Epclusa

Last updated on RxList: 6/16/2021
Epclusa Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Epclusa?

Epclusa (sofosbuvir and velpatasvir) is a fixed-dose combination of a hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitor, and an HCV NS5A inhibitor, and is indicated for the treatment of adult patients with chronic HCV genotype 1, 2, 3, 4, 5 or 6 infection: without cirrhosis or with compensated cirrhosis; or with decompensated cirrhosis for use in combination with ribavirin.

What Are Side Effects of Epclusa?

Common side effects of Epclusa include:

  • headache
  • fatigue
  • low blood iron (anemia)
  • nausea
  • insomnia
  • diarrhea
  • weakness
  • rash
  • depression

Dosage for Epclusa

The recommended dosage of Epclusa is one tablet (400 mg of sofosbuvir and 100 mg of velpatasvir) taken orally once daily with or without food.

What Drugs, Substances, or Supplements Interact with Epclusa?

Epclusa may interact with:

  • rifampin and other antimycobacterials,
  • St. John's wort,
  • carbamazepine and other anticonvulsants,
  • antacids,
  • H2-receptor antagonists,
  • proton-pump inhibitors,
  • antiarrhythmics,
  • topotecan,
  • HIV antiretrovirals, and
  • HMG-CoA reductase inhibitors

Epclusa During Pregnancy and Breastfeeding

Tell your doctor all medications and supplements you use. Epclusa is not recommended for use during pregnancy. It is also not recommended for men whose female partners are pregnant. It is unknown if Epclusa passes into breast milk. Consult your doctor before breastfeeding.

Additional Information

Our Epclusa (sofosbuvir and velpatasvir) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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Epclusa Consumer Information

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Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have new or worsening symptoms such as:

  • loss of appetite, upper stomach pain;
  • dark urine, clay-colored stools; or
  • jaundice (yellowing of the skin or eyes).

If you also take a heart rhythm medicine called amiodarone: Taking amiodarone with sofosbuvir and velpatasvir can cause dangerous side effects on your heart. Get medical help right away if you take these medicines and you have:

  • very slow heartbeats, chest pain, shortness of breath;
  • confusion, memory problems; or
  • weakness, extreme tiredness, light-headed feeling (like you might pass out).

Common side effects may include:

  • headache;
  • tiredness;
  • nausea, diarrhea; or
  • sleep problems (insomnia).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Epclusa (Sofosbuvir and Velpatasvir Fixed-dose Combination Tablets)

QUESTION

Hepatitis C virus causes an infection of the ______________. See Answer
Epclusa Professional Information

SIDE EFFECTS

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

  • Serious Symptomatic Bradycardia When Coadministered with Amiodarone [see WARNINGS AND PRECAUTIONS].

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 EPCLUSA is administered with ribavirin, refer to the prescribing information for ribavirin for a description of ribavirin-associated adverse reactions.

Clinical Trials In Adult Subjects

Adverse Reactions In Subjects Without Cirrhosis Or With Compensated Cirrhosis

The adverse reactions data for EPCLUSA in patients without cirrhosis or with compensated cirrhosis were derived from three Phase 3 clinical trials (ASTRAL-1, ASTRAL-2, and ASTRAL-3) which evaluated a total of 1035 subjects infected with genotype 1, 2, 3, 4, 5, or 6 HCV, without cirrhosis or with compensated cirrhosis, who received EPCLUSA for 12 weeks. EPCLUSA was studied in placebo- and active-controlled trials [see Clinical Studies].

The proportion of subjects who permanently discontinued treatment due to adverse events was 0.2% for subjects who received EPCLUSA for 12 weeks.

The most common adverse reactions (adverse events assessed as causally related by the investigator and at least 10%) were headache and fatigue in subjects treated with EPCLUSA for 12 weeks.

Adverse reactions, all grades, observed in greater than or equal to 5% of subjects receiving 12 weeks of treatment with EPCLUSA in ASTRAL-1 include headache (22%), fatigue (15%), nausea (9%), asthenia (5%), and insomnia (5%). Of subjects receiving EPCLUSA who experienced these adverse reactions, 79% had an adverse reaction of mild severity (Grade 1). With the exception of asthenia, each of these adverse reactions occurred at a similar frequency or more frequently in subjects treated with placebo compared to subjects treated with EPCLUSA (asthenia: 3% versus 5% for the placebo and EPCLUSA groups, respectively).

The adverse reactions observed in subjects treated with EPCLUSA in ASTRAL-2 and ASTRAL-3 were consistent with those observed in ASTRAL-1. Irritability was also observed in greater than or equal to 5% of subjects treated with EPCLUSA in ASTRAL-3.

Adverse Reactions In Subjects Coinfected With HCV And HIV-1

The safety assessment of EPCLUSA in subjects with HCV/HIV-1 coinfection was based on an open-label clinical trial (ASTRAL-5) in 106 subjects who were on stable antiretroviral therapy [see Clinical Studies]. The safety profile in HCV/HIV-1 coinfected subjects was similar to that observed in HCV mono-infected subjects. The most common adverse reactions occurring in at least 10% of subjects were fatigue (22%) and headache (10%).

Adverse Reactions In Subjects With Decompensated Cirrhosis

The safety assessment of EPCLUSA in subjects infected with genotype 1, 2, 3, 4, or 6 HCV with decompensated cirrhosis was based on one Phase 3 trial (ASTRAL-4) including 87 subjects who received EPCLUSA with ribavirin for 12 weeks. All 87 subjects had Child-Pugh B cirrhosis at screening. On the first day of treatment with EPCLUSA with ribavirin, 6 subjects and 4 subjects were assessed to have Child-Pugh A and Child-Pugh C cirrhosis, respectively [see Clinical Studies].

The most common adverse reactions (adverse events assessed as causally related by the investigator, all grades with frequency of 10% or greater) in the 87 subjects who received EPCLUSA with ribavirin for 12 weeks were fatigue (32%), anemia (26%), nausea (15%), headache (11%), insomnia (11%), and diarrhea (10%). Of subjects who experienced these adverse reactions, 98% had adverse reactions of mild to moderate severity.

A total of 4 (5%) subjects permanently discontinued EPCLUSA with ribavirin due to an adverse event; there was no adverse event leading to discontinuation that occurred in more than 1 subject.

Decreases in hemoglobin to less than 10 g/dL and 8.5 g/dL during treatment were observed in 23% and 7% of subjects treated with EPCLUSA with ribavirin for 12 weeks, respectively. Ribavirin was permanently discontinued in 17% of subjects treated with EPCLUSA with ribavirin for 12 weeks, due to adverse reactions.

Less Common Adverse Reactions Reported In Clinical Trials

The following adverse reactions occurred in less than 5% of subjects without cirrhosis or with compensated cirrhosis treated with EPCLUSA for 12 weeks and are included because of a potential causal relationship.

Rash: In the ASTRAL-1 study, rash occurred in 2% of subjects treated with EPCLUSA and in 1% of subjects treated with placebo. No serious adverse reactions of rash occurred, and all rashes were mild or moderate in severity.

Depression: In the ASTRAL-1 study, depressed mood occurred in 1% of subjects treated with EPCLUSA and was not reported by any subject taking placebo. No serious adverse reactions of depressed mood occurred, and all events were mild or moderate in severity.

The following adverse reactions occurred in less than 10% of subjects with decompensated cirrhosis (ASTRAL-4) treated with EPCLUSA with ribavirin for 12 weeks and are included because of a potential causal relationship.

Rash: Rash occurred in 5% of subjects treated with EPCLUSA with ribavirin. No serious adverse reactions of rash occurred, and all rashes were mild or moderate in severity.

Laboratory Abnormalities

Lipase Elevations

In ASTRAL-1, isolated, asymptomatic lipase elevations of greater than 3xULN were observed in 3% and 1% of subjects treated with EPCLUSA and placebo for 12 weeks, respectively; and in 6% and 3% of subjects treated with EPCLUSA in ASTRAL-2 and ASTRAL-3, respectively.

In the Phase 3 trial of subjects with decompensated cirrhosis (ASTRAL-4), lipase was assessed when amylase values were greater than or equal to 1.5xULN. Isolated, asymptomatic lipase elevations of greater than 3xULN were observed in 2% of subjects treated with EPCLUSA with ribavirin for 12 weeks.

Creatine Kinase

In ASTRAL-1, isolated, asymptomatic creatine kinase elevations greater than or equal to 10xULN were reported in 1% and 0% of subjects treated with EPCLUSA and placebo for 12 weeks, respectively; and in 2% and 1% of subjects treated with EPCLUSA in ASTRAL-2 and ASTRAL-3, respectively.

In the Phase 3 trial with decompensated cirrhosis (ASTRAL-4), isolated, asymptomatic creatine kinase elevations greater than or equal to 10xULN were reported in 1% of subjects treated with EPCLUSA with ribavirin for 12 weeks.

Indirect Bilirubin

Increases in indirect bilirubin up to 3 mg/dL above baseline were noted among HIV-1/HCV coinfected subjects treated with EPCLUSA and an atazanavir/ritonavir-based antiretroviral regimen. The elevated indirect bilirubin values were not associated with clinical adverse events, and all subjects completed 12 weeks of EPCLUSA without dose adjustment or treatment interruption of either EPCLUSA or HIV antiretroviral agents.

Adverse Reactions In Adult Liver Transplant Recipients

The safety assessment of EPCLUSA in liver transplant recipients was based on an open-label clinical trial (Trial 2104) in 79 adults without cirrhosis or with compensated cirrhosis who received EPCLUSA for 12 weeks [see Clinical Studies]. One subject discontinued treatment due to an adverse event on Day 7. The adverse reactions observed were consistent with the known safety profile of EPCLUSA. Adverse reactions occurring in at least 5% of subjects were headache (18%), fatigue (15%), nausea (8%), diarrhea (6%), and asthenia (5%).

Adverse Reactions In Adults With Severe Renal Impairment Requiring Dialysis

In an open-label trial (Trial 4062), in which a total of 59 adults with HCV with compensated liver disease (with or without cirrhosis) and ESRD requiring dialysis received EPCLUSA for 12 weeks, the most common adverse reaction was nausea (7%) [see Clinical Studies].

Adverse Reactions In Pediatric Subjects 3 Years Of Age And Older

The safety assessment of EPCLUSA in pediatric subjects 3 years of age and older is based on data from a Phase 2, open-label clinical trial (Study 1143) that enrolled 216 subjects who were treated with EPCLUSA for 12 weeks [see Clinical Studies]. The adverse reactions observed in pediatric subjects 6 years of age and older were consistent with those observed in clinical trials of EPCLUSA in adults.

Among the 41 pediatric subjects less than 6 years of age, gastrointestinal adverse reactions were reported more commonly compared to subjects 6 years of age and older. Vomiting and product use issue (spitting up the drug) were reported in 15% and 10% of subjects, respectively; these adverse reactions were mild (Grade 1 or 2) and led to treatment discontinuation in 5 (12%) subjects [see Use In Specific Populations and Clinical Studies].

Postmarketing Experience

The following adverse reactions have been identified during post approval use of sofosbuvir. 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 [see WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS].

Skin And Subcutaneous Tissue Disorders

Skin rashes, sometimes with blisters or angioedema-like swelling

Angioedema

DRUG INTERACTIONS

Potential For Other Drugs To Affect EPCLUSA

Sofosbuvir and velpatasvir are substrates of drug transporters P-gp and BCRP while GS-331007 (the predominant circulating metabolite of sofosbuvir) is not. In vitro, slow metabolic turnover of velpatasvir by CYP2B6, CYP2C8, and CYP3A4 was observed.

Drugs that are inducers of P-gp and/or moderate to strong inducers of CYP2B6, CYP2C8, or CYP3A4 (e.g., rifampin, St. John's wort, carbamazepine) may decrease plasma concentrations of sofosbuvir and/or velpatasvir, leading to reduced therapeutic effect of EPCLUSA. The use of these agents with EPCLUSA is not recommended [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. EPCLUSA may be coadministered with P-gp, BCRP, and CYP inhibitors.

Potential For EPCLUSA To Affect Other Drugs

Velpatasvir is an inhibitor of drug transporters P-gp, breast cancer resistance protein (BCRP), OATP1B1, OATP1B3, and OATP2B1. Coadministration of EPCLUSA with drugs that are substrates of these transporters may increase the exposure of such drugs.

Established And Potentially Significant Drug Interactions

Clearance of HCV infection with direct acting antivirals may lead to changes in hepatic function, which may impact the safe and effective use of concomitant medications. For example, altered blood glucose control resulting in serious symptomatic hypoglycemia has been reported in diabetic patients in postmarketing case reports and published epidemiological studies. Management of hypoglycemia in these cases required either discontinuation or dose modification of concomitant medications used for diabetes treatment.

Frequent monitoring of relevant laboratory parameters (e.g., 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 (e.g., certain immunosuppressants) is recommended to ensure safe and effective use. Dose adjustments of concomitant medications may be necessary.

Table 4 provides a listing of established or potentially clinically significant drug interactions. The drug interactions described are based on studies conducted with either EPCLUSA, the components of EPCLUSA (sofosbuvir and velpatasvir) as individual agents, or are predicted drug interactions that may occur with EPCLUSA [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].

Table 4 : Potentially Significant Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interactiona

Concomitant Drug Class: Drug Name Effect on Concentrationb Clinical Effect/Recommendation
Acid Reducing Agents: ↓ velpatasvir Velpatasvir solubility decreases as pH increases. Drugs that increase gastric pH are expected to decrease concentration of velpatasvir.
Antacids (e.g., aluminum and magnesium hydroxide) Separate antacid and EPCLUSA administration by 4 hours.
H2-receptor antagonistsc (e.g., famotidine) H2-receptor antagonists may be administered simultaneously with or 12 hours apart from EPCLUSA at a dose that does not exceed doses comparable to famotidine 40 mg twice daily.
Proton-pump inhibitorsc (e.g., omeprazole) Coadministration of omeprazole or other proton-pump inhibitors is not recommended. If it is considered medically necessary to coadminister, EPCLUSA should be administered with food and taken 4 hours before omeprazole 20 mg. Use with other proton-pump inhibitors has not been studied.
Antiarrhythmics: amiodarone Effect on amiodarone, sofosbuvir, and velpatasvir concentrations unknown Coadministration of amiodarone with a sofosbuvir-containing regimen may result in serious symptomatic bradycardia. The mechanism of this effect is unknown. Coadministration of amiodarone with EPCLUSA is not recommended; if coadministration is required, cardiac monitoring is recommended [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS].
digoxinc ↑ digoxin Therapeutic concentration monitoring of digoxin is recommended when coadministered with EPCLUSA. Refer to digoxin prescribing information for monitoring and dose modification recommendations for concentration increases of less than 50%.
Anticancers: topotecan ↑ topotecan Coadministration is not recommended.
Anticonvulsants: carbamazepinec phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir Coadministration is not recommended.
Antimycobacterials: rifabutinc rifampinc rifapentine ↓ sofosbuvir ↓velpatasvir Coadministration is not recommended.
HIV Antiretrovirals: efavirenzc ↓velpatasvir Coadministration of EPCLUSA with efavirenz-containing regimens is not recommended.
Regimens containing tenofovir DF ↑ tenofovir Monitor for tenofovir-associated adverse reactions in patients receiving EPCLUSA concomitantly with a regimen containing tenofovir DF. Refer to the prescribing information of the tenofovir DF-containing product for recommendations on renal monitoring.
tipranavir/ritonavir ↓ sofosbuvir ↓ velpatasvir Coadministration is not recommended.
Herbal Supplements: St. John’s wort (Hypericum perforatum) ↓ sofosbuvir ↓ velpatasvir Coadministration is not recommended.
HMG-CoA Reductase Inhibitors: rosuvastatinc ↑ rosuvastatin Coadministration of EPCLUSA with rosuvastatin may significantly increase the concentration of rosuvastatin, which is associated with increased risk of myopathy, including rhabdomyolysis. Rosuvastatin may be administered with EPCLUSA at a dose that does not exceed 10 mg.
atorvastatinc ↑ atorvastatin Coadministration of EPCLUSA with atorvastatin may be associated with increased risk of myopathy, including rhabdomyolysis. Monitor closely for HMG-CoA reductase inhibitor-associated adverse reactions, such as myopathy and rhabdomyolysis.
DF = disoproxil fumarate.
a This table is not all inclusive.
b ↓ = decrease, ↑ = increase.
c These interactions have been studied in healthy adults.

Drugs Without Clinically Significant Interactions With EPCLUSA

Based on drug interaction studies conducted with the components of EPCLUSA (sofosbuvir or velpatasvir) or EPCLUSA, no clinically significant drug interactions have been observed with the following drugs [see CLINICAL PHARMACOLOGY]:

  • EPCLUSA: atazanavir/ritonavir, cyclosporine, darunavir/ritonavir, dolutegravir, elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, emtricitabine, raltegravir, or rilpivirine.
  • Sofosbuvir: ethinyl estradiol/norgestimate, methadone, or tacrolimus.
  • Velpatasvir: ethinyl estradiol/norgestimate, ketoconazole, or pravastatin.

See Table 4 for use of EPCLUSA with certain HIV antiretroviral regimens [see DRUG INTERACTIONS].

Read the entire FDA prescribing information for Epclusa (Sofosbuvir and Velpatasvir Fixed-dose Combination Tablets)

© Epclusa Patient Information is supplied by Cerner Multum, Inc. and Epclusa Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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