Risk for gastrointestinal adverse events in the form of nausea, vomiting, abdominal pain, constipation and diarrhoea motivates vigilance against insufficient intake of food, especially of carbohydrate.

Common adverse reactions of elbasvir and grazoprevir that can be confused with an acute porphyric attack are nausea, vomiting, abdominal pain, constipation and diarrhoea. These side effects may potentially be porphyrinogenic if leading to a decrease in carbohydrate intake.

This combination product contains two substances: elbasvir and grazoprevir. Neither elbasvir nor grazoprevir has potential for mechanism–based inhibition or induction of CYP450 enzymes, and both of them are probably not porphyrinogenic.

Grazoprevir is a reversibly binding macrocyclic inhibitor of hepatitis C virus (HCV) non-structural protein (NS) 3/4A and elbasvir is a small molecule inhibitor of HCV NS5A.

Elbasvir and gazoprevir is to be used in combination for the treatment of chronic HCV infection. The combination is administered orally. Elbasvir has a half-life of about 24 hour and grazoprevir has a half-life of about 31 hours (SPC).

Elbasvir is metabolized primarily by CYP 3A. In human liver microsomes, elbasvir did not inhibit any major CYP isoform (CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4). Elbasvir was also not a time-dependent inhibitor of CYP3A. In vitro, elbasvir was a weak inhibitor of UGT1A1. In incubations with human hepatocytes, elbasvir did not cause induction of CYP3A4, CYP1A2 or CYP2B6. Clinical interaction studies confirmed that elbasvir is a CYP3A/P-gp substrate and also that it is a mild inhibitor of P-gp and BCRP (EMA Assessment report, scientific discussion). Grazoprevir is also metabolized primarily by CYP 3A, and it is a substrate of OATP1B1, OATP1B3, and P-glycoprotein (P-gp). In vitro studies of grazoprevir showed some potential to inhibit intestinal CYP 3A4 and BCRP, but no evidence of time-dependent inhibition of either CYP3A or CYP2C8, and no potential to induce CYP3A4, CYP1A2, or CYP2B6. Clinical interaction studies showed that grazoprevir is a CYP3A/P-gp and OATP1B1/3 substrate and weak inhibitor of CYP3A and BCRP (EMA Assessment report, scientific discussion).