Stieprox Shampoo 1.5% w/w

1. Section 6.1 – Typographical error corrected – ‘coconut diethanolamide’ replaces ‘coconut diethanolamine’

1. Section 6.1 – Typographical error corrected – ‘coconut diethanolamide’ replaces ‘coconut diethanolamine’

• Minor QRD/editorial updates to sections 2,4.3,4.6, 5.3 & 6.1 of the SPC
• Update to HPRA details in section 4.8 of the SPC

• Minor QRD/editorial updates to sections 2,4.3,4.6, 5.3 & 6.1 of the SPC
• Update to HPRA details in section 4.8 of the SPC

Change to address of the MA Holder

Change to address of the MA Holder

Changes to:

 

 

Section 4.2 - Posology and method of administration,
Section 4.8 - Undesirable effects

 

Changes to:

 

 

Section 4.2 - Posology and method of administration,
Section 4.8 - Undesirable effects

 

The following section had slight changes to bring them in line with the QRD format:

Section 4.5 Interactions with Other Medicaments and Other Forms of Interaction, 4.7 Effects on Ability to Drive and Use Machines, 4.9 Overdose and 6.5  Nature and Contents of Container

 

Section 1. TRADE NAME OF THE MEDICINAL PRODUCT

The name has been updated from ‘Stieprox 1.5% w/w Shampoo’ to ‘Stieprox 15mg/g Shampoo’ as requested from the IMB.

 

Section 2. QUALITATIVE AND QUANTITATIVE COMPOSITION

The section on an excipient with a known effect has been added to include the excipient;

dipropylene glycol.

 

Section 4.2 Posology and Method of Administration

An additional statement was added:

The shampoo should remain in contact with the scalp for a total contact time of 3-5 minutes over the two applications.

 

And the following additional information was added:

A mild shampoo can be used in between applications of Stieprox.

 

The information under the subheading Paediatric population was added to:

The safety and efficacy of Stieprox in children under 12 years of age have not been established. .

 

Section 4.6 Fertility, pregnancy and Lactation

The information in this section was expanded from:

Ciclopirox Olamine has been used topically for many years without apparent adverse consequences.  However, the safety of Stieprox in pregnant and lactating women has not been established.

 

To:

 

Fertility

Studies in animals given oral or subcutaneous ciclopirox olamine did not reveal any impairment of fertility.

 

Pregnancy

The safety of ciclopirox olamine during human pregnancy has not been established. Studies in animals given oral or subcutaneous ciclopirox olamine did not reveal any developmental toxicity.

No effects during pregnancy are anticipated since systemic exposure is low.

 

Breast-feeding

It is not known if ciclopirox olamine is excreted in human milk. Risk to the infant is likely to be low since systemic exposure is low.

Patients should be advised to ensure that any residual product is fully washed off the breast prior to breast-feeding.

 

Section 4.8 Undesirable Effects

This section was updated from:

 

Ciclopirox Olamine may rarely cause skin irritation.  If irritation occurs and persists, treatment with Stieprox should be discontinued.

 

To:

 

The following convention has been used for the classification of adverse events:

 

Very common ≥1/10

Common ≥1/100 to <1/10

Uncommon ≥1/1000 to <1/100

Rare ≥1/10000 to <1/1000

Very rare <1/10000

 

Skin and subcutaneous tissue disorders

Common:         Application site irritation including, pruritus, burning sensation and application site rash*

Uncommon:     Erythema*

 

Post-marketing

 

Immune system disorders

Rare:    Application site hypersensitivity

 

Skin and subcutaneous tissue disorders

Rare:    Skin exfoliation*

            Eczema

            Alopecia*

            Hair colour changes

*Since these effects are also symptoms of the underlying disease, it is expected that these adverse reactions would manifest as worsening of symptoms.

 

 

Section 5.1 Pharmacodynamic Properties

 

The information on the Pharmacotherapeutic group was added:

other antifungals for topical dermatological use. ATC code: D01AE14.

 

The following wording in this section was rearranged, the information remains the same:

 

Current wording

Present wording

Ciclopirox Olamine is a broad spectrum antifungal agent which inhibits the growth of pathogenic dermatophytes, yeast and Malassezia furfur.  It has been shown in vitro to inhibit Pityrosporum ovale and Pityrosporum orbiculare, the yeast forms of Mallassezia furfur which have been implicated as the causative organisms in conditions such as dandruff and seborrhoeic dermatitis.  Ciclopirox Olamine exhibits some antibacterial activity against a variety of Gram-positive and Gram-negative bacteria.    It also has anti-inflammatory activity as result of its ability to inhibit the synthesis of prostaglandins and leukotrienes.  Ciclopirox Olamine has been shown to significantly reduce arachidonic acid-induced ear-oedema test, as measured by percentage change from control inflamed ears in mice.   Stieprox is as effective and well tolerated as 2% ketoconazole shampoo in the treatment of severe dandruff and seborrhoeic dermatitis.

Mechanism of action Ciclopirox olamine is a hydroxypyridone antifungal agent which is active in vitro inhibiting the growth of various fungal species including the yeast Malassezia furfur (formerly known as Pityrosporum ovale or Pityrosporum orbiculare). The latter has been implicated as a causative organism in dandruff and seborrhoeic dermatitis. Ciclopirox olamine also exhibits some anti-inflammatory activity.   Pharmacodynamic effects Ciclopirox olamine 1.5% shampoo shows in vivo antifungal activity against Malassezia spp. A clinical study has shown that ciclopirox olamine 1.5% shampoo significantly reduced the count of Malassezia furfur spp. in samples obtained from the scalp of subjects with dandruff and/or seborrhoeic dermatitis.

 

 

Section 5.2 Pharmacokinetic Properties

 

The following wording in this section was rearranged:

 

Current wording

Present wording

Following topical application of Ciclopirox Olamine as a 1% cream to human skin, about 1.3% of the dose is absorbed systemically.  Ciclopirox Olamine is excreted in urine with approximately 80% of an oral dose excreted as the glucuronide metabolite.  The biological half-life is approximately 1.7 hours.   The potential for systemic absorption of Ciclopirox Olamine from a wash-off shampoo containing 1.5% Ciclopirox Olamine is extremely low.

Absorption The potential for clinically significant systemic absorption of ciclopirox olamine from a wash-off shampoo containing 1.5% ciclopirox olamine is expected to be low.   Distribution Following oral administration of ciclopirox olamine to humans, affinity of ciclopirox olamine to serum proteins was found to be 96±2% in the concentration range of 0.01 to 11.0 µg/mL.   Metabolism The metabolic patterns after oral and dermal application are similar. Glucuronidation of ciclopirox olamine appears to be the major form of its metabolism.    Elimination Following oral administration of ciclopirox olamine to humans, 96% of the administered dose is excreted within 12 hours. Ciclopirox olamine is excreted in urine with approximately 80% of an oral dose excreted as the glucuronide metabolite.

 

 

Section 5.3 was updated to include:

 

Carcinogenicity

A dermal carcinogenic study in mice at concentrations of 1% and 5% ciclopirox olamine formulated in polyethylene glycol 400 applied to the intact skin, twice a week, for one year, followed by a six-month non-treatment period was conducted. No tumours were observed in any of the mice at the site of application. Overall incidence of neoplasms was similar among the treated and control groups. In addition, there is no evidence that ciclopirox olamine is carcinogenic following oral or subcutaneous administration to a number of animal species.

 

Mutagenicity

Ciclopirox olamine did not cause gene mutation or chromosomal damage in several bacterial mutagen assays or in two mammalian assays. In a battery of in vitro genotoxicity assays with ciclopirox free acid, one assay was weakly positive. The weight of evidence provided by the in vitro and in vivo assessments suggest that ciclopirox does not present a genotoxic hazard to humans.

 

Reproductive Toxicology

Reproductive studies in mice, rats, rabbits and monkeys, at doses of ciclopirox olamine 10 times that of a topical human dose, have revealed no significant evidence of impaired fertility or harm to the foetus. There is evidence that ciclopirox olamine crosses the placental barrier in animals.

 

 

The following section had slight changes to bring them in line with the QRD format:

Section 4.5 Interactions with Other Medicaments and Other Forms of Interaction, 4.7 Effects on Ability to Drive and Use Machines, 4.9 Overdose and 6.5  Nature and Contents of Container

 

Section 1. TRADE NAME OF THE MEDICINAL PRODUCT

The name has been updated from ‘Stieprox 1.5% w/w Shampoo’ to ‘Stieprox 15mg/g Shampoo’ as requested from the IMB.

 

Section 2. QUALITATIVE AND QUANTITATIVE COMPOSITION

The section on an excipient with a known effect has been added to include the excipient;

dipropylene glycol.

 

Section 4.2 Posology and Method of Administration

An additional statement was added:

The shampoo should remain in contact with the scalp for a total contact time of 3-5 minutes over the two applications.

 

And the following additional information was added:

A mild shampoo can be used in between applications of Stieprox.

 

The information under the subheading Paediatric population was added to:

The safety and efficacy of Stieprox in children under 12 years of age have not been established. .

 

Section 4.6 Fertility, pregnancy and Lactation

The information in this section was expanded from:

Ciclopirox Olamine has been used topically for many years without apparent adverse consequences.  However, the safety of Stieprox in pregnant and lactating women has not been established.

 

To:

 

Fertility

Studies in animals given oral or subcutaneous ciclopirox olamine did not reveal any impairment of fertility.

 

Pregnancy

The safety of ciclopirox olamine during human pregnancy has not been established. Studies in animals given oral or subcutaneous ciclopirox olamine did not reveal any developmental toxicity.

No effects during pregnancy are anticipated since systemic exposure is low.

 

Breast-feeding

It is not known if ciclopirox olamine is excreted in human milk. Risk to the infant is likely to be low since systemic exposure is low.

Patients should be advised to ensure that any residual product is fully washed off the breast prior to breast-feeding.

 

Section 4.8 Undesirable Effects

This section was updated from:

 

Ciclopirox Olamine may rarely cause skin irritation.  If irritation occurs and persists, treatment with Stieprox should be discontinued.

 

To:

 

The following convention has been used for the classification of adverse events:

 

Very common ≥1/10

Common ≥1/100 to <1/10

Uncommon ≥1/1000 to <1/100

Rare ≥1/10000 to <1/1000

Very rare <1/10000

 

Skin and subcutaneous tissue disorders

Common:         Application site irritation including, pruritus, burning sensation and application site rash*

Uncommon:     Erythema*

 

Post-marketing

 

Immune system disorders

Rare:    Application site hypersensitivity

 

Skin and subcutaneous tissue disorders

Rare:    Skin exfoliation*

            Eczema

            Alopecia*

            Hair colour changes

*Since these effects are also symptoms of the underlying disease, it is expected that these adverse reactions would manifest as worsening of symptoms.

 

 

Section 5.1 Pharmacodynamic Properties

 

The information on the Pharmacotherapeutic group was added:

other antifungals for topical dermatological use. ATC code: D01AE14.

 

The following wording in this section was rearranged, the information remains the same:

 

Current wording

Present wording

Ciclopirox Olamine is a broad spectrum antifungal agent which inhibits the growth of pathogenic dermatophytes, yeast and Malassezia furfur.  It has been shown in vitro to inhibit Pityrosporum ovale and Pityrosporum orbiculare, the yeast forms of Mallassezia furfur which have been implicated as the causative organisms in conditions such as dandruff and seborrhoeic dermatitis.  Ciclopirox Olamine exhibits some antibacterial activity against a variety of Gram-positive and Gram-negative bacteria.    It also has anti-inflammatory activity as result of its ability to inhibit the synthesis of prostaglandins and leukotrienes.  Ciclopirox Olamine has been shown to significantly reduce arachidonic acid-induced ear-oedema test, as measured by percentage change from control inflamed ears in mice.   Stieprox is as effective and well tolerated as 2% ketoconazole shampoo in the treatment of severe dandruff and seborrhoeic dermatitis.

Mechanism of action Ciclopirox olamine is a hydroxypyridone antifungal agent which is active in vitro inhibiting the growth of various fungal species including the yeast Malassezia furfur (formerly known as Pityrosporum ovale or Pityrosporum orbiculare). The latter has been implicated as a causative organism in dandruff and seborrhoeic dermatitis. Ciclopirox olamine also exhibits some anti-inflammatory activity.   Pharmacodynamic effects Ciclopirox olamine 1.5% shampoo shows in vivo antifungal activity against Malassezia spp. A clinical study has shown that ciclopirox olamine 1.5% shampoo significantly reduced the count of Malassezia furfur spp. in samples obtained from the scalp of subjects with dandruff and/or seborrhoeic dermatitis.

 

 

Section 5.2 Pharmacokinetic Properties

 

The following wording in this section was rearranged:

 

Current wording

Present wording

Following topical application of Ciclopirox Olamine as a 1% cream to human skin, about 1.3% of the dose is absorbed systemically.  Ciclopirox Olamine is excreted in urine with approximately 80% of an oral dose excreted as the glucuronide metabolite.  The biological half-life is approximately 1.7 hours.   The potential for systemic absorption of Ciclopirox Olamine from a wash-off shampoo containing 1.5% Ciclopirox Olamine is extremely low.

Absorption The potential for clinically significant systemic absorption of ciclopirox olamine from a wash-off shampoo containing 1.5% ciclopirox olamine is expected to be low.   Distribution Following oral administration of ciclopirox olamine to humans, affinity of ciclopirox olamine to serum proteins was found to be 96±2% in the concentration range of 0.01 to 11.0 µg/mL.   Metabolism The metabolic patterns after oral and dermal application are similar. Glucuronidation of ciclopirox olamine appears to be the major form of its metabolism.    Elimination Following oral administration of ciclopirox olamine to humans, 96% of the administered dose is excreted within 12 hours. Ciclopirox olamine is excreted in urine with approximately 80% of an oral dose excreted as the glucuronide metabolite.

 

 

Section 5.3 was updated to include:

 

Carcinogenicity

A dermal carcinogenic study in mice at concentrations of 1% and 5% ciclopirox olamine formulated in polyethylene glycol 400 applied to the intact skin, twice a week, for one year, followed by a six-month non-treatment period was conducted. No tumours were observed in any of the mice at the site of application. Overall incidence of neoplasms was similar among the treated and control groups. In addition, there is no evidence that ciclopirox olamine is carcinogenic following oral or subcutaneous administration to a number of animal species.

 

Mutagenicity

Ciclopirox olamine did not cause gene mutation or chromosomal damage in several bacterial mutagen assays or in two mammalian assays. In a battery of in vitro genotoxicity assays with ciclopirox free acid, one assay was weakly positive. The weight of evidence provided by the in vitro and in vivo assessments suggest that ciclopirox does not present a genotoxic hazard to humans.

 

Reproductive Toxicology

Reproductive studies in mice, rats, rabbits and monkeys, at doses of ciclopirox olamine 10 times that of a topical human dose, have revealed no significant evidence of impaired fertility or harm to the foetus. There is evidence that ciclopirox olamine crosses the placental barrier in animals.

 

 

This approval was for the official addition of ‘Trading as Stiefel’ to the end of the MAH address in section 7.

This approval was for the official addition of ‘Trading as Stiefel’ to the end of the MAH address in section 7.

Transfer of Marketing Authorisation from Stiefel Laboratories (UK) Ltd to GSK (Ireland) Ltd (Trading as Stiefel).

Transfer of Marketing Authorisation from Stiefel Laboratories (UK) Ltd to GSK (Ireland) Ltd (Trading as Stiefel).

Section 7: Address of Marketing Authorisation Holder changed

Section 10: Date of revision updated

Section 7: Address of Marketing Authorisation Holder changed

Section 10: Date of revision updated

Section 1

Change from 'Stieprox Shampoo 1.5% w/w' to 'Stieprox 1.5% w/w Shampoo'

 

Section 2

Addition of 'For full list of excipients, see section 6.1'

 

Section 3

Change from 'Shampoo for cutaneous use' to 'Shampoo. Clear, straw to light orange coloured viscous shampoo'

 

Section 6.1

Change of excipients

 

Section 6.2

Change from 'None' to 'Not applicable'

 

Section 6.3

Change to '3 years'

 

Section 6.4

Change from 'None' to 'This medicinal product does not require any special storage conditions'

 

Section 6.5

Addition of 20ml pack

 

Section 6.6

Change from 'There are no special instructions for the use or handling of this product' to 'No special requirements'

 

Section 9

Change from '5th October 2001' to 'Date of first authorization: 5th October 2001  Date of last renewal: 5th October 2006'

Change from 'March 2006' to 'August 2007'

Section 1

Change from 'Stieprox Shampoo 1.5% w/w' to 'Stieprox 1.5% w/w Shampoo'

 

Section 2

Addition of 'For full list of excipients, see section 6.1'

 

Section 3

Change from 'Shampoo for cutaneous use' to 'Shampoo. Clear, straw to light orange coloured viscous shampoo'

 

Section 6.1

Change of excipients

 

Section 6.2

Change from 'None' to 'Not applicable'

 

Section 6.3

Change to '3 years'

 

Section 6.4

Change from 'None' to 'This medicinal product does not require any special storage conditions'

 

Section 6.5

Addition of 20ml pack

 

Section 6.6

Change from 'There are no special instructions for the use or handling of this product' to 'No special requirements'

 

Section 9

Change from '5th October 2001' to 'Date of first authorization: 5th October 2001  Date of last renewal: 5th October 2006'

Change from 'March 2006' to 'August 2007'