Drugs associated with generalized non-allergic pruritus: A World Health Organization pharmacovigilance database analysis
Description
Chronic pruritus without skin lesions may be related to medication use and can seriously affect quality of life. In this study, we analyzed 268,799 reports from VigiBase, the global pharmacovigilance database, to identify the drugs most frequently associated with generalized pruritus without skin lesions, excluding allergic, dermatological, and renal causes. The main classes of drugs involved were systemic antibiotics, vaccines, immunosuppressants, iodinated contrast agents, anticancer drugs, analgesics, and antivirals. Positive relapse cases also highlighted statins, anti-tuberculosis drugs, antacids, and certain anti-inflammatory agents. The study confirmed known associations and highlighted lesser-known triggers. These findings help clinicians evaluate and manage drug-induced pruritus.
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DataSource: Data were collected from VigiBase, which contained over 37 million individual case safety reports (ICSRs) from over 150 countries at the time of the analysis. Each ICSR contains a timestamp of upload time and geographical origin of the report, information regarding patient demographic data (sex, age group), the seriousness of the case, and the type of adverse drug reaction (ADR) observed and its outcome. The data set is subject to variable completeness levels, with possible missing data. ADRs are described by the standardized terminology defined in the Medical Dictionary for Regulatory Activities (MedDRA®). MedDRA® provides a multiaxial hierarchical classification articulated in five levels of terms, from the most specific level called “Lowest Level Terms” (LLTs) to the highest level which groups them into “System Organ Classes”. Active substances of drugs are classified according to the Anatomical Therapeutic Chemical (ATC) classification system, in which drugs are grouped based on anatomical groups (ATC), therapeutic classes (ATC2), pharmacological subclasses (ATC3 and ATC4) and active substances (ATC5). Data Extraction and inclusion Criteria: ICSR data from database inception (1968) to March 30th, 2024 were extracted as .txt files by the Bordeaux Regional Pharmacovigilance Centre. ICSRs were selected for extraction if they presented one or more terms that could indicate a condition related to generalized (not localized) pruritus. The defined inclusion terms, formalized in MedDRA LLTs, are listed in Mendeley supplementary Table 1. Exclusion Criteria: To focus on cases of non-allergic DIP without skin lesions, a codified list (based on MedDRA) of exclusion terms was established by expert consensus (available in Mendeley supplementary Table 2). The exclusion terms mainly included terms related to allergic, dermatological or renal failure conditions. In addition, we only retained ICSRs fulfilling our exposure definition, i.e., involving a single drug notified as a “suspect”, and administered by a systemic route (detailed in Mendeley supplementary Table 3). Cases involving several suspected drugs or a drug administered by a local route were therefore excluded. ICSRs presenting irrelevant seriousness criteria ("death", "life-threatening", "congenital anomaly/birth defect") or involving an unclassified drug in the ATC classification at the time of analyses, were also excluded. A descriptive analysis of patient and case-related characteristics was conducted on ICSRs, including patient demographics (gender and age), ADR information (seriousness criteria), location (region), type of report and reporter status. A frequency-based assessment of drug classes was carried out in two analyses, one on all extracted cases, and the other on cases with a “positive rechallenge”. Analyses were performed using two different software tools (with Power BI and R studio).
Institutions
- Universite de Bretagne OccidentaleBretagne, Brest