Ledipasvir

Ledipasvir and sofosbuvir tablets (90 mg/400 mg) are a fixed-dose combination of ledipasvir and sofosbuvir, which are direct-acting antiviral agents against the hepatitis C virus [see Microbiology (12.4) ].

• Ledipasvir and sofosbuvir is indicated for the treatment of adults and pediatric patients 3 years of age and older with chronic hepatitis C virus (HCV) [see Dosage and Administration (2.2 and 2.3) and Clinical Studies (14) ]: genotype 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis genotype 1 infection with decompensated cirrhosis, for use in combination with ribavirin genotype 1 or 4 infection who are liver transplant recipients without cirrhosis or with compensated cirrhosis, for use in combination with ribavirin Ledipasvir and sofosbuvir is a fixed-dose combination of ledipasvir, a hepatitis C virus (HCV) NS5A inhibitor, and sofosbuvir, an HCV nucleotide analog NS5B polymerase inhibitor, and is indicated for the treatment of chronic hepatitis C virus (HCV) in adults and pediatric patients 3 years of age and older: Genotype 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis Genotype 1 infection with decompensated cirrhosis, in combination with ribavirin Genotype 1 or 4 infection who are liver transplant recipients without cirrhosis or with compensated cirrhosis, in combination with ribavirin.ICD-10: B18.2

• If ledipasvir and sofosbuvir is administered with ribavirin, the contraindications to ribavirin also apply to this combination regimen. Refer to the ribavirin prescribing information for a list of contraindications for ribavirin [see Dosage and Administration (2.2) ] .contraindicated

Testing prior to the initiation of therapy: Test all patients for HBV infection by measuring HBsAg and anti-HBc. ( 2.1 ) Recommended treatment regimen and duration in patients 3 years of age and older: ( 2.2 ) HCV Genotype Patient Population Regimen and Duration Genotype 1 Treatment-naïve without cirrhosis or with compensated cirrhosis (Child-Pugh A) Ledipasvir and sofosbuvir 12 weeks Treatment-experienced without cirrhosis Ledipasvir and sofosbuvir 12 weeks Treatment-experienced with compensated cirrhosis (Child-Pugh A) Ledipasvir and sofosbuvir 24 weeks Treatment-naïve and treatment-experienced with decompensated cirrhosis (Child-Pugh B or C) Ledipasvir and sofosbuvir + ribavirin 12 weeks Genotype 1 or 4 Treatment-naïve and treatment-experienced liver transplant recipients without cirrhosis, or with compensated cirrhosis (Child-Pugh A) Ledipasvir and sofosbuvir + ribavirin 12 weeks Genotype 4, 5, or 6 Treatment-naïve and treatment-experienced without cirrhosis or with compensated cirrhosis (Child-Pugh A) Ledipasvir and sofosbuvir 12 weeks Recommended dosage in adults: One tablet (90 mg of ledipasvir and 400 mg of sofosbuvir) taken orally once daily with or without food. ( 2.3 ) Recommended dosage in pediatric patients 3 years and older: Recommended dosage of ledipasvir and sofosbuvir in pediatric patients 3 years of age and older is based on weight. Refer to Table 2 of the full prescribing information for specific dosing guidelines based on body weight.

Risk of Hepatitis B Virus Reactivation: Test all patients for evidence of current or prior HBV infection before initiation of HCV treatment. Monitor HCV/HBV coinfected patients for HBV reactivation and hepatitis flare during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated. ( 5.1 ) Bradycardia with amiodarone coadministration: Serious symptomatic bradycardia may occur in patients taking amiodarone, particularly in patients also receiving beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease. Coadministration of amiodarone with ledipasvir and sofosbuvir is not recommended. In patients without alternative, viable treatment options, cardiac monitoring is recommended. ( 5.2 , 6.2 , 7.2 ) 5.1 Risk of Hepatitis B Virus Reactivation in Patients Coinfected with HCV and HBV Hepatitis B virus (HBV) reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals, and who were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive and also in patients with serologic evidence of resolved HBV infection (i.e., HBsAg negative and anti-HBc positive).

The following serious adverse reactions are described below and elsewhere in labeling: Serious Symptomatic Bradycardia When Coadministered with Amiodarone [see Warnings and Precautions (5.2) ]. The most common adverse reactions (incidence greater than or equal to 10%, all grades) observed with treatment with ledipasvir and sofosbuvir were fatigue, headache, and asthenia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Asegua Therapeutics at 1-800-445-3235 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. If ledipasvir and sofosbuvir is administered with ribavirin to adults, refer to the prescribing information for ribavirin for a description of ribavirin-associated adverse reactions. Clinical Trials in Adult Subjects The safety assessment of ledipasvir and sofosbuvir was based on pooled data from three randomized, open-label Phase 3 clinical trials (ION-3, ION-1, and ION-2) of subjects with genotype 1 HCV with compensated liver disease (with and without cirrhosis) including 215, 539, and 326 subjects who received ledipasvir and sofosbuvir tablets (90 mg/400 mg) once daily by mouth for 8, 12, and 24 weeks, respectively [see Clinical Studies (14) ].

Pediatric Use: No data are available regarding the safety of ledipasvir and sofosbuvir in pediatric patients with renal impairment. ( 8.4 ) 8.1 Pregnancy Risk Summary If ledipasvir and sofosbuvir is administered with ribavirin, the combination regimen is contraindicated in pregnant women and in men whose female partners are pregnant. Refer to the 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 ledipasvir and sofosbuvir pose a risk to pregnancy outcomes. In animal reproduction studies, no evidence of adverse developmental outcomes was observed with ledipasvir or sofosbuvir at exposures greater than those in humans at the recommended human dose (RHD) [see Data ] . During organogenesis in the rat and rabbit, systemic exposures (AUC) to ledipasvir were approximately 4 (rats) and 2 (rabbits) times the exposure in humans at the RHD, while exposures to the predominant circulating metabolite of sofosbuvir (GS-331007) were ≥3 (rats) and 7 (rabbits) times the exposure in humans at the RHD. In rat pre/postnatal development studies, maternal systemic exposures (AUC) to ledipasvir and GS-331007 were approximately 5 and 7 times, respectively, the exposure in humans at the RHD.

Metabolism

Absorption The pharmacokinetic properties of ledipasvir, sofosbuvir, and the predominant circulating metabolite GS-331007 have been evaluated in healthy adult subjects and in subjects with chronic hepatitis C. Following oral administration of ledipasvir and sofosbuvir tablets (90 mg/400 mg), ledipasvir median peak concentrations were observed 4 to 4.5 hours post-dose.

No specific antidote is available for overdose with ledipasvir and sofosbuvir. If overdose occurs, the patient must be monitored for evidence of toxicity. Treatment of overdose with ledipasvir and sofosbuvir consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient. Hemodialysis is unlikely to result in significant removal of ledipasvir since ledipasvir is highly bound to plasma protein. Hemodialysis can efficiently remove the predominant circulating metabolite of sofosbuvir, GS-331007, with an extraction ratio of 53%.

• Oct 10, 2014NDANDA205834Gilead Sciences Inc
• Aug 28, 2019NDANDA212477Gilead Sciences Inc

1. 1Fatigue4,13022%
2. 2Headache3,70619%
3. 3Nausea1,2426.5%
4. 4Drug Ineffective1,1376.0%
5. 5Diarrhoea9134.8%
6. 6Hepatitis C8844.6%
7. 7Insomnia8354.4%
8. 8Vomiting4422.3%
9. 9Dizziness4392.3%
10. 10Drug Dose Omission4362.3%
11. 11Hepatocellular Carcinoma4012.1%
12. 12Treatment Failure3742.0%
13. 13Rash3611.9%
14. 14Asthenia3371.8%
15. 15Arthralgia3301.7%

The 10 most recently updated of 138 ClinicalTrials.gov registrations naming Ledipasvir as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Impact of Interferon Free Regimens in Patients With Chronic HCV and Successfully Treated HCC
  Completed · Phase 3 · Interventional · 150 enrolled · National Hepatology & Tropical Medicine Research Institute
  NCT02771405updated 2026-04-13
• Switching Regimen in Treating Cirrhotic HCV GT1b Subjects
  Completed · Phase 2 · Interventional · 138 enrolled · Humanity and Health Research Centre
  NCT02583685updated 2025-03-26
• Determine the Efficacy and Safety of Harvoni in Genotype 1 Chronic Hepatitis c Infected People Who Are Alcoholics
  Completed · Phase 4 · Interventional · 16 enrolled · University of Nebraska
  NCT02759861updated 2023-12-29
• A Registry for Participants With Cirrhosis Who Achieve a Sustained Virologic Response Following Treatment With a Sofosbuvir-Based Regimen Without Interferon for Chronic Hepatitis C Infection
  Terminated · Observational · 1,609 enrolled · Gilead Sciences
  NCT02292706updated 2023-10-04
• Safety and Efficacy of Sofosbuvir-Based Regimens in the Treatment of Egyptian Patients With Hepatitis C Infection
  Completed · Phase 4 · Interventional · 10,000 enrolled · Tanta University
  NCT02992457updated 2023-08-25
• Pharmacokinetics of Ledipasvir/Sofosbuvir in Hepatitis C Virus-Infected Children With Hematological Malignancy
  Completed · Phase 1 · Phase 2 · Interventional · 24 enrolled · Ain Shams University
  NCT03903185updated 2023-08-22
• Harvoni Treatment Porphyria Cutanea Tarda
  Completed · Phase 2 · Interventional · 23 enrolled · Wake Forest University Health Sciences
  NCT03118674updated 2023-07-03
• Cardiovascular Disease in HIV and Hepatitis C: Risk Outcomes After Hepatitis C Eradication
  Completed · Phase 4 · Interventional · 87 enrolled · University of Maryland, Baltimore
  NCT03823911updated 2023-05-22
• Hepatitis C Positive Donor Into Hepatitis C Negative Recipients
  Withdrawn · Early phase 1 · Interventional · 0 enrolled · University of Maryland, Baltimore
  NCT03702218updated 2023-05-06
• Ledipasvir+Sofosbuvir and Sofosbuvir+Velpatasvir for Pts With Indolent Bcell Lymphoma Associated With HCV Infection
  Completed · Phase 2 · Interventional · 40 enrolled · Fondazione Italiana Linfomi - ETS
  NCT02836925updated 2023-03-31

Frequently asked questions

How does Ledipasvir work?

Ledipasvir and sofosbuvir tablets (90 mg/400 mg) are a fixed-dose combination of ledipasvir and sofosbuvir, which are direct-acting antiviral agents against the hepatitis C virus [see Microbiology (12.4) ].

What is Ledipasvir used for?

According to FDA labeling, Ledipasvir carries indications including: Ledipasvir and sofosbuvir is indicated for the treatment of adults and pediatric patients 3 years of age and older with chronic hepatitis C virus (HCV) [see Dosage and Administration (2.2 and 2.3) and Clinical Studies (14) ]: genotype 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis genotype 1 infection with decompensated cirrhosis, for use in combination with ribavirin genotype 1 or 4 infection who are liver transplant recipients without cirrhosis or with compensated cirrhosis, for use in combination with ribavirin Ledipasvir and sofosbuvir is a fixed-dose combination of ledipasvir, a hepatitis C virus (HCV) NS5A inhibitor, and sofosbuvir, an HCV nucleotide analog NS5B polymerase inhibitor, and is indicated for the treatment of chronic hepatitis C virus (HCV) in adults and pediatric patients 3 years of age and older: Genotype 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis Genotype 1 infection with decompensated cirrhosis, in combination with ribavirin Genotype 1 or 4 infection who are liver transplant recipients without cirrhosis or with compensated cirrhosis, in combination with ribavirin.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Ledipasvir?

Ledipasvir is classified as Hepatitis C Virus NS5A Inhibitor, Breast Cancer Resistance Protein Inhibitors, P-Glycoprotein Inhibitors, Blood & Lymphatic Fluid Function Alteration, Decreased RNA Replication.

What are the brand names for Ledipasvir?

Ledipasvir is marketed under brand names including Harvoni.

What are the contraindications for Ledipasvir?

Ledipasvir labeling lists contraindications including: If ledipasvir and sofosbuvir is administered with ribavirin, the contraindications to ribavirin also apply to this combination regimen. Refer to the ribavirin prescribing information for a list of contraindications for ribavirin [see Dosage and Administration (2.2) ] .. Always consult the full prescribing information and a clinician.