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.
Based on its analysis of Periodic Safety Update Reports (PSURs) for medicinal products containing gemcitabine, the Pharmacovigilance Risk Assessment Committee (PRAC) reached the following conclusions.
In view of the available data on acute generalized exanthematous pustulosis (AGEP) from two post-marketing case reports with a confirmed diagnosis and causal relationship, probably associated with the use of gemcitabine, including a close temporal association, a case with a positive de-challenge test and the absence of alternative causes, the PRAC considers that a causal relationship between the use of gemcitabine and AGEP is at least possible. The PRAC concluded that the instructions for medical use of medicinal products containing gemcitabine should be amended accordingly. In addition, other types of severe cutaneous adverse reactions (SCARs), namely Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), are already listed as adverse reactions of gemcitabine in the "Adverse reactions" section of the instructions for medical use. Given the seriousness of AGEP and SJS/TEN, a general warning about SCARs should be added. The Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) agrees with the scientific conclusions made by the PRAC.
Based on the scientific conclusions on gemcitabine, the CMDh considers that the benefit/risk balance of medicinal products containing gemcitabine does not change, provided that the proposed amendments are made to the instructions for medical use.
Changes to be made to the relevant sections of the instruction for medical use (new text underlined and in bold).
“Special precautions for use” section
A warning with the following content should be added:
During treatment with gemcitabine, severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP), which may be life-threatening or fatal, have been observed. Patients should be informed of the signs and symptoms and closely monitored for skin reactions. If signs and symptoms suggestive of these reactions appear, gemcitabine should be discontinued immediately.
“Adverse reactions” section
The following adverse reaction should be added to the subsection “Skin and subcutaneous tissue disorders” with the frequency “not known”:
Acute generalized exanthematous pustulosis.
Changes to the safety information on gemcitabine-containing medicinal products based on the results of the meeting of the Pharmacovigilance Risk Assessment Committee (PRAC) of 28–31 August 2023
The European Medicines Agency (EMA) has published the minutes of the Pharmacovigilance Risk Assessment Committee (PRAC) meeting of 28–31 August 2023. Following the meeting, a decision was made on the need to introduce safety-related changes to the registration materials/instructions for medical use of medicinal products containing gemcitabine.
Gemcitabine (gemcitabine) – – PSUSA/00001519/202301
General information
Gemcitabine is a nucleoside analogue indicated for the treatment of non-small cell lung cancer, pancreatic cancer, urothelial cancer (of the bladder, renal pelvis, ureter, and urethra), breast cancer, ovarian cancer, cervical cancer, and biliary tract cancer
Based on the evaluation of PSURs, PRAC reviewed the benefit/risk balance of medicinal products containing gemcitabine and made the following recommendations.
Summary of recommendations and conclusions
- Based on the analysis of safety and efficacy data, the benefit/risk balance of the use of medicinal products containing gemcitabine for the approved indications remains unchanged.
- Nevertheless, the package insert should be updated to include a warning about severe cutaneous adverse reactions and to add acute generalized exanthematous pustulosis as an adverse reaction with a frequency of “not known”. Thus, the existing provisions of the package insert should be amended1.
- In the next PSUR, the registration certificate holder (RCH) must provide a cumulative review of cases of cardiomyopathy and retinopathy. In addition, RCHs of medicinal products containing gemcitabine must provide a comprehensive review of cases of pulmonary arterial hypertension, including data from clinical studies, post-authorization studies, and literature sources, and discuss whether an update of the instructions for medical use is necessary.
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1 Update of the sections “Special warnings and precautions for use” and “Adverse reactions” of the package insert. The risk assessment report and PRAC recommendation are forwarded to the CMDh for a decision.
List of medicinal products containing gemcitabine (gemcitabine) and authorized for medical use in Ukraine (according to the State Register of Medicinal Products as of 22.11.2023)
To analyze the published information, the applicant must use the original text available at the link:
