By Andrew Reynolds @projectinform

The POSITIVELY AWARE/Project Inform Hepatitis Drug Guide includes medications for the treatment of hepatitis B (HBV) and hepatitis C (HCV) that are FDA approved, expected to be approved this year, or are likely to be approved through June 2018. The guide also lists “off-label” recommendations (that is, treatment options that may not yet be FDA approved, but which are acceptable according to medical providers and other experts). The information provided on the FDA-approved drugs comes from the package labels, as well as other sources such as the AASLD/IDSA Recommendations for Testing, Managing, and Treating Hepatitis C (HCV Guidance), AASLD Hepatitis B Guidance, conference presentations, and medical journals. For the yet-to-be-FDA-approved drugs, the information comes from conference presentations and scientific/medical journals.

Hepatitis C treatment comprises two or more medications—all pills—taken together.  Some treatments are a fixed-dose combination (FDC) pill that contains medications from two (or more) different classes in one pill (for example, Epclusa, which is one pill containing velpatasvir and sofosbuvir), or they may be two (or more) separate pills (for example, Daklinza with Sovaldi). Some regimens may include weight-based ribavirin. There is no pegylated interferon used for the treatment of HCV any longer.

Hepatitis B is treated with one medication at a time: Either an antiviral like Viread (tenofovir) or Epivir-HBV (lamivudine), or with pegylated interferon.

What’s new in 2017?

The biggest change to this year’s edition is the addition of hepatitis B (HBV) to the Drug Guide. HBV is a significant health problem in the United States—indeed, throughout the world—and as this country moves towards a viral hepatitis elimination strategy, we must include it in the guide to raise awareness and inform people who are at risk and need testing, or who are chronically infected and need monitoring or treatment.

We have seen several additional changes in hepatitis C medications since last year’s publication as well. Sofosbuvir/velpatasvir received FDA approval in July 2016, and was given the brand name Epclusa. Additionally Viekira Pak was reformulated so it can be taken once daily, and its name was changed to Viekira XR. Harvoni was updated to include its new approval for its use in adolescents age 12 and older, marking the first FDA-approved DAA treatment for children.

A note on soon-to-be-approved DAAs: Gilead’s next treatment regimen (sofosbuvir + velpatasvir + voxilaprevir) and AbbVie’s next one (glecaprevir + pibrentasvir) will be reviewed by the FDA in July or August, well after our press date. Although we wish we could have held onto the issue until the approval of this treatment and give you the brand name and all relevant package insert information, we could not delay going to press. Upon approval, an updated drug page can be found at
positivelyaware.com which you can download and print.

Each drug page includes:

Drug names

Drug names can be confusing. We include the brand name, the generic name, and an abbreviation. For example, Sovaldi is the brand name of sofosbuvir. Sovaldi can be abbreviated as SOV; sofosbuvir is abbreviated as SOF. Drugs that have been FDA approved will have a brand name, while those that have not yet reached that stage will only have a generic (or common) name. In some cases, it might not even have a name, but rather a series of letters and numbers (for example, MK-5172). For those drugs which have been FDA approved, the brand name will appear first, at the top of the page, followed by the common name(s); for all other drugs the common or generic name will appear first.

FDA status

We will indicate if a drug is approved, and any drug that has been submitted for FDA approval will have an estimate of its approval date.

Drug class

The “direct-acting antiviral” or DAA era of HCV treatment has seen the development of several different classes of hepatitis medications. Currently, there are five classes of HCV drugs, four of them DAAs. There are currently four multi-class fixed-dose combinations. Two more are up for FDA approval in July or August: sofosbuvir + velpatasvir + voxilaprevir (from Gilead Sciences) and glecaprevir + pibrentasvir (from AbbVie). Of this following list, only the nucleoside analogs are not DAAs:

  • Nucleoside analogs
  • NS3/4A protease inhibitors
  • Nucleotide NS5B polymerase inhibitors
  • Non-nucleoside NS5B polymerase inhibitors
  • NS5A inhibitors

Genotype (HCV only)

Genotype (GT) refers to the strains or variations of HCV. Worldwide, there are as many as 11 distinct genotypes, but for this guide we will only refer to GT 1–6. In the U.S., GT 1–4 are most prevalent, with GT 1 the most common overall. Within each genotype, there are several subtypes that are indicated by numbers and letters (GT 1a, GT 1b, etc.). Although different genotypes can play a role in disease progression or severity, it is especially important to know one’s genotype to determine the correct treatment. We will list the genotype(s) that the specific HCV medication works against, both those that are FDA approved as well as those that have enough evidence to be used off-label.

Approved for HIV/HCV co-infection

We will note HCV drugs approved for use in HIV/HCV co-infected patients, both those that are FDA approved and those that are off-label.

Dosage

HBV drugs are either oral tablets or an injectable. All HCV drugs are oral, and may need to be taken at different times, and with differing food restrictions. Sometimes the same drug is taken differently depending upon a variety of factors such as genotype or liver health. This section will describe the dosage requirements for the drug, as well as provide details about restrictions and other relevant information.

Manufacturer

This section includes the name of the company that makes the drug.

Average Wholesale Price (AWP)

The AWP is the measure used by insurance companies—both private and public—to determine the average cost of prescription drugs. HCV drugs are very expensive, and there is great concern over the burden these high costs are going to place on programs such as Medicaid and Medicare, as well as the Veterans Administration and private insurance carriers. Patients should never have to pay for medications at this price, but it’s still important to know these costs when shopping for health insurance coverage. Each of the pharmaceutical companies has a Patient Assistance Program (PAP) to help uninsured and underinsured people cover all or part of the costs. There are also pharmaceutical co-pay programs and non-profit organizations that can help with some additional support for co-pays. A list of HCV drug patient assistance and co-pay programs appears on page 35.

Potential side effects and adverse events

This section offers information about side effects and adverse events associated with the drugs. It’s not an exhaustive list, but rather a selection of the most commonly reported side effects. The information comes from the package insert and study data for the FDA-approved drugs, and clinical trial data for the ones that have yet to receive FDA approval. Since HCV medications are never taken alone, we’ll cover potential side effects that are associated with the entire regimen, as opposed to a single drug. It may be hard to separate one cause of a side effect from another, and in the end, it doesn’t really matter what the cause is but only that you are experiencing it. Everyone experiences side effects differently: Just because it’s listed doesn’t mean you will automatically have it. Talk to your medical provider about side effects before starting treatment, communicate with him or her about any you may have during treatment, and get blood tests as directed to look for side effects.

A note on the risk of hepatitis B reactivation in some patients treated with Direct-Acting Antivirals (DAAs) for hepatitis C: On October 4, 2016 the FDA made a safety announcement, also known as a “Boxed Warning,” about the potential risk of HBV reactivation in some patients taking any hepatitis C DAA. A Boxed Warning is the most important warning the FDA can issue. In this case, there were a number of unexpected cases of hepatitis B reactivation in people who were cured of HCV using the DAAs, leading to hepatic flares, liver failure (some requiring transplant), or in some cases, death. See here for more information on this warning.

Potential drug interections

This section provides information about the variety of known and potential drug interactions. Like the side effects section, it’s not an exhaustive list of interactions, but rather a list of the most important ones. You can find a complete list in the package insert, but you should also talk to your medical provider and/or pharmacist about any medications you are taking so you can minimize drug interactions. The information comes from the package insert and clinical trial data for the FDA-approved drugs, and clinical trial data for the ones that have yet to receive FDA approval.

More information

This section contains information that does not fit in any of the above sections, but is still important for you to know.