PRAC

1. An agency of the European Union
Written consultation – PRAC example
Improving awareness on medicine safety through participation
EURORDIS Summer School 2018

2. Practical exercise Number 1
Updated advice on use of high-dose ibuprofen
EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has completed a review
confirming a small increase in the risk of cardiovascular problems, such as heart
attacks and strokes, in patients taking high doses of ibuprofen (at or above 2,400
mg per day). The review clarifies that the risk with high-dose ibuprofen is similar to the
risk seen with some other non-steroidal anti-inflammatory drugs (NSAIDs), including
COX-2 inhibitors and diclofenac.
No increase in cardiovascular risk is seen with ibuprofen at doses up to 1,200 mg per
day, which is the highest dose generally used for over-the-counter (OTC) preparations
taken by mouth in the European Union (EU).
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3. Practical exercises
The PRAC concluded that the benefits of ibuprofen outweigh the risks but
recommended updating advice on the use of high-dose ibuprofen to minimise the
cardiovascular risk. High doses of ibuprofen (2,400 mg per day or higher) should be
avoided in patients with serious underlying heart or circulatory conditions, such as
heart failure, heart disease and circulatory problems or in those who have previously
had a heart attack or stroke.
In addition, doctors should carefully assess a patient’s risk factors for heart or
circulatory conditions, before initiating long-term treatment with ibuprofen, particularly
if high doses are required. Risk factors for these conditions include smoking, high
blood pressure, diabetes and high blood cholesterol.
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4. Exercise
Please read the updated advice and Information for Patients sections (and other
sections if you have time).
Do you have any comments regarding:
• The language used to explain the issue?
• The clarity of the message?
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5. Practical exercise Number 2
PRAC written consultation for combined hormonal contraceptives (CHC)
On 5 February 2013, further to evaluation of pharmacovigilance data, France informed
the European Medicines Agency, pursuant to Article 31 of Directive 2001/83/EC, of
their consideration that the benefit risk balance of combined hormonal contraceptives
(CHC) had become unfavourable in the currently authorised indication due to the
increased risk of thromboembolism (TE) and therefore it was in the interest of the
European Union to refer the matter to the Pharmacovigilance and Risk Assessment
Committee (PRAC).
The PRAC was requested to give a recommendation on whether the indication of
medicinal products should be restricted and/or any other regulatory measures taken.
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6. Overall this review confirmed previous understanding of the level of risk of VTE and
ATE with CHCs containing low dose of ethinylestradiol (<50μg) as small. For VTE there
is good evidence for slight differences in the size of the risk according to the
progestogen. For ATE the data are insufficient to determine whether the risk differs
between CHCs.
The review has also reinforced the importance of ensuring that clear and up-to-date
information is provided to women who use these medicines and to the healthcare
professionals giving advice and clinical care.
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7. The PRAC requested that the product information of CHCs should be updated to help
women make informed decisions about their choice of contraception together with their
healthcare professional.
It is important that women are made aware of the risk of VTE and its signs and
symptoms, and that doctors take into consideration a woman’s individual risk factors
when prescribing a contraceptive.
In preparation of the update of product information, the PRAC requested the input of
patients and consumers on the best way to present data related to the risk of these
products.
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8. Text:
• Out of 10,000 women who are not using any combined hormonal contraceptive and are
not pregnant, between 1 and 3 will develop a blood clot in a year
• Out of 10,000 women who are using a combined hormonal contraceptive that contains
levonorgestrel, norgestimate or norethisterone such as [product name] about 6 will
develop a blood clot in a year.
• Out of 10,000 women who are using a combined hormonal contraceptive that contains
desogestrel, gestodene or drospirenone such as [product name] between about 9 and 12
women will develop a blood clot in a year.
• The exact number of blood clots will vary according to your personal medical history (see
“Factors that increase your risk of a blood clot” below)
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9. Table
Risk of developing a blood clot
in a year
Women who are not using a combined hormonal
pill/patch/ring and are not pregnant
Between 1 and 3 out of 10,000
women
Women using a combined contraceptive pill containing
levonorgestrel, norgestimate or norethisterone such
as [product name]**
About 6 out of 10,000 women
Women using a combined contraceptive pill containing
desogestrel, gestodene or drospirenone*
About 9-12 out of 10,000 women
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10. Bar graph
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11. Paling palette
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12. Questions
1. Which of the above-listed options do you consider the easiest to understand
and why?
a. text
b. table
c. bar graph
d. Paling palette
Please specify if you think a combination of more than one of the above would be
useful.
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2. Are you aware of any other useful ways of presenting information on the risk
of VTE associated with combined contraceptives?

13. 3. Do you think including the risk of VTE during pregnancy would help you put the size
of the risk with combined contraceptives into perspective? Please give your
reasons.
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4. Other than pregnancy, can you think of any other comparisons that would help put
the size of the risk of VTE with a combined contraceptive into perspective?