Loratadine and pseudoephedrine
- Procedure started
- Under evaluation
- CHMP opinion
- European Commission final decision
Loratadine is an anti-histamine compound belonging to the H-1 antagonist group. Pseudoephedrine is a nasal decongestant, which exerts its sympathomimetic effects indirectly, predominantly through release of adrenergic mediators from postganglionic nerve terminals.
The combination of loratadine and pseudoephedrine has been authorised nationally and through Mutual Recognition in Austria, Belgium, Finland, France, Greece, Italy, Luxembourg, Portugal and Spain.
In early 1999, the Medical Products Agency (MPA) was made aware of data from the Swedish Medical Birth Registry (SMBR), which indicated that use of loratadine in the first trimester of pregnancy might be associated with an increased risk of hypospadia in the male newborn. The database consisted of 1,020 infants born to women who reported use of loratadine before the first antenatal visit.
During 1999, this signal was evaluated by the MPA, the SMBR and the MAH of the product in Sweden, Schering Plough, both by review of the clinical cases, and from a preclinical point of view. This evaluation resulted in the conclusion that this may have been a random finding. Furthermore, data from a preclinical study performed by the MAH in 1999 did not indicate that loratadine has an antiandrogenic effect, which could be one possible mechanism.
In an analysis from November 2001, the previous signal appeared reinforced. Among 2,780 exposed pregnancies there were in total 15 cases of hypospadia vs. the expected incidence of 6-7 cases. Based on these data, the MPA considered that it could not be excluded that the use of loratadine during the first trimester of pregnancy may be associated with an increased risk of hypospadia.
On 25 April 2002, Sweden triggered a referral to the EMEA under Article 31 of Directive 2001/83/EC, as amended, based on the data from the Swedish Medical Birth Registry, which could not exclude that the use of loratadine during the first trimester of pregnancy may be associated with increased risk of hypospadia. The referral procedure started 26 April 2002. The Rapporteur and Co-Rapporteur appointed were: Dr P Neels and Dr T Salmonson, respectively. Written explanations were provided by the Marketing Authorisation Holders by 14 August 2002, 24 January 2003, 2 May 2003, 4 August 2003 and 10 October 2003.
Based on evaluation of the currently available data and the Rapporteurs' assessment reports, the CPMP considered that the benefit/risk profile of loratadine and pseudoephedrine containing medicinal products remains unchanged, and therefore adopted an opinion on 20 November 2003 recommending
that the Marketing Authorisations for loratadine and pseudoephedrine containing medicinal products should be maintained in accordance with the SPC set out in Annex III of the Opinion.
in the indication:
“symptomatic treatment of seasonal allergic rhinitis when accompanied by nasal congestion”.
The list of product names concerned is given in the Annex I. The scientific conclusions are provided in the Annex II, together with the amended Summary of Product Characteristics in the Annex III.
The final opinion was converted into a Decision by the European Commission on 28 April 2003.
* Notes: The information given in this document and Annexes reflect only the CPMP Opinion dated 20 November 2003. The Member States competent authorities will continue to keep the product under regular review.
About this medicine
Loratadine and pseudoephedrine
|International non-proprietary name (INN) or common name||
About this procedure
Article 31 referrals
This type of referral is triggered when the interest of the Union is involved, following concerns relating to the quality, safety or efficacy of a medicine or a class of medicines.
European Commission final decision
Key dates and outcomes
|CHMP opinion date||
|EC decision date||
Opinion following an Article 31 referral for Loratadine and pseudoephedrine International Non-Proprietary Name (INN): loratadine and pseudoephedrine: Background information (PDF/133.51 KB)Adopted
First published: 28/04/2003
Last updated: 28/04/2003
Loratadine and pseudoephedrine - Article 31 referral - Annex I, II, III (PDF/238.13 KB)Adopted
First published: 14/07/2004
Last updated: 14/07/2004
Description of documents published
Please note that some of the listed documents apply only to certain procedures.
- Overview - lay-language summary of the stage of the procedure
- Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
- Scientific background – further background information from the triggering Member State on the issues leading to the initiation of the procedure (if applicable)
- List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
- Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
- List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
- List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. healthcare professionals, patient organisations, individual patients) (if applicable)
- Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
- Scientific conclusions – scientific conclusions of the PRAC and/or CHMP and/or CMDh
- Assessment report – PRAC or CHMP assessment and conclusions on the issues investigated, including divergent positions (if applicable)
- Divergent positions – divergent positions of the CHMP or CMDh members for pharmacovigilance procedures (if applicable)
- Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
- Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
- Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)
- Timetable for implementation of CMDh position – agreed timeframe to submit and finalise the variation(s) implementing the outcome of the procedure (if applicable)
Note that older documents may have different titles.