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Pronunciation

led-i-PAS-vir/soe-FOS-bue-vir

Classifications

Therapeutic Classification: antivirals

Pharmacologic Classification: NS5A inhibitors, polymerase inhibitors

Indications

REMS


Action

  • Ledipasvir: inhibits NS5A, a protein required for viral replication.
  • Sofosbuvir: inhibits RNA-dependent RNA polymerase, resulting in inhibition of viral replication.
Therapeutic effects:
  • Decreased HCV RNA levels with decreased severity and sequelae of chronic HCV.

Pharmacokinetics

Ledipasvir

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Protein Binding: >99.8%.

Metabolism/Excretion: Minimal metabolism, undergoes biliary excretion. Mostly excreted unchanged in feces (86%), 1% eliminated in urine.

Half-Life: 47 hr.

Sofosbuvir

Absorption: Rapidly metabolized following absorption (extensive first-pass effect).

Distribution: Unknown.

Protein Binding: 61–65%.

Metabolism/Excretion: Extensively metabolized with much conversion to GS-461203, an active antiviral moiety, then converted GS-331007, which does not have antiviral activity. 80% excreted in urine mostly as GS-331007 (3.5% as unchanged drug), 14% excreted in feces, 2.5% excreted in expired air.

Half-Life: Sofosbuvir: 0.4 hr; GS-331007: 27 hr.

Time/Action Profile

(blood levels)

ROUTEONSETPEAKDURATION
ledipasvirunknown4–5 hr24 hr
sofosbuvirunknown0.8–1 hr24 hr



Sofosbuvir (2–4 hr for GS-331007).



Contraind./Precautions

Contraindicated in:

Use Cautiously in:

Adv. Reactions/Side Effects

GI: diarrhea, hepatitis B virus reactivation, nausea

Neuro: fatigue, headache, insomnia

Interactions

Drug-drug:

Drug-Natural Products:

Route/Dosage

Availability

Assessment

Lab Test Considerations:

Implementation

Patient/Family Teaching

Evaluation/Desired Outcomes

US Brand Names

Harvoni