DAKLINZA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DAKLINZA (DAKLINZA).
Daclatasvir is a direct-acting antiviral that inhibits the hepatitis C virus (HCV) NS5A protein, which is essential for viral RNA replication and virion assembly.
| Metabolism | Primarily metabolized by CYP3A4; also a substrate of P-glycoprotein (P-gp). |
| Excretion | Primarily hepatobiliary excretion: ~90% eliminated in feces (unchanged and as metabolites); renal excretion is minimal (<1% unchanged in urine). |
| Half-life | Terminal half-life is approximately 12-15 hours in healthy subjects; clinically, supports once-daily dosing. |
| Protein binding | Approximately 99% bound primarily to human serum albumin. |
| Volume of Distribution | Apparent volume of distribution (Vd/F) is approximately 105 L (1.4 L/kg for a 70 kg individual), indicating extensive tissue distribution. |
| Bioavailability | Absolute bioavailability is not determined; however, relative bioavailability from oral administration is sufficient for once-daily dosing (no significant food effect). |
| Onset of Action | Oral: Peak plasma concentrations reached in 2-3 hours; antiviral effect (HCV RNA decline) observed within 24 hours. |
| Duration of Action | Duration of antiviral effect correlates with drug exposure; trough levels maintained at therapeutic concentrations throughout the 24-hour dosing interval with once-daily dosing. |
60 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for any degree of renal impairment including dialysis. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 30 mg once daily; Child-Pugh C: not recommended. |
| Pediatric use | Not approved for pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; use with caution due to potential comorbidities and polypharmacy. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DAKLINZA (DAKLINZA).
| Breastfeeding | No data on presence in human milk; M/P ratio unknown. Consider developmental benefits of breastfeeding vs. mother's clinical need; use caution. |
| Teratogenic Risk | No adequate human studies; animal studies show no evidence of fetal harm. Risk cannot be excluded in first trimester; avoid use in pregnancy unless benefit outweighs potential risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
Concomitant use with strong inducers of CYP3A4 (e.g., rifampin, St. John's wort, carbamazepine) due to reduced daclatasvir exposure; hypersensitivity to daclatasvir.
| Precautions | Risk of hepatitis B virus (HBV) reactivation in patients co-infected with HCV and HBV; bradycardia with concomitant use of amiodarone; hepatotoxicity; pregnancy testing recommended for women of childbearing potential. |
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| Monitor hepatic function (ALT, AST, bilirubin) and HCV RNA levels during therapy; no specific fetal monitoring required. |
| Fertility Effects | No human data on fertility; animal studies show no impairment at clinically relevant doses. |