Direct-acting Antivirals for the Treatment of HCV During Pregnancy and Lactation

Abbreviations: DAC, daclatasvir; ELB, elbasvir; GLE, glecaprevir; GZR, grazoprevir; LDV, ledipasvir; PIB, pibrentasvir; SOF, sofosbuvir; VEL, velpatasvir; VOX, voxilaprevir.

Abbreviations: DAC, daclatasvir; ELB, elbasvir; GD, gestation day; GLE, glecaprevir; GZR, grazoprevir; LD, lactation day; LDV, ledipasvir; PIB, pibrentasvir; RHD, recommended human dose; SOF, sofosbuvir; VEL, velpatasvir; VOX, voxilaprevir.
^aTransfer into milk was studied in rats.
^bExposure to predominant circulating metabolite of sofosbuvir (GS-331007).
^cAt a high dose (4.6-fold RHD), an increased incidence of skeletal variations (vertebrae, sternea, ribs) in rats was observed. These effects are likely related to a decrease in maternal body weight gain and decreased food intake.
^dA possible teratogenic effect was indicated in rabbits where an increase in total visceral malformations was seen in exposed animals at AUC exposures up to 0.7-fold RHD for SOF/VEL and 0.5-fold RHD for SOF/VEL/VOX.
^eMaternal toxicity with some embryofoetal toxicity precluded the ability to evaluate glecaprevir in the rabbit at human clinical exposures.

Authors and Disclosures

Jolien J. M. Freriksen^1,2, Minou van Seyen¹, Ali Judd³, Diana M. Gibb³, Intira J. Collins³, Rick Greupink², Frans G. M. Russel², Joost P. H. Drenth⁴, Angela Colbers¹ and David M. Burger<sup>1

1</sup>Department of Pharmacy, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
²Department of Pharmacology and Toxicology, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
³MRC Clinical Trials Unit at University College London, London, UK
⁴Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
Jolien J. M. Freriksen and Minou van Seyen shared 1st author.

Correspondence
Jolien J. M. Freriksen, Department of Pharmacy, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands. Email: Jolien.Freriksen@radboudumc.nl

Author contributions
J.F. and M.S. performed the literature search, collected the data and wrote the paper; A.J., D.G. and I.C. contributed to the design of the review and wrote the paper; R.G., F.R. and J.D. provided feedback during the research and writing process; A.C. and D.B. contributed to the design of the review and provided feedback during the research and writing process. All authors approved the final version of the article.