General

Genetic Implications: Genetic Implications

Pronunciation:
da-kla-tass-veer


Trade Name(s)

  • Daklinza

Ther. Class.
antivirals

Pharm. Class.
NS5A inhibitors

Indications

Genetic implicationTreatment of chronic hepatitis C virus (HCV) genotype 1 or 3 infection in combination with sofosbuvir.

Action

Genetic implicationActs as a direct acting antiviral. Inhibits NS5A, a HCV-encoded protein, resulting in inhibited viral RNA replication and virion assembly.

Therapeutic Effect(s):

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)

ROUTEONSETPEAKDURATION
POunknown2 hr24 hr

Contraindication/Precautions

Contraindicated in:

  • Concurrent use of strong CYP3A inducers.

Use Cautiously in:

  • Cirrhosis (sustained virologic response is ↓);
  • Concurrent use with dabigatran;
  • Receiving immunosuppressant or chemotherapy medications (↑ risk 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

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

Drug-Natural Products:

Concurrent use of St. John's wort ↓ levels 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

Assessment

  • Monitor for signs and symptoms of chronic hepatitis C.
  • Monitor for clinical and laboratory signs of hepatitis flare or HBV reactivation during therapy and post-treatment follow-up in patients with serologic evidence of HBV infection. Initiate therapy for HBV infection as indicated.

Lab Test Considerations:

Test all patients for current or prior hepatitis B virus (HBV) infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before starting therapy. Monitor for HBV reactivation during and following therapy.

  • Genetic implicationObtain NS5A resistance testing in patients with HCV genotype 1a and cirrhosis prior to starting therapy.

Potential Diagnoses

Implementation

  • Must be administered in conjunction with sofosbuvir. If sofosbuvir is permanently discontinued, daclatasvir must also be discontinued.
  • PO: Administer once daily without regard to food for 12 wk.

Patient/Family Teaching

  • Instruct patient to take daclatasvir with sofosbuvir as directed. Take missed dose as soon as remembered in same day. If not until next day, skip dose and take next dose as scheduled; do not double doses. Advise patient to read Patient Information for each medication before starting therapy and with each Rx refill in case of changes.
  • Advise patient receiving beta-blockers or having underlying significant cardiovascular/hepatic disease to notify health care professional if signs and symptoms of bradycardia (near-fainting or fainting, dizziness, malaise, weakness, excessive tiredness, shortness of breath, chest pain, confusion, memory problems) occur.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's wort.
  • Advise female patient to notify health care professional if pregnancy is planned or suspected or if breast feeding.

Evaluation/Desired Outcomes

Decreased presence of HCV with decreased sequelae of HCV infection.

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Citation

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TY - ELEC T1 - daclatasvir ID - 110355 A1 - Quiring,Courtney, AU - Sanoski,Cynthia A, AU - Vallerand,April Hazard, BT - Davis's Drug Guide UR - https://emergency.unboundmedicine.com/emergency/view/Davis-Drug-Guide/110355/all/daclatasvir PB - F.A. Davis Company ET - 16 DB - Emergency Central DP - Unbound Medicine ER -