Periodic Benefit–Risk Evaluation Report: A Review of Changes

A periodic benefit–risk evaluation report (PBRER) is a retrospective evaluation document enabling marketing authorisation holders to present the results of a critical analysis of the benefit–risk ratio of a medicinal product. PBRER submission and content requirements changed with the adoption of the second edition of the Guideline on Good Pharmacovigilance Practice of the Eurasian Economic Union (EAEU GVP Guideline) in 2022.The aim of the study was to analyse the changes to the EAEU GVP Guideline requirements for the submission procedure and the content of PBRERs.The authors analysed the main changes concerning the procedure for submitting PBRERs on multi-source and well-established medicinal products, herbal and homoeopathic medicines. The authors evaluated the updated requirements for the content of PBRER sections. The analysis identified no significant changes in the aim and concept of PBRERs.The results of the analysis described in this article will help marketing authorisation holders improve the quality of PBRERs and ensure compliance with the new requirements of the EAEU GVP Guideline

Analysis of the Causes for Renal Dysfunction during Antibiotic Therapy in a Patient with Lyme Disease

Adverse drug reactions (ADRs) are recorded throughout the lifecycle of a medicinal product. In the post-marketing period, new ADRs are primarily identified via drug safety signals. In order to assess a signal and establish causality between an adverse drug reaction and a suspected medicinal product, it is necessary to evaluate the signal strength and quality.The aim of the study was to analyse the information submitted to Russian regulatory authorities by a patient and check it for a potential causal association of acute tubulointerstitial nephritis (ATIN) with the use of ceftriaxone and with the patient’s principal diagnosis, Lyme disease.Materials and methods: the authors analysed the patient’s submission received by the Ministry of Health of the Russian Federation in 2022 with a complaint that the treatment of Lyme disease with ceftriaxone had caused ATIN. The probability of a causal relationship between the medicinal product and the ADR was evaluated using the Naranjo algorithm.Results: according to the review of literature and the spontaneous reports collected in Pharmacovigilance 2.0, the database in the Automated Information System of the Russian Federal Service for Surveillance in Healthcare, both ceftriaxone and the underlying condition (Lyme disease) may cause renal abnormalities. Ceftriaxone is potentially nephrotoxic; it mainly affects the tubular system of the kidneys. Borreliosis may cause kidney damage as well; such damage manifests clinically as rapidly progressing and fatal damage to the glomeruli.Conclusions: the probability of a causal relationship between the development of ATIN in the complainant and the use of ceftriaxone was categorised as “possible”. However, the information available did not allow for establishing a definite relationship between kidney damage and the use of the medicinal product. Further monitoring of similar cases is necessary to minimise the risks of developing this pathology during treatment with ceftriaxone

Fluoroquinolone antibiotics: safety of use by the example of ciprofloxacin

Due  to repeated reports of adverse effects with the  use  of fluoroquinolone antibiotics,  these drugs become  over  and  over  again the  object of the  close  attention of pharmacovigilance  specialists and  health care  specialists. The aim: to study the  frequency and  the  nature of adverse reactions associated with the  use  of ciprofloxacin, based  on the  analysis of the  spontaneous reports received by  the  Russian pharmacovigilance service. Materials and  Methods: A retrospective analysis of the  spontaneous reports of ciprofloxacin was conducted on the  data-base «Pharmacovigilance» of the  automated information system of Roszdravnadzor from 2008 to 2018. Results: 3403  adverse reactions that occurred in 2083  patients using ciprofloxacin were recorded. The  most frequently developed reactions were  from skin and  subcutaneous tissues (37.3 %), general disorders and  disorders at the  injection site (21.1 %), gastrointestinal tract reactions (14.9 %). More than a one third of the  reports contained information about serious adverse reactions. Unexpected reactions were identified as not  recorded in the  instructions for the medical use of ciprofloxacin: bradycardia, atrial arrhythmia, cyanosis, increased blood pressure. Conclusions: fluoroquinolone antibiotics with proven efficacy and years of experience in clinical use, continue to be drugs whose  safety requires constant monitoring. The  results of the  study confirmed the  possibility of detecting a wide  range of the  adverse reactions using the  method of spontaneous reports. Regulatory authorities of the  Russian Federation should recommend to registration certificate holders to include the  information of adverse reactions of ciprofloxacin that were registered in the  post-marketing period in the  instructions for medical use

Problems of interchangeability of systemic interferons for treatment of multiple sclerosis

Problems of interchangeability of systemic interferons for treatment of multiple sclerosis are described. An analysis of 1,643 spontaneous reports existing in the Russian database for the period 2009 to 2015 was made in order to identify information on adverse reactions that occurred after replacement of systemically used interferons. Since 2010-2011 there have been reports on adverse reactions and lack of efficacy caused by the replacement of one systemic interferon for treatment of multiple sclerosis with another one with the same INN. Most of the reports indicated a «possible» degree of reliability of the cause-effect relationship. Most of the spontaneous reports of adverse reactions when replacing interferons beta-1a and beta-1b contained information about adult patients. More than half of the spontaneous reports of adverse reactions contained information on clinically signifiant events. When interferons beta-1a and beta-1b were replaced, there were mainly general disorders, reactions at the injection site, musculoskeletal disorders and neurologic disorders observed. The reference medication was well tolerated but replacing for a bioanalogous drug resulted in ineffectiveness or development of adverse reactions. The results of the study demonstrated that the data of spontaneous reports are important for making decision on the interchangeability of systemic interferons for the treatment of multiple sclerosis

ON THE ISSUE OF SAFETY OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS

Non-steroidal anti-inflammatory drugs (NSAIDs) are liders in selling both in the Russian Federation and worldwide. The combination of  analgesic, anti-inflammatory and antipyretic effects make the drugs  of this group very popular in patients with various diseases. The  realization of NSAIDs in pharmacies occurs both by prescription and  over-the-counter, so the safety assessment of the use of this group  of drugs remains relevant. In the current practice, self-administration (responsible selfmedication) of drugs of the NSAID  group is an additional factor affecting the safety of their intake. According to the studies, about 40 % of patients taking  NSAIDs consider that NSAIDS are absolutely safe, and more than 30  % of those taking OTC NSAIDs use them in excess of the  recommended dosages. We analyzed 3963 individual case safety  reports (ICSR) in the federal database «Pharmacovigilance» from  07.12.2008 to 31.08.2017. The inclusion criterions was the presence of information on the off-label application of NSAIDs in the ICSR,  reports of adverse effects that may be associated with the use of this drug or erroneous reports on the active substance, which was  not present in this drug. The most frequent mistakes in the  application were an increase of the daily dose, a change in the  method of administration to patient who are contraindicated with this drug. There were 9 ICSR of burning sensation in the anus with the  introduction of ibuprofen suppositories (not in the label), and 7 ICSR  of ineffectiveness of the active substance, which was not present in this drug

Analysis of spontaneous reports of adverse reactions, developed in the use of drugs during pregnancy

The article presents data obtained in a retrospective analysis of spontaneous messages (SM) on drug adverse reactions during pregnancy, recieved in the Russian base «Pharmacovigilance» AIS Roszdravnadzor, for the period 1 January 2015 to 31 December 2015 included