Daclatasvir

Indications

Daclatasvir is used for: Chronic hepatitis C virus infection in adults.

Adult Dose

Hepatitis C Indicated for use with sofosbuvir for chronic hepatitis C virus (HCV) genotypes 1 and 3 infection Genotype 1 Without cirrhosis or with compensated (Child-Pugh A) cirrhosis: 60 mg (plus sofosbuvir 400 mg) PO qDay for 12 weeks Decompensated (Child-Pugh B or C) cirrhosis or posttransplant: 60 mg (plus sofosbuvir 400 mg) PO qDay plus ribavirin for 12 weeks Genotype 3 Without cirrhosis: 60 mg (plus sofosbuvir 400 mg) PO qDay for 12 weeks Compensated (Child-Pugh A) or decompensated (Child-Pugh B or C) cirrhosis, or posttransplant: 60 mg (plus sofosbuvir 400 mg) PO qDay plus ribavirin for 12 weeks Hepatic impairment (any degree): No dose adjustment required

Child Dose

Renal Dose

Renal impairment (any degree): No dose adjustment required

Administration

May be taken with or without food.

Contra Indications

Hypersensitivity. Co-administration w/ strong CYP3A4 inducers & P-gp eg phenytoin, carbamazepine, oxcarbazepine, phenobarb, rifampicin, rifabutin, rifapentine, systemic dexamethasone, St. John's wort.

Precautions

Patients w/ genotype 1 infection & compensated cirrhosis; receiving amiodarone; decompensated liver disease; prior exposure to a NS5A inhibitor; pre-, peri- or post-liver transplant or other organ transplant; HIV/HCV, HBV co-infected patients. Rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. May impair ability to drive or operate machinery. Women of childbearing potential. Pregnancy & lactation. Childn & adolescents <18 yr. Lactation Unknown if distributed in human breast milk

Pregnancy-Lactation

Pregnancy No data in pregnant women are available If daclatasvir and sofosbuvir are administered with ribavirin, the warnings and precautions for ribavirin, in particular the pregnancy avoidance warning, apply to this combination regimen (see ribavirin prescribing information) Lactation Unknown if distributed in human breast milk The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Interactions

May lead to lower exposure & loss of efficacy w/ phenytoin, carbamazepine, oxcarbazepine, phenobarb, rifampicin, rifabutin, rifapentine, systemic dexamethasone & St. John's wort. Decreased plasma levels & therapeutic effect w/ strong or moderate CYP3A4 & P-gp inducers. Increased plasma levels w/ strong CYP3A4 inhibitors. May increase systemic exposure of P-gp, OATP, 1B1, OCT1 or BCRP substrates. Boceprevir, telaprevir, atazanavir/ritonavir, efavirenz, cobicistat-containing, clarithromycin, telithromycin, erythromycin, dabigatran, etexilate, posaconazole, voriconazole, amiodarone, digoxin, Ca channel blockers, HMG-CoA reductase inhibitors.

Side Effects

Side effects of Daclatasvir : >10% Headache (14%), Fatigue (14%) 1-10% Nausea (8%), Diarrhea (5%), Elevated lipase, >3 x ULN (2%)

Mode of Action

Inhibits NS5A, a nonstructural protein encoded by HCV. Binds to the N-terminus within domain 1 of NS5A, which may cause structural distortions that interfere with NS5A functions, and thereby inhibits both viral RNA replication and virion assembly.