What is Sovaldi (sofosbuvir)?

Sovaldi (sofosbuvir) is an oral, direct-acting antiviral agent used to treat infections with the hepatitis C virus (HCV). 

After administration, Sovaldi is first converted to an active form which interferes with multiplication of the ribonucleic acid (RNA) of HCV leading to decreased numbers of hepatitis C virus in the body. Sovaldi is effective for treating infection with HCV genotype 1, 2, 3, or 4, and in clinical trials, 50% to 90% of individuals treated with the drug cleared the hepatitis C virus from their blood.

Common side effects of Sovaldi include:

Other side effects of Sovaldi include:

Serious side effects of Sovaldi include:

Drug interactions of Sovaldi include drugs which may reduce blood levels of Sovaldi:

Sovaldi and amiodarone should not be combined with another direct-acting antiviral agent because combining them may significantly reduce heart rate, especially in people who are taking beta-blockers or have underlying heart problems. 

There hasn’t been enough research and evaluation of Sovaldi in pregnant women. However, ribavirin, which is combined with Sovaldi, should not be used in pregnant women. Male partners of females of reproductive potential shouldn't use it either. 

Researchers don’t know if Sovaldi is secreted into breast milk. Consult your doctor before breastfeeding

What are the important side effects of Sovaldi (sofosbuvir)?

The most common side effects reported by patients include:

Other side effects include:

Sovaldi (sofosbuvir) side effects list for healthcare professionals

The following serious adverse reactions are described below and elsewhere in the labeling:

  • Serious Symptomatic Bradycardia When Coadministered with Amiodarone.

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.

When Sovaldi is administered with ribavirin or peginterferon alfa/ribavirin, refer to the respective prescribing information for a description of adverse reactions associated with their use.

Adverse Reactions In Adult Subjects

The safety assessment of Sovaldi was based on pooled Phase 3 clinical trial data (both controlled and uncontrolled) including:

  • 650 subjects who received Sovaldi + ribavirin (RBV) combination therapy for 12 weeks,
  • 98 subjects who received Sovaldi + ribavirin combination therapy for 16 weeks,
  • 250 subjects who received Sovaldi + ribavirin combination therapy for 24 weeks,
  • 327 subjects who received Sovaldi + peginterferon (Peg-IFN) alfa + ribavirin combination therapy for 12 weeks,
  • 243 subjects who received peginterferon alfa + ribavirin for 24 weeks, and
  • 71 subjects who received placebo (PBO) for 12 weeks.

The proportion of subjects who permanently discontinued treatment due to adverse events was 4% for subjects receiving placebo, 1% for subjects receiving Sovaldi + ribavirin for 12 weeks, less than 1% for subjects receiving Sovaldi + ribavirin for 24 weeks, 11% for subjects receiving peginterferon alfa + ribavirin for 24 weeks and 2% for subjects receiving Sovaldi + peginterferon alfa + ribavirin for 12 weeks.

Adverse events observed in at least 15% of subjects in the Phase 3 clinical trials outlined above are provided in Table 5. A side-by-side tabulation is displayed to simplify presentation; direct comparison across trials should not be made due to differing trial designs.

The most common adverse events (at least 20%) for Sovaldi + ribavirin combination therapy were fatigue and headache. The most common adverse events (at least 20%) for Sovaldi + peginterferon alfa + ribavirin combination therapy were:

Table 5 : Adverse Events (All Grades and without Regard to Causality) Reported in ≥15% of Subjects with HCV in Any Treatment Arm

Interferon-free RegimensInterferon-containing Regimens
PBO 12 weeksSovaldi + RBVa 12 weeksSovaldi + RBVa 24 weeksPeg-IFN alfa + RBVb 24 weeksSovaldi + Peg-IFN alfa + RBVa 12 weeks
N=71N=650N=250N=243N=327
Fatigue24%38%30%55%59%
Headache20%24%30%44%36%
Nausea18%22%13%29%34%
Insomnia4%15%16%29%25%
Pruritus8%11%27%17%17%
Anemia0%10%6%12%21%
Asthenia3%6%21%3%5%
Rash8%8%9%18%18%
Decreased Appetite10%6%6%18%18%
Chills1%2%2%18%17%
Influenza Like Illness3%3%6%18%16%
Pyrexia0%4%4%14%18%
Diarrhea6%9%12%17%12%
Neutropenia0%<1%<1%12%17%
Myalgia0%6%9%16%14%
Irritability1%10%10%16%13%
aSubjects received weight-based ribavirin (1000 mg per day if weighing <75 kg or 1200 mg per day if weighing ≥75 kg).
bSubjects received 800 mg ribavirin per day regardless of weight.

With the exception of anemia and neutropenia, the majority of events presented in Table 5 occurred at severity of grade 1 in Sovaldi-containing regimens.

Less Common Adverse Reactions Reported In Clinical Trials (Less Than 1%)

The following adverse reactions occurred in less than 1% of subjects receiving Sovaldi in a combination regimen in any one trial. These events have been included because of their seriousness or assessment of potential causal relationship.

Hematologic Effects

pancytopenia (particularly in subjects receiving concomitant pegylated interferon).

Psychiatric Disorders

severe depression (particularly in subjects with pre-existing history of psychiatric illness), including suicidal ideation and suicide.

Laboratory Abnormalities

Changes in selected hematological parameters are described in Table 6. A side-by-side tabulation is displayed to simplify presentation; direct comparison across trials should not be made due to differing trial designs.

Table 6 : Percentage of Subjects Reporting Selected Hematological Parameters

Hematological ParametersInterferon-free RegimensInterferon-containing Regimens
PBO 12 weeksSovaldi + RBVa 12 weeksSovaldi + RBVa 24 weeksPeg-IFN + RBVb 24 weeksSovaldi + Peg-IFN + RBVa 12 weeks
N=71N=647N=250N=242N=327
Hemoglobin (g/dL)
<1008%6%14%23%
<8.501%<1%2%2%
Neutrophils (x109/L)
≥0.5 - <0.751%<1%012%15%
<0.50<1%02%5%
Platelets (x109/L)
≥25 - <503%<1%1%7%<1%
<2500000
aSubjects received weight-based ribavirin (1000 mg per day if weighing <75 kg or 1200 mg per day if weighing ≥75 kg).
bSubjects received 800 mg ribavirin per day regardless of weight.

Bilirubin Elevations

Total bilirubin elevation of more than 2.5xULN was observed in none of the subjects in the Sovaldi + peginterferon alfa + ribavirin 12 weeks group and in 1%, 3% and 3% of subjects in the peginterferon alfa + ribavirin 24 weeks, Sovaldi + ribavirin 12 weeks and Sovaldi + ribavirin 24 weeks groups, respectively. Bilirubin levels peaked during the first 1 to 2 weeks of treatment and subsequently decreased and returned to baseline levels by post-treatment Week 4. These bilirubin elevations were not associated with transaminase elevations.

Creatine Kinase Elevations

Creatine kinase was assessed in the FISSION and NEUTRINO trials. Isolated, asymptomatic creatine kinase elevation of greater than or equal to 10xULN was observed in less than 1%, 1% and 2% of subjects in the peginterferon alfa + ribavirin 24 weeks, Sovaldi + peginterferon alfa + ribavirin 12 weeks and Sovaldi + ribavirin 12 weeks groups, respectively.

Lipase Elevations

Isolated, asymptomatic lipase elevation of greater than 3xULN was observed in less than 1%, 2%, 2%, and 2% of subjects in the Sovaldi + peginterferon alfa + ribavirin 12 weeks, Sovaldi + ribavirin 12 weeks, Sovaldi + ribavirin 24 weeks and peginterferon alfa + ribavirin 24 weeks groups, respectively.

Patients With HCV/HIV-1 Coinfection

Sovaldi used in combination with ribavirin was assessed in 223 HCV/HIV-1 coinfected subjects. The safety profile in HCV/HIV-1 coinfected subjects was similar to that observed in HCV mono-infected subjects. Elevated total bilirubin (grade 3 or 4) was observed in 30/32 (94%) subjects receiving atazanavir as part of the antiretroviral regimen. None of the subjects had concomitant transaminase increases. Among subjects not taking atazanavir, grade 3 or 4 elevated total bilirubin was observed in 2 (1.5%) subjects, similar to the rate observed with HCV mono-infected subjects receiving Sovaldi + ribavirin in Phase 3 trials.

Adverse Reactions In Pediatric Subjects 3 Years Of Age And Older

The safety assessment of Sovaldi in pediatric subjects 3 years of age and older is based on data from 106 subjects who were treated with Sovaldi plus ribavirin for 12 weeks (genotype 2 subjects) or 24 weeks (genotype 3 subjects) in a Phase 2, open-label clinical trial. The adverse reactions observed were consistent with those observed in clinical studies of Sovaldi plus ribavirin in adults. Among pediatric subjects 3 years to < 12 years of age taking Sovaldi in combination with ribavirin oral solution, decreased appetite was observed in 13% (7/54) subjects.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Sovaldi. Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiac Disorders

Serious symptomatic bradycardia has been reported in patients taking amiodarone who initiate treatment with a sofosbuvir-containing regimen.

Skin And Subcutaneous Tissue Disorders

Skin rashes, sometimes with blisters or angioedema-like swelling Angioedema

What drugs interact with Sovaldi (sofosbuvir)?

Potentially Significant Drug Interactions

Sofosbuvir is a substrate of drug transporter P-gp and breast cancer resistance protein (BCRP) while the predominant circulating metabolite GS-331007 is not. Drugs that are P-gp inducers in the intestine (e.g., rifampin or St. John's wort) may decrease sofosbuvir plasma concentration, leading to reduced therapeutic effect of Sovaldi, and thus concomitant use with Sovaldi is not recommended.

Information on potential drug interactions with Sovaldi is summarized in Table 7. The table is not all-inclusive.

Fluctuations in INR values may occur in patients receiving warfarin concomitant with HCV treatment, including treatment with Sovaldi. Frequent monitoring of INR values is recommended during treatment and post-treatment follow-up.

Table 7 : Potentially Significant Drug Interactions: Alteration in Dosage or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interactiona

Concomitant Drug Class: Drug NameEffect on ConcentrationbClinical Comment
Antiarrhythmics: amiodaroneEffect on amiodarone and sofosbuvir concentrations unknownCoadministration of amiodarone with a sofosbuvir-containing regimen may result in serious symptomatic bradycardia. The mechanism of this effect is unknown. Coadministration of amiodarone with Sovaldi is not recommended; if coadministration is required, cardiac monitoring is recommended.
Anticonvulsants: Carbamazepine
phenytoin
phenobarbital
oxcarbazepine
↓ sofosbuvir
↓ GS-331007
Coadministration of Sovaldi with carbamazepine, phenytoin, phenobarbital or oxcarbazepine is expected to decrease the concentration of sofosbuvir, leading to reduced therapeutic effect of Sovaldi. Coadministration is not recommended.
Antimycobacterials: Rifabutin
rifampin
rifapentine
↓ sofosbuvir
↓GS-331007
Coadministration of Sovaldi with rifabutin or rifapentine is expected to decrease the concentration of sofosbuvir, leading to reduced therapeutic effect of Sovaldi. Coadministration is not recommended. Coadministration of Sovaldi with rifampin, an intestinal P-gp inducer, is not recommended.
Herbal Supplements: St. John’s wort (Hypericum perforatum)↓ sofosbuvir
↓GS-331007
Coadministration of Sovaldi with St. John’s wort, an intestinal P-gp inducer, is not recommended.
HIV Protease Inhibitors: tipranavir/ritonavir↓ sofosbuvir
↓GS-331007
Coadministration of Sovaldi with tipranavir/ritonavir is expected to decrease the concentration of sofosbuvir, leading to reduced therapeutic effect of Sovaldi. Coadministration is not recommended.
aThis table is not all-inclusive.
b↓= decrease.

Drugs Without Clinically Significant Interactions With Sovaldi

Based on drug interaction studies conducted with Sovaldi, no clinically significant drug interactions have been either observed or are expected when Sovaldi is combined with the following drugs:

Summary

Sovaldi (sofosbuvir) is an oral, direct-acting antiviral agent used to treat infections with the hepatitis C virus (HCV). Common side effects of Sovaldi include fatigue, headache, nausea, insomnia, anemia, and itching. Other side effects of Sovaldi include decreased appetite, diarrhea, irritability, rash, muscle pain, and flu-like symptoms. Serious side effects of Sovaldi include reduced blood cells, severe depression, and increases in bilirubin levels. There hasn’t been enough research and evaluation of Sovaldi in pregnant women. However, ribavirin, which is combined with Sovaldi, should not be used in pregnant women. Researchers don’t know if Sovaldi is secreted into breast milk. Consult your doctor before breastfeeding.

Treatment & Diagnosis

Medications & Supplements

FDA Logo

Report Problems to the Food and Drug Administration

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

Medically Reviewed on 5/14/2020
References
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.
CONTINUE SCROLLING FOR RELATED SLIDESHOW