In accordance with paragraph 8 of Section IV of the Procedure for Conducting 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 about 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 etoposide, drew the following conclusions.
In view of the available data on opportunistic infections from clinical studies, literature, and spontaneous reports, including in some cases a close temporal relationship, and in view of the probable mechanism of action, the PRAC considers that a causal relationship between the use of etoposide and opportunistic infections such as Pneumocystis pneumonia is at least possible. The PRAC concluded that the instructions for medical use of medicinal products containing etoposide should be amended accordingly.
In view of the data available in the literature on an increased risk of hypersensitivity reactions when an in-line filter is used in the infusion system, the PRAC considers that a causal relationship between the use of etoposide (excluding etoposide phosphate) with an in-line filter and this increased risk is at least possible. The PRAC concluded that the instructions for medical use of medicinal products containing etoposide (excluding etoposide phosphate) for intravenous administration 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 on etoposide, the CMDh considers that the benefit/risk balance of medicinal products containing etoposide remains unchanged, provided that the proposed changes are made to the package inserts.
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
The warning should be amended as follows (only medicinal products for injection/infusion, except medicinal products containing etoposide phosphate):
Hypersensitivity
Physicians should be aware of the possible occurrence of an anaphylactic reaction to <medicinal product>, manifesting as chills, fever, tachycardia, bronchospasm, dyspnea and hypotension, which can lead to a fatal outcome. Treatment is symptomatic. The use of <medicinal product> should be discontinued immediately, followed by the administration of vasopressor agents, corticosteroids, antihistamines or plasma expanders, at the physician's discretion. An increased risk of infusion-related hypersensitivity reactions was observed with the use of in-line filters during etoposide administration. In-line filters should not be used.
“Adverse reactions” section
The following adverse reaction should be added for all medicinal products containing etoposide or etoposide phosphate, under the subsection “Infections and infestations”:
*including opportunistic infections, such as pneumocystis pneumonia
Changes to the safety information of medicinal products containing etoposide following the meeting of the Pharmacovigilance Risk Assessment Committee (PRAC) of 25–28 September 2023
The European Medicines Agency (EMA) published the minutes of the meeting of the Pharmacovigilance Risk Assessment Committee (PRAC) of September 25–28, 2023. Based on the results of 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 etoposide.
Etoposide – PSUSA/00001333/202302
Etoposide is a topoisomerase inhibitor indicated for the treatment of neoplastic diseases.
Based on the assessment of the PSUR, PRAC reviewed the benefit/risk balance of medicinal products containing etoposide and provided 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 etoposide for the approved indications remains unchanged.
- Nevertheless, the instructions for medical use should be updated by supplementing the existing information on the adverse reaction “infections” with the words “opportunistic infections”, such as pneumocystis pneumonia. In addition, the existing warning on hypersensitivity reactions should be amended to include an increased risk of hypersensitivity reactions when an in-line filter built into the infusion system is used. Thus, the existing provisions of the instructions for medical use must be amended1.
- In the next PSUR, all registration certificate holders must provide an overview of the interaction of etoposide (etoposide) with CYP3A4 inducers and inhibitors, and also discuss the need to update the instructions for medical use.
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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 etoposide and authorized for medical use in Ukraine (according to the State Register of Medicinal Products as of 07.12.2023)
To analyze the published information, the applicant must use the original text available at the link:
