Ledipasvir/sofosbuvir

Ledipasvir/sofosbuvir, sold under the trade name Harvoni among others, is a medication used to treat hepatitis C.[8] It is a fixed-dose combination of ledipasvir and sofosbuvir.

[10] Common side effects include muscle pains, headache, nausea, rash, and cough.

[6] NS5A polymorphisms also have an effect on viral resistance with the most common resistance-associated amino acid substitutions detected at Q30R, Y93H or N, and L31M in patients with a rapid virological response (RVR).

[18][6] A single amino acid substitution S282T contributes to viral resistance and decreases the activity of sofosbuvir in ledipasvir/sofosbuvir by approximately 2 to 18 fold.

[22] Ledipasvir/sofosbuvir is a substrate for the drug transporters P-Glycoprotein (P-gp) and breast cancer resistance protein (BCRP).

[18] Intestinal absorption of these drug transporter substrates may be decreased by inducers such as rifampin and St. John's wort .

[23] Patients are also advised to stay away from H2 receptor antagonists (H2RA) and proton-pump inhibitors (PPI) because they decrease the concentration of ledipasvir (its solubility is pH-dependent and is higher under acidic conditions).

[28][18] It is then predominantly converted to the inactive phosphate free circulating metabolite GS-331007 (eliminated 76% through renal passive filtration) which has a median peak plasma concentration at 3.5 to 4 hours after the medication is ingested.

[6][30] Note: The maximum concentration is 32% higher in healthy individuals than those infected with Hepatitis C.[6] Note: The maximum concentration is 24% higher in healthy individuals than those infected with Hepatitis C.[6] An analytical method based on LC tandem MS has been developed for the simultaneous extraction and determination of ledipasvir/sofosbuvir in human plasma using antiviral daclatasvir as an internal standard.