daclatasvir (da-kla-tass-veer) Daklinza

 Indications

Treatment of chronic hepatitis C virus (HCV) genotype

1 or 3 infection in combination with sofosbuvir.

Action

Acts as a direct acting antiviral. Inhibits NS5A, a HCVencoded

protein, resulting in inhibited viral RNA replication

and virion assembly. Therapeutic Effects:

Decreased presence of HCV with decreased sequelae of

HCV infection.

Pharmacokinetics

Absorption: Well absorbed (67%) following oral

administration.

Distribution: Unknown.

Protein Binding: 99%.

Metabolism and Excretion: Metabolized mostly

by the CYP3A enzyme system. 88% excreted in feces

(53% as unchanged drug); 6.6% excreted unchanged

in urine.

Half-life: 12–15 hr.

TIME/ACTION PROFILE (blood levels)

ROUTE ONSET PEAK DURATION

PO unknown 2 hr 24 hr

Contraindications/Precautions

Contraindicated in: Concurrent use of strong

CYP3A inducers.

Use Cautiously in: Cirrhosis (sustained virologic

response isp); Concurrent use with dabigatran; Receiving

immunosuppressant or chemotherapy medications

(qrisk of hepatitis B virus reactivation); OB: Consider

benefits and risks carefully; Lactation: Beneficial effects

of breast feeding should be weighed against potential

adverse drug effects; Pedi: Safety and effectiveness not

established.

Exercise Extreme Caution in: Concurrent use of

amiodarone (with sofosbuvir).

Adverse Reactions/Side Effects

CNS: fatigue, headache. GI: diarrhea, nausea. Misc:

HEPATITIS B VIRUS REACTIVATION.

Interactions

Drug-Drug: Strong CYP3A inducers including

carbamazepine, phenytoin and rifampin mayplevels

and effectiveness; concurrent use contraindicated.

Moderate CYP3A inducers including bosentan,

dexamethasone, efavirenz, modafinil, nafcillin

and rifapentine mayplevels and effectiveness (qdose

required). Concurrent use with amiodarone and sofosbuvirqrisk

of serious bradycardia and should be

avoided, especially if beta blockers are being used/

concurrent cardiovascular/liver disease is present.

Strong CYP3A inhibitors, including atazanavir/ritonavir,

clarithromycin, indinavir, itraconazole,

ketoconazole, nefazodone, nelfinavir, posaconazole,

saquinavir, and voriconazoleqblood levels

and risk of adverse effects (pdose required). Concurrent

use of moderate CYP3A inhibitors, including

atazanavir, ciprofloxacin, darunavir/ritonavir,

diltiazem, erythromycin, fluconazole, fosamprenavir

and verapamilqblood levels and mayqrisk of

adverse reactions (clinical monitoring recommended).

qlevels and risk of toxicity with digoxin (pinitial dose

of digoxin/pdose of chronic digoxin may be necessary,

careful clinical monitoring recommended).qlevels

and risk of adverse effects including myopathy with

HMG-CoA reductase inhibitors (monitor effects and

pdose if necessary).

Drug-Natural Products: Concurrent use of St.

John’s wortplevels and effectiveness; concurrent use

contraindicated. 

Route/Dosage

PO (Adults): Genotype 1 (without cirrhosis or with

compensated cirrhosis [Child-Pugh A])—60 mg

once daily with sofosbuvir for 12 wk; Genotype 1 (with

decompensated cirrhosis [Child-Pugh B or C] or

post-liver transplant)—60 mg once daily with sofosbuvir

and ribavirin for 12 wk; Genotype 3 (without

cirrhosis)—60 mg once daily with sofosbuvir for 12

wk; Genotype 3 (with compensated cirrhosis [Child-

Pugh A], decompensated cirrhosis [Child-Pugh B or

C], or post-liver transplant)—60 mg once daily with

sofosbuvir and ribavirin for 12 wk; Concurrent use of

strong CYP3A inhibitors—30 mg once daily; Concurrent

use of moderate CYP3A inducers or nevirapine—

90 mg once daily.

Availability

Tablets: 30 mg, 60 mg, 90 mg.