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 the analysis of Periodic Safety Update Reports (PSURs) for medicinal products containing aciclovir, PSUSA/00000048/202406, the Pharmacovigilance Risk Assessment Committee (PRAC) reached the following conclusions.
In view of the available data on dosing regimens for obese patients obtained from the scientific literature and spontaneous reports, the PRAC concluded that at present it is not possible to provide an unambiguous recommendation on a particular dosing regimen. At the same time, the information on dosing in obese patients needs to be updated. In particular, it must be stated that dosing based on actual body weight may lead to increased plasma concentrations of the medicinal product compared with non-obese patients, and therefore a dose reduction should be considered.
PRAC concluded that the instructions for medical use of all medicinal products containing aciclovir [for intravenous use] should be amended accordingly.
Having considered the PRAC recommendations, the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) agrees with the overall conclusions of the PRAC and the grounds for the recommendations.
Based on the scientific conclusions regarding aciclovir [for intravenous use], the CMDh considers that the benefit/risk balance of medicinal products containing aciclovir [for intravenous use] remains unchanged, provided that the proposed amendments are made to the instructions for medical use.
Changes to be made to the relevant sections of the instructions for medical use (new text underlined and in bold, deleted text – strikethrough).
- Section "Posology and method of administration"
The dosing regimen for patients with obesity should be added or updated accordingly.
The reference to the section “Pharmacological properties”, subsection “Pharmacokinetics” applies only to those registration certificate holders (RCHs) whose instructions for medical use contain pharmacokinetic data on obesity in this subsection.
For patients with obesity, the dose should be calculated from the recommended adult dose using ideal body weight rather than actual body weight.
In obese patients receiving intravenous acyclovir dosed on actual body weight, plasma concentrations of the medicinal product may be increased (see the section “Pharmacological Properties”). Therefore, dose reduction should be considered for obese patients, especially for patients with impaired renal function or elderly patients.
- “Special precautions for use” section
The dosing recommendations for patients with obesity should be removed from the section "Special warnings and precautions for use"
Changes to the safety information for medicinal products containing aciclovir [for intravenous use] following the meeting of the Pharmacovigilance Risk Assessment Committee (PRAC) of 13-16 January 2025
The European Medicines Agency (EMA) has published the minutes of the Pharmacovigilance Risk Assessment Committee (PRAC) meeting of 13-16 January 2025. Following the meeting, a decision was made on the need to introduce safety-related changes to the registration materials/package inserts of medicinal products containing aciclovir [for intravenous use].
Aciclovir (aciclovir) – PSUSA/00000048/202406
Aciclovir is a direct-acting antiviral agent indicated for the treatment of herpesvirus infection in humans, including herpes simplex virus types 1 and 2, varicella zoster virus, Epstein-Barr virus and cytomegalovirus.
Based on the assessment of Periodic Safety Update Reports (PSURs), the PRAC reviewed the benefit/risk balance of medicinal products containing aciclovir and made the following recommendations.
Summary of recommendations and conclusions
- Based on the analysis of safety and efficacy data, the benefit/risk balance of medicinal products containing aciclovir [except those intended for intravenous use] for the approved indications remains unchanged.
- Based on the analysis of safety and efficacy data, the benefit/risk balance of medicinal products containing aciclovir [for intravenous use] for the approved indications remains unchanged, provided that changes are made regarding dosing for obese patients and that this warning is removed (where necessary) from the relevant section of the instructions for medical use. Accordingly, the existing provisions of the instructions for medical use must be amended1.
- In the next PSUR, registration certificate holders of medicinal products containing aciclovir [for ophthalmic use] must provide a review of the “risk of developing resistance to aciclovir in herpetic keratitis” based on literature data in both immunocompromised and immunocompetent populations and discuss the need to update the instructions for medical use and/or risk minimization measures. In addition, all registration certificate holders must provide a cumulative review of severe cutaneous adverse reactions (SCARs), paying particular attention to the most serious types of SCARs [acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)], including information from all sources and an assessment of the causal relationship of all identified cases, preferably using the WHO-UMC causality assessment criteria.
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1 Update of the sections “Method of administration and doses” and “Special precautions for use” of the instructions for medical use. The risk assessment report and the PRAC recommendation are forwarded to the CMDh for a decision.
List of medicinal products containing aciclovir [for intravenous use] that are authorized for medical use in Ukraine (according to the State Register of Medicinal Products as of 02.04.2025).
TO ANALYZE THE PUBLISHED INFORMATION AND SUBMIT THE CORRESPONDING APPLICATION FOR AMENDMENTS TO THE REGISTRATION MATERIALS, THE APPLICANT MUST USE THE ORIGINAL TEXT POSTED AT THE LINKS:
