Calcitonin

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On 19 July 2012, the European Medicines Agency (EMA) completed a review of the benefits and risks of calcitonin-containing medicines, concluding that there was evidence of a small increased risk of cancer with long-term use of these medicines. The Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended that they should only be authorised for short-term use in Paget’s disease, acute bone loss due to sudden immobilisation and hypercalcaemia caused by cancer. The Committee also concluded that the benefits of calcitonin-containing medicines did not outweigh their risks in the treatment of osteoporosis and that they should no longer be used for this condition.

After a re-examination, the Committee confirmed its recommendation on 15 November 2012.

What is calcitonin?

Calcitonin is a hormone that increases the amount of calcium in the bones and lowers the calcium level in the blood.

Calcitonin, manufactured in the laboratory, is used in medicines to treat or prevent conditions that involve the loss of calcium from the bones. It has been used in the European Union (EU) for the treatment of osteoporosis (a disease that makes bones fragile), Paget’s disease (a bone disease that involves bone remodelling and can cause deformity), and hypercalcaemia (increased blood calcium) caused by cancer. It is also used to prevent acute bone loss due to sudden immobilisation such as in patients with recent osteoporotic fractures.

Calcitonin-containing medicines have been available in the EU as solutions for injection or infusion (drip into a vein) since 1973, and as a nasal spray since 1987. They are currently marketed in most EU countries.

Why were calcitonin-containing medicines reviewed?

This review was initiated following preliminary findings from two studies of an unlicensed oral calcitonin medicine, which pointed to a possible association with prostate cancer. These findings were made available to EU national authorities in November 2010.

A possible association between calcitonin and prostate cancer was first investigated by the United Kingdom (UK) medicines regulatory agency in 2004, but a causal association could not be established with the evidence available at the time. The issue was also investigated in 2009 and 2010 by the EMA’s Pharmacovigilance Working Party (PhVWP), but there was insufficient evidence at the time for any regulatory action

Following the receipt of the data from the studies on the unlicensed oral medicine, the UK medicines agency asked the CHMP to carry out a full assessment of the benefit-risk balance of calcitonin-containing medicines and to issue an opinion on whether their marketing authorisations should be maintained, varied, suspended or withdrawn across the EU.

Which data has the CHMP reviewed?

In addition to the two studies of the unlicensed oral calcitonin medicine, the CHMP reviewed available data on the benefits and risks of calcitonin-containing medicines provided by the companies that market these medicines as well as data from the scientific literature and from third parties. The CHMP also reviewed post-marketing safety data, randomised controlled studies and experimental cancer studies.

What are the conclusions of the CHMP?

The CHMP noted that the available data suggest that a higher proportion of patients treated with calcitonin for long periods of time may develop cancer of various types, compared with patients taking placebo. Although the cancer rates reported in the studies were low, the increase in cancer rates seen with calcitonin varied between 0.7% in studies with the oral formulation to 2.4% in the studies with the nasal formulation. Taking into account the limited benefit of calcitonin when used to treat post-menopausal osteoporosis to reduce the risk of vertebral fractures, the CHMP concluded that the benefits of calcitonin did not outweigh the risks in this condition. As the nasal spray is only used in osteoporosis, the CHMP recommended that this formulation should no longer be used.

The benefit-risk balance remains positive only for the following uses:

  • treatment of Paget’s disease for patients who cannot be treated with alternative treatments;
  • prevention of acute bone loss due to sudden immobilisation such as in patients with recent osteoporotic fractures;
  • treatment of hypercalcaemia caused by cancer.

However, the CHMP recommended that even for these uses, calcitonin treatment should be given for the shortest possible time using the smallest effective dose. The Committee maintained its recommendations after re-examination.

What are the recommendations for patients?
  • Calcitonin will no longer be used for the treatment of osteoporosis. Patients being treated for osteoporosis with calcitonin nasal sprays or other formulations are advised to speak to their doctor at a routine appointment, who will recommend suitable alternative treatment.
  • Patients receiving injectable calcitonin who have any questions should speak to their doctor or pharmacist.
What are the recommendations for prescribers?
  • Prescribers should note that calcitonin should no longer be used for the treatment of osteoporosis.
  • Calcitonin will only be available as a solution for injection and infusion, and should only be used for:
    • prevention of acute bone loss due to sudden immobilisation, with a recommended treatment period of two weeks and a maximum treatment period of four weeks;
    • Paget's disease, restricted to patients who do not respond to alternative treatments or for whom such treatments are not suitable, and with treatment normally limited to three months (longer treatment and periodic retreatment may be considered taking into account the benefits and risks);
    • hypercalcaemia caused by cancer.
  • Treatment with calcitonin should be limited to the shortest possible time using the smallest effective dose.

The European Commission issued a decision on 13 February 2013.

Name Language First published Last updated
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC BG = bălgarski 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC ES = español 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC CS = čeština 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC DA = dansk 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC DE = Deutsch 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC ET = eesti keel 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC EL = elliniká 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC EN = English 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC FR = français 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC IT = italiano 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC LV = latviešu valoda 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC LT = lietuvių kalba 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC HU = magyar 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC MT = Malti 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC NL = Nederlands 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC PL = polski 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC PT = português 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC RO = română 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC SK = slovenčina 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC SL = slovenščina 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC FI = suomi 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC SV = svenska 19/07/2013  

Key facts

Approved nameCalcitonin
International non-proprietary name (INN) or common name

calcitonin

Associated names
Class
Reference numberEMEA/H/A-31/1291
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 date19/07/2012

All documents

Name Language First published Last updated
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC BG = bălgarski 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC ES = español 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC CS = čeština 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC DA = dansk 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC DE = Deutsch 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC ET = eesti keel 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC EL = elliniká 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC EN = English 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC FR = français 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC IT = italiano 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC LV = latviešu valoda 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC LT = lietuvių kalba 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC HU = magyar 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC MT = Malti 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC NL = Nederlands 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC PL = polski 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC PT = português 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC RO = română 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC SK = slovenčina 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC SL = slovenščina 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC FI = suomi 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of a procedure under Article 31 of Directive 2001/83/EC SV = svenska 19/07/2013  
Calcitonin Article-31 referral - Annex I BG = bălgarski 19/07/2013  
Calcitonin Article-31 referral - Annex I ES = español 19/07/2013  
Calcitonin Article-31 referral - Annex I CS = čeština 19/07/2013  
Calcitonin Article-31 referral - Annex I DA = dansk 19/07/2013  
Calcitonin Article-31 referral - Annex I DE = Deutsch 19/07/2013  
Calcitonin Article-31 referral - Annex I ET = eesti keel 19/07/2013  
Calcitonin Article-31 referral - Annex I EL = elliniká 19/07/2013  
Calcitonin Article-31 referral - Annex I EN = English 19/07/2013  
Calcitonin Article-31 referral - Annex I FR = français 19/07/2013  
Calcitonin Article-31 referral - Annex I IT = italiano 19/07/2013  
Calcitonin Article-31 referral - Annex I LV = latviešu valoda 19/07/2013  
Calcitonin Article-31 referral - Annex I LT = lietuvių kalba 19/07/2013  
Calcitonin Article-31 referral - Annex I HU = magyar 19/07/2013  
Calcitonin Article-31 referral - Annex I MT = Malti 19/07/2013  
Calcitonin Article-31 referral - Annex I NL = Nederlands 19/07/2013  
Calcitonin Article-31 referral - Annex I PL = polski 19/07/2013  
Calcitonin Article-31 referral - Annex I PT = português 19/07/2013  
Calcitonin Article-31 referral - Annex I RO = română 19/07/2013  
Calcitonin Article-31 referral - Annex I SK = slovenčina 19/07/2013  
Calcitonin Article-31 referral - Annex I SL = slovenščina 19/07/2013  
Calcitonin Article-31 referral - Annex I FI = suomi 19/07/2013  
Calcitonin Article-31 referral - Annex I SV = svenska 19/07/2013  
Calcitonin Article-31 referral - Annex I IS = Islenska 19/07/2013  
Calcitonin Article-31 referral - Annex I NO = Norsk 19/07/2013  
Calcitonin Article-31 referral - Annex II BG = bălgarski 19/07/2013  
Calcitonin Article-31 referral - Annex II ES = español 19/07/2013  
Calcitonin Article-31 referral - Annex II CS = čeština 19/07/2013  
Calcitonin Article-31 referral - Annex II DA = dansk 19/07/2013  
Calcitonin Article-31 referral - Annex II DE = Deutsch 19/07/2013  
Calcitonin Article-31 referral - Annex II ET = eesti keel 19/07/2013  
Calcitonin Article-31 referral - Annex II EL = elliniká 19/07/2013  
Calcitonin Article-31 referral - Annex II EN = English 19/07/2013  
Calcitonin Article-31 referral - Annex II FR = français 19/07/2013  
Calcitonin Article-31 referral - Annex II IT = italiano 19/07/2013  
Calcitonin Article-31 referral - Annex II LV = latviešu valoda 19/07/2013  
Calcitonin Article-31 referral - Annex II LT = lietuvių kalba 19/07/2013  
Calcitonin Article-31 referral - Annex II HU = magyar 19/07/2013  
Calcitonin Article-31 referral - Annex II MT = Malti 19/07/2013  
Calcitonin Article-31 referral - Annex II NL = Nederlands 19/07/2013  
Calcitonin Article-31 referral - Annex II PL = polski 19/07/2013  
Calcitonin Article-31 referral - Annex II PT = português 19/07/2013  
Calcitonin Article-31 referral - Annex II RO = română 19/07/2013  
Calcitonin Article-31 referral - Annex II SK = slovenčina 19/07/2013  
Calcitonin Article-31 referral - Annex II SL = slovenščina 19/07/2013  
Calcitonin Article-31 referral - Annex II FI = suomi 19/07/2013  
Calcitonin Article-31 referral - Annex II SV = svenska 19/07/2013  
Calcitonin Article-31 referral - Annex III BG = bălgarski 19/07/2013  
Calcitonin Article-31 referral - Annex III ES = español 19/07/2013  
Calcitonin Article-31 referral - Annex III CS = čeština 19/07/2013  
Calcitonin Article-31 referral - Annex III DA = dansk 19/07/2013  
Calcitonin Article-31 referral - Annex III DE = Deutsch 19/07/2013  
Calcitonin Article-31 referral - Annex III ET = eesti keel 19/07/2013  
Calcitonin Article-31 referral - Annex III EL = elliniká 19/07/2013  
Calcitonin Article-31 referral - Annex III EN = English 19/07/2013  
Calcitonin Article-31 referral - Annex III FR = français 19/07/2013  
Calcitonin Article-31 referral - Annex III IT = italiano 19/07/2013  
Calcitonin Article-31 referral - Annex III LV = latviešu valoda 19/07/2013  
Calcitonin Article-31 referral - Annex III LT = lietuvių kalba 19/07/2013  
Calcitonin Article-31 referral - Annex III HU = magyar 19/07/2013  
Calcitonin Article-31 referral - Annex III MT = Malti 19/07/2013  
Calcitonin Article-31 referral - Annex III NL = Nederlands 19/07/2013  
Calcitonin Article-31 referral - Annex III PL = polski 19/07/2013  
Calcitonin Article-31 referral - Annex III PT = português 19/07/2013  
Calcitonin Article-31 referral - Annex III RO = română 19/07/2013  
Calcitonin Article-31 referral - Annex III SK = slovenčina 19/07/2013  
Calcitonin Article-31 referral - Annex III SL = slovenščina 19/07/2013  
Calcitonin Article-31 referral - Annex III FI = suomi 19/07/2013  
Calcitonin Article-31 referral - Annex III SV = svenska 19/07/2013  
Calcitonin Article-31 referral - Annex III IS = Islenska 19/07/2013  
Calcitonin Article-31 referral - Annex III NO = Norsk 19/07/2013  
Calcitonin Article-31 referral - Annex IV BG = bălgarski 19/07/2013  
Calcitonin Article-31 referral - Annex IV ES = español 19/07/2013  
Calcitonin Article-31 referral - Annex IV CS = čeština 19/07/2013  
Calcitonin Article-31 referral - Annex IV DA = dansk 19/07/2013  
Calcitonin Article-31 referral - Annex IV DE = Deutsch 19/07/2013  
Calcitonin Article-31 referral - Annex IV ET = eesti keel 19/07/2013  
Calcitonin Article-31 referral - Annex IV EL = elliniká 19/07/2013  
Calcitonin Article-31 referral - Annex IV EN = English 19/07/2013  
Calcitonin Article-31 referral - Annex IV FR = français 19/07/2013  
Calcitonin Article-31 referral - Annex IV IT = italiano 19/07/2013  
Calcitonin Article-31 referral - Annex IV LV = latviešu valoda 19/07/2013  
Calcitonin Article-31 referral - Annex IV LT = lietuvių kalba 19/07/2013  
Calcitonin Article-31 referral - Annex IV HU = magyar 19/07/2013  
Calcitonin Article-31 referral - Annex IV MT = Malti 19/07/2013  
Calcitonin Article-31 referral - Annex IV NL = Nederlands 19/07/2013  
Calcitonin Article-31 referral - Annex IV PL = polski 19/07/2013  
Calcitonin Article-31 referral - Annex IV PT = português 19/07/2013  
Calcitonin Article-31 referral - Annex IV RO = română 19/07/2013  
Calcitonin Article-31 referral - Annex IV SK = slovenčina 19/07/2013  
Calcitonin Article-31 referral - Annex IV SL = slovenščina 19/07/2013  
Calcitonin Article-31 referral - Annex IV FI = suomi 19/07/2013  
Calcitonin Article-31 referral - Annex IV SV = svenska 19/07/2013  
Calcitonin Article-31 referral - Annex IV IS = Islenska 19/07/2013  
Calcitonin Article-31 referral - Annex IV NO = Norsk 19/07/2013  
Assessment report for calcitonin containing medicinal products (English only) 19/07/2013  
Questions and answers on the review of calcitonin-containing medicines - Outcome of re-examination (English only) 16/11/2012  
Calcitonin: Product information as approved by the CHMP on 15 November 2012, pending endorsement by the European Commission (English only) 16/11/2012  
Questions and answers on the review of calcitonin-containing medicines (English only) 20/07/2012  
Calcitonin: Product information as approved by the CHMP on 19 July 2012, pending endorsement by the European Commission (English only) 20/07/2012  

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 calcitonin