Pharmacokinetic Consideration of Venetoclax in Acute Myeloid Leukemia Patients: A Potential Candidate for TDM? A Short Communication.

BACKGROUND: Venetoclax (VNX)-based regimens have demonstrated significantly favorable outcomes in patients with acute myeloid leukemia (AML) and are now becoming the standard treatment. Tyrosine kinase inhibitors are administered at a fixed dose, irrespective of body surface area or weight. For such orally targeted therapies, real-world data have highlighted a larger pharmacokinetic (PK) interindividual variability (IIV) than expected. Even if VNX PKs have been well characterized and described in the literature, only 1 clinical trial-based PK study has been conducted in patients with AML. This study aimed to evaluate the PK of VNX in AML patients. MATERIAL AND METHODS: We retrospectively analyzed all patients treated with a combination of VNX-azacitidine between January and July 2022 at our center, using at least 1 available VNX blood sample. Based on a previously published population PK model, individual PK parameters were estimated to evaluate the exposure and IIV. RESULTS: and Discussion. Twenty patients received VNX in combination with azacitidine, according to the PK data. A total of 93 plasma concentrations were collected. The dose of VNX was 400 mg, except in 7 patients who received concomitant posaconazole (VNX 70 mg). The patients' weight ranged from 49 kg to 108 kg (mean = 78 kg). Mean individual clearance was 13.5 ± 9.4 L/h with mean individual daily area under the concentration-time curves of 35.8 mg.h/L with significant IIV (coefficient of variation = 41.1%). Ten patients were still alive (8 in complete response), but all experienced at least 1 hematological toxicity of grade ≥ 3. CONCLUSIONS: Based on the observed large PK variability in the data from our real-world AML patients, the risk of drug interactions and the recommended fixed-dosage regimen of VNX therapeutic drug monitoring may be useful.

COVID-19 Vaccines and Roles of the Health Regulatory Authority in Tunisia.

Given the unstoppable spread of coronavirus disease (COVID-19), the development of a vaccine was needed to contain the pandemic. In such a situation of global emergency, regulatory authorities ensured timely, safe, and equitable access to the vaccine.This article aims to outline the roles of the Tunisian regulatory authority, the Directorate of Pharmacy and Medicines (DPM) at the Ministry of Health, in registration and procurement of the COVID-19 vaccine.Requirement to grant the Exceptional Provisional Authorizations of Marketing (EPAM) for COVID-19 vaccines was 27 days versus 869 days for conventional marketing authorizations (MAs). The DPM has optimized its activity through: early dialogue with manufacturers, online submission, the use of distance communication technologies. It has demonstrated unprecedented flexibility through the continuous and rolling review approach.Regulatory authorities in Tunisia and around the world have partnered with manufacturers to speed up administrative procedures while ensuring the quality, safety, and efficacy of vaccines.