Some common drugs that are strong CYP3A inducers include dexamethasone, phenytoin, carbamazepine, rifampin and St. John's Wort. Daclatasvir is a CYP3A and p-glycoprotein substrate, therefore, drugs that are strong inducers or inhibitors of these enzyme will interfere with daclatasvir levels in the body. Dose modifications are made with concomitant use of daclatasvir and drugs that affect CYP3A or p-gp. When taking daclatasvir with non-nucleoside reverse transcriptase inhibitors, the dose of daclatasvir is increased to overcome CYP3A induction. The dose for daclatasvir should be lowered when taking with antifungals, such as ketoconazole. Currently, there are no required dosage adjustments with concurrent use of daclatasvir and immunosuppressants, narcotic analgesics, antidepressants, sedatives, and cardiovascular agents. Concurrent use with amiodarone, sofosbuvir and daclatasvir has may result in an increased risk for serious slowing of the heart rate. Pharmacology The role of NS5A in HCV replication NS5A is a zinc-binding protein dimer serving as a regulator in the replication cycle of HCV. It contains an amino-terminal amphipathic helix and three different domains with different binding affinities. The N-terminus binds to cellular membranes and is essential for the formation of replication complexes. Domain 1 (amino acid 401–60012) is an RNA binding region of NS5A and domain 2 serves in the RNA replication. Virus assembly is associated with domain 3. NS5A not only binds to cellular membranes, other non-structural proteins of the HCV replication-complex and viral RNA, but also to co-factors like PI4KA. PI4KA is a kinase, which phosphorylates a hydroxyl group of phosphatidylinositol in its inositol-ring at position four. This phosphorylation generates phosphatidylinositol 4-phosphate (PI4P), a docking site normally located at the Golgi membrane. PI4P is necessary for the recruitment of effector proteins participating in transport vesicles of lipid transfer. Resulting from that PI4P is crucial for maintaining the Golgi membrane structure and Golgi-secretion. By binding PI4KA on its domain 1 and accumulating PI4P away from the Golgi apparatus, NS5A induces the formation of a membranous web, a membrane structure arising from the endoplasmic reticulum via recruitment of lipid vesicles. The replication complex of HCV is located on this web-like structure. Out of these membranes and lipid drops, which had been recruited via PI4P, the virions can be assembled after viral-RNA replication. The RNA replication and assembly of virions depend on the ratio between two different forms of NS5A. Depending on the phosphorylation rate of NS5A, it is differentiated between NS5A (p56) and the hyperphosphorylated NS5A