CHRONOPHARMACOVIGILANCE: TIME-DEPENDENT PATTERNS OF ADVERSE DRUG REACTIONS AND THEIR REGULATORY IMPLICATIONS

Said Salim Said; Burhani Simai; Ahmad Makame Mwadini; Sabra Salim Rashid

doi:10.22270/ujpr.v11i1.1490

Said Salim Said Zanzibar Food and Drug Agency (ZFDA), Zanzibar, Tanzania.
Burhani Simai Zanzibar Food and Drug Agency (ZFDA), Zanzibar, Tanzania.
Ahmad Makame Mwadini Zanzibar Food and Drug Agency (ZFDA), Zanzibar, Tanzania.
Sabra Salim Rashid Medicine Policy Unit, Ministry of Health, Zanzibar, Tanzania.

10.22270/ujpr.v11i1.1490

Keywords:

Adverse drug reactions, chronopharmacovigilance, circadian rhythm, drug safety, pharmacovigilance, regulatory science

Abstract

Chronopharmacology is the study of the effects of biological rhythms, especially circadian rhythms, on pharmacokinetics and pharmacodynamics of drugs and their therapeutic efficacy and safety. The rhythmic nature of physiological functions like hormone secretion, enzymatic activity, gastrointestinal function, renal clearance, cardiovascular function, and immune response plays an important role in governing the temporal profiles of absorption, distribution, metabolism, and excretion of drugs. There is increasing evidence that adverse drug reactions (ADRs) are not randomly timed but rather follow a predictable pattern with a close association with biological clocks. Therefore, the onset of medication can have a profound effect on either the occurrence or intensity of ADRs. This review focuses on the issue of time-dependent patterns of ADRs in the integrated framework of chrono-pharmacology and chronopharmacovigilance. It outlines the mechanistic explanations provided by circadian biology to time-dependent patterns of drug safety and clinical evidence of time-dependent differences in the occurrence of ADRs in a broad range of therapeutic classes. The data underscores the challenges of conventional pharmacovigilance where biological timing is not considered as a drug-related risk factor. The review also delves into the implications that time-dependent patterns of ADRs have on pharmacovigilance and regulation. The use of time-dependent variables in drug safety monitoring, trial designs, and risk management plans may enable better signal detection and improved benefit-risk assessments. The use of chronopharmacological concepts in regulatory science can, therefore, facilitate the development of personalized medicine, where the dosing regimen will be optimized for safety. It can, therefore, be concluded that the appreciation of temporal variability in ADRs is an important milestone in more accurate drug safety profiling.