Applies to ledipasvir / sofosbuvir: oral packet, oral tablet.
Warning
Oral route (Tablet)
Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with ledipasvir/sofosbuvir. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals 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.
Serious side effects
Along with its needed effects, ledipasvir / sofosbuvir may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur while taking ledipasvir / sofosbuvir:
Incidence not known
- Chest pain or discomfort
- lightheadedness, dizziness, or fainting
- slow or irregular heartbeat
- trouble breathing
- unusual tiredness
Other side effects
Some side effects of ledipasvir / sofosbuvir may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.
Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
More common
- Cough
- diarrhea
- headache
- irritability
- lack or loss of strength
- muscle pain
- nausea
- trouble sleeping
Less common
- Discouragement
- dizziness
- feeling sad or empty
- lack of appetite
- loss of interest or pleasure
- trouble concentrating
For Healthcare Professionals
Applies to ledipasvir / sofosbuvir: oral pellet, oral tablet.
General
The most common side effects reported with this drug were fatigue, headache, asthenia, and nausea. When this drug was studied with ribavirin, the most common side effects to this combination were consistent with known ribavirin side effects; frequency and severity of the expected side effects were not increased. Therapy was permanently discontinued due to side effects in 0%, less than 1%, and 1% of patients using this drug for 8, 12, and 24 weeks, respectively, and less than 1%, 0%, and 2% for patients using this drug with ribavirin for 8, 12, and 24 weeks, respectively.
Among 174 liver transplant recipients with compensated liver disease using this drug with ribavirin for 12 weeks, 1% permanently discontinued this drug due to a side effect.
Among 162 patients with decompensated liver disease (pretransplant or posttransplant) using this drug with ribavirin for 12 weeks, 4% died, 2% had a liver transplantation, and less than 1% had a liver transplantation and died during therapy or within 30 days after stopping therapy. Due to the advanced liver disease in these patients (who had increased risk of disease progression leading to liver failure and death), the contribution of drug effect to outcomes could not be reliably assessed. This drug was permanently discontinued due to a side effect in 2% of patients.
The most common side effect in patients with hepatitis C virus (HCV) with compensated liver disease (with or without cirrhosis) and severe renal dysfunction was fatigue. The most common side effects in patients with HCV with compensated liver disease (with or without cirrhosis) and end-stage renal disease requiring dialysis were insomnia and headache.
If this drug is used with ribavirin, the manufacturer product information for ribavirin should be consulted for associated side effects.[Ref]
Hematologic
Decreased hemoglobin (less than 10 g/dL: up to 39%; less than 8.5 g/dL: up to 13%) has been reported in liver transplant recipients and/or patients with decompensated liver disease using this drug with ribavirin for 12 or 24 weeks. Ribavirin was permanently discontinued in up to 19% of patients. Immunosuppressive agents were modified in up to 10% of liver transplant recipients (modified dose due to improved organ function in at least 7%).
Very common (10% or more): Decreased hemoglobin (up to 39%)
Other
Very common (10% or more): Asthenia (up to 36%), fatigue (up to 18%)[Ref]
Nervous system
Very common (10% or more): Headache (up to 29%)
Common (1% to 10%): Dizziness[Ref]
Respiratory
Very common (10% or more): Cough (up to 11%)
Common (1% to 10%): Dyspnea
Gastrointestinal
Common (1% to 10%): Nausea, diarrhea, increased lipase[Ref]
Increased lipase (greater than 3 times the upper limit of normal [3 x ULN]) was reported in less than 1%, 2%, and 3% of patients using this drug for 8, 12, and 24 weeks, respectively. Increased lipase (greater than 3 x ULN) was reported in 1%, 3%, and 9% of patients with compensated cirrhosis using placebo, this drug plus ribavirin for 12 weeks, and this drug for 24 weeks, respectively. Lipase elevation was transient and asymptomatic.[Ref]
Psychiatric
Depression (especially in patients with history of psychiatric illness) was reported in patients using sofosbuvir-containing regimens. Suicidal ideation and suicide have been reported in less than 1% of patients using sofosbuvir with ribavirin or pegylated interferon/ribavirin in other clinical trials.[Ref]
Common (1% to 10%): Insomnia, irritability
Frequency not reported: Depression
Sofosbuvir:
-Frequency not reported: Depression, suicidal ideation, suicide[Ref]
Dermatologic
Common (1% to 10%): Rash
Frequency not reported: Stevens-Johnson syndrome
Postmarketing reports: Skin rashes (sometimes with blisters or angioedema-like swelling), angioedema
Hepatic
Increased bilirubin (greater than 1.5 x ULN) was reported in 3%, less than 1%, and 2% of patients using this drug for 8, 12, and 24 weeks, respectively. Increased bilirubin (greater than 1.5 x ULN) was reported in 3%, 11%, and 3% of patients with compensated cirrhosis using placebo, this drug plus ribavirin for 12 weeks, and this drug for 24 weeks, respectively.[Ref]
Common (1% to 10%): Increased bilirubin
Postmarketing reports: Hepatitis B reactivation[Ref]
Cardiovascular
Frequency not reported: Severe bradycardia, heart block
Postmarketing reports: Serious symptomatic bradycardia (including fatal cardiac arrest, cases requiring pacemaker intervention)[Ref]
Severe bradycardia and heart block have been reported when this drug was used with amiodarone and/or other agents that lower heart rate.
Serious symptomatic bradycardia has been reported in patients taking amiodarone who started therapy with this drug.[Ref]
Musculoskeletal
Creatine kinase was not evaluated in some phase 3 clinical trials for this drug, but was evaluated in at least 1 trial. Isolated, asymptomatic creatine kinase elevations (at least 10 x ULN) were reported in 1% of patients using this drug for 12 weeks; such elevations were previously reported in patients using sofosbuvir with ribavirin or peginterferon/ribavirin in other clinical trials.[Ref]
Common (1% to 10%): Myalgia, elevated creatine kinase
Sofosbuvir:
-Frequency not reported: Elevated creatine kinase[Ref]
