HARVONI

Combination product

Pronunciation: le-DIP-as-veer and soe-FOS-byoo-veer (har-VOE-nee)

What it isNS5A inhibitor plus nucleotide NS5B polymerase inhibitor; chronic hepatitis C genotypes 1, 4, 5 and 6.

Why this oneSingle daily tablet, usually ribavirin-free; 8 weeks suffices for select noncirrhotic genotype 1 patients.

What limits itNot pangenotypic, unlike newer regimens; acid suppressants cut absorption and amiodarone causes serious bradycardia.

Pearls

Approved from age 3; add ribavirin in decompensated cirrhosis.

Components (2)

Ledipasvir ballicule — decagon mechanism diagram — Ledipasvir

Sofosbuvir ballicule — decagon mechanism diagram — Sofosbuvir

FDA-approved for

chronic hepatitis C, genotypes 1, 4, 5, 6 (adults and ≥3 y) (2014)

FDA label

Read the full label on DailyMed ↗

BOXED WARNING Risk of hepatitis B virus (HBV) reactivation in patients coinfected with HCV and HBV; some cases fulminant hepatitis, hepatic failure, death. Test all patients for HBV before initiating and monitor during/after treatment.

FDA dosing	Population	Start	Target	Max
Chronic HCV genotype 1, 4, 5, or 6, without cirrhosis or with compensated cirrhosis	Adults	1 tablet (90 mg ledipasvir/400 mg sofosbuvir) QD	12 weeks (8 weeks may be considered in treatment-naive GT1 without cirrhosis, HCV RNA <6 million IU/mL)	Up to 24 weeks (treatment-experienced GT1 with compensated cirrhosis)
Chronic HCV GT1 with decompensated cirrhosis, or GT1/4 liver transplant recipients	Adults	1 tablet QD + ribavirin	12 weeks
Chronic HCV genotype 1, 4, 5, or 6, without cirrhosis or with compensated cirrhosis	Pediatric ≥3 y	≥35 kg: 90 mg/400 mg QD; 17 to <35 kg: 45 mg/200 mg QD; <17 kg: 33.75 mg/150 mg QD (oral pellets)	12 weeks	Up to 24 weeks (treatment-experienced with compensated cirrhosis)

Renal No adjustment for any degree of renal impairment, including ESRD on dialysis

Hepatic No adjustment for mild, moderate, or severe hepatic impairment (Child-Pugh A, B, or C)

Instructions

Take one tablet orally once daily with or without food
Test all patients for HBV (HBsAg and anti-HBc) before initiating
Coadministration of amiodarone is not recommended (serious symptomatic bradycardia)
Not recommended with P-gp inducers (e.g., rifampin, St. John's Wort)

Available strengths

tab 45/200, 90/400 mg
pellet 33.75/150, 45/200 mg
pellets 33.75/150, 45/200 mg/packet

Contraindications

If used in combination with ribavirin, all contraindications to ribavirin also apply to HARVONI combination therapy

Cautions

Risk of HBV reactivation in HCV/HBV coinfected patients
Serious symptomatic bradycardia when coadministered with amiodarone
Reduced therapeutic effect with P-gp inducers
Risks associated with ribavirin combination treatment

Adverse reactions

Fatigue
Headache
Asthenia
Nausea
Diarrhea
Insomnia

Pregnancy No adequate human data. If given with ribavirin, the combination is contraindicated in pregnancy and in male partners of pregnant women.

Lactation Unknown whether components are present in human milk. If given with ribavirin, ribavirin lactation information applies.

Cost

HARVONI

Strength		#/mo	generic $/mo	CostPlus
45/200 mg	tab	30 qd		not offered
90/400 mg	tab	30 qd		not offered

NADAC is a voluntary CMS survey of what retail community pharmacies pay for the drugs they stock. HARVONI is dispensed outside retail pharmacies, so it rarely appears on surveyed invoices.

Other forms: Ledipasvir (in HARVONI)

Clinical profile

Therapeutic safety burden2 / 4

Overdose danger1 / 4

Weight-gain liability0 / 4

Sedation liability0 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk1 / 4

Defining liabilityHBV reactivation and interacting-drug bradycardia

Part D rank #922.

Self-check

Which HCV genotypes are listed for HARVONI?
1, 4, 5 and 6.
What viral reactivation is boxed for HARVONI in coinfected patients?
Hepatitis B reactivation in HCV/HBV coinfection.

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