Protopic 0.1% Ointment

  • Name:

    Protopic 0.1% Ointment

  • Company:
    info
  • Active Ingredients:

    Tacrolimus Monohydrate

  • Legal Category:

    Product subject to medical prescription which may not be renewed (A)

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 27/08/20

files-icon(Click to Download)
Summary of Product Characteristics last updated on medicines.ie: 27/8/2020

Click on this link to Download PDF directly

LEO Pharma

LEO Pharma

Company Products

Medicine NameActive Ingredients
Medicine Name Dovobet Gel Active Ingredients Betamethasone dipropionate, Calcipotriol monohydrate
Medicine Name Dovonex Cream Active Ingredients Calcipotriol hydrate
Medicine Name Dovonex Ointment Active Ingredients Calcipotriol
Medicine Name Dovonex Psoriasis 50 microgram/g ointment Active Ingredients Calcipotriol
Medicine Name Enstilar Cutaneous Foam Active Ingredients Betamethasone dipropionate, Calcipotriol monohydrate
Medicine Name Fucibet Cream Active Ingredients Betamethasone Valerate, Fusidic Acid
Medicine Name Fucibet Lipid Cream Active Ingredients Betamethasone Valerate, Fusidic Acid
Medicine Name Fucidin Cream Active Ingredients Fusidic Acid
Medicine Name Fucidin H Cream Active Ingredients Fusidic Acid Hemihydrate, Hydrocortisone Acetate
Medicine Name Fucidin Ointment Active Ingredients Sodium Fusidate
Medicine Name Fucidin Suspension Active Ingredients Fusidic Acid Hemihydrate
Medicine Name Fucidin Tablets Active Ingredients Sodium Fusidate
Medicine Name innohep 10,000 IU in 0.5 ml syringe (Treatment in VTE) Active Ingredients Tinzaparin sodium
Medicine Name innohep 10,000 IU/ml Solution for Injection (Prophylaxis and Haemodialysis) Active Ingredients Tinzaparin sodium
Medicine Name innohep 12,000 IU in 0.6ml syringe (Treatment in VTE) Active Ingredients Tinzaparin sodium
Medicine Name innohep 14,000 IU in 0.7 ml syringe (Treatment in VTE) Active Ingredients Tinzaparin sodium
Medicine Name innohep 16,000 IU in 0.8ml syringe (Treatment in VTE) Active Ingredients Tinzaparin sodium
Medicine Name innohep 18,000 IU in 0.9ml syringe (Treatment in VTE) Active Ingredients Tinzaparin sodium
Medicine Name innohep 2,500 IU syringe (Prophylaxis and Haemodialysis) Active Ingredients Tinzaparin sodium
Medicine Name Innohep 20,000 IU/ml Solution for Injection (Treatment in VTE) Active Ingredients Tinzaparin sodium
Medicine Name innohep 3,500 IU syringe (Prophylaxis and Haemodialysis) Active Ingredients Tinzaparin sodium
Medicine Name innohep 4,500 IU syringe (Prophylaxis and Haemodialysis) Active Ingredients Tinzaparin sodium
Medicine Name innohep 8,000 IU in 0.4ml syringe (Treatment in VTE) Active Ingredients Tinzaparin sodium
Medicine Name Kyntheum 210 mg Solution for Injection Active Ingredients Brodalumab
Medicine Name Locoid Cream 0.1% Active Ingredients Hydrocortisone 17-Butyrate
1 - 0 of 41 items.Total: Infinity pages

When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 27 August 2020 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.3 - Preclinical safety data

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 27 August 2020 PIL

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 4 - possible side effects

Updated on 20 June 2019 SmPC

Reasons for updating

  • File format updated to PDF

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 21 August 2018 PIL

Reasons for updating

  • Improved presentation of PIL

Updated on 13 July 2018 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.1 - List of excipients
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.2 - added excipients with known effect

Excipient with known effect

Butylhydroxytoluene (E321) 15 micrograms/g ointment.

​​

4.4 - Editorial changes (Older people --> Elderly) + addition of excipient warning:

​​

Excipients warnings

Protopic ointment contains butylhydroxytoluene (E321) as an excipient, which may cause local skin reactions (e.g. contact dermatitis), or irritation to the eyes and mucous membranes.

​​

4.6 - relocation of fertility from beginning of section to end of sections

​​

5.2 - editorial change to the heading metabolism --> biotransformation

​​

6 addition of excipients:

Butylhydroxytoluene (E321)

All-rac-α-tocopherol

​​

​​

Updated on 13 July 2018 PIL

Reasons for updating

  • Change to section 2 - excipient warnings
  • Change to section 4 - how to report a side effect
  • Change to section 6 - what the product contains

Updated on 19 December 2017 PIL

Reasons for updating

  • New PIL for new product

Updated on 19 December 2017 PIL

Reasons for updating

  • Change to section 6 - manufacturer
  • Change to section 6 - date of revision

Updated on 18 July 2016 PIL

Reasons for updating

  • Improved electronic presentation

Updated on 4 July 2016 SmPC

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 4 July 2016 PIL

Reasons for updating

  • Correction of spelling/typing errors

Updated on 4 July 2016 SmPC

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

- In section 7, LEO Pharma is added as the new MAH
- In section 10, the date of revision of the text is updated

Updated on 1 July 2016 PIL

Reasons for updating

  • Change to date of revision
  • Change to marketing authorisation holder
  • Change to MA holder contact details

Updated on 21 December 2015 PIL

Reasons for updating

  • Change to side-effects
  • Change to date of revision

Updated on 21 December 2015 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.8:
Addition of Ophthalmic Herpes Infection with frequency unknown (reported during post-marketing experience)

Date of revision of text updated to 16/12/2015

Updated on 2 July 2015 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

The following AR included in section 4.8

Section 4.8
Skin and subcutaneous tissue disorders
Not Known: Lentigo

Updated on 26 June 2015 PIL

Reasons for updating

  • Change to side-effects

Updated on 18 December 2013 PIL

Reasons for updating

  • Addition of information on reporting a side effect.

Updated on 27 November 2013 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to Section 4.8 – Undesirable effects - how to report a side effect

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

2.       QUALITATIVE AND QUANTITATIVE COMPOSITION

 

1 g of Protopic 0.03% ointment contains 0.3 mg of tacrolimus as tacrolimus monohydrate (0.03%).

 

For thea full list of excipients, see section 6.1.

 

 

 

4.2     Posology and method of administration

 

Elderly Older peoplepatients

Specific studies have not been conducted in older peopleelderly patients. However, the clinical experience available in this patient population has not shown the necessity for any dosage adjustment.

 

Older peopleElderly patients

Specific studies have not been conducted in older peopleelderly patients (see flare treatment section above).

 

4.3     Contraindications

 

Hypersensitivity to the active substance, macrolides in general, or to any of the excipients listed in section 6.1.

 

4.6     Fertility, Pregnancy and lactation

 

Breast-feeding

Human data demonstrate that, after systemic administration, tacrolimus is excreted into breast milk. Although clinical data have shown that systemic exposure from application of tacrolimus ointment is low, breast-feeding during treatment with Protopic ointment is not recommended.

 

4.7     Effects on ability to drive and use machines

 

Protopic ointment has no or negligibleis administered topically and is unlikely to have an effect influenceeffect on the ability to drive or use machines.

 

4.8     Undesirable effects

 

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 online reporting option (preferred method) accessible from the IMB homepage (www.imb.ie). A downloadable report form is also accessible from the IMB website, which may be completed manually and submitted to the IMB via ‘freepost’ (see details below). Alternatively, the traditional post-paid ‘yellow card’ option may also be used.

 

FREEPOST

Pharmacovigilance Section

Irish Medicines Board

Kevin O’Malley House

Earlsfort Centre

Earlsfort Terrace

Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Updated on 5 July 2013 PIL

Reasons for updating

  • Change of manufacturer

Updated on 4 July 2013 SmPC

Reasons for updating

  • Change to MA holder contact details

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Astellas Pharma Europe B.V.

Sylviusweg 62

2333 BE Leiden

Netherlands

Updated on 18 September 2012 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.4     Special warnings and precautions for use

 

The potential for local immunosuppression (possibly resulting in infections or cutaneous malignancies) in the long term (i.e. over a period of years) is unknown (see section 5.1).

Protopic contains the active substance tacrolimus, a calcineurin inhibitor. In transplant patients, prolonged systemic exposure to intense immunosuppression following systemic administration of calcineurin inhibitors has been associated with an increased risk of developing lymphomas and skin malignancies. In patients using tacrolimus ointment, cases of malignancies, including cutaneous (i.e. cutaneous T Cell lymphomas) and other types of lymphoma, and skin cancers have been reported (see section 4.8) Protopic should not be used in patients with congenital or acquired immunodeficiencies or in patients on therapy that cause immunosuppression.

 

4.8     Undesirable effects

 

Post-marketing

Cases of malignancies, including cutaneous (i.e. cutaneous T Cell lymphomas) and other types of lymphoma, and skin cancers, have been reported in patients using tacrolimus ointment (see section 4.4).

 

Updated on 27 July 2012 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.4       Special warnings and precautions for use

Protopic should not be used in patients with congenital or acquired immunodeficiencies or in patients on therapy that cause immunosuppression.

The effect of treatment with Protopic ointment on the developing immune system of children aged below 2 years has not been established (see section 4.1).Exposure of the skin to sunlight should be minimised and the use of ultraviolet (UV) light from a solarium, therapy with UVB or UVA in combination with psoralens (PUVA) should be avoided during use of Protopic ointment (see section 5.3). Physicians should advise patients on appropriate sun protection methods, such as minimisation of the time in the sun, use of a sunscreen product and covering of the skin with appropriate clothing. Protopic ointment should not be applied to lesions that are considered to be potentially malignant or pre-malignant.

Exposure of the skin to sunlight should be minimised and the use of ultraviolet (UV) light from a solarium, therapy with UVB or UVA in combination with psoralens (PUVA) should be avoided during use of Protopic ointment (see section 5.3). Physicians should advise patients on appropriate sun protection methods, such as minimisation of the time in the sun, use of a sunscreen product and covering of the skin with appropriate clothing. Protopic ointment should not be applied to lesions that are considered to be potentially malignant or pre-malignant.

The development of any new change different from previous eczema within a treated area should be reviewed by the physician.

The use of tacrolimus ointment is not recommended in patients with a skin barrier defect, such as Netherton’s syndrome, lamellar ichthyosis, generalized erythroderma or cutaneous Graft Versus Host Disease. These skin conditions may increase systemic absorption of tacrolimus. Oral use of tacrolimus is also not recommended to treat these skin conditions. Post-marketing cases of increased tacrolimus blood level have been reported in these conditions.

 

Care should be exercised if applying Protopic to patients with extensive skin involvement over an extended period of time, especially in children (see section 4.2). Patients, particularly paediatric patients should be continuously evaluated during treatment with Protopic with respect to the response to treatment and the continuing need for treatment. After 12 months this evaluation should include suspension of Protopic treatment in paediatric patients (see section 4.2).

The potential for local immunosuppression (possibly resulting in infections or cutaneous malignancies) in the long term (i.e. over a period of years) is unknown (see section 5.1).

Protopic contains the active substance tacrolimus, a calcineurin inhibitor. In transplant patients, prolonged systemic exposure to intense immunosuppression following systemic administration of calcineurin inhibitors has been associated with an increased risk of developing lymphomas and skin malignancies. In patients using tacrolimus ointment, cases of malignancies, including cutaneous and other types of lymphoma, and skin cancers have been reported (see section 4.8) Protopic should not be used in patients with congenital or acquired immunodeficiencies or in patients on therapy that cause immunosuppression.

Patients with atopic dermatitis treated with Protopic have not been found to have significant systemic tacrolimus levels

Lymphadenopathy was uncommonly (0.8%) reported in clinical trials. The majority of these cases were related to infections (skin, respiratory tract, tooth) and resolved with appropriate antibiotic therapy. Transplant patients receiving immunosuppressive regimens (e.g. systemic tacrolimus) are at increased risk for developing lymphoma; therefore patients who receive Protopic and who develop lymphadenopathy should be monitored to ensure that the lymphadenopathy resolves. Lymphadenopathy present at initiation of therapy should be investigated and kept under review. In case of persistent lymphadenopathy, the aetiology of the lymphadenopathy should be investigated. In the absence of a clear aetiology for the lymphadenopathy or in the presence of acute infectious mononucleosis, discontinuation of Protopic should be considered.

The effect of treatment with Protopic ointment on the developing immune system of children aged below 2 years has not been established (see section 4.1).

Emollients should not be applied to the same area within 2 hours of applying Protopic ointment. Concomitant use of other topical preparations has not been assessed. There is no experience with concomitant use of systemic steroids or immunosuppressive agents.

Protopic ointment has not been evaluated for its efficacy and safety in the treatment of clinically infected atopic dermatitis. Before commencing treatment with Protopic ointment, clinical infections at treatment sites should be cleared. Patients with atopic dermatitis are predisposed to superficial skin infections. Treatment with Protopic may be associated with an increased risk of folliculitis and herpes viral infections (herpes simplex dermatitis [eczema herpeticum], herpes simplex [cold sores], Kaposi’s varicelliform eruption) (see section 4.8).  In the presence of these infections, the balance of risks and benefits associated with Protopic use should be evaluated.

Emollients should not be applied to the same area within 2 hours of applying Protopic ointment. Concomitant use of other topical preparations has not been assessed. There is no experience with concomitant use of systemic steroids or immunosuppressive agents.

The potential for local immunosuppression (possibly resulting in infections or cutaneous malignancies) in the long term (i.e. over a period of years) is unknown (see section 5.1).

Protopic contains the active substance tacrolimus, a calcineurin inhibitor. In transplant patients, prolonged systemic exposure to intense immunosuppression following systemic administration of calcineurin inhibitors has been associated with an increased risk of developing lymphomas and skin malignancies. In patients using tacrolimus ointment, cases of malignancies, including cutaneous and other types of lymphoma, and skin cancers have been reported (see section 4.8).

Protopic should not be used in patients with congenital or acquired immunodeficiencies or in patients on therapy that cause immunosuppression.

 

The effect of treatment with Protopic ointment on the developing immune system of children aged below 2 years has not been established (see section 4.1).

Patients with atopic dermatitis treated with Protopic have not been found to have significant systemic tacrolimus levels.

Lymphadenopathy was uncommonly (0.8%) reported in clinical trials. The majority of these cases were related to infections (skin, respiratory tract, tooth) and resolved with appropriate antibiotic therapy. Transplant patients receiving immunosuppressive regimens (e.g. systemic tacrolimus) are at increased risk for developing lymphoma; therefore patients who receive Protopic and who develop lymphadenopathy should be monitored to ensure that the lymphadenopathy resolves. Lymphadenopathy present at initiation of therapy should be investigated and kept under review. In case of persistent lymphadenopathy, the aetiology of the lymphadenopathy should be investigated. In the absence of a clear aetiology for the lymphadenopathy or in the presence of acute infectious mononucleosis, discontinuation of Protopic should be considered.

Exposure of the skin to sunlight should be minimised and the use of ultraviolet (UV) light from a solarium, therapy with UVB or UVA in combination with psoralens (PUVA) should be avoided during use of Protopic ointment (see section 5.3). Physicians should advise patients on appropriate sun protection methods, such as minimisation of the time in the sun, use of a sunscreen product and covering of the skin with appropriate clothing. Protopic ointment should not be applied to lesions that are considered to be potentially malignant or pre-malignant.

The development of any new change different from previous eczema within a treated area should be reviewed by the physician.

The use of tacrolimus ointment is not recommended in patients with a skin barrier defect, such as Netherton’s syndrome, lamellar ichthyosis, generalized erythroderma or cutaneous Graft Versus Host Disease. These skin conditions may increase systemic absorption of tacrolimus. Oral use of tacrolimus is also not recommended to treat these skin conditions. Post-marketing cases of increased tacrolimus blood level have been reported in these conditions.

 

Care should be exercised if applying Protopic to patients with extensive skin involvement over an extended period of time, especially in children (see section 4.2). Patients, particularly paediatric patients should be continuously evaluated during treatment with Protopic with respect to the response to treatment and the continuing need for treatment. After 12 months this evaluation should include suspension of Protopic treatment in paediatric patients (see section 4.2).

Care should be taken to avoid contact with eyes and mucous membranes. If accidentally applied to these areas, the ointment should be thoroughly wiped off and/or rinsed off with water.

The use of Protopic ointment under occlusion has not been studied in patients. Occlusive dressings are not recommended.

 

As with any topical medicinal product, patients should wash their hands after application if the hands are not intended for treatment.

Tacrolimus is extensively metabolised in the liver and although blood concentrations are low following topical therapy, the ointment should be used with caution in patients with hepatic failure (see section 5.2).

The use of tacrolimus ointment is not recommended in patients with a skin barrier defect, such as Netherton’s syndrome, lamellar ichthyosis, generalized erythroderma or cutaneous Graft Versus Host Disease. These skin conditions may increase systemic absorption of tacrolimus. Oral use of tacrolimus is also not recommended to treat these skin conditions. Post-marketing cases of increased tacrolimus blood level have been reported in these conditions.

 

Care should be exercised if applying Protopic to patients with extensive skin involvement over an extended period of time, especially in children (see section 4.2).

 

The development of any new change different from previous eczema within a treated area should be reviewed by the physician.

 

10.       DATE OF REVISION OF THE TEXT

July 2012

 

 

 

Updated on 18 August 2011 PIL

Reasons for updating

  • Change to MA holder contact details

Updated on 17 August 2011 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.2     Posology and method of administration

 

Protopic treatment should be initiated by physicians with experience in the diagnosis and treatment of atopic dermatitis.

 

Protopic can be used for short-term and intermittent long-term treatment. Treatment should not be continuous.

 

Protopic is available in two strengths, Protopic 0.03% and Protopic 0.1% ointment.

 

Posology

 

Flare treatment

Protopic can be used for short-term and intermittent long-term treatment. Treatment should not be continuous on a long-term basis.

 

 

4.4     Special warnings and precautions for use

The use of  Protopic tacrolimus ointment is not recommended in patients with a skin genetic epidermal barrier defect, such as Netherton’s syndrome, lamellar ichthyosis, generalized erythroderma or cutaneous Graft Versus Host Disease. These skin conditions may increase systemic absorption of tacrolimus. Oral use of tacrolimus is also not recommended to treat these skin conditions. Post-marketing cases of increased tacrolimus blood level have been reported in these conditions.

is not recommended due to the potential for permanently increased systemic absorption of tacrolimus. The safety of Protopic ointment has not been established in patients with generalised erythroderma

 

 

4.8     Undesirable effects

System Organ Class

Very Common

1/10

Common

1/100,

<1/10

Uncommon

1/1000,

<1/100

Not known (cannot be estimated from the available data)

Infections and infestations

 

Local skin infection regardless of specific aetiology including but not limited to:

Eczema herpeticum,

Folliculitis,

Herpes simplex,

Herpes virus infection,

Kaposi’s varicelliform eruption*

 

 

Metabolism and nutrition disorders

 

Alcohol intolerance (facial flushing or skin irritation after consumption of an alcoholic beverage)

 

 

Nervous system disorders

 

Paraesthesias and dysaesthesias (hyperaesthesia, burning sensation)

 

 

Skin and subcutaneous tissue disorders

 

Pruritus

 

Acne*

Rosacea*

General disorders and administration site conditions

Application site burning,

Application site pruritus

Application site warmth,

Application site erythema,

Application site pain,

Application site irritation,

Application site paraesthesia,

Application site rash

 

 

Application site oedema*

Investigations

 

 

 

Drug level increased* (see section 4.4)

 

 

General disorders and administration site conditions

Very common:     Application site burning, application site pruritus

Common:             Application site warmth, application site erythema, application site pain, application site irritation, application site paraesthesia, application site rash

 

Infections and infestations

Common:             Herpes viral infections (herpes simplex dermatitis [eczema herpeticum], herpes simplex [cold sores], Kaposi’s varicelliform eruption)

 

Skin and subcutaneous tissue disorders

Common:                     Folliculitis, pruritus

Uncommon:                 Acne

 

Nervous system disorders

Common:                     Paraesthesias and dysaesthesias (hyperaesthesia, burning sensation)

 

Metabolism and nutrition disorders

Common:             Alcohol intolerance (facial flushing or skin irritation after consumption of an alcoholic beverage)

 

The following adverse reactions have been reported during post-marketing experience:

Skin and subcutaneous tissue disorders: Rosacea

 

 

10.     DATE OF REVISION OF THE TEXT

23 June 2011

Updated on 24 June 2011 PIL

Reasons for updating

  • Change to date of revision
  • Change due to user-testing of patient information

Updated on 12 May 2011 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.2  Posology and method of administration

Protopic can be used for short-term and intermittent long-term treatment.  Treatment should not be continuous.

Posology

Flare treatment

Protopic can be used for short-term and intermittent long-term treatment. Treatment should not be continuous on a long-term basis.

4.4 Special warnings and precautions for use

The use of tacrolimus ointment is not recommended in patients with a skin barrier defect such as Netherton’s syndrome, lamellar ichthyosis, generalized erythroderma or cutaneous Graft Versus Host Disease. These skin conditions may increase systemic absorption of tacrolimus. Oral use of tacrolimus is also not recommended to treat skin conditions. Post-Marketing cases of increased tacrolimus blood level have been reported in these conditions.

 

 

4.8 Undesirable effect

System Organ Class

Very Common >1/10

Common

>1/100,

 <1/10

Uncommon >1/1000, 1/100

Not Known(cannot be estimated from the available data)

Infections and infestations

 

Local skin infection regardless of specific etiology including but not limited to:Eczema herpeticum, Folliculitis, Herpes simplex, Herpes virus infection, Kaposi’s varicelliform eruption*

 

 

Metabolism and nutrition disorders

 

Alcohol intolerance (facial flushing or skin irritation after consumption of an alcoholic beverage)

 

 

Nervous system disorders

 

Paraesthesias and dysaethesias (hyperaesthesia, burning sensation)

 

 

Skin and subcutaneous tissue disorders

 

Pruritus

Acne*

Rosacea*

General disorders and administration site conditions

Application site burning, Application site pruritus

Application site warmth

Apllication site erythema,

Application site pain

Application site irritation,

Application site paraesthesia,

Application site rash,

 

Application site oedema*

Invesigations

 

 

 

Drug level increased* (see section 4.4)

 

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Other dermatologicals, ATC code: D11AH01

 

 

10. DATE OF REVISION OF THE TEXT

 

Feb 2011

 

Updated on 11 May 2009 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to how the medicine works
  • Change to date of revision
  • Changes to therapeutic indications

Updated on 5 May 2009 SmPC

Reasons for updating

  • Change to section 10 - Date of revision of the text
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 7 - Marketing authorisation holder

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

 

Section  4.1     Therapeutic indications update

 

Treatment of moderate to severe atopic dermatitis in adults who are not adequately responsive to or are intolerant of conventional therapies such as topical corticosteroids.

 

 

Was updated to read:

 

Treatment of moderate to severe atopic dermatitis in adults who are not adequately responsive to or are intolerant of conventional therapies such as topical corticosteroids.

 

Maintenance treatment of moderate to severe atopic dermatitis for the prevention of flares and the prolongation of flare-free intervals in patients experiencing a high frequency of disease exacerbations (i.e. occurring 4 or more times per year) who have had an initial response to a maximum of 6 weeks treatment of twice daily tacrolimus ointment (lesions cleared, almost cleared or mildly affected).

 

 

Section  4.2     Posology and method of administration

 

The sentence: Treatment should be intermittent and not continuous was removed and replaced by:

Protopic can be used for short-term and intermittent long-term treatment. Treatment should not be continuous.

 

Protopic ointment should be applied as a thin layer to affected areas of the skin., was changed to read: Protopic ointment should be applied as a thin layer to affected or commonly affected areas of the skin.

 

 

The following paragraphs were omitted:

Each affected region of the skin should be treated with Protopic until clearance occurs and then treatment should be discontinued. Generally, improvement is seen within one week of starting treatment. If no signs of improvement are seen after two weeks of treatment, further treatment options should be considered. Protopic can be used for short term and intermittent long term treatment. At the first signs of recurrence (flares) of the disease symptoms, treatment should be re-initiated.

 

Use in elderly (65 years of age and above)

Specific studies have not been conducted in elderly patients. However, the clinical experience available in this patient population has not shown the necessity for any dosage adjustment.

 

As clinical efficacy studies were performed with abrupt cessation of treatment, no information is available on whether tapering of the dosage would reduce recurrence rate.

 

 

 

 

 

The following paragraph was inserted:

 

Treatment

Protopic treatment should begin at the first appearance of signs and symptoms. Each affected region of the skin should be treated with Protopic until lesions are cleared, almost cleared or mildly affected. Thereafter, patients are considered suitable for maintenance treatment (see below). At the first signs of recurrence (flares) of the disease symptoms, treatment should be re-initiated.

 

Generally, improvement is seen within one week of starting treatment. If no signs of improvement are seen after two weeks of treatment, further treatment options should be considered.

 

Maintenance

Patients who are responding to up to 6 weeks treatment using tacrolimus ointment twice daily (lesions cleared, almost cleared or mildly affected) are suitable for maintenance treatment.

 

Protopic ointment should be applied once a day twice weekly (e.g. Monday and Thursday) to areas commonly affected by atopic dermatitis to prevent progression to flares. Between applications there should be 23 days without Protopic treatment.

 

Adult patients (16 years of age and above) should use Protopic 0.1% ointment, children (2 years of age and above) should use the lower strength Protopic 0.03% ointment.

 

If signs of a flare reoccur, twice daily treatment should be re-initiated (see treatment section above).

 

After 12 months, a review of the patient`s condition should be conducted by the physician and a decision taken whether to continue maintenance treatment in the absence of safety data for maintenance treatment beyond 12 months. In children, this review should include suspension of treatment to assess the need to continue this regimen and to evaluate the course of the disease.

 

 

 

Section 4.4      Special warnings and precautions for use

 

The following sentence was inserted: The development of any new change different from previous eczema within a treated area should be reviewed by the physician.

 

 

Section 4.8      Undesirable effects

 

The following paragraf was added:

In a study of maintenance treatment (twice weekly treatment) in adults and children with moderate and severe atopic dermatitis the following adverse events were noted to occur more frequently than in the control group: application site impetigo (7.7% in children) and application site infections (6.4% in children and 6.3% in adults).

 

 

Section 5.1      Pharmacodynamic properties

 

The following paragraph was inserted:

 

The efficacy and safety of tacrolimus ointment in maintenance treatment of mild to severe atopic dermatitis was assessed in 524 patients in two Phase III multicentre clinical trials of similar design, one in adult patients ( 16 years) and one in paediatric patients (2-15 years). In both studies, patients with active disease entered an open-label period (OLP) during which they treated affected lesions with tacrolimus ointment twice daily until improvement had reached a predefined score (Investigators Global Assessment [IGA] ≤ 2, i.e. clear, almost clear or mild disease) for a maximum of 6 weeks. Thereafter, patients entered a double-blind disease control period (DCP) for up to 12 months. Patients were randomised to receive either tacrolimus ointment (0.1% adults; 0.03% children) or vehicle, once a day twice weekly on Mondays and Thursdays. If a disease exacerbation occurred, patients were treated with open-label tacrolimus ointment twice daily for a maximum of 6 weeks until the IGA score returned to ≤ 2.

The primary endpoint in both studies was the number of disease exacerbations requiring a substantial therapeutic intervention during the DCP, defined as an exacerbation with an IGA of 3-5 (i.e. moderate, severe and very severe disease) on the first day of the flare, and requiring more than 7 days treatment. Both studies showed significant benefit with twice weekly treatment with tacrolimus ointment with regard to the primary and key secondary endpoints over a period of 12 months in a pooled population of patients with mild to severe atopic dermatitis. In a subanalysis of a pooled population of patients with moderate to severe atopic dermatitis these differences remained statistically significant (Table 4). No adverse events not reported previously were observed in these studies.

 

Table 4        Efficacy (moderate to severe subpopulation)

 

 

Adults, ≥ 16 years

Children, 2-15 years

Tacrolimus 0.1%

Twice weekly

(N=80)

Vehicle

Twice weekly

(N=73)

Tacrolimus 0.03%

Twice weekly

(N=78)

Vehicle

Twice weekly

(N=75)

Median number of DEs requiring substantial intervention adjusted for time at risk (% of patients without DE requiring substantial intervention)

 

1.0 (48.8%)

 

5.3 (17.8%)

 

1.0 (46.2%)

 

2.9 (21.3%)

Median time to first DE requiring substantial intervention

142 days

15 days

217 days

36 days

Median number of DEs adjusted for time at risk (% of patients without any DE periods)

 

1.0 (42.5%)

 

6.8 (12.3%)

 

1.5 (41.0%)

 

3.5 (14.7%)

Median time to first DE

123 days

14 days

146 days

17 days

Mean (SD) percentage of days of DE exacerbation treatment

16.1 (23.6)

39.0 (27.8)

16.9 (22.1)

29.9 (26.8)

DE: disease exacerbation

P<0.001 in favour of tacrolimus ointment 0.1% (adults) and 0.03% (children) for the primary and key secondary endpoints

 

 

Section 7: MARKETING AUTHORISATION HOLDER

 

Updated from:

 

Astellas Pharma GmbH

Neumarkter Str. 61

D-81673 Mnchen

Germany

 

To

 

Astellas Pharma Europe B.V.

Elisabethhof 19

2353 EW Leiderdorp

Netherlands

 

 

Section 10.      DATE OF REVISION OF THE TEXT

 

Updated from 03/05/2007 to April 2009

 

Updated on 27 August 2008 PIL

Reasons for updating

  • Change to further information section
  • Change to date of revision

Updated on 16 August 2007 SmPC

Reasons for updating

  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Changes Document

 

Protopic 0.03% and 0.1% SPC

May 2007 v Nov 2006

 

 

5.2     Pharmacokinetic properties

Absorption

Correction of the adult high dose from 0.3% to 0.1%, and insertion of data from infants from age of 5 months, as follows:


“Most atopic dermatitis patients (adults and children) treated with single or repeated application of tacrolimus ointment (0.03 - 0.1%), and infants from age of 5 months treated with tacrolimus ointment (0.03%) had blood concentrations < 1.0 ng/ml.”

 

 

5.3 Clinical Data

Reproduction toxicity

Correction: Reduced sperm function was noted in male rats at high subcutaneous doses as opposed to high oral doses, as had stated in the previous version of the SPC.

 

 

10. Date of Revision of Text

Updated from 20/11/2006 to 03/05/2007

 

EMEA website address updated from http://www.emea.eu.int/ to http://www.emea.europa.eu

Updated on 19 January 2007 PIL

Reasons for updating

  • Change due to harmonisation of patient information leaflet

Updated on 18 January 2007 SmPC

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Changes Document – Protopic SPC

June 2006 v Nov 2006

 

Changes apply to both strengths (0.03% 0.1%)

 

No changes to the content  were introduced. However, the whole product information was adjusted to the QRD 7.1 template which required mainly changes of template sentences and rearrangements of whole paragraphs.

 

Section 2:

Insertion of new text: “For a full list of excipients, see section 6.1”.

 

Section 4.4:

Re-wording of heading: “Special warnings and special precautions for use”

 

Section 4.6

First paragraph: wording re-arranged but content unchanged.

 

Insertion of new text: “Protopic ointment should not be used during pregnancy unless clearly necessary”.

 

Section 4.8:

Insertion of new text: “Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness”.

 

Section 6.6

Re-wording of heading:Instructions for use and handling and Special precautions for disposal”

 

Insertion of new text: “Any unused product or waste material should be disposed of in accordance with local requirements”.

 

Section 9

Date of first authorisation changed to: 28/02/2002

Date of renewal: 20/11/2006

 

Section 10

Date of revision of the text: 20/11/2006

 

Insertion of new text: “Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http://www.emea.eu.int/

Updated on 31 July 2006 PIL

Reasons for updating

  • Change of manufacturer
  • Change of licence holder
  • Change to warnings or special precautions for use
  • Change to date of revision
  • Change to dosage and administration
  • Change to side-effects

Updated on 7 July 2006 SmPC

Reasons for updating

  • New SPC for medicines.ie

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 17 September 2004 PIL

Reasons for updating

  • New PIL for medicines.ie