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XAMIOL 50 MICROGRAM/G + 0.5 MG/G GEL

Active substance: CALCIPOTRIOL MONOHYDRATE

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SUMMARY OF PRODUCT CHARACTERISTICS
1

NAME OF THE MEDICINAL PRODUCT
Xamiol 50 micrograms/g + 0.5 mg/g gel

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
One gram of gel contains 50 micrograms of calcipotriol (as monohydrate) and 0.5 mg
of betamethasone (as dipropionate).
Excipient: 160 micrograms butylated hydroxytoluene/g gel.
For a full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Gel.
An almost clear, colourless to slightly off-white gel.

4.

CLINICAL PARTICULARS

4.1.

Therapeutic indications
Topical treatment of scalp psoriasis in adults.

4.2

Posology and method of administration
Posology
Xamiol gel should be applied to affected areas once daily. The recommended
treatment period is 4 weeks. If it is necessary to continue or restart treatment after this
period, treatment should be continued after medical review and under regular medical
supervision.
When using calcipotriol containing medicinal products, the maximum daily dose
should not exceed 15 g. The body surface area treated with calcipotriol containing
medicinal products should not exceed 30 % (see section 4.4).
All the affected scalp areas may be treated with Xamiol gel. Usually an amount
between 1 g and 4 g per day is sufficient for treatment of the scalp (4 g corresponds to
one teaspoon).
Special populations
Renal and hepatic impairment
The safety and efficacy of Xamiol gel in patients with severe renal insufficiency or
severe hepatic disorders have not been evaluated.
Paediatric population

The safety and efficacy of Xamiol gel in children below 18 years have not been
established. Currently available data in children aged 12 to 17 years are described in
section 4.8 and 5.1, but no recommendation on a posology can be made.
Method of administration
The bottle should be shaken before use and Xamiol gel applied to the affected area.
Xamiol gel should not be applied directly to the face or eyes. The hands should be
washed after use. In order to achieve optimal effect, it is not recommended to wash
the hair immediately after application of Xamiol gel. Xamiol gel should remain on the
scalp during the night or during the day.

4.3.

Contraindications
Hypersensitivity to the active substances or to any of the excipients.
Xamiol gel is contraindicated in erythrodermic, exfoliative and pustular psoriasis.
Due to the content of calcipotriol, Xamiol gel is contraindicated in patients with
known disorders of calcium metabolism.
Due to the content of corticosteroid, Xamiol gel is contraindicated in the following
conditions: Viral (e.g. herpes or varicella) lesions of the skin, fungal or bacterial skin
infections, parasitic infections, skin manifestations in relation to tuberculosis or
syphilis, perioral dermatitis, atrophic skin, striae atrophicae, fragility of skin veins,
ichthyosis, acne vulgaris, acne rosacea, rosacea, ulcers, wounds, perianal and genital
pruritus.

4.4.

Special warnings and precautions for use
Effects on endocrine system
Xamiol gel contains a potent group III steroid and concurrent treatment with other
steroids on the scalp must be avoided. Adverse reactions found in connection with
systemic corticosteroid treatment, such as adrenocortical suppression or impact on the
metabolic control of diabetes mellitus, may occur also during topical corticosteroid
treatment due to systemic absorption. Application under occlusive dressings should
be avoided since it increases the systemic absorption of corticosteroids. Application
on large areas of damaged skin or on mucous membranes or in skin folds should be
avoided since it increases the systemic absorption of corticosteroids (see section 4.8).
In a study in patients with both extensive scalp and extensive body psoriasis using a
combination of high doses of Xamiol gel (scalp application) and high doses of
Dovobet ointment (body application), 5 of 32 patients showed a borderline decrease
in cortisol response to adrenocorticotropic hormone (ACTH) challenge after 4 weeks
of treatment (see section 5.1).
Effects on calcium metabolism
Due to the content of calcipotriol, hypercalcaemia may occur if the maximum daily
dose (15 g) is exceeded. Serum calcium is, however, quickly normalised when
treatment is discontinued. The risk of hypercalcaemia is minimal when the
recommendations relevant to calcipotriol are followed.

Treatment of more than 30 % of the body surface should be avoided (see section 4.2).
Local adverse reactions
Skin of the face and genitals are very sensitive to corticosteroids. The medicinal
product should not be used in these areas. Uncommon local adverse reactions (such as
eye irritation or irritation of facial skin) were observed, when the medicinal product
was accidentally administered in the area of face, or accidentally to the eyes or
conjunctives (see sections 4.8 and 5.1). The patient must be instructed in correct use
of the medicinal product to avoid application and accidental transfer to the face,
mouth and eyes. Hands must be washed after each application to avoid accidental
transfer to these areas.
Concomitant skin infections
When lesions become secondarily infected, they should be treated with
antimicrobiological therapy. However, if infection worsens, treatment with
corticosteroids should be stopped.
Discontinuation of treatment
When treating psoriasis with topical corticosteroids, there may be a risk of
generalised pustular psoriasis or of rebound effects when discontinuing treatment.
Medical supervision should therefore continue in the post-treatment period.
Long-term use
With long-term use there is an increased risk of local and systemic corticosteroid
adverse reactions. The treatment should be discontinued in case of adverse reactions
related to long-term use of corticosteroid (see section 4.8).
Unevaluated uses
There is no experience for the use of Xamiol gel in guttate psoriasis.
Concurrent treatment and UV exposure
Dovobet ointment for body psoriasis lesions has been used in combination with
Xamiol gel for scalp psoriasis lesions, but there is no experience of combination of
Xamiol with other topical anti-psoriatic products at the same treatment area, other
anti-psoriatic medicinal products administered systemically or with phototherapy.
During Xamiol gel treatment, physicians are recommended to advise patients to limit
or avoid excessive exposure to either natural or artificial sunlight. Topical calcipotriol
should be used with UVR only if the physician and patient consider that the potential
benefits outweigh the potential risks (see section 5.3).
Adverse reactions to excipients
Xamiol gel contains butylated hydroxytoluene (E321), which may cause local skin
reactions (e.g. contact dermatitis), or irritation to the eyes and mucous membranes.

4.5

Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed.

4.6.

Fertility, pregnancy and lactation
Pregnancy

There are no adequate data from the use of Xamiol gel in pregnant women. Studies in
animals with glucocorticoids have shown reproductive toxicity (see section 5.3), but a
number of epidemiological studies have not revealed congenital anomalies among
infants born to women treated with corticosteroids during pregnancy. The potential
risk for humans is uncertain. Therefore, during pregnancy, Xamiol gel should only be
used when the potential benefit justifies the potential risk.
Breastfeeding
Betamethasone passes into breast milk, but risk of an adverse effect on the infant
seems unlikely with therapeutic doses. There are no data on the excretion of
calcipotriol in breast milk. Caution should be exercised when prescribing Xamiol gel
to women who breast-feed.
Fertility
Studies in rats with oral doses of calcipotriol or betamethasone dipropionate
demonstrated no impairment of male and female fertility.

4.7

Effects on ability to drive and use machines
Xamiol gel has no influence on the ability to drive and use machines.

Undesirable effects
The clinical trial programme for Xamiol gel has so far included more than 4,400
patients of whom more than 1,900 were treated with Xamiol gel. Approximately 8 %
of patients treated with Xamiol gel experienced a non-serious adverse reaction.
These reactions are usually mild and cover mainly various skin reactions with pruritus
being the most common.
Based on data from clinical trials and postmarket use the following adverse reactions
are listed for Xamiol gel.
The adverse reactions are listed by MedDRA System Organ Class, and the individual
adverse reactions are listed starting with the most frequently reported. Within each
frequency grouping, the adverse reactions are listed in order of decreasing
seriousness.
The following terminologies have been used in order to classify the frequencies of
adverse reactions:
Very common 1/10
Common
1/100 to <1/10
Uncommon
1/1,000 to <1/100
1/10,000 to <1/1,000
Rare
Very rare
<1/10,000
Not known (cannot be estimated from the available data)
Eye disorders
Uncommon







4.8

Eye irritation

Skin and subcutaneous tissue disorders
Common
Pruritus
Uncommon

Exacerbation of psoriasis

Burning sensation of skin
Skin pain or irritation
Folliculitis
Dermatitis
Erythema
Acne
Dry skin
Rash
Pustular rash

The following adverse reactions are considered to be related to the pharmacological
classes of calcipotriol and betamethasone, respectively:
Calcipotriol
Adverse reactions include application site reactions, pruritus, skin irritation, burning
and stinging sensation, dry skin, erythema, rash, dermatitis, eczema, psoriasis
aggravated, photosensitivity and hypersensitivity reactions including very rare cases
of angioedema and facial oedema. Systemic effects after topical use may appear very
rarely causing hypercalcaemia or hypercalciuria (see section 4.4).
Betamethasone (as dipropionate)
Local reactions can occur after topical use, especially during prolonged application,
including skin atrophy, telangiectasia, striae, folliculitis, hypertrichosis, perioral
dermatitis, allergic contact dermatitis, depigmentation and colloid milia. When
treating psoriasis there may be a risk of generalised pustular psoriasis.
Systemic reactions due to topical use of corticosteroids are rare in adults, however
they can be severe. Adrenocortical suppression, cataract, infections, impact on the
metabolic control of diabetes mellitus and increase of intra-ocular pressure can occur,
especially after long term treatment. Systemic reactions occur more frequently when
applied under occlusion (plastic, skin folds), when applied on large areas and during
long term treatment (see section 4.4).
Paediatric population
No new adverse events and no new adverse reactions were seen in 109 adolescents
aged 12-17 years with scalp psoriasis treated with Xamiol gel for 8 weeks. However,
due to the size of the studies, no firm conclusion can be drawn as to the safety profile
of Xamiol gel in adolescents compared to that in adults. See section 5.1.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions
via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9.

Overdose
Use above the recommended dose may cause elevated serum calcium which should
rapidly subside when treatment is discontinued.

Excessive prolonged use of topical corticosteroids may suppress the pituitary-adrenal
functions, resulting in secondary adrenal insufficiency which is usually reversible. In
such cases, symptomatic treatment is indicated.
In case of chronic toxicity, the corticosteroid treatment must be discontinued
gradually.
It has been reported that due to misuse one patient with extensive erythrodermic
psoriasis treated with 240 g of Dovobet ointment weekly (corresponding to a daily
dose of approximately 34 g) for 5 months (maximum recommended dose 15 g daily)
developed Cushing’s syndrome and pustular psoriasis after abruptly stopping
treatment.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Antipsoriatics. Other antipsoriatics for topical use,
Calcipotriol, combinations. ATC Code: D05AX52
Calcipotriol is a vitamin D analogue. In vitro data suggest that calcipotriol induces
differentiation and suppresses proliferation of keratinocytes. This is the proposed
basis for its effect in psoriasis.
Like other topical corticosteroids, betamethasone dipropionate has anti-inflammatory,
antipruritic, vasoconstrictive and immunosuppresive properties, however, without
curing the underlying condition. Through occlusion the effect can be enhanced due to
increased penetration of the stratum corneum. The incidence of adverse events will
increase because of this. In general, the mechanism of the anti-inflammatory activity
of the topical steroids is unclear.
Adrenal response to ACTH was determined by measuring serum cortisol levels in
patients with both extensive scalp and body psoriasis, using up to 106 g per week
combined Xamiol gel and Dovobet ointment. A borderline decrease in cortisol
response at 30 minutes post ACTH challenge was seen in 5 of 32 patients (15.6 %)
after 4 weeks of treatment and in 2 of 11 patients (18.2 %) who continued treatment
until 8 weeks. In all cases, the serum cortisol levels were normal at 60 minutes post
ACTH challenge. There was no evidence of change of calcium metabolism observed
in these patients. With regard to HPA suppression, therefore, this study shows some
evidence that very high doses of Xamiol gel and Dovobet ointment may have a weak
effect on the HPA axis.
The efficacy of once daily use of Xamiol gel was investigated in two randomised,
double-blind, 8-week clinical studies including a total of more than 2,900 patients
with scalp psoriasis of at least mild severity according to the Investigator’s Global
Assessment of disease severity (IGA). Comparators were betamethasone dipropionate
in the gel vehicle, calcipotriol in the gel vehicle and (in one of the studies) the gel
vehicle alone, all used once daily. Results for the primary response criterion (absent
or very mild disease according to the IGA at week 8) showed that Xamiol gel was
statistically significantly more effective than the comparators. Results for speed of
onset based on similar data at week 2 also showed Xamiol gel to be statistically
significantly more effective than the comparators.

% of patients
with absent or
very mild
disease

Betamethasone
dipropionate
(n=1,118)

Calcipotriol
(n=558)

Gel vehicle
(n=136)

week 2

53.2 %

42.8 %1

17.2 %1

11.8 %1

week 8
1

Xamiol gel
(n=1,108)

69.8 %

62.5 %1

40.1 %1

22.8 %1

Statistically significantly less effective than Xamiol gel (P<0.001)

Another randomised, investigator-blinded clinical study including 312 patients with
scalp psoriasis of at least moderate severity according to the IGA investigated use of
Xamiol gel once daily compared with Dovonex Scalp solution twice daily for up to 8
weeks. Results for the primary response criterion (absent or very mild disease
according to the IGA at week 8) showed that Xamiol gel was statistically significantly
more effective than Dovonex Scalp solution.
% of patients
with absent or
very mild disease
week 8
1

Xamiol gel
(n=207)

Dovonex Scalp
solution
(n=105)

68.6 %

31.4 %1

Statistically significantly less effective than Xamiol gel (P<0.001)

A randomised, double-blind long-term clinical study including 873 patients with scalp
psoriasis of at least moderate severity (according to the IGA) investigated the use of
Xamiol gel compared with calcipotriol in the gel vehicle. Both treatments were
applied once daily, intermittently as required, for up to 52 weeks. Adverse events
possibly related to long-term use of corticosteroids on the scalp, were identified by an
independent, blinded panel of dermatologists. There was no difference in the
percentages of patients experiencing such adverse events between the treatment
groups (2.6 % in the Xamiol gel group and 3.0 % in the calcipotriol group; P=0.73).
No cases of skin atrophy were reported.
Paediatric population
Effects on calcium metabolism were investigated in two uncontrolled open 8-week
studies including in total 109 adolescents aged 12-17 years with scalp psoriasis who
used up to 69 g per week of Xamiol gel. No cases of hypercalcaemia and no clinically
relevant changes in urinary calcium were reported. The adrenal response to ACTH
challenge was measured in 30 patients; one patient showed a decrease in cortisol
response to ACTH challenge after 4 weeks of treatment, which was mild, without
clinical manifestations, and reversible.

5.2.

Pharmacokinetic properties
The systemic exposure to calcipotriol and betamethasone dipropionate from topically
applied Xamiol gel is comparable to Dovobet ointment in rats and minipigs. Clinical
studies with radiolabelled ointment indicate that the systemic absorption of
calcipotriol and betamethasone from Dovobet ointment formulation is less than 1% of
the dose (2.5 g) when applied to normal skin (625 cm2) for 12 hours. Application to
psoriasis plaques and under occlusive dressings may increase the absorption of topical
corticosteroids. Absorption through damaged skin is approx. 24 %.

Following systemic exposure, both active ingredients – calcipotriol and
betamethasone dipropionate – are rapidly and extensively metabolised. Protein
binding is approx. 64%. Plasma elimination half-life after intravenous application is
5-6 hours. Due to the formation of a depot in the skin elimination after dermal
application is in order of days. Betamethasone is metabolised especially in the liver,
but also in the kidneys to glucuronide and sulphate esters. The main route of excretion
of calcipotriol is via faeces (rats and minipigs) and for betamethasone dipropionate it
is via urine (rats and mice). In rats, tissue distribution studies with radiolabelled
calcipotriol and betamethasone dipropionate, respectively, showed that the kidney and
liver had the highest level of radioactivity.
Calcipotriol and betamethasone dipropionate were below the lower limit of
quantification in all blood samples of 34 patients treated for 4 or 8 weeks with both
Xamiol gel and Dovobet ointment for extensive psoriasis involving the body and
scalp. One metabolite of calcipotriol and one metabolite of betamethasone
dipropionate were quantifiable in some of the patients.

5.3.

Preclinical safety data
Studies of corticosteroids in animals have shown reproductive toxicity (cleft palate,
skeletal malformations). In reproduction toxicity studies with long-term oral
administration of corticosteroids to rats, prolonged gestation and prolonged and
difficult labour were detected. Moreover, reduction in offspring survival, body weight
and body weight gain was observed. There was no impairment of fertility. The
relevance for humans is unknown.
A dermal carcinogenicity study with calcipotriol in mice revealed no special hazard to
humans.
Photo(co)carcinogenicity studies in mice suggest that calcipotriol may enhance the
effect of UVR to induce skin tumours.
No carcinogenicity or photocarcinogenicity studies have been performed with
betamethasone dipropionate.
In local tolerability studies in rabbits, Xamiol gel caused mild to moderate skin
irritation and a slight transient irritation of the eye.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Paraffin, liquid
Polyoxypropylene-15 stearyl ether
Castor oil, hydrogenated
Butylhydroxytoluene (E321)
All-rac- -tocopherol

α

6.2

Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed
with other medicinal products.

6.3

Shelf life
2 years.
After first opening: 3 months.

6.4

Special precautions for storage
Do not refrigerate. Keep the bottle in the outer carton in order to protect from light.

6.5

Nature and contents of container
High-density polyethylene bottles with low-density polyethylene nozzle and a highdensity polyethylene screw cap. The bottles are placed in cartons.
Pack sizes: 15, 30, 60 and 2 x 60 g.
Not all pack sizes may be marketed.

6.6.

Special precautions for disposal and other handling
Any unused medicinal product or waste material should be disposed of in accordance
with local requirements.

7

MARKETING AUTHORISATION HOLDER
LEO Pharma A/S
Industriparken 55
DK-2750 Ballerup
Denmark

8

MARKETING AUTHORISATION NUMBER(S)
PL 05293/0006

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
25/09/2008

10

DATE OF REVISION OF THE TEXT

13/07/2014

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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