Human papillomavirus vaccines - Cervarix, Gardasil, Gardasil 9, Silgard

  • Procedure started
  • Under evaluation
  • PRAC recommendation
  • CHMP opinion
  • European Commission final decision
Current status:
European Commission final decision

Overview

HPV vaccines: EMA confirms evidence does not support that they cause CRPS or POTS

Reports after HPV vaccination consistent with what would be expected in this age group

EMA has now completed its review of the evidence surrounding reports of two syndromes, complex regional pain syndrome (CRPS) and postural orthostatic tachycardia syndrome (POTS) in young women given human papillomavirus (HPV) vaccines. These vaccines are given to protect them from cervical cancer and other HPV-related cancers and pre-cancerous conditions. In line with its initial recommendations, EMA confirms that the evidence does not support a causal link between the vaccines (Cervarix, Gardasil/Silgard and Gardasil 9) and development of CRPS or POTS. Therefore there is no reason to change the way the vaccines are used or amend the current product information.

CRPS is a chronic pain syndrome affecting a limb, while POTS is a condition where the heart rate increases abnormally on sitting or standing up, together with symptoms such as dizziness, fainting and weakness, as well as headache, aches and pains, nausea and fatigue. In some patients they can severely affect the quality of life. The syndromes are recognised to occur in the general population, including adolescents, regardless of vaccination.

Symptoms of CRPS and POTS may overlap with other conditions, making diagnosis difficult in both the general population and vaccinated individuals. However, available estimates suggest that in the general population around 150 girls and young women per million aged 10 to 19 years may develop CRPS each year, and at least 150 girls and young women per million may develop POTS each year. The review found no evidence that the overall occurrence of these syndromes in vaccinated girls were different from expected occurrence in these age groups, even taking into account possible underreporting. The review noted that some symptoms of CRPS and POTS may overlap with chronic fatigue syndrome (CFS, also known as myalgic encephalomyelitis or ME). Many of the reports considered in the review have features of CFS and some patients had diagnoses of both POTS and CFS. Results of a large published study that showed no link between HPV vaccine and CFS were therefore particularly relevant.

The Agency's review included published research, data from clinical trials and reports of suspected side effects from patients and healthcare professionals, as well as data supplied by Member States. The Agency's Pharmacovigilance Risk Assessment Committee (PRAC) was responsible for the initial review. In reaching its recommendations, it also consulted a group of leading experts in the field, and took into account detailed information received from a number of patient groups that also highlighted the impact these syndromes can have on patients and families.

The findings of the PRAC were passed to the Agency's Committee for Medicinal Products for Human Use (CHMP), along with further representations from patient groups. The CHMP concurred that the available evidence does not support that CRPS and POTS are caused by HPV vaccines. It therefore did not recommend any changes to the terms of licensing or the product information for these medicines.

The review recognised that more than 80 million girls and women worldwide have now received these vaccines, and in some European countries they have been given to 90% of the age group recommended for vaccination. Use of these vaccines is expected to prevent many cases of cervical cancer (cancer of the neck of the womb, which is responsible for over 20,000 deaths in Europe each year) and various other cancers and conditions caused by HPV. The benefits of HPV vaccines therefore continue to outweigh the known side effects. The safety of these vaccines, as with all medicines, will continue to be carefully monitored and will take into account any future new evidence of side effects that becomes available.

The CHMP's position will now be passed to the European Commission for a legally binding decision. The assessment report containing the evidence supporting the Agency's review will be published shortly on EMA's website.

Key facts

About this medicine
Approved name
Human papillomavirus vaccines - Cervarix, Gardasil, Gardasil 9, Silgard
International non-proprietary name (INN) or common name
Cervarix : Bivalent HPV vaccine (types 16, 18) -Gardasil : quadrivalent HPV vaccine (types 6, 11, 16, 18)Gardasil 9 : 9-valent HPV vaccine (types 6, 11, 16, 18, 31, 33, 45, 52 and 58)Silgard : quadrivalent HPV vaccine (types 6, 11, 16, 18)
Associated names
  • Cervarix
  • Gardasil
  • Gardasil 9
  • Silgard
About this procedure
Current status
European Commission final decision
Reference number
EMEA/H/A-20/1421
Type
Article 20 procedures

This type of procedure is triggered for medicines that have been authorised via the centralised procedure in case of quality, safety or efficacy issues.

Decision making model
PRAC-CHMP-EC
Authorisation model
Centrally authorised product(s)
Key dates and outcomes
Procedure start date
09/07/2015
PRAC recommendation date
06/11/2015
CHMP opinion/CMDh position date
19/11/2015
EC decision date
12/01/2016
Outcome
No further action

All documents

Procedure started

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Opinion provided by Committee for Medicinal Products for Human Use

European Commission final decision

  • List item

    HPV vaccines - Article-20 procedure - EMA confirms evidence does not support that they cause CRPS or POTS (PDF/104.36 KB)

    Adopted

    First published: 20/11/2015
    Last updated: 20/01/2016
    EMA/749763/2015

  • List item

    HPV vaccines - Article-20 procedure - Scientific conclusion - Annex (PDF/75 KB)


    First published: 20/01/2016
    Last updated: 20/01/2016

  • List item

    HPV vaccines - Article-20 procedure - EMA confirms evidence does not support that they cause CRPS or POTS (PDF/104.36 KB)

    Adopted

    First published: 20/11/2015
    Last updated: 20/01/2016
    EMA/749763/2015

  • Document description

    • Annex I - List of the medicines affected by the referral
    • Annex II - Scientific conclusions of the CHMP or CMDh
    • Annex III - Changes to the summary of product characteristics, labelling or package leaflet - available when the CHMP or CMDh recommends changes to the product information. Also includes conditions for lifting of suspensions, if applicable
    • Annex IV - Conditions of the marketing authorisation - available when the CHMP or CMDh recommends other measures to be taken for the marketing authorisation such as safety measures or additional studies
    • Notification - A letter from a Member State, the European Commission or a marketing-authorisation holder requesting the initiation of a referral procedure
    • Rationale for triggering - Background provided by the party triggering the referral explaining the issues leading to the initiation of the procedure
    • PRAC list of questions - Questions agreed by the PRAC requesting further information to evaluate the issues identified
    • PRAC timetable - Timeframe agreed by the PRAC to receive information, assess the issues and adopt a recommendation
    • PRAC / CHMP or CMDh assessment report - The assessment and conclusions of the PRAC and CHMP or CMDh on the issues investigated

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