Names and pronunciation
(le-dip′as-vir/soe-fos′bue-veer) Harvoni
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Drug reference
(le-dip′as-vir/soe-fos′bue-veer) Harvoni
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Func. class.: Antiviral, antihepatitis agent
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Chem. class.: NS5A inhibitor
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ACTION: A combination product with an HCV NS5A inhibitor (ledipasvir) and a nucleotide analog HCV NS5B polymerase inhibitor (sofosbuvir)
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USES: Chronic hepatitis C virus (HCV) genotype 1 infection in patients with compensated liver disease
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CONTRAINDICATIONS: Hyper- sensitivity Precautions: Decompensated hepatic dis- ease, decompensated cirrhosis, severe renal impairment (eGFR <30 mL/min/1.73 m2), end-stage renal failure requiring dialy- sis, pregnancy, breastfeeding
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Black Box Warning: Hepatitis B exacer- bation Black Box Warning: Hepatitis B: test prior to initiating therapy; risk of fulmi- nant hepatitis and death
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SIDE EFFECTS CNS: Fatigue, headache, insomnia GI: Nausea, vomiting, diarrhea INTEG: Rash MS: Myalgia
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INTERACTIONS Increase: digoxin level—digoxin Decrease: ledipasvir level—antacids; separate by ≥4 hr Decrease: ledipasvir/sofosbuvir level— anticonvulsants, antimycobacterials (rifabutin, rifapentine), P-glycoprotein inducers; avoid using together Decrease: ledipasvir level—H2 receptor antagonists (famotidine), separate by ≥12 hr, max dose of H2 receptor antago- nist should not exceed famotidine 40 mg L bid equivalent Drug/Lab Test: Increase: bilirubin, lipase, CK
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DOSAGE AND ROUTES Treatment of chronic hepatitis C virus (HCV) genotype 1 infection: • Adult (treatment-naïve) without cirrho- sis: PO 1 tablet (90 mg ledipasvir; 400 mg sofosbuvir) daily with or without food; the recommended duration of treatment is 12 wk; however, 8-wk treatment can be con- sidered for patients with a baseline HCV RNA <6 million IU/mL. Recommendation includes patients coinfected with HIV Genotype 1 • Adult (treatment-naïve) with compen- sated (Child-Pugh A) cirrhosis: PO 1 tablet (90 mg ledipasvir; 400 mg sofos- buvir) daily with or without food; the recommended duration of treatment is 12 wk (recommendation includes pa- tients coinfected with HIV) • Adult (treatment-experienced) with- out cirrhosis: PO 1 tablet (90 mg ledip asvir; 400 mg sofosbuvir) daily with or without food; the recommended dura- tion of treatment is 12 wk (recommen- dation includes patients coinfected with HIV) • Adult (treatment-experienced) with compensated (Child-Pugh A) cirrhosis: PO 1 tablet (90 mg ledipasvir; 400 mg sofosbuvir) daily with or without food; for 24 wk • Adult (treatment-naïve and experi- enced) with decompensated (Child-Pugh B or C) cirrhosis: PO 1 tablet (90 mg ledip asvir; 400 mg sofosbuvir) PO daily with ribavirin (600 mg PO daily) for 12 wk. Ribavirin must be administered with food • Adult (treatment-naïve and experi- enced) transplantation and is without cir- rhosis or has compensated (Child-Pugh A) cirrhosis: PO 1 tablet (90 mg ledipasvir; 400 mg sofosbuvir) daily with ribavirin for 12 wk. Ribavirin must be administered with food • Child/adolescent 12-17 yr (treat- ment-naïve) without cirrhosis or with compensated (Child-Pugh A) cirrhosis: PO 1 tablet (90 mg ledipasvir; 400 mg sofosbuvir) daily with or without food × 12 wk • Child/adolescent 12-17 yr (treat- ment-experienced) without cirrhosis: PO 1 tablet (90 mg ledipasvir; 400 mg sofosbuvir) daily with or without food × 12 wk • Child/adolescent 12-17 yr (treatment- experienced) with compensated (Child- Pugh A) cirrhosis: PO 1 tablet (90 mg ledipasvir; 400 mg sofosbuvir) daily with or without food × 24 wk For the treatment of chronic hepa- titis C virus (HCV) genotype 4, 5, 6 infection • Adult (treatment-naïve or experienced) without cirrhosis or who have compen- sated (Child-Pugh A) cirrhosis: PO 1 tab- let (90 mg ledipasvir; 400 mg sofosbuvir) daily with or without food × 12 wk • Adult (treatment-naïve or experi- enced) who has undergone liver trans- plantation and is without cirrhosis or has compensated (Child-Pugh A) cirrhosis: PO 1 tablet (90 mg ledipas- vir; 400 mg sofosbuvir) daily with rib- avirin for 12 wk. Ribavirin must be administered with food in 2 divided doses • Child/adolescent 12-17 yr (treatment- naïve or experienced) without cirrhosis or who has compensated (Child-Pugh A) cirrhosis: PO 1 tablet (90 mg ledipasvir; 400 mg sofosbuvir) daily with or without food × 12 wk
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Available forms: Tab 90 mg ledipa- sir/400 mg sofosbuvir
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Administer: • Without regard to food
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Assess: • Hepatitis C: monitor hepatitis C RNA, serum bilirubin, creatinine • Pregnancy/breastfeeding: use only if benefits outweigh fetal risk; cautious use in breastfeeding, excretion unknown
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Evaluate: • Therapeutic response: hepatitis C RNA reduction • CHC is decreased
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To report effects to the prescriber • To notify all providers of product use • To take at the same time each day, to use for full course even if feeling better, to take missed doses when remembered on the same day; not to double doses • That the product will not decrease transmission of infection in others • If antacids (magnesium, aluminum) are needed, take 4 hr before or after this product
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PHARMACOKINETICS Ledipasvir: >99.8% protein binding, elimination biliary excretion, half-life 47 hr, peak 4-5 hr Sofosbuvir: 61%-65% protein binding, elimination by the kidneys, 80% recov- ered in the urine, peak 0.8-1 hr, half-life 0.4 hr, metabolite 27 hr
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• Adult (treatment-naïve) without cirrho- sis: PO 1 tablet (90 mg ledipasvir; 400 mg sofosbuvir) daily with or without food; the recommended duration of treatment is 12 wk; however, 8-wk treatment can be con- sidered for patients with a baseline HCV RNA <6 million IU/mL. Recommendation includes patients coinfected with HIV Genotype 1
PDF pages 760, 761
• Adult (treatment-naïve) with compen- sated (Child-Pugh A) cirrhosis: PO 1 tablet (90 mg ledipasvir; 400 mg sofos- buvir) daily with or without food; the recommended duration of treatment is 12 wk (recommendation includes pa- tients coinfected with HIV)
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• Adult (treatment-experienced) with- out cirrhosis: PO 1 tablet (90 mg ledip asvir; 400 mg sofosbuvir) daily with or without food; the recommended dura- tion of treatment is 12 wk (recommen- dation includes patients coinfected with HIV)
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• Adult (treatment-experienced) with compensated (Child-Pugh A) cirrhosis: PO 1 tablet (90 mg ledipasvir; 400 mg sofosbuvir) daily with or without food; for 24 wk
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• Adult (treatment-naïve and experi- enced) with decompensated (Child-Pugh B or C) cirrhosis: PO 1 tablet (90 mg ledip asvir; 400 mg sofosbuvir) PO daily with ribavirin (600 mg PO daily) for 12 wk. Ribavirin must be administered with food
PDF pages 760, 761
• Adult (treatment-naïve and experi- enced) transplantation and is without cir- rhosis or has compensated (Child-Pugh A) cirrhosis: PO 1 tablet (90 mg ledipasvir; 400 mg sofosbuvir) daily with ribavirin for 12 wk. Ribavirin must be administered with food
PDF pages 760, 761
• Child/adolescent 12-17 yr (treat- ment-naïve) without cirrhosis or with compensated (Child-Pugh A) cirrhosis: PO 1 tablet (90 mg ledipasvir; 400 mg sofosbuvir) daily with or without food × 12 wk
PDF pages 760, 761
• Child/adolescent 12-17 yr (treat- ment-experienced) without cirrhosis: PO 1 tablet (90 mg ledipasvir; 400 mg sofosbuvir) daily with or without food × 12 wk
PDF pages 760, 761
• Child/adolescent 12-17 yr (treatment- experienced) with compensated (Child- Pugh A) cirrhosis: PO 1 tablet (90 mg ledipasvir; 400 mg sofosbuvir) daily with or without food × 24 wk For the treatment of chronic hepa- titis C virus (HCV) genotype 4, 5, 6 infection
PDF pages 760, 761
• Adult (treatment-naïve or experienced) without cirrhosis or who have compen- sated (Child-Pugh A) cirrhosis: PO 1 tab- let (90 mg ledipasvir; 400 mg sofosbuvir) daily with or without food × 12 wk
PDF pages 760, 761
• Adult (treatment-naïve or experi- enced) who has undergone liver trans- plantation and is without cirrhosis or has compensated (Child-Pugh A) cirrhosis: PO 1 tablet (90 mg ledipas- vir; 400 mg sofosbuvir) daily with rib- avirin for 12 wk. Ribavirin must be administered with food in 2 divided doses
PDF pages 760, 761
• Child/adolescent 12-17 yr (treatment- naïve or experienced) without cirrhosis or who has compensated (Child-Pugh A) cirrhosis: PO 1 tablet (90 mg ledipasvir; 400 mg sofosbuvir) daily with or without food × 12 wk
PDF pages 760, 761