In accordance with paragraph 8 of Section IV of the Procedure for Expert Evaluation, the applicant must amend the instructions for medical use of the medicinal product upon receipt of new data, including bringing the instructions for medical use into line with the approved instructions for medical use of the original (reference) medicinal product, and ensure that the information on the medicinal product corresponds to current scientific knowledge.
The Pharmacovigilance Risk Assessment Committee (PRAC), based on the analysis of Periodic Safety Update Reports (PSURs) for medicinal products containing flurbiprofen, drew the following conclusions.
In view of the available literature data, the instructions for medical use of medicinal products of the same therapeutic class and the plausible mechanism of action, the PRAC considers that a warning about the possible masking effect of flurbiprofen [for systemic use, oromucosal forms and transdermal patches] on the symptoms of infection, which may lead to delayed initiation of appropriate treatment and worsening of its course, should be introduced into the instructions for medical use. The PRAC concluded that the instructions for medical use of medicinal products containing flurbiprofen [for systemic use, oromucosal forms and transdermal patches] should be amended accordingly.
Taking into account the available data in the instructions for medical use of medicinal products of the same therapeutic class and the plausible mechanism of action, the PRAC considers that a warning about the risk of use during pregnancy should be introduced for topical medicinal products containing flurbiprofen [oromucosal forms and transdermal patches]. The PRAC concluded that the instructions for medical use of medicinal products containing flurbiprofen [oromucosal forms and transdermal patches] should be amended accordingly.
The Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) agrees with the scientific conclusions drawn by PRAC.
Based on the scientific conclusions regarding flurbiprofen, the CMDh considers that the benefit-risk balance of medicinal products containing flurbiprofen remains unchanged, provided that the proposed changes to the instructions for medical use are made.
Changes to be made to the relevant sections of the instruction for medical use (new text underlined and in bold).
All medicinal products containing flurbiprofen for systemic use, oromucosal forms, and transdermal patches.
Section "Dosage and Administration".
The lowest effective dose should be used for the shortest duration necessary to relieve symptoms (see section “Special warnings and precautions for use”).
“Special warnings and precautions for use” section.
Masking of symptoms of underlying infections.
Epidemiological studies suggest that systemic nonsteroidal anti-inflammatory drugs (NSAIDs) may mask symptoms of infection, which may lead to a delayed start of appropriate treatment and thereby worsen the course of the infection. This has been observed in bacterial community-acquired pneumonia and bacterial complications of varicella. If [name of the medicinal product] is used while the patient has fever or pain associated with an infection, monitoring for the development of the infection is recommended.
Changes to be made to the relevant sections of the instruction for medical use (new text underlined and in bold).
All medicinal products containing flurbiprofen in oromucosal forms and transdermal patches.
If the instructions for medical use of a medicinal product already contain similar or stricter warnings regarding use during pregnancy, these warnings remain valid and must be retained.
If the package insert contains a statement about the absence of teratogenic effect or systemic exposure, this text should be removed.
“Contraindications” section.
[…]
– third trimester of pregnancy
Section “Use during pregnancy or breastfeeding.”
[…] Pregnancy
There are no clinical data on the use of [name of medicinal product] during pregnancy. Even if the systemic exposure is lower compared with oral use, it is unknown whether the systemic exposure to [name of medicinal product] achieved after topical use may be harmful to the embryo/fetus. During the first and second trimesters of pregnancy, [name of medicinal product] should not be used without urgent need. If used, the dose should be as low as possible and the duration of treatment as short as possible.
During the third trimester of pregnancy, systemic use of prostaglandin synthesis inhibitors, including [name of the medicinal product], may cause cardiopulmonary and renal toxicity in the fetus. In the last stages of pregnancy, prolonged bleeding may occur in both the mother and the child, and delayed labor may be observed. Therefore, [name of the medicinal product] is contraindicated during the last trimester of pregnancy (see section “Contraindications”).
List of medicinal products containing flurbiprofen (flurbiprofen) and authorized for medical use in Ukraine (according to the State Register of Medicinal Products as of 22.09.2023)
To analyze the published information, the applicant must use the original text available at the link:
