Pharmacy Gathering

LEO Pharma Indonesia

12 November 2020
 • Daivobet Gel 15gram
• Daivobet Oint 15gram
PSORIASIS • Daivobet Oint 30 gram
• Daivonex Oint 30 gram

• Fucidin Cream 5Gram

• Fucidin Cream 15 Gram
• Fucidin Oint 5 Gram
• Fucidin Oint 15 Gram

• PROTOPIC 0.03%
• PROTOPIC 0.1%
• Fucicort Cream 5 gr

• Nerisona C 10 Gram
• Nerisona Fatty Oint 10 Gram
BOXTER • Travocort Cream 5 Gram
• Ultraproct N Supp
 An Overview of Psoriasis and
Management Using Topical Therapy

For healthcare professionals only

Full prescribing information available upon request

LEO©/ID/DVB/14/2018 APPROVED XX/XX/XXXX LEO© LEO PHARMA 2019.

ALL TRADEMARKS MENTIONED BELONG TO THE LEO PHARMA GROUP
 Psoriasis: Definition and Clinical Presentation

Psoriasis is a non-contagious chronic condition that causes redness, scaling, and

thickening of the skin due to rapid production and accumulation of skin cells.1,2

1.National Psoriasis Foundation. Available at: https://www.psoriasis.org/about-psoriasis. Accessed on: 17 Dec 2018
2. National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Questions and Answers about Psoriasis. Available at:
www.niams.nih.gov/Health_Info/Psoriasis/default.asp. Accessed on:. 17 Dec 2018
 Psoriasis Trigger Factors
Stress

Extreme weather Infections

Smoking
Skin injury
Psoriasis

Excessive alcohol Some drugs

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Questions and Answers about Psoriasis. Available at:
www.niams.nih.gov/Health_Info/Psoriasis/default.asp. Accessed on 17 Dec 2018.
 Types of Psoriasis

Plaque Guttate Inverse

Pustular Erythrodermic

International Federation of Psoriasis Associations (IFPA). Psoriasis is a serious disease deserving global attention. Available
https://ifpa-pso.com/wp-content/uploads/2017/01/Brochure-Psoriasis-is-a-serious-disease-deserving-global-attention.pdf. Accessed
on 18 Dec 2018
 Common Areas Affected by Psoriasis
FRONT VIEW BACK VIEW

.
Pardasani A, et al. Am Fam Physician. 2000;61(3):725–733
 Assessment of Psoriasis Severity

<3% 3-10% >10%

of the total skin area of the total skin area of the total skin area
has psoriasis. Isolated has psoriasis. More has psoriasis. Larger
patches of plaques on visible areas of plaques patches of plaques on
limbs on limbs, torso and face, palms and soles
scalp
• National Psoriasis Foundation. Psoriasis severity. Available at: http://www.psoriasis.org/about-psoriasis/treatments/severity. Accessed on: 17 Dec 2018
Psoriasis: Mild, moderate, severe What to do? Whom should you see?. Available at:
https://www.canadianskin.ca/images/Articles/Volume_4_Issue_1/Psoriasis_mild_moderate_severe.pdf. Accessed on: 17 Dec 2018
 Psoriasis Related Facts

Psoriasis is not
contagious1 Psoriasis is not due to Psoriasis can also
poor hygiene2 affect nails, scalp, and
joints1

Psoriasis is Psoriasis can last for many

manageable1 years3

1. National Psoriasis foundation. About Psoriasis. Available at: https://www.psoriasis.org/about-psoriasis. Accessed on: 17 Dec 2018.
2. Learn about psoriasis. Available at: https://www.skincancer.asn.au/page/2187/about-psoriasis. Accessed on: 18 Dec 2018
3. Questions and answers about psoriasis. Available at: https://www.niams.nih.gov/health_info/Psoriasis/default.asp. Accessed on: 17 Dec 2018 .
Topical Treatment of Psoriasis
 Psoriasis Treatment Pyramid:
Stepwise Treatment
Severe psoriasis
Biologics

Systemic therapy
Acitretin
Methotrexate
Cyclosporine

Phototherapy
UVB
PUVA
Moderate psoriasis

Topical therapy
Calcipotriol + betamethasone
Steroids
Vitamin D analogues
Tazarotene/dithranol/tar/calcineurin inhibitors

Mild psoriasis
Murphy and Reich. J Eur Acad Dermatol Venereol. 2011 Jun;25 Suppl (4):3-8
 Topical Treatment Options for Psoriasis

Emollients Vitamin D
Topical retinoids
analogues

Topical Tar-based Calcineurin

corticosteroids preparations inhibitors

Vitamin D
analogue ⁄
Dithranol Salicylic acid
corticosteroid
fixed combination

Vitamin D analogues and topical corticosteroids are highly recommended

topical treatments for psoriasis.

1. Murphy G, et al. JEADV. 2011;25(Suppl 4):3–8.

2. Mason AR, et al. Cochrane Database Sys Rev. 2013;3 Art. No.: CD005028.
Rationale for Combining
Vitamin D Analogues and
Corticosteroids for
Psoriasis Treatment
 Vitamin D Analogues and Corticosteroids

Vitamin D
Corticosteroids
analogue

Durable response Increased speed of action

(diesel) (turbo)
 Synergistic Action Leading to Improved Safety
Profile
Attenuation of adverse effects
Protection against corticosteroid-induced skin
atrophy by:
• Inhibiting keratinocyte proliferation
Vitamin D • Stimulating keratinocyte differentiation
analogue
• Stimulating collagen synthesis
• Stimulating extracellular matrix production
• Restoring epidermal permeability and
antimicrobial barrier

Reduction of perilesional skin

irritation caused by vitamin D Corticosteroids
analogue

Segaert S, et al. J Drugs Dermatol. 2013;12(8):e129–137.

 Side Effects of Prolonged Treatment With
Topical Steroids

Vitamin D can
counteract steroid
Skin Atrophy Striae induced skin
atrophy by
restoring
epidermal barrier
function

Hypopigmentation Acne

1. Coondoo A, et al. Indian Dermatol J. 2014;5(4):416.

2. Norsgaard, et al. Arch Dermatol Res. 2014;306:719–729.
Clinical Efficacy of Calcipotriol
(Vitamin D Analogue) and
Betamethasone (Corticosteroid)
Combination
 Daivobet® Gel is Effective in the Treatment of
Psoriasis Vulgaris
Data from multicentre, prospective randomised double blind study (364 patients)
Results of a 8-week, double-blind study
Weeks
0 2 4 6 8 10
0

–10
% changes in PASI

–20

–30

–40

–50

–60 Two-compound gel

Betamethasone
–70 Calcipotriol
Gel Vehicle

The two-compound gel had a good safety profile and was more
efficacious than its individual ingredients in the treatment of psoriasis
vulgaris.

Fleming et al. Eur J Dermatol 2010;20:1–7. PASI: Psoriasis activity score index.
 Lower Recurrence Rates in Patients on
Daivobet® Gel
With the use of Daivobet® gel, 45.3% of patients did not experience any
recurrence of psoriasis within 6 months.
Kaplan-Meier curve of time in days from end of first calcipotriol/
betamethasone dipropionate treatment to first recurrence of psoriasis.

1.0
0.9
0.8
0.7
Probability

0.6
0.5
0.4
0.3
0.2
0.1
0.0
0 25 50 75 100 125 150 175 200
Time (days)

After first course of Daivobet® gel treatment, the probability of experiencing a first
re-occurrence within 50 days was approximately 20%–25%, whereas the
probability of experiencing a first recurrence within 150 days was between 40%
and 45%.

Clareus BW, et al. Eur J Dermatol. 2009.19(6):1–5.

 Long-term Safety Profile in Body Psoriasis
Calcipotriol–Betamethasone Dipropionate
Results of a 52-week safety study: Adjudicated corticosteroid reactions
Two-compound (n= 207) Alternating (n=2 13) Calcipotriol (n=206)
Reaction No. of patients % No. of patients % No. of patients %
Adrenal insufficiency 0 0.0 0 0.0 1 0.5
Cellulitis 0 0.0 0 0.0 1 0.5
Ecchymosis 1 0.5 0 0.0 0 0.0
Folliculitis 3 1.4 1 0.5 0 0.0
Furuncle 0 0.0 2 0.9 0 0.0
Hypertrichosis 0 0.0 0 0.0 1 0.5
Purpura 1 0.5 0 0.0 1 0.5
Rash pustular 0 0.0 1 0.5 0 0.0
Skin atrophy 4 1.9 1 0.5 2 1.0
Skin depigmentation 2 1.0 0 0.0 0 0.0
Skin papilloma 0 0.0 1 0.5 0 0.0
Skin striae 0 0.0 1 0.5 0 0.0
Total number of reactions 11 7 6
Total number of patients 10 4.8 6 2.8 6 2.9

Treatment with the two-compound product for

up to 52 weeks appears to be well tolerated.

Kragballe K, et al. Br J Dermatol. 2006;154:1155–1160.

 Long-term Safety in Scalp Psoriasis
Calcipotriol–Betamethasone Dipropionate

Results of a 52-week study: Incidence of adverse events

Two-compound Calcipotriol
group (n = 419) group
(n = 431)
Any corticosteroid-related event 11 (2.6) 13 (3.0)
Odds ratio (95% CI) 0.87 (0.38–1.96)
Specific corticosteroid-related events
Ocular hypertension 0 1 (0.2) • No atrophy
Infected dermatitis 0 1 (0.2) • No striae
Folliculitis 3 (0.7) 3 (0.7) • No adrenal suppression
Impetigo 0 1 (0.2)
Pustular rash 1 (0.2) 0
Acne 1 (0.2) 2 (0.5)
Dermatitis 3 (0.7) 1 (0.2)
Rosacea 3 (0.7) 5 (1.2)

Luger TA, et al. Dermatology. 2008;217:321–328.

 Guideline
Recommendations
 German Guidelines for the Treatment of
Psoriasis
At least class III steroids; also applies to fixed-dose drug
combinations
Therapy Efficacy Evidence Safety/ Safety/ Feasibility Feasibility Cost/
level tolerability tolerability (patient) (doctor) benefit
of for
induction maintenance
therapy therapy
Calcineurin inhibitors ++ 2/3 ++ Not indicated ++ –1) ++

Dithranol +++ 2 ++ Not indicated +2) +2) +++

–3) –3)
Corticosteroids ++++ 4) 1 +++ + ++ +++ +++
Coal tar +/- 4 + Not indicated - +/- -

Tazarotene ++ 2 ++ ++ +/-5) +/-5) ++

Vitamin D3 +++ 1 +++ +++ ++ +++ ++
derivatives
Global assessment: Poor Good
- +/- + ++ +++ ++++
1) No strong consensus (>75%) was achieved using the DELPHI method. The recommendation was therefore made based on a majority vote of 54% (guideline
expert committee). Alternatively, members voted for ‘++’. The reason for the discussion was ‘off-label’ prescribing. The opinions on the effort involved diverged
significantly. 2) Inpatient; 3) Outpatient; 4) At least class III steroids; also applies to fixed-dose drug combinations; 5) No strong consensus (>75%) was achieved using
the DELPHI method. The recommendation was therefore made based on a majority vote of 69% (guideline expert committee). Alternatively, members voted for ‘-’.
The reason for the discussion was poor availability, i.e., available only via international pharmacies. The opinions on the effort involved diverged significantly.

Nast A, et al. JDDG. 2012;10(Suppl 2):S1–95.

 Expert Opinion of a Panel of Dermatologists

Based on efficacy data, adherence, and cost, is there a topical

treatment for plaque psoriasis that can be recommended as a
first-line agent (excluding face and skin folds)?

• The recommended first-line induction treatment for

1 plaque psoriasis is a combination of a vitamin D
analogue and a topical steroid (grade D).

• The recommended first-line induction treatment

for scalp psoriasis can be either a combination of
2 a vitamin D analogue and a topical steroid, or a
topical steroid alone (grade A).

Experts’ agreement (mean): 7.26 ⁄ 10

Paul C, et al. JEADV. 2012;26(Suppl 3):1–10.

 Daivobet® Gel and Daivobet®
Ointment – A Fixed-Dose
Combination Product Containing
Calcipotriol and Betamethasone
Dipropionate
 Daivobet® Gel and Ointment – Indication and
Mechanism of Action
Daivobet® Gel is indicated for Topical Dual action mechanism of Daivobet®
treatment of scalp plaque psoriasis containing calcipotriol and
vulgaris in adults. betamethasone.
Daivobet® Ointment is indicated for
Psoriasis vulgaris

Daivobet® gel patient information leaflet. LEO Pharma Inc July 2018
. Daivobet® Ointment Daivobet® Gel
 Effectiveness of Daivobet® – Before and After
Pictures of Real Patient Experiences

Combination of calcipotriol and Combination of calcipotriol and

betamethasone dipropionate gel used once betamethasone dipropionate gel used once
daily for 8 weeks1
daily for 8 weeks1

Combination of calcipotriol and

betamethasone dipropionate scalp gel used Combination of calcipotriol and
once daily for 1 week2 betamethasone dipropionate scalp gel used
once daily for 1 week2
1. Langley RGB. Dermatology. 2011;222:148–156.
2. Jemec GB. J Eur Acad Dermatol Venereol. 2011;25(1):27–32.
 Effectiveness of Daivobet® – Before and After
Pictures of Real Patient Experiences
Before After Before After

Combination of calcipotriol and

betamethasone dipropionate gel used once daily for 2 weeks

Calcipotriol and betamethasone

dipropionate scalp gel used once
daily for 13 days – complete
clearance
Cited with permission from Professor Segaert
 Take-Home Messages

Psoriasis is a non-contagious chronic condition that causes redness, scaling, and thickening of
the skin due to rapid production and accumulation of skin cells.

Vitamin D analogues and topical corticosteroids are highly recommended topical

treatments for psoriasis.

Vitamin D analogues and corticosteroids have complementary mechanisms of action,

thus enhancing efficacy while also improving the safety profile.

Topical betamethasone dipropionate–calcipotriol ointment/gel has been extensively

tested in thousands of patients with psoriasis, including in 2 long-term 52-week trials, with
no safety signals or steroid-related side effects and lower recurrence rates

The availability of a gel formulation and once-daily application of the combination product
Daivobet® will help improve convenience and adherence of managing body and scalp psoriasis.
 Abbreviated Product Information
Daivobet® Ointment
Composition: 1 g of Daivobet® ointment contains: Active ingredients: Calcipotriol 50 micrograms (as hydrate 52.2 mcg), Betamethasone 0.5 mg (as dipropionate 0.643 mg).

•
• Pharmacodynamic Properties: Calcipotriol is a vitamin D analogue. In vitro data suggests that calcipotriol induces differentiation and suppresses proliferation of keratinocytes.
The dipropionate ester of betamethasone is a glucocorticoid exhibiting the general properties of corticosteroids. In pharmacological doses, corticosteroids are used primarily for
their anti-inflammatory and/or immunosuppressive effects.
•
• Indications: Psoriasis vulgaris
•
• Posology and Method of Administration: Daivobet® should be applied to the affected area once daily. The recommended treatment period is 4 weeks. After this period repeated
treatment with Daivobet® can be initiated under medical supervision. The maximum daily dose should not exceed 15 g, the maximum weekly dose should not exceed 100 g, and
the treated area should not be more than 30% of the body surface. There is no recommendation for the use of this product in children and adolescent below 18 years.
•
• 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
•
• Contra-indications: Known hypersensitivity to the active substances or to any of the excipients. Due to the content of calcipotriol, Daivobet® is contraindicated in patients with
known disorders of calcium metabolism. Due to the content of corticosteroid Daivobet® 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, rosacea, perioral dermatitis, acne vulgaris, atrophic
skin, striae atrophicae, fragility of skin veins, ichthyosis, acne rosacea, ulcers, wounds, perianal and genital pruritus. Daivobet® is contraindicated guttate, erythrodermic,
exfoliative and pustular psoriasis. Daivobet® is contraindicated in patients with severe renal insufficiency or severe hepatic disorders.
•
• Special Warnings and Special Precaution for Use
• The patient must be instructed in correct use of the product to avoid application and accidental transfer to the scalp, face, mouth and eyes. Hands must be washed after each
application. The risk of hypercalcaemia is minimal when the recommendations relevant to calcipotriol are fulfilled. Due to the content of calcipotriol, hypercalcaemia may occur
if the maximum weekly dose (100 g) is exceeded. Serum calcium is quickly normalized, however, when treatment is discontinued. Daivobet® contains a group III-steroid (strong)
and concurrent treatment with other steroid must be avoided. Adverse effects 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 on large areas of damaged
skin and under occlusive dressings or on mucous membrane or in skin folds should be avoided since it increases the systemic absorption of corticosteroids. Skin of the face and
genitals are very sensitive to corticosteroids. Long term treatment of these parts of body should be avoided. These areas should only be treated with weaker corticosteroids.
When lesions become secondarily infected, they should be treated with antimicrobiological therapy. However, when infection worsens, treatment with corticosteroids should be
stopped. 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. With long-term use there is an increased risk of local and systemic corticosteroid undesirable effects. The
treatment should be discontinued in case of undesirable effects related to long-term use of corticosteroid. There may be a risk of rebound when discontinuing a long-term
treatment with corticosteroids. There is no experience for the use of this product on the scalp. There is no experience with concurrent use of other anti-psoriatic products
administered locally or systemically or with phototherapy. During Daivobet® treatment physicians may wish to advise patients to limit or avoid excessive exposure to either
natural or artificial sunlight. Topical calcipotriol should be used with UV radiation only if the physician and patient consider that the potential benefits outweigh the potential
risks. When treating psoriasis with topical corticosteroids there may be a risk of generalized pustular psoriasis. Caution should be exercised in patients with severe liver and
kidney disease due to lack of experience. Daivobet® ointment contains butylhydroxytoluene (E321). This may cause local skin reactions (e.g. contact dermatitis), or irritation to
the eyes and mucous membranes.
•
 Abbreviated Product Information
Daivobet® Ointment (cont’d)
• Pregnancy and Lactation: Pregnancy: There are no adequate data from the use of Daivobet® in pregnant women. Studies in animals with glucocorticoids have shown
reproductive toxicity, but a number of epidemiological studies have not revealed congenital anomalies among infants born to women treated with corticosteroid during
pregnancy. The potential risk for human is uncertain. Therefore, during pregnancy, Daivobet® should only be used when the potential benefit justifies the potential risk.
• Lactation: 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 Daivobet® to women who breast feed. The patient should be instructed not to use Daivobet® on the
breast when breast feeding.
•
• Undesirable Effects: Based on data from clinical trials and postmarket use the common undesirable effects are pruritus, rash and burning sensation of skin. Uncommon
undesirable effects are skin pain or irritation, dermatitis, erythema, exacerbation of psoriasis, folliculitis and application site pigmentation changes.
• Pustular psoriasis is a rare undesirable effect. Undesirable effects observed for calcipotriol and betamethasone, respectively: Calcipotriol: Undesirable effects 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.
• Betamethasone (as dipropionate): This product contains a potent corticosteroid.
• 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 effects due
to topical use of corticosteroids are rare in adults, however they can be severe.
• Adrenocortical suppression, cataract, infections and increase of intra-ocular pressure can occur, especially after long term treatment. Systemic effects occur more
frequently when applied under occlusion (plastic, skin folds), when applied on large areas and during long term treatment.
•
• Storage Conditions: Do not store above 30°C. Can be used for 12 months after opening. Pack sizes: Box of 15 g tube, box of 30 g tube.
•
• Shelf life: 2 years
•
• Daivobet® Ointment API version July 2018
 Abbreviated Product Information
Daivobet® Gel
• Composition: Active ingredients: Calcipotriol 50 microgram/g (as monohydrate), betamethasone 0.5 mg/g (as dipropionate).
•
• Indications: Topical treatment of scalp plaque psoriasis vulgaris in adults.
•
• Posology and method of administration: Daivobet® Gel should be applied to affected areas once daily. The recommended treatment period is 4 weeks for scalp areas. After this period
repeated treatment with Daivobet® Gel can be initiated under medical supervision. When using calcipotriol containing products, the maximum daily dose should not exceed 15 g, and the
maximum weekly dose should not exceed 100 g. The body surface area treated with calcipotriol containing products should not exceed 30%. There is no recommendation for the use of this
product in children and adolescent below 18 years. Shake the bottle before use. In order to achieve optimal effect, it is not recommended to take a shower or bath, immediately after
application of Daivobet® Gel. Daivobet® Gel should remain on the skin during the night or during the day.
•
• Contraindications: Hypersensitivity to the active substances or to any of the excipients. Due to the content of calcipotriol, Daivobet® Gel is contraindicated in patients with known disorders
of calcium metabolism. Due to the content of corticosteroid, Daivobet® 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 and wounds. Daivobet® Gel is contraindicated in guttate, erythrodermic, exfoliative and pustular psoriasis. Daivobet® Gel is contraindicated in
patients with severe renal insufficiency or severe hepatic disorders.
•
• Special warning and precautions for use: Daivobet® Gel contains a potent group III steroid and concurrent treatment with other steroids must be avoided. Adverse effects
• 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. Due to the
content of calcipotriol, hypercalcaemia may occur if the maximum weekly dose (100 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. 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. 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 drug was accidentally administered in the area of face,
• or accidentally to the eyes or conjunctives. The patient must be instructed in correct use of the 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. When lesions become secondarily infected, they should be treated with antimicrobiological therapy. However, if
infection worsens, treatment with corticosteroids should be stopped. 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. With long-term use there is an increased risk of local and systemic
corticosteroid undesirable effects, including hypothalamic pituitary adrenal (HPA) axis suppression. The treatment should be discontinued in case of undesirable effects related to long term
use of corticosteroid. There is no experience with concurrent use of other anti-psoriatic products administered systemically or with phototherapy. During Daivobet® 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. Daivobet® Gel contains butylated hydroxytoluene (E321), which may cause local skin reactions (e.g. contact
dermatitis), or irritation to the eyes and mucous membranes.
•
• Interaction with other medicinal products and other forms of interaction: No interaction studies have been performed.
•
• Pregnancy and lactation: Pregnancy: There are no adequate data from the use of
 Abbreviated Product Information
Daivobet® Gel
• Pregnancy and lactation: Pregnancy: There are no adequate data from the use of Daivobet® Gel in pregnant women. Studies in animals with glucocorticoids have shown reproductive
toxicity, 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, Daivobet® Gel should only be used when the potential benefit justifies the potential risk.
• Lactation: Betamethasone passes into breast milk, butrisk 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 Daivobet® Gel to women who breast-feed.
•
• Use in children: Daivobet® Gel is not recommended for use in children and adolescents below 18 years due to lack of data on safety and efficacy.
•
• Renal and hepatic impairment: The safety and efficacy of Daivobet® Gel in patients with severe renal insufficiency or severe hepatic disorders have not been evaluated. Daivobet® Gel is
contraindicated in patients with severe renal or severe hepatic
• impairment.
• Undesirable effects: Based on data from clinical trials the only known common adverse drug reaction is pruritus. Uncommon adverse drug reactions are burning sensation of skin, skin
pain or irritation, folliculitis, dermatitis, erythema, acne, dry skin, exacerbation of psoriasis, rash, pustular rash, and eye irritation. Calcipotriol: Adverse drug 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. 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 effects due to topical use of
corticosteroids are rare in adults, however, they can be severe. Adrenocortical suppression, cataract, infections and increase of intra-ocular pressure can occur, especially after long-term
treatment. Systemic effects occur more frequently when applied under occlusion (plastic, skin folds), when applied on large areas and during long-term treatment.
•
• 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.
•
• Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
•
• Shelf life
• Unopened container: 3 years.
• Discard 3 months after first opening.
•
• Special precautions for storage
• Do not refrigerate. Keep the bottle in the outer carton in order to protect from light.
• Do not store above 30°C.
•
• Pack Size: 15g
•
• Daivobet® Gel API version July 2018
•
 12 November 2020

p. 045

Fucidin ®
Untuk Infeksi Kulit
dan Jaringan lunak
For healthcare professionals only
Full prescribing information available upon request

.
ALL TRADEMARKS MENTIONED BELONG TO THE LEO PHARMA GROUP.
 Profil Pasien

Adapted from approved Fucidn® Master Detail Aid SA/FCD/2/2016 Approved 23/03/2016
 Infeksi kulit yang diasosiasiakan disebabkan oleh
Staphylococcus aureus [1/3]

Folliculitis Furuncles (Bisul) Carbuncles

Description: Superficial Description: Abses kecil Description: Gabungan

atau inflamasi yang lebih pada folikel rambut yang dari infeksi folikel
dalam pada folikel rambut dalam, Nampak (gabungan bisul) yang
yang menyebabkan lesi kemerahan, benjolan lunak disertai rasa nyeri dan
papulopustular 1–5 yang berisi purulent and abses 1–3,6
necrotic debris1–3,5

1. Olaniyi R, Pozzi C, Grimaldi L, et al. Curr Top Microbiol Immunol. 2016. [Epub ahead of print]; 2. Creech CB, Al-Zubeidi DN, Fritz SA. Infect Dis Clin North Am. 2015;29(3):429–464; 3. Rigopoulos D, Larios G. Acta Dermato Venereologica.
2008;88(Suppl 216):7–13
Foliculitis image is taken from LEO® Global Database
Furuncles image is taken from Shutter stock photo ID: 236990716 (No copy right issues).
Carbuncle Image is taken from: Amit Kumar C Jain, Nisha ST, Viswanath S. Carbuncle in Diabetics-Our Experience. Sch. J. App. Med. Sci., 2013; 1(5):493-495. Journal Committee mentioned that the image is an open access. Can be used.
 Infeksi kulit yang diasosiasiakan disebabkan oleh
Staphylococcus aureus [2/3]

Impetigo Ecthyma Paronychia

Description: Infeksi Description: Bentuk Description: Erythema,

superficial yang impetigo yang yang lebih Kemerahan, bengkak lunak,
menyebabkan lesi bullous dalam, ditandai dengan infeksi bernanah pada ujung
or non-bullous1–3 ulcer (luka) diatas plak jari/kuku 4,5
yang berkerak 1

1. Olaniyi R, Pozzi C, Grimaldi L, et al. Curr Top Microbiol Immunol. 2016. [Epub ahead of print]; 2. Creech CB, Al-Zubeidi DN, Fritz SA. Infect Dis Clin North Am. 2015;29(3):429–464; 3. Rigopoulos D, Larios G. Acta
Dermato Venereologica. 2008;88(Suppl 216):7–13; 4. Rigopoulos D, Larios G, Gregoriou S, et al. Am Fam Physician. 2008;77(3):339–346; 5. Kirchhoff C, Stegmaier J, Volkering C, et al. MMW Fortschr
Med. 2007;149(10):34–35.
Impetigo image: Copyright DermNet New Zealand. Photo by Prof R Suhonen
Ecthyma image: Empinotti JC, Uyeda H, Ruaro RT, Galhardo AP, Bonatto DC. Pyodermitis. An Bras Dermatol. 2012 Mar-Apr;87(2):277-84. Approval to use the image is granted.
Paronychia image is taken from LEO® Global Database
 Infeksi kulit yang diasosiasiakan disebabkan oleh
Staphylococcus aureus [3/3]

Abses Selulitis Luka infeksi

Description: Description: Description:

Ditandai dengan Ditandai dengan S. aureus is adalah salah
pembengkakan, merah, kemerahan, bengkak, satu bakteri pathogen
ada masa yang lunak 1 lunak, nyeri, lymphangitis predominan pada luka
dan demam1 dalam dan kronik (Luka
paska operasi) dan infeksi
kaki pada penderita
diabetes.2-4

1. Olaniyi R, Pozzi C, Grimaldi L, et al. Curr Top Microbiol Immunol. 2016. [Epub ahead of print]; 2. Serra R, Grande R, Butrico L, et al. Expert Rev Anti Infect Ther. 2015;13(5):605–613; 3. Pourtaheri S, Miller F, Dabney K, et al. Spine
Deform. 2015;3(6):533–540; 4. Noviello S, Esposito I, Pascale R, et al. Infez Med. 2012;20(Suppl 1):20–27.

Abscesses image: Shutter stock photo ID: 522330913 (No copy right issues)
Cellulitis image: Shutter stock photo ID: 621113786 (No copy right issues)
Wounds infections image: Shutter stock photo ID: 603665054 (No copy right issues)
 Fucidin® : Penetrasi yang baik pada kulit
• Fusidic Acid (Asam fusidic) memilki struktur yang mirip dengan
steroid, sehinga memiliki kemampuan penetrasi yang baik pada kulit 4
• Fucidin® berpenetrasi pada kulit utuh sama seperti corticsoterid 1,4

1. Rigopoulos D, Larios G. Fusidic acid: a valuable agent for controlling Staphylococcus aureus skin infections. Acta Derm Venereol 2008; Suppl 216: 1–39. 4. Winkelman W, Gratton D. Topical antibacterials. Clin Dermatol 1989;7:156-62.
5. Vickers CF. Percutaneous absorption of sodium fusidice and fusidic acid. Br J Dermatol 1969;81:902–8.
 Fucidin® memiliki penetrasi yang baik pada kulit yang utuh
dan rusak

1. Rigopoulos D, Larios G. Fusidic acid: a valuable agent for controlling Staphylococcus aureus skin infections. Acta Derm Venereol 2008; Suppl
216: 1–39.
 Efikasi klinis asam fusidic pada infeksi kulit

Asam fusidic ointment dan cream memiliki efektivitas yang sama pada terapi infeksi kulit 1,2 dengan
‘excellent’ yang tinggi atau ‘good' response rate 1
(Staphylococcus aureus adalah pathogen terisolasi yang terbanyak 2)

90.3 92
100

80

60

40

20

0
Abscess/boil Impetigo Paronychia Wounds and Overall efficacy
other secondary in skin
infections infections

Fusidic acid ointment Fusidic acid cream

Randomized multicentre trial in 487 patients with superficial skin sepsis in real-world scenario1
Comparative trial in 101 patients with superficial skin sepsis 2

1. Baldwin RJ, Cranfield R. A multi-centre general practice trial comparing Fucidin Ointment and Fucidin Cream. Br J Clin Pract. 1981;35(4):157–160
2. Pakrooh H. Comparative trial of fucidin ointment and fucidin cream in skin sepsis. J Int Med Res. 1980;8(6):425–429.
 Asam fusidic vs Mupirocin pada infeksi kulit

• Asam fusidic lebih efektif dibandingkan dengan Mupirocin pada terapi infeksi kulit superfisial 1
• Adverse effects lebih tinggi pada Mupirocin secara numerik pada beberapa studi 1, 3, 6
• Kepatuhan pasien dan akseptansi kosmetik lebih tinggi pada Asam Fusidic dibandingkan dengan Mupirocin 1, 3

Staphylococcus
100
* *p<0.05 aureus was isolated,
95 and was the most
patients responding

predominant
Percentage of

to treatment1

90 pathogen in most of
these studies1-3
85
80
75
70
Primary skin infections Superficial skin infections

Fusidic acid

Randomized comparative clinical trial in 354 patients with superficial skin sepsis1

1. Morley PA, Munot LD. Curr Med Res Opin. 1988;11(2):142–148; 2. White DG, Collins PO, Rowsell RB. J Infect. 1989;18(3):221–229; 3. Langdon CG, Mahapatra KS. Current Ther Research. 1990; 48:174–179; 4. Jasuja DK, et al. Indian J Dermatol
Venereol Leprol. 2001;67(3):132–134; 5. Gilbert M. J Am Acad Dermatol. 1989;20(6):1083–1087; 6. Sutton JB. Curr Ther Res. 1992;51(5):673–678; 7. George A, Rubin G. Br J Gen Pract. 2003;53(491):480–487.
 Asam fusidic vs Mupirocin pada Impetigo

• Asam fusidic memiliki efektifitas yang sama dengan Mupirocin pada terapi Impetigo, 2
• Adverse effects lebih tinggi pada Mupirocin secara numerik 1, 2
• Kepatuhan pasien dan akseptansi kosmetik lebih tingga pada Asam Fusidic dibandingkan dengan Mupirocin1,2

100 97 97.6 7.4

8

experiencing adverse effects

responding to treatment
Percentage of patients

Percentage of patients
95
6
88
90 5 4.1
84 4
85
3 1.9
2 1
80
1
75 0
Morley PA Sutton Morley PA Sutton JB

Fusidic acid Mupirocin Fusidic acid Mupirocin

Randomized comparative clinical trial in 354 patients with superficial skin sepsis 1
Comparative clinical trial in 177 patients with facial impetigo in real world practice 2

1. Morley PA, Munot LD. Curr Med Res Opin. 1988;11(2):142–148; 2. Sutton JB. Curr Ther Res. 1992;51(5):673–678.
 Fucidin® dapat ditoleransi dengan baik
1,2-5

6
7
7

Adapted from reference 6

1. Spergel JM. Immunology and treatment of atopic dermatitis. Amer J Clin Derm 2008; 9(4):233-44. 2.Walling HW, et al. Update on the management of chronic eczema: new approaches
and emerging treatment options. Clin Cosmetic Invest Dearmatol 2010; 3: 99-117. 3. Lifschitz C. The Impact of Atopic Dermatitis on Quality of Life. Ann Nutr Metab 2015; 66(suppl 1); 34-
40. 4. Lee BW, Detzel PR. Treatment of Childhood Atopic Dermatitis and Economic Burden of Illness in Asia Pacific Countries, Ann Nutr Metab 2015: 66(suup 1); 18-24. 5. Skov L,
Baadsgaard S. Bacterial superantigens and inflammatory skin disease. Clin Exp Dermatol 2000; 25:57-61 6. Leung DYM. The role of Staphylococcus aureus in atopic eczema. Acta Derm
Venereol 2008; Suppl 216: 21-7. 7. David TJ, Cambridge GC. Bacterial infectionand atopic aczema. Arch Dis Childhood 1986; 61:20-3 .
Fucicort®: Hasil klinis yang lebih baik dibandingkan dengan
Gentamicin/betamethasone pada hari ke 12 (P=0.03)1

1. Spergel JM. Immunology and treatment of atopic dermatitis. Amer J Clin Derm 2008; 9(4):233-44.
 Asam fusidic topical pada infeksi kulit: Pandangan guideline

Sejumlah guideline dan badan internasional

merekomendasikan Asam fusidic topical sebagai first-line
terapi untuk infeksi kulit, termasuk impetigo.1-8

Resistensi Staphylococcus aureus terhadap Asam fusidic

sangat rendah dibandingkan dengan antibiotic lainnya.2

1. Cole C, Gazewood J. Am Fam Physician. 2007;75(6):859–864; 2. van Bijnen EM, Paget WJ, den Heijer CD, et al. BMC Fam Pract. 2014;15:175; 3. Hartman-Adams H, Banvard C, Juckett G. Am Fam Physician. 2014;90(4):229–235; 4. Topical
antibiotics. Available at: http://www.bpac.org.nz/BPJ/2014/October/docs/BPJ64-topical-antibiotics.pdf; 5. Guidelines for the management of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)-related skin and soft tissue
infections in primary care. Available at: http://www.bccdc.ca/resource-gallery/Documents/Statistics%20and%20Research/Statistics%20and%20Reports/Epid/Antibiotics/MRSAguidelineFINALJuly7.pdf; 6. Superficial bacterial skin infections - Guidelines
for prescribing topical antibiotics for impetigo and folliculitis. Available at: http://m.medsask.usask.ca/professional/guidelines/superficial-bacterial-skin-infections.php; 7. Koning S, van der Sande R, Verhagen AP, et al. Cochrane Database Syst
Rev. 2012;1:CD003261; 8. Conejo-Fernández AJ, Martínez-Chamorro MJ, Couceiro JA, et al. An Pediatr (Barc). 2016;84(2):121.e1–e121.
 In vitro kerentanan Staphylococcus aureus terhadap Asam
fusidic

Asam fusidic adalah antimikroba yang paling potensial

semua sampel Staphylococcus aureus yang terisolasi
isolates (n=879) rentan terhadap Asam fusidic were 1
50
45 43.1
39.6
40 37.1
Chart Title

35 30.7
30 27.1
25
20
15 13.1
9.1
10 7 5.8
5 0.8
0 0.3
0

1. Stratchounski LS, Dekhnich AV, Kretchikov VA, et al. . J Chemother. 2005;17(1):54–60.

 Penetrasi pada kulit dan konsentrasi pada sisi target
Asam fusidic memperlihatkan penetrasi kulit yang bagus, baik pada kulit yang utuh dan
rusak, dan dapat mencapai konsentrasi yang cukup pada sisi target
Semua preparat terapi memiliki keterbatasn untuk berpenetrasi pada kulit yang utuh
Asam fusidic:
• Kemampuan yang luar biasa untuk berpenetrasi pada kulit manusia yang utuh dan rusak 1-4
• Penetrasi pada kulit sebading dengan topical steroid 1
• Mencapai konsentrasi antimikroba pada lapisan dalam epidermis dan dermis 1-4

Mupirocin Aminoglycosides Tetracycline Beta-lactam antibiotics

(Neomycin, gentamicin)

• Penetrasi pada kulit utuh • Tidak dapat diserap pada • Penetrasi yang buruk • Hanya dapat digunakan
terbatas 1,2 kulit yang utuh1,2 pada intact skin1 secara sistemik, namun
pemakaian secara
sistemik memiliki
konsentasri yang rendah
pada sisi target
• Can be used only 1

1. Rigopoulos D, Larios G. Acta Dermato Venereologica. 2008;88(Suppl 216):7–13; 2. Winkelman W, Gratton D. Clin Dermatol. 1989;7(3): 156–162; 3. Bonamonte D, Fortina AB, Neri L, et al. G Ital Dermatol Venereol. 2014;149:453–459; 4. Schöfer
H, Simonsen L. Eur J Dermatol. 2010;20(1):6–15.
 Perkembangan resistensi

Asam fusidic memiliki risiko resisten dan resisten silang yang sangat rendah
dibandingkan dengan preparat lainnya pada terapi infeksi kulita dan eksim

Asam fusidic :
▪ Risiko resisten yang sangat rendah, bahkan setelah puluhan tahun digunakan pada
pengalaman klinis1-5
▪ Prevalensi resistensi bakteri Asam fusidic di Eropa sekitar 2.8% 5
▪ Tidak ada resisten silang dengan antibiotik lain Karena struktur yang unik 1-5

Mupirocin Aminoglycosides Tetracycline Beta-lactam

(Neomycin, antibiotics
gentamicin)
• Risiko resistensi pada • Concerns terhadap • Penggunaan • Peningkatan
pemakaian jangka resisten dan resisten terbatas, Karena resistensi bakter 1
panjang 1,2 silang telah resisistensi 1
dilaporkan pada
beberapa literature 1,2

1. Rigopoulos D, Larios G. Acta Dermato Venereologica. 2008;88(Suppl 216):7–13; 2. Winkelman W, Gratton D. Clin Dermatol. 1989;7(3): 156–162; 3. Bonamonte D, Fortina AB, Neri L, et al. G Ital Dermatol Venereol. 2014;149:453–459; 4. Schöfer
H, Simonsen L. Eur J Dermatol. 2010;20(1):6–15; 5. van Bijnen EM, Paget WJ, den Heijer CD, et al. BMC Fam Pract. 2014;15:175.
 Profil Keamanan
Asam fusidic memiliki profil keamanan yang lebih baik dibandingkan dengan preparat
terapi lainnya yang digunakan untuk terapi infeksi kulit dan eksim
Asam fusidic:
• Kejadian side efek yang lebih sedikit, iritasi dan reaksi alergi 1-4
• Tidak terlihat adanya alergi silang 1-4
Mupirocin1,2 Aminoglycosides Tetracycline1 Beta-lactam
(Neomycin, antibiotics1
gentamicin)1,2
• Potensi rendah akan • Side-effects berupa • Potensi rendah akan • Efek samping pada
kejadian sensitisation ototoxicity and kejadian sensitisation saluran pencernaan dan
• Iritasi local mungkin terjadi nephrotoxicity • Efek samping yaitu risiko alergi
Karena polyethylene glycol menjadi concern dizziness, drug-induced • Potensi rendah akan
base • Reaksi alergi dan lupus kejadian sensitisation
• Adverse event: sensitive kontak erythematosus,noda
1) MP 4.2% vs FCD 1.8%5 dilaporkan: pada tulang dan gigi
2) MP 7.4% vs FCD 1.0%6 • 1) Fucidin®: 0.8%
• Perlu diperhatikan pada saat 2) Neomycin: 2.2%
penggunaan Mupirocin, 3) Gentamycin: 3.2%
pada pasien gagal ginjal
atau pasien dengan luka
terbuka yang luas, Karena
akan menyebabkan
nephrotoxicity
1. Rigopoulos D, Larios G. Acta Dermato Venereologica. 2008;88(Suppl 216):7–13; 2. Winkelman W, Gratton D. Clin Dermatol. 1989;7(3): 156–162; 3. Bonamonte D, Fortina AB, Neri L, et al. G Ital Dermatol Venereol. 2014;149:453–459; 4. Schöfer
H, Simonsen L. Eur J Dermatol. 2010;20(1):6–15. 5. Langdon et., al. Curr Ther Res 1990 Jul; 48(1): 174 -180 6. Morley PA et al., 1988
Fucidin® Cream 5gr &15gr
Mengandung: Fucidic Acid 20mg
Indikasi: Untuk terapi infeksi kulit yag disebabkan oleh
Staphylocci atau organisme lain yang sensitive terhadap
Fucidin, contohnya, Impetigo Contagiosa, Superficial
foliculitis, luka yang infeksi, Sycosis barbae, carbuncles,
hidradentis axillaries, abscesse, Paronychya dan
Erythrasma

Fucidin® Ointment 5gr &15gr

Mengandung: Sodium Fusidate 20mg
Indikasi: Untuk terapi infeksi kulit yag disebabkan oleh
Staphylocci atau organisme lain yang sensitive terhadap
Fucidin, contohnya, Impetigo Contagiosa, Superficial
foliculitis, luka yang infeksi, Sycosis barbae, carbuncles,
hidradentis axillaries, abscesse, Paronychya dan
Erythrasma

Fucicort® cream 5gr

Mengandung: Fucidic Acid 20mg, Betamethasone as
valerate 1 mg
Indikasi: Untuk peradanagn kulit dimana terjadi
infeksi yang karenaoleh bakteri atau diduga karena
bakteri. Peradangan kulit termasuk atopic eczema,
discoid eczema, statis eczema, seborrheic dermatitis,
contact dermatitis, lichen simples chronicus. Psoriasis,
discoid lupus erythematous
Fucidin® dan Fucicort® adalah pilihan yang tepat
untuk terapi infeksi kulit