Linoladiol N and Linoladiol HN

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The European Medicines Agency recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams

A limit to the duration of use and other measures put in place to manage potential risk of side effects

On 25 April 2014, the EMA’s Committee for Medicinal Products for Human Use (CHMP) updated recommendations on the use of two high-strength estradiol-containing creams, Linoladiol N and Linoladiol HN.

The Linoladiol N cream is only to be used inside the vagina for treating postmenopausal women with vaginal atrophy due to a lack of the hormone estrogen, while the Linoladiol HN cream is for postmenopausal women with mild, inflammatory skin conditions around the genital area. Treatment with both creams should be limited to a maximum duration of 4 weeks.

In addition, Linoladiol HN is no longer to be used to treat lichen sclerosus, a skin condition that commonly affects the genital area, because of a lack of evidence of benefit in this condition.

In December 2013, the CHMP had concluded a review of the benefits and risks of both creams and made recommendations on their use. Following a request by the company for a re-examination of Linoladiol N, the recommendations for this cream have been updated, taking into account new measures to manage the potential risk of side effects.

The CHMP reiterated the need to limit treatment with both creams to 4 weeks because of their relatively high estradiol content and the potential risks of side effects from estradiol being absorbed systemically (throughout the body). Systemic absorption of estradiol may be associated with risks similar to those seen in systemic hormone replacement therapy (HRT), including blood clots, stroke and endometrial (womb) cancer. The product information of Linoladiol N and Linoladiol HN have been updated to inform patients and healthcare professionals about these potential risks.

In addition, for Linoladiol N, the cream with the higher amount of estradiol, the CHMP has required the company to limit the amount of cream available in the packs to prevent patients from using them for longer than recommended.

The CHMP’s recommendations were sent to the European Commission which endorsed them and issued a final, legally binding decision valid throughout the EU on 19 August 2014.

Information to patients

The European Medicines Agency has updated advice on how to use Linoladiol N and Linoladiol HN creams. Patients using these creams should be aware of the following:

  • Linoladiol N is only to be used inside the vagina for treating postmenopausal women with vaginal atrophy due to a lack of estrogen.
  • Linoladiol HN should only be used for treating postmenopausal women with mild, inflammatory skin conditions affecting the external genital area.
  • Linoladiol HN was previously being used to treat a condition called lichen sclerosus. If you have been using Linoladiol HN for this condition, contact your doctor to discuss alternative treatments.
  • Both creams should not be used for more than 4 weeks. This is because the creams contain the hormone estradiol which can be absorbed into the bloodstream and may increase your risks of side effects such as blood clots and strokes if the creams are used for extended periods.
  • Linoladiol N should be applied into the vagina while Linoladiol HN should be applied to the external genital area.
  • If you have any questions about your treatment, you should contact your doctor or pharmacist.
Information to healthcare professionals

The EMA has concluded a review of Linoladiol N and Linoladiol HN estradiol-containing creams and has updated recommendations on their use. The product information for both creams will be updated with the following recommendations:

  • Linoladiol N is indicated for the treatment of vaginal atrophy due to estrogen deficiency in postmenopausal women.
  • Linoladiol HN is indicated in the short-term treatment of acute, mild inflammatory skin diseases of the external genital area in postmenopausal women.
  • Linoladiol HN should no longer be prescribed for lichen sclerosus.

Both Linoladiol N and Linoladiol HN should not be used beyond four weeks due to the risks associated with possible systemic exposure to estradiol.

More about the medicine

The Linoladiol N cream (0.01 %w/w) contains 100 microgram of estradiol per gram, while Linoladiol HN (0.005 %w/w, 0.4 %w/w) contains 50 microgram of estradiol and 4 mg of the corticosteroid prednisolone per gram.

Linoladiol N and Linoladiol HN are a type of local ‘hormone replacement therapy’: they contain a female hormone, estradiol, used to replace the estradiol hormone the body no longer makes after menopause. Linoladiol HN also contains low-dose prednisolone, which acts as an anti-inflammatory agent.

Both medicines have been authorised in the EU through national procedures for over 40 years. Linoladiol N is marketed in Bulgaria, Czech Republic, Estonia, Germany, Hungary, Latvia, Lithuania and Slovakia, while Linoladiol HN is marketed in Estonia, Germany, Latvia and Lithuania.

More about the procedure

The review of the topical estradiol-containing medicines Linoladiol N and Linoladiol HN was triggered on 24 May 2012 by Germany, under Article 31 of Directive 2001/83/EC. The German medicines agency asked the CHMP to carry out a full assessment of the benefit-risk balance of these medicines and to issue an opinion on whether their marketing authorisations should be maintained, varied, suspended or withdrawn across the European Union.

The review has been carried out by the Committee for Medicinal Products for Human Use (CHMP) responsible for questions concerning medicines for human use.

The CHMP issued an opinion in December 2013. Following a request from the company, a re-examination of the opinion for Linoladiol N was carried out and concluded in April 2014. The final CHMP opinion was forwarded to the European Commission, which issued a final decision on 19 August 2014.

Name Language First published Last updated
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams BG = bălgarski 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams ES = español 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams CS = čeština 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams DA = dansk 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams DE = Deutsch 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams ET = eesti keel 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams EL = elliniká 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams EN = English 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams FR = français 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams IT = italiano 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams LV = latviešu valoda 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams LT = lietuvių kalba 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams HU = magyar 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams MT = Malti 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams NL = Nederlands 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams PL = polski 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams PT = português 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams RO = română 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams SK = slovenčina 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams SL = slovenščina 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams FI = suomi 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams SV = svenska 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams HR = Hrvatski 11/09/2014  

Key facts

Approved nameLinoladiol N and Linoladiol HN
International non-proprietary name (INN) or common name

estradiol

Associated names
Classhormonal
Reference numberEMEA/H/A-31/1336
TypeArticle 31 referrals

This type of referral is triggered when the interest of the Community is involved, following concerns relating to the quality, safety or efficacy of a medicine or a class of medicines.

StatusEuropean Commission final decision
Opinion date25/04/2014

All documents

Name Language First published Last updated
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams BG = bălgarski 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams ES = español 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams CS = čeština 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams DA = dansk 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams DE = Deutsch 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams ET = eesti keel 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams EL = elliniká 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams EN = English 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams FR = français 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams IT = italiano 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams LV = latviešu valoda 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams LT = lietuvių kalba 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams HU = magyar 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams MT = Malti 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams NL = Nederlands 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams PL = polski 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams PT = português 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams RO = română 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams SK = slovenčina 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams SL = slovenščina 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams FI = suomi 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams SV = svenska 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - EMA recommendations on the use of Linoladiol N and Linoladiol HN estradiol-containing creams HR = Hrvatski 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - CHMP assessment report (English only) 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I BG = bălgarski 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I ES = español 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I CS = čeština 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I DA = dansk 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I DE = Deutsch 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I ET = eesti keel 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I EL = elliniká 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I EN = English 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I FR = français 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I IT = italiano 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I LV = latviešu valoda 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I LT = lietuvių kalba 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I HU = magyar 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I MT = Malti 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I NL = Nederlands 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I PL = polski 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I PT = português 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I RO = română 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I SK = slovenčina 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I SL = slovenščina 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I FI = suomi 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I SV = svenska 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex I HR = Hrvatski 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II BG = bălgarski 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II ES = español 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II CS = čeština 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II DA = dansk 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II DE = Deutsch 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II ET = eesti keel 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II EL = elliniká 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II EN = English 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II FR = français 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II IT = italiano 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II LV = latviešu valoda 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II LT = lietuvių kalba 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II HU = magyar 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II MT = Malti 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II NL = Nederlands 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II PL = polski 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II PT = português 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II RO = română 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II SK = slovenčina 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II SL = slovenščina 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II FI = suomi 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II SV = svenska 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex II HR = Hrvatski 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex III BG = bălgarski 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex III ES = español 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex III CS = čeština 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex III DA = dansk 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex III DE = Deutsch 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex III ET = eesti keel 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex III EL = elliniká 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex III EN = English 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex III FR = français 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex III IT = italiano 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex III LV = latviešu valoda 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex III LT = lietuvių kalba 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex III HU = magyar 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex III MT = Malti 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex III NL = Nederlands 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex III PL = polski 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex III PT = português 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex III RO = română 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex III SK = slovenčina 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex III SL = slovenščina 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex III FI = suomi 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex III SV = svenska 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex III HR = Hrvatski 20/12/2013 11/09/2014
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV BG = bălgarski 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV ES = español 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV CS = čeština 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV DA = dansk 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV DE = Deutsch 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV ET = eesti keel 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV EL = elliniká 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV EN = English 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV FR = français 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV IT = italiano 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV LV = latviešu valoda 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV LT = lietuvių kalba 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV HU = magyar 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV MT = Malti 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV NL = Nederlands 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV PL = polski 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV PT = português 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV RO = română 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV SK = slovenčina 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV SL = slovenščina 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV FI = suomi 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV SV = svenska 11/09/2014  
Linoladiol N and Linoladiol HN Article-31 referral - Annex IV HR = Hrvatski 11/09/2014  

Document description

  • Questions and answers (Q&A) - easy-to-understand summary of key issues and Committee conclusions
  • Summary of Opinion - contains the CHMP opinion of the referred medicine(s)
  • List of the medicines affected by the referral (Annex I)
  • Scientific conclusions of the Committee (Annex II)

The following two documents are sometimes available:

  • Changes to the summary of product characteristics, labeling or package leaflet (also known as Annex III) - available when changes have been recommended by the Committee
  • Conditions of the marketing authorisation (also known as Annex IV) - available when the Committee recommends measures to be taken for the marketing authorisation(s) such as safety measures or extra studies

Current status:
European Commission final decision

More information on Linoladiol N and Linoladiol HN