Enstilar Cutaneous Foam

Updated following addition of site application erythema

Update to section 4.8 - addition of site application erythema

Section 2 Warnings and Precautions:

Deletion of sentence:

“Avoid excessive sunbathing, excessive use of  a solarium and other forms of light treatment, as your skin is sensitive to light.”

Section 6 What Enstilar looks like and contents of the pack:

New sentence and picture added:

“The foam has the appearance of a non-expanding foam that gradually collapses after spraying.”

Section 3 Pharmaceutical Form:

New sentence:

“The foam has the appearance of a non-expanding foam that gradually collapses after spraying.”

Section 4.4 Special warnings and precautions for use:

Deletion of warning regarding UV exposure:

“UV exposure:
During Enstilar 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).”

Section 5.3       Preclinical safety data

Deletion of statement regarding photocarcinogenicity studies.

Rewording of statement regarding dermal carcinogenicity studies.

Section 4 update to include application site pain.

New text added in red:

Duration of treatment

• apply the foam once daily. It may be more convenient to use the foam in the evening
• the normal treatment period is 4 weeks but your doctor may decide on a different treatment period.

 You may be told by your doctor to use Enstilar twice weekly once your psoriasis has cleared or almost cleared. Enstilar should be applied twice weekly on two non-consecutive days (e.g. Wednesday and Saturday) to areas previously affected by psoriasis. Between applications there should be 2-3 days without Enstilar treatment.

If symptoms reappear you should use Enstilar once daily as outlined above and contact your doctor to review your treatment.”

4.2       Posology and method of administration

 New text shown in red:

“Posology

Flare treatment

Enstilar foam should be applied to the affected area 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 supervision.

Long-term maintenance treatment

Patients who have responded at 4 weeks’ treatment using Enstilar once daily are suitable for long-term maintenance treatment. Enstilar should be applied twice weekly on two non-consecutive days to areas previously affected by psoriasis vulgaris. Between applications there should be 2-3 days without Enstilar treatment.

If signs of a relapse occur, flare treatment, as described above, should be re-initiated.

 Maximum dose

The daily maximum dose of Enstilar should not exceed 15 g, i.e. one 60 g can should last for at least 4 days of treatment. 15 g corresponds to the amount administered from the can if the actuator is fully depressed for approximately one minute. A two-second application delivers approximately 0.5 g. As a guide, 0.5 g of foam should cover an area of skin roughly corresponding to the surface area of an adult hand.

If using other topical products containing calcipotriol in addition to Enstilar, the total dose of all calcipotriol containing products should not exceed 15 g per day.

The total body surface area treated should not exceed 30%.

Special populations

Renal and hepatic impairment

The safety and efficacy of Enstilar foam in patients with severe renal insufficiency or severe hepatic disorders have not been evaluated.

Paediatric population

The safety and efficacy of Enstilar foam in children below 18 years have not been established. Currently available data in children aged 12 to 17 years are described in sections 4.8 and 5.1, but no recommendation on a posology can be made.

Method of administration

For cutaneous use.

The can should be shaken for a few seconds before use. Enstilar should be applied by spraying holding the can at least 3 cm from the skin. The foam can be sprayed holding the can in any orientation except horizontally.

Enstilar should be sprayed directly onto each affected skin area and rubbed in gently.

If used on the scalp, Enstilar should be sprayed into the palm of the hand and then applied to affected scalp areas with the fingertips. Hair washing instructions are provided in the package leaflet.

The hands should be washed after using Enstilar (unless Enstilar is used to treat the hands) to avoid accidentally spreading to other parts of the body as well as unintended drug absorption on the hands. Application under occlusive dressings should be avoided since it increases the systemic absorption of corticosteroids. It is recommended not to take a shower or bath immediately after application of Enstilar. Let the foam remain on the scalp and/or skin during the night or during the day.”

4.4       Special warnings and precautions for use

Minor clarifications are made to the local adverse reactions and concomitant skin infections sections.

 4.6       Fertility, pregnancy and lactation

Breast-feeding:
The statement regarding betamethasone passing into breast milk and risk of an adverse reaction in the infant has been changed from “seems unlikely” to “is very small” with therapeutic doses. 

 Fertility:
New text shown in red:

“Studies in rats with oral doses of calcipotriol or betamethasone dipropionate demonstrated no impairment of male and female fertility (see section 5.3). There are no data on human fertility.”

4.8       Undesirable effects

Application site pain is added as an uncommon undesirable effect.  A statement that application site burning is included in application site pain is added.

5.1       Pharmacodynamic properties

Study data regarding the PSO-Long trial added.

5.3       Preclinical safety data

The following statement is deleted

“The estimated systemic exposure following topical application of Enstilar to psoriasis patients is negligible compared to the concentrations of calcipotriol evaluated in the oral in vivo studies, and there is no appreciable reproductive risk to humans receiving therapeutic exposure to Enstilar.”

Section 4.2 Posology
New statement:

“Currently available data in children aged 12 to 17 years are described in sections 4.8 and 5.1, but no recommendation on a posology can be made.”

This replaces the statement “No data are available.”

Section 4.8 Undesirable Effects

New statement:

“Paediatric population

No clinically relevant differences between the safety profiles in adult and adolescent populations have been observed. A total of 106 adolescent subjects were treated in one open-label clinical trial. See section 5.1 for further details regarding this trial.”

Section 5.1 Pharmacodynamic properties

New statement:

“Paediatric population

The effects on calcium metabolism were investigated in an uncontrolled, open-label, 4‑week trial in 106 adolescents aged 12 to 17 years with scalp and body psoriasis. The subjects used up to 105 g Enstilar per week. No cases of hypercalcaemia and no clinically relevant changes in urinary calcium were reported.

The adrenal response to ACTH challenge was measured in a subset of 33 subjects with extensive plaque psoriasis involving at least 20% of the scalp and 10% of the body surface area. After 4 weeks of treatment with Enstilar, 2 subjects had a cortisol level ≤18 mcg/dL at 30 minutes after ACTH challenge, but had normal response at 60 minutes. A third subject had minimal cortisol response to the ACTH challenge test at baseline resulting in inconclusive results after the treatment. None of these cases had any clinical manifestations.”

Section 3 How to use Enstilar®

New subtitle “When used on the body” at beginning of ‘Instruction for proper use’ section

Additional statements added to end of point 6 of this section.

“In order to achieve optimal effect, it is recommended that the body is not washed immediately after application of Enstilar.

Let the foam remain on the skin during the night or during the day.”

New 5 point instructions added “When used on the scalp”

New 4 point instructions added “When you wash your hair, the following instructions might be useful”

Information on availability in Braille or alternative formats added.

Section 4.2 Posology
new statements:

“If used on the scalp, Enstilar should be sprayed into the palm of the hand and then applied to affected scalp areas with the fingertips. Hair washing instructions are provided in the package leaflet.”

“Let the foam remain on the scalp and/or skin during the night or during the day.”

 Section 4.8 Undesirable Effects

Administrative corrections to the tabulation and footnotes

Change to date format to Month Year.

4.4 Special warnings and precautions for use

Visual disturbance
Visual disturbance may be reported with systemic and topical corticosteroid use. If a
patient presents with symptoms such as blurred vision or other visual disturbances,
the patient should be considered for referral to an ophthalmologist for evaluation of
possible causes which may include cataract, glaucoma or rare diseases such as central
serous chorioretinopathy (CSCR) which have been reported after use of systemic and
topical corticosteroids.

4.8 Undesirable effects

The following adverse reaction has been added under the SOC Eye disorders with a frequency
not known: Vision, blurred (see also section 4.4)

10.     DATE OF REVISION OF THE TEXT

10 August 2018