The POSITIVELY AWARE Viral Hepatitis Drug Guide includes medications for the treatment of hepatitis B (HBV) and hepatitis C (HCV) that are FDA approved. Also included are medications that have an “off-label” recommendation—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.
Treatment
Treatment is comprised of two or more medications—all pills—taken together. Some treatments are a fixed-dose combination (FDC) that contains medications from at least two 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. Some regimens may include weight-based ribavirin. Pegylated interferon is no longer used for HCV treatment.
There are no combination therapies for Hepatitis B (HBV) at the moment, as it is treated with one medication at a time—either with an antiviral such as Viread (tenofovir), Epivir-HBV (lamivudine), or with pegylated interferon. The goal of HBV treatment is to slow or prevent the progression of liver disease. Hepatitis B treatment does not lead to a cure. Despite a concerted effort to develop a cure for HBV, we are many years away from achieving this goal.
What’s new in 2020?
There are no new HCV drugs under development in the United States; we have all the HCV treatments needed to cure nearly everyone. The challenge is helping people access treatment due to insurance restrictions and other barriers. If the U.S. committed itself to treating and curing everyone with HCV, we have the medications to do it.
Similarly, we don’t have any new drugs for HBV treatment that are close to reviewing. More than 50 HBV drugs and therapeutic vaccines are under development, but most are in the early stages of clinical trial development and are many years away from FDA approval. As new drugs are developed and get closer to FDA approval, Positively Aware will report on them and include them in future editions of the Drug Guide.
Each drug page will include, where applicable:
Drug names
Drug names can be confusing. We include the brand name, generic name, and an abbreviation. For example, Sovaldi is the brand name of sofosbuvir. Sovaldi can be abbreviated as SOV, and sofosbuvir is abbreviated as SOF. Additionally, HCV medications contain two or more drugs, so you may see several abbreviations and common names: Mavyret has a combination of glecaprevir and pibrentasvir, with the abbreviations of GLE/PIB. Drugs that have been FDA approved will appear under their brand name, while those that have not yet reached that stage will only have a generic (or common) name.
FDA status
All medications in this year’s Drug Guide are FDA approved.
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, and four multi-class fixed-dose combinations:
• 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 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, and so on). 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
Although all HCV antivirals can be used by people with HIV, only some are specifically FDA-approved for co-infection. The others are used off-label. We will note which drugs are which.
Dosage
HBV drugs are either oral tablets or an injectable. HCV drugs are all oral, 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 like 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 can be expensive, and there is much concern over the burden these high costs 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 people who are uninsured or underinsured 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 30 of the HCV Drug Guide.
Potential side effects and adverse events
This section offers information about side effects and adverse events associated with an HCV drug. 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 drugs 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, only that you are experiencing it. Everyone experiences side effects differently: Just because it’s listed doesn’t mean you will necessarily get it. Talk to your medical provider about side effects before starting treatment, communicate with them about any you may have during treatment, and get blood tests as directed to look for side effects.
Potential drug interactions
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 with your medical provider and/or pharmacist about any medications (including over the counter medications) you are taking so you can minimize drug interactions. The information comes from the package insert and clinical trial data for 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.
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 all hepatitis C DAAs. 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 among people who were cured of HCV using DAAs that led to hepatic flares, liver failure (requiring transplant) or in some cases, death. See page 33 for more information on this warning.
Special thanks to Brooke N. Stevens, PharmD, BCPS, AAHIVP, for reviewing the 2020 POSITIVELY AWARE Hepatitis Drug Guide. Dr. Stevens is an HIV clinical pharmacist at the LifeCare Clinic at Methodist Hospital and The Ryan White Center for Pediatric Infectious Disease and Global Health at Riley Hospital for Children, both at Indiana University Health (IU Health) in Indianapolis. She currently serves as a clinical preceptor (training pharmacy students) at IU Health, and is on the clinical faculty of the Midwest AIDS Training and Education Center. She serves on the “hub team” for the HCV Project ECHO (Extension for Community Healthcare Outcomes) at the Richard M. Fairbanks School of Public Health (RMFSPH). And thanks to Walgreens Community Pharmacy in Chicago for reviewing the drug prices in this guide.