Sofosbuvir and velpatasvir

Sofosbuvir and Velpatasvir may be found in some form under the following brand names:

• Epclusa

Sofosbuvir and velpatasvir are antiviral medications that prevent hepatitis C virus (HCV) from multiplying in your body.

Sofosbuvir and velpatasvir is a combination medicine used to treat chronic hepatitis C in adults with HCV genotype 1, 2, 3, 4, 5, or 6.

This medicine is given in combination with another antiviral medicine called ribavirin in people who also have advanced cirrhosis.

Sofosbuvir and velpatasvir may also be used for purposes not listed in this medication guide.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Usual Adult Dose for Chronic Hepatitis C:

1 tablet orally once a day

Recommended Regimen and Duration of Therapy:
-Therapy-naive and therapy-experienced, without cirrhosis and with compensated cirrhosis (Child-Pugh A): Sofosbuvir-velpatasvir for 12 weeks
-Therapy-naive and therapy-experienced, with decompensated cirrhosis (Child-Pugh B or C): Sofosbuvir-velpatasvir plus ribavirin for 12 weeks

Comments:
-Dose recommendations also apply to HCV/HIV-1-coinfected patients.
-In clinical trials, therapy-experienced patients received a peginterferon alfa/ribavirin-based regimen with or without an HCV nonstructural protein 3/4A (NS3/4A) protease inhibitor (boceprevir, simeprevir, or telaprevir).
-The manufacturer product information for ribavirin should be consulted regarding dosing and dose adjustments (if applicable).

Uses: For the treatment of chronic HCV genotype 1, 2, 3, 4, 5, or 6 infection
-In patients without cirrhosis or with compensated cirrhosis
-In combination with ribavirin: In patients with decompensated cirrhosis

Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective.

Other drugs may interact with sofosbuvir and velpatasvir, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• This medicine may be used with ribavirin. If you are also taking ribavirin, talk with the doctor about the risks and side effects that may happen.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine does not stop the spread of diseases like HIV or hepatitis that are passed through blood or having sex. Do not have any kind of sex without using a latex or polyurethane condom. Do not share needles or other things like toothbrushes or razors. Talk with your doctor.
• If you are taking digoxin, talk with your doctor. You may need to have your blood work checked more closely while you are taking it with sofosbuvir and velpatasvir.
• Slow heartbeat and the need to get a pacemaker have happened when amiodarone was given with sofosbuvir and certain other hepatitis C drugs. Sometimes, this has been deadly. Slow heartbeat has happened up to 2 weeks after starting hepatitis C treatment. You will need to be watched closely if you will be taking amiodarone with hepatitis C treatment. Follow what your doctor has told you to do. Call your doctor right away if you have signs of slow heartbeat like chest pain, confusion, dizziness, passing out or near-passing out, memory problems, shortness of breath, tiredness, or weakness.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.

• Antihepaciviral, NS5A Inhibitor
• Antihepaciviral, Polymerase Inhibitor (Anti-HCV)
• NS5A Inhibitor
• NS5B RNA Polymerase Inhibitor

Sofosbuvir: Sofosbuvir AUC0-24 were 126% and 143% higher in moderate and severe hepatic impairment, while the GS-331007 AUC0-24 were 18% and 9% higher, respectively. Population pharmacokinetics analysis in HCV-infected subjects indicated that cirrhosis (including decompensated cirrhosis) had no clinically relevant effect on the exposure of sofosbuvir and GS-331007.

There are no contraindications listed in the manufacturer's labeling. If sofosbuvir/velpatasvir is administered with ribavirin, the contraindications to ribavirin also apply. See ribavirin manufacturer's labeling information.

Canadian labeling: Hypersensitivity to sofosbuvir, velpatasvir, or any component of the formulation. If sofosbuvir/velpatasvir is administered with ribavirin, the contraindications to ribavirin also apply. See ribavirin manufacturer's labeling information.

Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Per US labeling: reduce afatinib by 10mg if not tolerated. Per Canadian labeling: avoid combination if possible; if used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification

Amiodarone: Sofosbuvir may enhance the bradycardic effect of Amiodarone. Avoid combination

Antacids: May decrease the serum concentration of Velpatasvir. Management: Separate administration of velpatasvir and antacids by at least 4 hours. Consider therapy modification

Asunaprevir: OATP1B1/SLCO1B1 Inhibitors may increase the serum concentration of Asunaprevir. Avoid combination

AtorvaSTATin: Velpatasvir may increase the serum concentration of AtorvaSTATin. Monitor therapy

Betrixaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Betrixaban. Management: Decrease the betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-glycoprotein inhibitor. Consider therapy modification

Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Management: Consider alternatives when possible; bilastine should be avoided in patients with moderate to severe renal insufficiency who are receiving p-glycoprotein inhibitors. Consider therapy modification

Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy

CarBAMazepine: May decrease the serum concentration of Sofosbuvir. Avoid combination

Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Monitor therapy

Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Consider therapy modification

CYP2B6 Inducers (Moderate): May decrease the serum concentration of Velpatasvir. Avoid combination

CYP2C8 Inducers (Strong): May decrease the serum concentration of Velpatasvir. Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Velpatasvir. Avoid combination

CYP3A4 Inducers (Strong): May decrease the serum concentration of Velpatasvir. Avoid combination

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling. Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Digoxin: Velpatasvir may increase the serum concentration of Digoxin. Monitor therapy

DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification

Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification

Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Consider therapy modification

Grazoprevir: OATP1B1/SLCO1B1 Inhibitors may increase the serum concentration of Grazoprevir. Avoid combination

H2-Antagonists: May decrease the serum concentration of Velpatasvir. Monitor therapy

Modafinil: May decrease the serum concentration of Sofosbuvir. Avoid combination

Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Monitor therapy

Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy

Nilotinib: May decrease the serum concentration of CYP2B6 Substrates. Monitor therapy

OXcarbazepine: May decrease the serum concentration of Sofosbuvir. Avoid combination

PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination

PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of Sofosbuvir. Avoid combination

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of Velpatasvir. Avoid combination

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

PHENobarbital: May decrease the serum concentration of Sofosbuvir. Avoid combination

Primidone: May decrease the serum concentration of Sofosbuvir. Avoid combination

Proton Pump Inhibitors: May decrease the serum concentration of Velpatasvir. Avoid combination

Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Monitor therapy

Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Monitor therapy

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Rifabutin: May decrease the serum concentration of Sofosbuvir. Avoid combination

Rifapentine: May decrease the serum concentration of Sofosbuvir. Avoid combination

RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy

Ritonavir: May decrease the serum concentration of Velpatasvir. Ritonavir may increase the serum concentration of Velpatasvir. Consider therapy modification

Rosuvastatin: Velpatasvir may increase the serum concentration of Rosuvastatin. Consider therapy modification

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Avoid combination

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Tenofovir Disoproxil Fumarate: Velpatasvir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Monitor therapy

Tipranavir: May decrease the serum concentration of Sofosbuvir. Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Topotecan: Velpatasvir may increase the serum concentration of Topotecan. Avoid combination

Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Consider therapy modification

VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination

Vitamin K Antagonists (eg, warfarin): Antihepaciviral NS5B RNA Polymerase Inhibitors may diminish the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Voxilaprevir: OATP1B1/SLCO1B1 Inhibitors may increase the serum concentration of Voxilaprevir. Avoid combination

Applies to sofosbuvir / velpatasvir: oral tablet

General

The most common side effects reported with this drug were fatigue, headache, nausea, and nasopharyngitis. When this drug was studied with ribavirin, the most common side effects were fatigue, anemia, nausea, headache, insomnia, and diarrhea.

If this drug is used with ribavirin, the manufacturer product information for ribavirin should be consulted for associated side effects.[Ref]

Other

Very common (10% or more): Fatigue (up to 32%)
Common (1% to 10%): Asthenia, irritability[Ref]

Nervous system

Very common (10% or more): Headache (up to 29%)[Ref]

Hematologic

Very common (10% or more): Anemia (26%), decreased hemoglobin (up to 23%)[Ref]

Decreases in hemoglobin to less than 10 g/dL and 8.5 g/dL during combination therapy were reported in 23% and 7% of subjects, respectively.[Ref]

Gastrointestinal

Very common (10% or more): Nausea (up to 15%)
Common (1% to 10%): Diarrhea, increased lipase[Ref]

Isolated, asymptomatic lipase elevations (greater than 3 times the upper limit of normal [3 x ULN]) were reported in up to 6% of subjects.[Ref]

Respiratory

Very common (10% or more): Nasopharyngitis (up to 12%)
Common (1% to 10%): Cough

Psychiatric

Very common (10% or more): Insomnia (up to 11%)
Uncommon (0.1% to 1%): Depressed mood[Ref]

Cardiovascular

Severe bradycardia and heart block have been reported when sofosbuvir plus another direct-acting antiviral was used with concomitant amiodarone and/or other agents that lower heart rate.

Serious symptomatic bradycardia has been reported in patients taking amiodarone who started therapy with a regimen containing sofosbuvir.[Ref]

Frequency not reported: Severe bradycardia, heart block
Postmarketing reports: Serious symptomatic bradycardia (including fatal cardiac arrest, cases requiring pacemaker intervention)[Ref]

Dermatologic

Common (1% to 10%): Rash
Postmarketing reports: Skin rashes (sometimes with blisters or angioedema-like swelling), angioedema[Ref]

Musculoskeletal

Common (1% to 10%): Back pain, arthralgia, increased creatine kinase[Ref]

Isolated, asymptomatic creatine kinase elevations (at least 10 x ULN) were reported in up to 2% of subjects.[Ref]

Hepatic

Increased indirect bilirubin (up to 3 mg/dL above baseline) was reported in HIV-1/HCV-coinfected patients using this drug and an atazanavir/ritonavir-based antiretroviral regimen.[Ref]

Frequency not reported: Increased indirect bilirubin[Ref]

Some side effects of sofosbuvir / velpatasvir may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

1 tablet orally once a day

Recommended Regimen and Duration of Therapy:
-Therapy-naive and therapy-experienced, without cirrhosis and with compensated cirrhosis (Child-Pugh A): Sofosbuvir-velpatasvir for 12 weeks
-Therapy-naive and therapy-experienced, with decompensated cirrhosis (Child-Pugh B or C): Sofosbuvir-velpatasvir plus ribavirin for 12 weeks

Comments:
-Dose recommendations also apply to HCV/HIV-1-coinfected patients.
-In clinical trials, therapy-experienced patients received a peginterferon alfa/ribavirin-based regimen with or without an HCV nonstructural protein 3/4A (NS3/4A) protease inhibitor (boceprevir, simeprevir, or telaprevir).
-The manufacturer product information for ribavirin should be consulted regarding dosing and dose adjustments (if applicable).

Uses: For the treatment of chronic HCV genotype 1, 2, 3, 4, 5, or 6 infection
-In patients without cirrhosis or with compensated cirrhosis
-In combination with ribavirin: In patients with decompensated cirrhosis