Dosing & Uses
Dosage Forms & Strengths
ledipasvir/sofosbuvir
tablet
- 90mg/400mg
Hepatitis C Virus Infection
Indicated for adults with chronic hepatitis C virus (HCV) genotypes 1, 4, 5, or 6 infection
1 tablet (90 mg/400 mg) PO qDay
Treatment duration
- The following regimens also apply to HCV/HIV-1 coinfection
-
Genotype 1
Treatment-naïve without cirrhosis or with compensated cirrhosis (Child-Pugh A): 12 weeks; may consider 8 weeks in treatment-naïve patients without cirrhosis who have pretreatment HCV RNA <6 million IU/mL
Treatment-experienced (ie, those who have failed a peginterferon alfa + ribavirin based regimen with or without an HCV protease inhibitor) without cirrhosis: 12 weeks
Treatment-experienced with compensated cirrhosis (Child-Pugh A): 24 weeks; may also consider adding daily weight-based ribavirin
Treatment-naïve and treatment-experienced with decompensated cirrhosis (Child-Pugh B or C), including those who have undergone liver transplantation: 12 weeks in combination with ribavirin
-
Genotypes 1 or 4
- Treatment-naïve and treatment-experienced without cirrhosis or with compensated cirrhosis (Child-Pugh A), including those who have undergone liver transplantation: 12 weeks in combination with ribavirin
-
Genotypes 4, 5, or 6
- Treatment-naïve and treatment-experienced, without cirrhosis or with compensated cirrhosis (Child-Pugh A): 12 weeks
-
Ribavirin dosing
- <75 kg with or without decompensated cirrhosis: 1000 mg PO q12hr
- ≥75 kg with or without decompensated cirrhosis: 1200 mg PO q12hr
- If initial dose is not well tolerated, reduced dose as clinically indicated based on hemoglobin levels; refer to the ribavirin prescribing information for further information
Dosage Modifications
Renal impairment
- Mild-to-severe (including ESRD requiring dialysis): No dosage adjustment necessary
- No safety data are available in subjects with both decompensated cirrhosis and severe renal impairment, including those on dialysis
- Refer to ribavirin tablet prescribing information regarding use in patients with renal impairment
Hepatic impairment
- Mild, moderate, or severe: No dosage adjustment required
- Decompensated cirrhosis: Safety and efficacy not established
Dosing Considerations
Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HCV direct acting antivirals (DDAs)
Dosage Forms & Strengths
ledipasvir/sofosbuvir
tablet
- 45mg/200mg
- 90mg/400mg
oral pellets
- 33.75mg/150mg per packet
- 45mg/200mg per packet
Hepatitis C Virus Infection
Indicated for pediatric patients aged ≥3 yr with hepatitis C virus (HCV) genotype 1, 4, 5 or 6 infection
<3 years: Safety and efficacy not established
≥3 years
<17 kg: 1 packet (33.75 mg/150 mg) of pellets PO qDay
17 to <35kg: 1 tablet or packet (45 mg/200 mg) PO qDay
≥35 kg: 1 tablet (90 mg/400 mg) PO qDay or 2 tablets or packets (45 mg/200 mg) PO qDay
Treatment duration
- The following regimens also apply to HCV/HIV-1 coinfection
-
Genotype 1
Treatment-naïve without cirrhosis or with compensated cirrhosis (Child-Pugh A): 12 weeks; may consider 8 weeks in treatment-naïve patients without cirrhosis who have pretreatment HCV RNA <6 million IU/mL
Treatment-experienced (ie, those who have failed a peginterferon alfa + ribavirin based regimen with or without an HCV protease inhibitor) without cirrhosis: 12 weeks
Treatment-experienced with compensated cirrhosis (Child-Pugh A): 24 weeks; may also consider adding daily weight-based ribavirin
Treatment-naïve and treatment-experienced with decompensated cirrhosis (Child-Pugh B or C), including those who have undergone liver transplantation: 12 weeks in combination with ribavirin
-
Genotypes 1 or 4
- Treatment-naïve and treatment-experienced without cirrhosis or with compensated cirrhosis (Child-Pugh A), including those who have undergone liver transplantation: 12 weeks in combination with ribavirin
-
Genotypes 4, 5, or 6
- Treatment-naïve and treatment-experienced, without cirrhosis or with compensated cirrhosis (Child-Pugh A): 12 weeks
Ribavirin dosing
- <47 kg: 15 mg/kg/day PO (divided dose AM and PM)
- 47-49 kg: 600 mg/day PO (ie, 200 mg AM, 400 mg PM)
- 50-65 kg: 800 mg/day PO (ie, 400 mg AM, 400 mg PM)
- 66-80 kg: 1000 mg/day PO (ie, 400 mg AM, 600 mg PM)
- >80 kg: 1200 mg/day PO (ie, 600 mg AM, 600 mg PM)
Dosage Modifications
Renal impairment
- Mild-to-severe (including ESRD requiring dialysis): No dosage adjustment necessary
- No safety data are available in subjects with both decompensated cirrhosis and severe renal impairment, including those on dialysis
- Refer to ribavirin tablet prescribing information regarding use in patients with renal impairment
Dosing Considerations
Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HCV direct acting antivirals (DDAs)
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Adverse Effects
>10%
Asthenia (31-36%)
Fatigue (4-18%)
Headache (13-29%)
Cough (5-11%)
1-10%
Nausea (6-9%)
Diarrhea (3-7%)
Dizziness (1-5%)
Dyspnea (3-9%)
Insomnia (3-6%)
Increased bilirubin >1.5 x ULN (<1 to 3%)
Increased lipase >3 x ULN (<1 to 3%)
Myalgia (4-9%)
Irritability (7-8%)
Frequency Not Defined
Asymptomatic creatine kinase elevation, Grades 3/4
Postmarketing Reports
Bradycardia in patients taking amiodarone who initiate ledipasvir/sofosbuvir therapy
Skin rash, sometimes with blisters or angioedema-like swelling
Warnings
Black Box Warnings
Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HCV direct acting antivirals (DDAs)
HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with DDAs and were not receiving HBV antiviral therapy
Some cases have resulted in fulminant hepatitis, hepatic failure, and death
Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up
Initiate appropriate patient management for HBV infection as clinically indicated
Contraindications
If coadministered with ribavirin, the contraindications to ribavirin also apply to this combination regimen
Cautions
Hepatitis B virus (HBV) reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV DDAs, and who were not receiving HBV antiviral therapy; HBV reactivation is characterized as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level (see Black Box Warnings and Dosing Considerations)
Do not use with other products that contain sofosbuvir (Sovaldi, Epclusa); duplicate therapy and increased risk for adverse effects
Drug interaction overview
Postmarketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is coadministered with sofosbuvir in combination with an investigational agent (daclatasvir, an investigational NS5A inhibitor) or simeprevir; coadministration is not recommended, if no alternative exists, inpatient cardiac monitoring is recommended for the first 48 hr and then daily home monitoring for at least the first 2 weeks
Due to amiodarone’s long half-life, patients discontinuing amiodarone just prior to starting ledipasvir/sofosbuvir therapy should undergo cardiac monitoring; patients who develop signs or symptoms of bradycardia, including near-fainting or fainting, dizziness or lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pains, confusion or memory problems should seek medical evaluation immediately
Ledipasvir and sofosbuvir are substrates of P-gp and BCRP; coadministration with P-gp inducers (eg, rifampin, St. John’s wort) is not recommended; may significantly decrease ledipasvir and sofosbuvir plasma concentrations and reduce therapeutic effect
Ledipasvir is an inhibitor of P-gp and BCRP; may increase intestinal absorption of coadministered substrates for these transporters
Coadministration of ledipasvir with acid-reducing agents may decrease ledipasvir solubility, resulting in decreased serum concentrations
If coadministered with ribavirin, the warnings and precautions for ribavirin also apply to this combination regimen
Frequent monitoring of relevant laboratory parameters (eg, International Normalized Ratio [INR] in patients taking warfarin, blood glucose levels in diabetic patients) or drug concentrations of concomitant medications such as cytochrome P450 substrates with a narrow therapeutic index (eg, certain immunosuppressants) is recommended to ensure safe and effective use; dose adjustments of concomitant medications may be necessary
Pregnancy & Lactation
Pregnancy
If the drug combination is administered with ribavirin, the combination regimen is contraindicated in pregnant women and in men whose female partners are pregnant; refer to ribavirin prescribing information for more information on ribavirin-associated risks of use during pregnancy
No adequate human data are available to establish whether or not the drug combination poses a risk to pregnancy outcomes; in animal reproduction studies, no evidence of adverse developmental outcomes was observed with the drug combination ledipasvir or sofosbuvir at exposures greater than those in humans at the recommended human dose (RHD)
Lactation
It is not known whether ledipasvir or sofosbuvir, the drug combination, or their metabolites are present in human breast milk, affect human milk production or have effects on the breastfed infant.
The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug combination and any potential adverse effects on the breastfed child from the drug combination or from the underlying maternal condition
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Ledipasvir: Inhibits HCV NS5A protein, which is required for viral replication; resistance selection in cell culture and cross-resistance studies indicate ledipasvir targets NS5A as its mode of action
Sofosbuvir: Nucleotide prodrug that undergoes metabolism to the active uridine analog triphosphate, an inhibitor of HCV NS5B RNA-dependent polymerase; its inhibition, in turn, suppresses viral replication
Absorption
Peak plasma concentration
- ledipasvir: 4-4.5 hr
- sofosbuvir: 0.8-1 hr
- GS-331007: 3.5-4 hr
Peak plasma level
- ledipasvir: 323 ng/mL
- sofosbuvir: 618 ng/mL
- GS-331007: 707 ng/mL
AUC
- ledipasvir: 7,290 ng•hr/mL
- sofosbuvir: 1,320 ng•hr/mL
- GS-331007: 12,000 ng•hr/mL
Distribution
Protein bound
- ledipasvir: >99.8%
- sofosbuvir: 61-65%
- GS-331007: minimal
Metabolism
ledipasvir: No detectable metabolism
sofosbuvir: Extensively metabolized in liver to form the pharmacologically active nucleoside analog triphosphate GS-461203; dephosphorylation results in formation of GS331007 (accounts for <90% of total systemic exposure of sofosbuvir)
Elimination
Half-life, terminal
- ledipasvir: 47 hr
- sofosbuvir: 0.5 hr
- GS-331007: 27 hr
Excretion
- ledipasvir: >98% feces (mostly unchanged); <1% urine
- GS-331007: 14% feces; 80% urine; 2.5% expired air
Administration
Oral Preparation (Oral Pellets)
Do not chew pellets
If pellets are administered with food, sprinkle on ≥1 spoonfuls of nonacidic soft food (eg, pudding, chocolate syrup, mashed potato, ice cream) at or below room temperature
Take pellets within 30 min of gently mixing with food and swallow entire contents without chewing to avoid a bitter aftertaste
Oral Administration
Take with or without food
Storage
Tablets and oral pellets: Store <30ºC; dispense in original bottle
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Patient Handout
Formulary
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