Treating Hepatitis C With Epclusa

First Drug Able to Treat All Types of HCV Infection

Photo courtesy Gilead Sciences

Epclusa (sofosbuvir and velpatasvir) is a fixed-dose combination drug used in the treatment of chronic hepatitis C (HCV) infection. The two drugs that comprise Epclusa work by blocking both an enzyme (RNA polymerase) and a protein (NS5A) vital to the replication of the virus.

Epclusa was approved in June, 2016 by the U.S. Food and Drug Administration (FDA) for use in adults 18 years of age and over and is the first direct-acting agent able to treat all six major HCV genotypes.

Epclusa is suitable for both previously untreated (treatment-naïve) patients, as well as those with partial or no response to prior HCV therapy (treatment-experienced).

Epclusa can be used in persons diagnosed with cirrhosis, although it is recommended that ribavirin is co-administered in cases of decompensated cirrhosis (i.e., where the liver is no longer functioning). Epclusa is reported to have cure rates approaching 100 percent in some groups, while its efficacy in persons with decompensated cirrhosis is said to be as high as 94 percent.

Hepatitis C Prevalence

Approximately 75 percent of Americans with HCV have genotype 1, while 20 to 25 percent have genotypes 2 or 3.  While only a small number of people in the U.S. is infected with genotypes 4, 5, or 6, they remain the predominant strains in the Middle East, southern Africa, and Asia.

In Egypt, the country with the largest HCV population, nearly one in seven people (14.5 percent) is believed to be infected.

Among people living with the HIV, the rate of HCV co-infection runs as high as 30 percent in the U.S. and Europe. Globally, the overall burden of HIV/HCV co-infection is around 4-5 million people, or between 10 and 15 percent.

Among this population, HCV therapies are considered vital with higher rates of co-existing liver impairment.

Epclusa's effectiveness in treating all major HCV genotypes makes it a particularly important drug from a global perspective, with only a few contraindications to treatments. (See "Contraindications and Considerations" below.)

Dosage and Pricing

Dosage is one tablet (400mg sofosbuvir/100mg velpatasvir) taken daily with or without food. Epclusa tablets are pink diamond-shaped, and film-coated, with "GSI" embossed on one side and "7916" on the other.

Epclusa is manufactured by Gilead Sciences, the same pharmaceutical behind the blockbuster HCV drugs Harvoni and Solvaldi. Long criticized for its headline-making prices—wherein Sovaldi was released at a wholesale price of $1,000 per pill, with Harvoni prices even higher—Gilead reversed its pricing structure by introducing Epclusa at price of $74,760 for a 12-week course (or roughly $890 per tablet).

Prescribing Recommendations

Epclusa is prescribed over a 12-week course for persons with chronic HCV infection, with or without compensated cirrhosis (in which the liver is still functional).

In persons with decompensated cirrhosis, Epclusa is prescribed for a 16-week course in combination with the drug ribavirin.

Common Side Effects

The most common side effects associated with the use of Epclusa (occurring in at least 5 percent of patients) are:

  • Headache
  • Fatigue
  • Nausea
  • Weakness and loss of energy
  • Insomnia
  • Irritability

In clinical research, side effects were generally considered low grade with less than 1 percent of participants discontinuing treatment as a result of adverse drug events.

In patients with decompensated cirrhosis, anemia and diarrhea are also commonly reported. Clinical research suggested that side effects associated with Epclusa and ribavirin use, while common, were typically mild to moderate, with only 5 percent of participants discontinuing therapy as a result of adverse drug events.

Drug Interactions

The following should also be avoided when using Epclusa:

  • Anti-cancer medication: Hycampin
  • Anticonvulsants: Tegretol, Dilantin, Trileptal, phenobarbital
  • Anti-tuberculosis medication: Mycobutin, Rifater, Rifamate, Rimactane, Rifadin, Priftin
  • HIV medication: Sustiva (efavirenz), boosted Aptivus (tipranavir/ritonavir)
  • Herbal supplements: St. John's Wort

Contraindications and Considerations

The anti-arrhythmia drug Codarone (amiodarone), used to treat irregular heartbeat, is not recommended for use with Epclusa unless deemed medically necessary. The combined use of these drugs can result in a serious slowing of the heart (bradycardia), the effect of which is still not fully understood. If co-administered, cardiac monitoring is strongly recommended.

Proton pump inhibitors are generally not recommended for use with Epclusa unless deemed medically necessary.  In such case, Epclusa should be taken with food 4 hours in advance of the proton pump inhibitor dose.

In persons co-infected with HIV who use the drug tenofovir (found in Truvada, Atripla, Complera, and Stribild), extra care should be taken when prescribing Epclusa. When used together, Epclusa can enhance kidney-related toxicities associated with tenofovir use. Regular renal monitoring is recommended.

Antacids (either aluminum- or magnesium-based) should be taken separately 4 hours before or after a Epclusa dose, while H2 receptor inhibitors (a.k.a. H2 blockers) should be taken either simultaneously with Epclusa or 12 hours apart.

The dosages of the statin drugs Lipitor (avorvastatin) and Crestor (rovustatin) may need to be reduced if prescribed alongside Epclusa as the pairing of these drugs can increase both the concentration and side effects of the cholesterol-lowering medications.

While there is no contraindication for the use of Epclusa in pregnancy, little human clinical data is available. However, animal studies into the use of both sofosbuvir and velpatasvir have shown no effect on fetal development. Specialist consultation is recommended during pregnancy to assess the urgency of Epclusa therapy, specifically whether to start immediately or to wait until after delivery.

It is recommended that all women of child-bearing age be monitored monthly for pregnancy during the course of therapy.  It is also recommended that both the woman and her male partner be provided at least two non-hormonal methods of contraception and that they be used during the course of therapy and for six months after.

Sources:

Gilead Science. "HIGHLIGHTS OF PRESCRIBING INFORMATION – EPCLUSA." Foster City, California

U.S. Food and Drug Administration. "FDA approves Epclusa for treatment of chronic hepatitis C viral infection." Silver Sand, Maryland; press release issued June 28, 2016.

Bloomberg News. "Gilead’s New Hepatitis C Drug Approved by FDA, Priced at $74,460." Article published June 28, 2016.

Mohamoud, D.; Mumtaz, G.; Riome, S.; et al. "The epidemiology of hepatitis C virus in Egypt: a systematic review and data synthesis." BMC Infectious Diseases. 2013; 13(288): DOI 10.1186/1461-2334-13-288.

American Association for the Study of Liver Disease (AASLD). "Assessing the Global and Regional Burden of Liver Disease." Washington, D.C. Press release issued November 3, 2013.

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