Epclusa

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

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

If you also take omeprazole (Prilosec) or an antacid, do not take it for at least 4 hours after you have taken your dose of sofosbuvir and velpatasvir (with food).

Taking this medication will not prevent you from passing hepatitis C to other people. Do not have unprotected sex or share razors or toothbrushes. Talk with your doctor about safe ways to prevent HCV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

• Importance of reading patient information provided by the manufacturer.1

• Advise patients to take sofosbuvir/velpatasvir once daily (with or without food) on a regular dosing schedule.1

• Importance of taking the recommended dosage of sofosbuvir/velpatasvir for the recommended duration of treatment;1 importance of not missing doses.1

• Inform patients that reactivation of HBV infection has occurred in coinfected patients being treated for HCV infection.25 Importance of informing clinician of any history of HBV infection or other liver problems (e.g., cirrhosis).25 Importance of immediately contacting a clinician if any signs or symptoms of serious liver injury (e.g., fatigue, weakness, loss of appetite, nausea and vomiting, yellowing of the eyes or skin, light-colored bowel movements) occur.25 (See Risk of HBV Reactivation in Patients Coinfected with HCV and HBV under Cautions.)

• If sofosbuvir/velpatasvir is used in a patient receiving amiodarone, advise the patient about the risk of serious symptomatic bradycardia and the importance of immediately contacting a clinician if signs or symptoms of bradycardia (e.g., near-fainting or fainting, dizziness, lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pain, confusion, memory problems) occur.1 (See Cardiovascular Effects under Cautions.)

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 If used in conjunction with ribavirin, advise men and women of importance of using 2 forms of effective contraception during and for 6 months after ribavirin therapy.1 349 377 (See Precautions Related to Fixed Combinations and Multiple-drug Treatment Regimens under Cautions.)

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

Sofosbuvir and velpatasvir combination is used with or without ribavirin to treat chronic hepatitis C infection in adults (including with or without cirrhosis).

This medicine is available only with your doctor's prescription.

Along with its needed effects, a medicine 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:

• Chest pain or discomfort
• lightheadedness, dizziness or fainting
• slow or irregular heartbeat
• trouble breathing
• unconsciousness
• unusual tiredness

Some side effects 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:

• Headache
• unusual tiredness or weakness

• Diarrhea
• discouragement
• feeling sad or empty
• irritability
• lack of appetite, nausea
• lack or loss of strength
• loss of interest or pleasure
• rash
• trouble concentrating
• trouble sleeping

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• Store in the original container at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Epclusa or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Epclusa. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Each Epclusa tablet contains 400 mg of sofosbuvir and 100 mg of velpatasvir. The tablets are pink, diamond-shaped, film-coated, and debossed with "GSI" on one side and "7916" on the other side.

Pregnancy

Risk Summary

If Epclusa 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 Epclusa poses a risk to pregnancy outcomes. In animal reproduction studies, no evidence of adverse developmental outcomes was observed with the components of Epclusa (sofosbuvir or velpatasvir) at exposures greater than those in humans at the recommended human dose (RHD) [see Data]. During organogenesis in the mouse, rat, and rabbit, systemic exposures (AUC) to velpatasvir were approximately 31 (mice), 6 (rats), and 0.4 (rabbits) times the exposure in humans at the RHD, while exposures to the predominant circulating metabolite of sofosbuvir (GS-331007) were approximately 4 (rats) and 10 (rabbits) times the exposure in humans at the RHD. In rat pre/postnatal development studies, maternal systemic exposures (AUC) to velpatasvir and GS-331007 were approximately 5 times the exposures of each component in humans at the RHD.

The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.

Data

Sofosbuvir: Sofosbuvir was administered orally to pregnant rats (up to 500 mg/kg/day) and rabbits (up to 300 mg/kg/day) on gestation days 6 to 18 and 6 to 19, respectively, and also to rats (oral doses up to 500 mg/kg/day) on gestation day 6 to lactation/post-partum day 20. No significant effects on embryo-fetal (rats and rabbits) or pre/postnatal (rats) development were observed at the highest doses tested. The systemic exposures (AUC) of the predominant circulating metabolite of sofosbuvir (GS-331007) during gestation were approximately 4 (rats) and 10 (rabbits) times the exposure in humans at the RHD.

Velpatasvir: Velpatasvir was administered orally to pregnant mice (up to 1000 mg/kg/day), rats (up to 200 mg/kg/day) and rabbits (up to 300 mg/kg/day) on gestation days 6 to 15, 6 to 17, and 7 to 20, respectively, and also to rats (oral doses up to 200 mg/kg) on gestation day 6 to lactation/post-partum day 20. No significant effects on embryo-fetal (mice, rats, and rabbits) or pre/postnatal (rats) development were observed at the highest doses tested. The systemic exposures (AUC) of velpatasvir during gestation were approximately 31 (mice), 6 (rats), and 0.4 (rabbits) times the exposure in humans at the RHD.

Lactation

Risk Summary

It is not known whether the components of Epclusa and its metabolites are present in human breast milk, affect human milk production, or have effects on the breastfed infant. The predominant circulating metabolite of sofosbuvir (GS-331007) was the primary component observed in the milk of lactating rats administered sofosbuvir, without effect on nursing pups. When administered to lactating rats, velpatasvir was detected in the milk of lactating rats and in the plasma of nursing pups without effects on the nursing pups [see Data].

The development and health benefits of breastfeeding should be considered along with the mother's clinical need for Epclusa and any potential adverse effects on the breastfed child from Epclusa or from the underlying maternal condition.

If Epclusa is administered with ribavirin, the nursing mother's information for ribavirin also applies to this combination regimen. Refer to the ribavirin prescribing information for more information on use during lactation.

Data

Sofosbuvir: No effects of sofosbuvir on growth and postnatal development were observed in nursing pups at the highest dose tested in rats. Maternal systemic exposure (AUC) to the predominant circulating metabolite of sofosbuvir (GS-331007) was approximately 5 times the exposure in humans at the RHD, with exposure of approximately 2% that of maternal exposure observed in nursing pups on lactation day 10. In a lactation study, sofosbuvir metabolites (primarily GS-331007) were excreted into the milk of lactating rats following administration of a single oral dose of sofosbuvir (20 mg/kg) on lactation day 2, with milk concentrations of approximately 10% that of maternal plasma concentrations observed 1 hour post-dose.

Velpatasvir: No effects of velpatasvir on growth and postnatal development were observed in nursing pups at the highest dose tested in rats. Maternal systemic exposure (AUC) to velpatasvir was approximately 5 times the exposure in humans at the RHD. Velpatasvir was present in the milk (approximately 173% that of maternal plasma concentrations) of lactating rats following a single oral dose of velpatasvir (30 mg/kg), and systemic exposure (AUC) in nursing pups was approximately 4% that of maternal exposure on lactation day 10.

Females and Males of Reproductive Potential

If Epclusa is administered with ribavirin, the information for ribavirin with regard to pregnancy testing, contraception, and infertility also applies to this combination regimen. Refer to ribavirin prescribing information for additional information.

Pediatric Use

Safety and effectiveness of Epclusa have not been established in pediatric patients.

Geriatric Use

Clinical trials of Epclusa included 156 subjects aged 65 and over (12% of total number of subjects in the Phase 3 clinical trials). No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. No dosage adjustment of Epclusa is warranted in geriatric patients [see Clinical Pharmacology (12.3)].

Renal Impairment

No dosage adjustment of Epclusa is required for patients with mild or moderate renal impairment. The safety and efficacy of Epclusa have not been established in patients with severe renal impairment (eGFR less than 30 mL/min/1.73 m2) or ESRD requiring hemodialysis. No dosage recommendation can be given for patients with severe renal impairment or ESRD [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)]. Refer to ribavirin prescribing information regarding use of ribavirin in patients with renal impairment.

Hepatic Impairment

No dosage adjustment of Epclusa is required for patients with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, or C) [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14)].

Clinical and hepatic laboratory monitoring (including direct bilirubin), as clinically indicated, is recommended for patients with decompensated cirrhosis receiving treatment with Epclusa and ribavirin [see Adverse Reactions (6.1)].

Each Epclusa tablet contains 400 mg of sofosbuvir and 100 mg of velpatasvir, is pink, diamond-shaped, film-coated, debossed with "GSI" on one side and "7916" on the other. Each bottle contains 28 tablets (NDC 61958-2201-1), polyester coil, and is closed with a child-resistant closure.

Store below 30 °C (86 °F). Dispense only in original container.

NDC 61958-2201-1
28 tablets

Epclusa®
(sofosbuvir and velpatasvir)
tablets
400 mg / 100 mg

Take 1 tablet once daily

Note to pharmacist:
Do not cover ALERT box with pharmacy label.

ALERT: Find out about medicines that
should NOT be taken with Epclusa

Epclusa contains a combination of sofosbuvir and velpatasvir. Sofosbuvir and velpatasvir are antiviral medications that prevent hepatitis C virus (HCV) from multiplying in your body.

Epclusa is used to treat chronic hepatitis C in adults with HCV genotype 1, 2, 3, 4, 5, or 6.

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

You should not use Epclusa if you are allergic to sofosbuvir or velpatasvir.

To make sure Epclusa is safe for you, tell your doctor if you have:

• a history of hepatitis B;

• kidney disease (or if you are on dialysis);

• liver problems other than hepatitis;

• HIV (human immunodeficiency virus); or

• if you have recently used a heart rhythm medicine called amiodarone (Cordarone, Pacerone).

It is not known whether Epclusa will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Epclusa is sometimes used in combination with ribavirin. Ribavirin can cause birth defects or death in an unborn baby. You may need to have a negative pregnancy test before using these medications together, and every month during your treatment.

• If you are a woman, do not use Epclusa with ribavirin if you are pregnant.

• If you are a man, do not use this drug combination if your sexual partner is pregnant. An unborn baby could also be harmed if a man fathers the child while he is taking ribavirin.

• Use effective birth control to prevent pregnancy while either sexual partner is using these medications together. Keep using this birth control for at least 6 months after treatment ends. Tell your doctor right away if a pregnancy occurs while either the mother or the father is using Epclusa with ribavirin.

It is not known whether sofosbuvir and velpatasvir passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

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 Epclusa may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Animal studies have failed to reveal evidence of fetal harm. There are no controlled data in human pregnancy. Pregnancy must be avoided in female patients and female partners of male patients using a ribavirin-containing regimen. All animal species exposed to ribavirin have shown significant teratogenic and/or embryocidal effects. Females of reproductive potential and their male partners should not receive ribavirin unless they are using effective contraception during therapy and for 6 months after therapy. AU TGA pregnancy category B1: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have not shown evidence of an increased occurrence of fetal damage. AU TGA pregnancy category X: Drugs which have such a high risk of causing permanent damage to the fetus that they should not be used in pregnancy or when there is a possibility of pregnancy. US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

Combination therapy: Use of a ribavirin-containing regimen is contraindicated in pregnant women and in the male partners of women who are pregnant. Monotherapy: This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus. -According to some authorities: As a precaution, use is not recommended. For combination therapy: -AU TGA pregnancy category: X For monotherapy: -AU TGA pregnancy category: B1 -US FDA pregnancy category: Not assigned. Risk summary: No data available on use of this drug in pregnant women to inform a drug-related risk. Comments: -If applicable, the manufacturer product information for ribavirin should be consulted regarding use during pregnancy and use in females and males of reproductive potential. -Effective contraception is required during ribavirin therapy and for 6 months after the last dose; local protocol should be consulted regarding contraception timing.