Antiviral therapy for hepatitis C: Has anything changed for pregnant/lactating women?

Table 1 Main pharmacokinetic properties of the new direct-acting antivirals

Drug		Molecular weight	Effect of food on absorption	Cytochrome P450 enzymes interaction			Binding to plasma protein	Half-life
				Enzyme	Effect of the drug on the enzyme	Effect of the enzyme on the drug
Sofosbuvir		529.45 Da	Increased absorption, slower rate	NO	None	None	85%	0.5 h/26 h1
Simeprevir		749.93 Da	Increased absorption, slower rate	CYP3A4	Inhibitor	Alter AUC	> 99.9%	10-41 h
Daclatasvir		738.98 Da	Decreased absorption2	CYP3A4	Weak inducer	Alter AUC	> 99%	12-15 h
Ledipasvir		888.9 Da	No effect	CYP3A4	Weak inducer	None	> 99.8%	47 h
Viekirax	Ombitasvir	894.1	Increased absorption	CYP3A4	Inhibitor	Alter AUC	99.9%	21-25 h
	Paritaprevir	765.8 Da					98.6%	5.5 h
	Ritonavir	720.9 Da					99%	4 h
Dasabuvir		493.5 Da	Increased absorption	CYPC19	Inducer	None	99.5% (94.5%3)	6 h
				CYP2C8	None	Alter AUC
				CYP3A4	None	Alter AUC3
				CYPC19	Inducer	None

¹GS-331007 metabolite;

²Following a high-fat meal;

³Dasabuvir M1 metabolite. AUC: Area under the curve; NO: Not metabolized by P450 enzymes; CYP: Cytochrome.

Table 2 Effect of new direct-acting antivirals in pregnancy and Food and Drug Administration Pregnancy Categories

Drug		Embryotoxicity and/or teratogenicity1	Dose-escalation2	Transfer across placenta	Transfer into milk	FDA Pregnancy Category3
Sofosbuvir		No	28-fold	Yes	Yes	B
Simeprevir		Yes	4-fold	Yes	Yes	C
Daclatasvir		Yes	4-fold	Yes	Yes	NA4
Ledipasvir		No	Maternal toxic doses	Yes	Yes	B
Viekirax	Ombitasvir	Yes	4-fold	Minimal	Yes	B
	Paritaprevir		32-fold
	Ritonavir		8-fold
Dasabuvir		No	48-fold	Minimal	Yes	B

¹Based on animal studies;

²Dose escalation above therapeutic dose;

³FDA Pregnancy Category without association with ribavirin. NA: Not available; FDA: The Food and Drug Administration.