEALAND DATA SHEET
50 microgram/gram topical ointment
QUALITATIVE AND QUANTITATIVE COMPOSITION
ointment contains calcipotriol 50 microgram per gram
ointment contains the anhydrous form of calcipotriol.
For full list of excipients, see section 6.1 List of excipients.
is a topical ointment. It is a smooth, white preservative free ointment base.
ointment is indicated for the topical treatment of psoriasis vulgaris, including
plaque psoriasis in adults and children (see section 4.4 Special warnings and precautions for
use - paediatric population). In adult patients, Daivonex
ointment may also be used in
combination with systemic acitretin or cyclosporin.
Dosage and method of administration
ointment should be applied topically to the affected area once or twice daily (i.e.
in the morning and/or in the evening). Initially, twice daily application of the ointment is
usually preferred. Application may then be reduced to once daily, provided individual clinical
response is satisfactory. After satisfactory improvement has occurred, treatment should be
If recurrence develops after reduction in frequency of application or after discontinuation, the
treatment may be reinstituted at the initial dosage. Experience is lacking in the use of
calcipotriol for periods longer than 1 year.
The maximum recommended weekly dose of Daivonex
ointment is 100 g/week.
When using a combination of ointment and cream the total maximum dose
should not exceed
100 g per week.
It should be noted that there are no long-term clinical studies assessing the safety of using
ointment during exposure to 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 physician and patient consider that the potential benefits outweigh the
Twice daily application of Daivonex
ointment in combination with systemic cyclosporin or
acitretin has been shown to enhance the efficacy of cyclosporin or acitretin (see Section 5.1
Pharmacodynamic properties Clinical efficacy and safety).
Children under 6 years:
There is limited experience of using Daivonex
ointment in this age group. A maximum safe
dose has not been established.
Children aged 6 to 12 years:
ointment should be applied to the affected area twice daily. Maximum weekly
dose should not exceed 50 g.
Children over 12 years:
ointment should be applied to the affected area twice daily. Maximum weekly
dose should not exceed 75 g.
There is no experience of use of Daivonex
ointment in combination with other therapies for
psoriasis in children.
ointment should not be used for more than 8 weeks in children.
Method of Administration
ointment is indicated FOR TOPICAL USE ONLY and NOT FOR
Allergic sensitisation to any constituent of Daivonex
Patients with known disorders of calcium metabolism.
NOT FOR OPHTHALMIC USE.
Special warnings and precautions for use
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
ointment is not recommended for use in patients with generalised pustular
psoriasis, guttate psoriasis and erythrodermic exfoliative psoriasis.
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
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.
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
used for the approved indication.
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
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.
Safety has not been established in patients with renal impairment.
Safety has not been established in patients with hepatic impairment.
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.
Interaction with other medicines and other forms of interaction
There is no experience of concomitant therapy with other topical antipsoriatic drugs applied to
the same skin area.
ointment should not be used concurrently with calcium or vitamin D supplements,
or with drugs which enhance the systemic availability of calcium.
Fertility, pregnancy and lactation
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.
It is not known whether calcipotriol is excreted in breast milk, therefore, Daivonex
should be used during lactation only if the benefits clearly outweigh the risks.
ointment should not be applied to the chest area during breast feeding to avoid
possible ingestion by infants.
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.
Effects on ability to drive and use machines
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
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
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.
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
ointment treatment was discontinued in 2.3% of paediatric patients due to
Adverse Events in the vehicle-controlled study
(Reported adverse events have been classified using standard WHO terms)
Skin and appendages disorders
generalised skin inflammation
Gastro-intestinal system disorders
Urinary system disorders
crystals in urine
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
Hypercalcaemia has been reported rarely at the recommended dose of Daivonex
when used for the approved indication. Excessive use may cause elevated serum calcium,
which rapidly subsides when treatment is discontinued; in such cases, the monitoring of
serum calcium levels once weekly until the serum calcium returns to normal levels is
For advice on the management of overdose please contact the National Poisons Centre on
0800 POISON (0800 764 766).
Mechanism of action
Calcipotriol is a non-steroidal antipsoriatic agent, derived from vitamin D. Calcipotriol
exhibits a vitamin D-like effect by competing for the 1,25(OH)
Calcipotriol is as potent as 1,25(OH)
, the naturally occurring active form of vitamin
regulating cell proliferation and cell differentiation, but much less active than 1,25(OH)
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
Clinical efficacy and safety
Clinical trials with Daivonex
Ointment undertaken in adults and children are summarised
Topical treatment of psoriasis in adults using twice daily calcipotriol 50 µg/g ointment
Two double-blind, multicentre, randomised studies assessed the efficacy and safety of
calcipotriol ointment 50 µg/g twice daily vs betamethasone 17-valerate ointment
0.1% twice daily in patients with psoriasis. The mean study duration was 6 weeks. The
primary efficacy endpoint was the percentage reduction of the Psoriasis Area &
Severity Index (PASI) score. The mean reduction in PASI score was statistically significant
(p<0.001) favouring calcipotriol in one study (MC 288); there was no significant difference
between treatments in the second study (MC 188).
Table 1: Twice-daily administration of calcipotriol 50 µg/g ointment in adults
Calcipotriol (n = 342)
(n = 342)
Calcipotriol (n = 201)
(n = 200)
Percentage reduction in
(mean±sd or mean
n.s. - not significant
Topical treatment of psoriasis in adults using once daily calcipotriol 50 µg/g regimen
Two double-blind, multicentre, randomised, vehicle-controlled studies of 8 weeks duration
assessed the efficacy and safety of calcipotriol ointment 50 µg/g once daily. Efficacy was
assessed using the Psoriasis Grading Scale to score erythema, scaling, plaque elevation and
overall severity. The primary efficacy parameter was the plaque elevation subscore. There
was a statistically significant difference (p<0.001) favouring calcipotriol.
Table 2: Once daily administration of calcipotriol 50 µg/g ointment in adults
(Intention to treat population)
Calcipotriol (n = 118)
Calcipotriol (n = 99)
Vehicle (n = 116)
Vehicle (n = 99)
Calcipotriol treatment of psoriasis with cyclosporin A in adults
One double-blind, randomised, multicentre, vehicle-controlled study assessed the efficacy
and safety of calcipotriol ointment 50 µg/g twice daily with cyclosporin 2 mg/kg/day in
patients with severe psoriasis for 6 weeks. Change in PASI score was the primary efficacy
endpoint. There was a statistically significant difference (p<0.01) favouring combination
Table 3.1: Administration of calcipotriol 50 µg/g ointment with cyclosporin A in adults
Calcipotriol + cyclosporin
Vehicle + cyclosporin
2 mg/kg/day (n = 32)
2 mg/kg/day (n = 34)
Change in PASI from baseline
Calcipotriol treatment of psoriasis with acitretin in adults
One double-blind, multicentre, randomised, vehicle-controlled study assessed the efficacy
and safety of calcipotriol ointment 50 µg/g twice daily with acitretin (20-70 mg/day) for 12
weeks in patients with severe/extensive psoriasis unresponsive to topical treatment alone.
The percentage of patients achieving marked improvement or clearance at the end of
treatment was the primary efficacy endpoint. There was a statistically significant difference
(p<0.01) favouring combination therapy.
Table 3.2: Administration of calcipotriol 50 µg/g ointment with acitretin in adults
(Intention to treat population)
(n = 76)
(n = 59)
Patients with marked improvement or clearance
Baseline PASI (mean±sd)
End PASI (mean±sd)
Topical treatment of psoriasis in children using twice daily calcipotriol 50 µg/g
One double-blind, multicentre, randomised, vehicle-controlled study assessed the safety and
efficacy of calcipotriol 50 µg/g ointment in children of 2 to 14 years with mild to moderate psoriasis
not involving more than 30% of the body surface area.
The study was of 8 weeks duration. The primary efficacy end point was the change in PASI
score. Nine of the 77 children in the trial were under the age of 7 years; 22.2% of children
below 7 years of age received calcipotriol. There was no statistically significant change
observed over placebo.
Table 4: Administration of calcipotriol 50µg/g ointment in children
(Intention to treat)
(n = 43)
Reduction in PASI from baseline to end
Pharmacokinetic studies with
H-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 5 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
O from the metabolic degradation of
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
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 2-10% of calcipotriol from the applied dose was systemically absorbed.
Preclinical safety data
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 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.
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 these findings is unknown.
Calcipotriol did not elicit any genotoxic effects in
assays for gene mutations (Ames
mutagenicity assay and mouse lymphoma TK locus assay) or chromosomal damage (human
lymphocyte chromosome aberration test or mouse micronucleus test).
List of excipients
Dibasic sodium phosphate dihydrate
Disodium edetate dihydrate
Polyoxyethylene stearyl ether (also known as steareth-2)
White soft paraffin
Unopened container: 2 years
After first opening of container: 6 months
Special precautions for storage
Store below 25ºC.
For ease of application, do not refrigerate
6.5 Nature and contents of container
ointment is available in aluminium tubes of 15g, 30g or 100g.
6.6 Special precautions for disposal
Any unused medicine or waste material should be disposed of in accordance with local
LEO Pharma Ltd
Level 31, Vero Centre
48 Shortland Street
Toll Free No. 0800 497 456
DATE OF FIRST APPROVAL
30 May 1991
DATE OR REVISION OF THE TEXT
29 April 2019
LEO Pharma A/S
Registered proprietor of the trademark LEO
LION Device and
Summary table of changes
Summary of new information
Reformat to Medsafe SPC format