[Risk assessment of drugs during breastfeeding]. / Évaluation des risques liés aux médicaments pendant l'allaitement.

Medication intake during the postpartum period is common with discontinuation of breastfeeding sometimes unnecessarily recommended for fear of adverse effects in the breastfed infant, while exposure through human milk is generally low. The assessment of risks associated with medication intake during breastfeeding is based, among other things, on the little clinical evidence available in specialized sources of information, and on pharmacokinetic principles. A decision-making support is presented to facilitate communication with mothers, foster medication adherence and prevent unnecessary interruption of breastfeeding.

La prise de médicaments pendant la période postnatale est courante et associée à un arrêt de l'allaitement parfois recommandé à tort par crainte d'effets indésirables chez l'enfant allaité, alors que l'exposition à travers le lait maternel est généralement faible. L'évaluation des risques d'utilisation de médicaments pendant l'allaitement repose, entre autres, sur le peu de preuves cliniques disponibles, documentées dans des sources d'information spécialisées, et sur les principes pharmacocinétiques. Un algorithme d'aide à la décision est proposé pour faciliter la communication avec les mères, renforcer l'adhésion thérapeutique et éviter une interruption inutile de l'allaitement.

Maternal drugs and breastfeeding: Risk assessment from pharmacokinetics to safety evidence - A contribution from the ConcePTION project.

Human milk is the most appropriate form of nutrition for infants while taking medication during the postpartum period is common. Discontinuation of breastfeeding is sometimes wrongly recommended for fear of adverse effects in the breastfed infant whereas only a few drugs are strictly contraindicated while breastfeeding. Most drugs are transferred from the mother's blood to the milk, but the breastfed infant usually ingests a small drug amount through human milk. As population-based evidence is still scarce on safety of drugs during breastfeeding, risk assessment relies on the little clinical evidence available and on pharmacokinetic principles, as well as on specialized sources of information that are essential for clinical decision-making. Risk assessment should not only be based on the drug's potential risk for the breastfed infant but should always take into account the benefits associated to breastfeeding, the risks of untreated maternal disease and the maternal willingness to breastfeed. Identifying situations with potential for drug accumulation in the breastfed infant is decisive while assessing the risk. Health care providers should always assume that mothers will be concerned and use risk communication as a key to ensure medication adherence and prevent unnecessary interruption of breastfeeding. When a mother still expresses concerns, decision support algorithms may facilitate communication and some strategies can be offered to minimize the drug exposure in the breastfed infant even when clinically not justified.

Population pharmacokinetic modelling to quantify the magnitude of drug-drug interactions between amlodipine and antiretroviral drugs.

PURPOSE: Drug-drug interactions (DDIs) with antiretroviral drugs (ARVs) represent an important issue in elderly people living with HIV (PLWH). Amlodipine is a commonly prescribed antihypertensive drug metabolized by CYP3A4, thus predisposed to a risk of DDIs. Guidance on the management of DDIs is mostly based on theoretical considerations derived from coadministration with other CYP3A4 inhibitors. This study aimed at characterizing the magnitude of DDIs between amlodipine and ARV drugs in order to establish dosing recommendations. METHODS: A population pharmacokinetic analysis was developed using non-linear mixed effect modelling (NONMEM) and included 163 amlodipine concentrations from 55 PLWH. Various structural and error models were compared to characterize optimally the concentration-time profile of amlodipine. Demographic and clinical characteristics as well as comedications were tested as potential influential covariates. Model-based simulations were performed to compare amlodipine exposure (i.e. area under the curve, AUC) between coadministered ARV drugs. RESULTS: Amlodipine concentration-time profile was best described using a one-compartment model with first-order absorption and a lag-time. Amlodipine apparent clearance was influenced by both CYP3A4 inhibitors and efavirenz (CYP3A4 inducer). Model-based simulations revealed that amlodipine AUC increased by 96% when coadministered with CYP3A4 inhibitors, while efavirenz decreased drug exposure by 59%. CONCLUSION: Coadministered ARV drugs significantly impact amlodipine disposition in PLWH. Clinicians should adjust amlodipine dosage accordingly, by halving the dosage in PLWH receiving ARV with inhibitory properties (mainly ritonavir-boosted darunavir), whereas they should double amlodipine doses when coadministering it with efavirenz, under appropriate monitoring of clinical response and tolerance.