HCV DRUG PAGES

DRUG CLASS

sofosbuvir: Nucleotide analog NS5B polymerase inhibitor

velpatasvir: NS5A inhibitor

Genotype: 1 2 3 4 5 6

HIV/HCV co-infection: Approved use

Manufacturer: Gilead Sciences

AWP: $29,904 / month

Dosage

A fixed-dose combination sofosbuvir 400 mg/velpatasvir 100 mg. Take one tablet once daily with or without food. Ribavirin may be included in patients with decompensated cirrhosis. Take your missed dose as soon as possible, unless it is closer to the time of your next dose. Never double your dose.

Black Box Warning

Before starting treatment with any DAA, including Epclusa, patients should take a blood test to check for hepatitis B (HBV) infection. HBV infection could get worse or reactivate again during or after DAA treatment, potentially leading to serious liver problems including liver failure or death. Patients with HBV or some with past infection should be monitored during HCV DAA treatment, and some may need to take HBV treatment. For more information, see HBV Reactivation for more information and consult your medical provider.

What are the potential side effects and adverse events?

Epclusa is a very well-tolerated medication with minimal side effects. Indeed, in the clinical trials for Epclusa, there were very few people—0.2%—who discontinued treatment due to side effects. In patients without cirrhosis or in those with compensated cirrhosis, the most commonly reported side effects are headache and fatigue. Less frequently reported side effects include nausea, insomnia, and asthenia (weakness). All of these side effects are considered to be mild. In patients with decompensated cirrhosis, the above side effects can occur, with an addition of diarrhea. Again, these are all considered mild to moderate, and very few people have to discontinue treatment because of them. Lab abnormalities such as elevations in bilirubin levels and lipase levels have been observed, and although not likely to be significant, should be monitored while undergoing treatment. Epclusa has not been studied in pregnant women or nursing mothers, so we do not know what, if any, impact it would have on fetal development or nursing babies.

If used with ribavirin, pregnant women or women who are trying to become pregnant cannot take it; women of childbearing age and their male partners must use two forms of birth control throughout treatment and for six months after treatment. Changes in hematological (blood) values are also common, and routine blood testing to look for anemia, neutropenia, and other blood conditions is recommended.

What are the potential drug interactions?

Be sure to tell your medical provider or pharmacist about all the medications, supplements, and herbs you take, whether they are prescribed, over-the-counter, or illicit, before starting this regimen, and inform them of any changes as they happen. Epclusa should not be taken within 4 hours of antacids. If taking H2-receptor antagonists, take Epclusa at the same time, otherwise you have to wait 12 hours to take it at a dose that does not exceed doses comparable to famotidine 40 mg twice per day. You can take proton pump inhibitors comparable to omeprazole 20 mg or lower, but must have an empty stomach. Epclusa should not be taken with the following HIV medications: efavirenz or tipranavir/ritonavir. It should not be taken with the antimycobacterials rifabutin, rifampin, or rifapentine, nor should it be taken with the anticonvulsants carbamazepine, phenytoin, phenobarbital, or oxcarbazepine. Do not take with the anti-cancer drug topotecan. It cannot be taken with St. John’s wort. After FDA approval, several cases of symptomatic bradycardia (very low heart rate), and cases of fatal heart attacks and cases requiring a pacemaker have been associated with the use of Epclusa with amiodarone. Signs of bradycardia include fainting, dizziness, lightheadedness, weakness, excessive fatigue, shortness of breath, chest pains and confusion or memory problems. Consult a medical provider should any of these occur. No sofosbuvir-based HCV regimens are to be used with amiodarone.

More information

Epclusa marks an exciting development for treating HCV: One pill, once per day taken without ribavirin for 12 weeks for all genotypes with minimal side effects and high cure rates is an extraordinary achievement when one considers that the first DAA came on the scene less than 5 years ago. It is an effective and highly tolerable treatment option for people with GT3, with SVR12 rates as high as 98% for treatment-naïve patients without cirrhosis. The presence of cirrhosis looks to lower the SVR12 rates a bit (93%), but this is still an interferon- and ribavirin-free option for this hard-to-treat patient group. The ASTRAL-4 Study, which looked at patients with decompensated liver disease resulted in an SVR12 of 83% of people taking Epclusa alone, but it increased to 94% when ribavirin was added. This is also an excellent choice for HIV/HCV co-infected persons: The ASTRAL-5 Study, which looked at treating HIV/HCV co-infected persons with SOF/VEL, had an overall 95% SVR12, including 100% in people with cirrhosis and 97% in treatment-experienced people.

DRUG CLASS
Nucleotide analog NS5B polymerase inhibitor

Genotype
1 2 3 4

HIV/HCV co-infection
Approved use

Manufacturer
Gilead Sciences

AWP
$33,600 / month

Dosage

Take one 400 mg tablet once daily with or without food; must be taken in combination with either ribavirin and pegylated interferon, ribavirin alone, or in combination with another DAA (see below for details). Sovaldi should never be taken by itself. Take your missed dose as soon as possible, unless it is closer to the time of your next dose. Never double your dose. The chart on this page summarizes the various treatment regimens.

Black Box Warning

Before starting treatment with any DAA, including Sovaldi, patients should take a blood test to check for hepatitis B (HBV) infection. HBV infection could get worse or reactivate again during or after DAA treatment, potentially leading to serious liver problems including liver failure or death. Patients with HBV or some with past infection should be monitored during HCV DAA treatment, and some may need to take HBV treatment. See HBV Reactivation for more information; consult your medical provider.

What are the potential side effects and adverse events?

See black box warning. When sofosbuvir was taken with amiodarone (see interactions), several cases of serious symptomatic bradycardia (a potentially dangerous, very low heart rate) occurred, as well as cases of fatal heart attacks and cases requiring a pacemaker. Signs of bradycardia include fainting, dizziness, lightheadedness, weakness, excessive fatigue, shortness of breath, chest pains, and confusion or memory problems. Consult a medical provider should any of these occur. When Sovaldi is taken with pegylated interferon (drug page online only) and ribavirin (not recommended for use any longer) or ribavirin alone, the most common side effects reported by people taking this regimen are related to those two medications: fatigue, headaches, nausea, fever, chills, and arthralgia (joint pain). For more information on the side effects of each of these medications, see their respective drug pages. Pegylated interferon has been associated with depression, anxiety, and, in rare cases, suicidal thoughts. If you have a history of any of these conditions, talk to your provider before starting it. When Sovaldi is used with ribavirin, pregnant women or women who are trying to become pregnant cannot take it; women of childbearing age and their male partners must use two forms of birth control throughout treatment and for six months after treatment. Changes in hematological (blood) values are also common, and routine blood testing to look for anemia, neutropenia, and other blood conditions is recommended.

What are the potential drug interactions?

Be sure to tell your medical provider or pharmacist about all the medications, supplements, and herbs you take, whether prescribed, over-the-counter, or illicit.
Sovaldi cannot be taken with the antiarrythmic medication amiodarone; see side effects. No sofosbuvir-based HCV regimens are to be used with amiodarone. Sovaldi cannot be taken with the HIV medication tipranavir/ritonavir, but is safe to take with other HIV medications. Sovaldi has no interactions with methadone. Do not take Sovaldi with St. John’s wort, rifabutin, or rifapentine. Anticonvulsants such as phenobarbital, carbamazepine, phenytoin, and oxcarbazepine should not be used, as they reduce the concentrations of Sovaldi, thus reducing its therapeutic effectiveness.

More information

Sovaldi is a drug with a lot of “firsts”—first drug of its class, first drug to receive FDA approval for use without interferon, and the first DAA to receive FDA approval for use in HIV/HCV co-infected patients. Approved in 2013, the original dosage and duration is already pretty much obsolete when compared to other HCV treatments. It can still be used in combination with Olysio or Daklinza for the treatment of genotype 1, but there are several other options that are easier to take, more effective, and, likely, less expensive. Sovaldi is a key component of Harvoni, Epclusa, and Vosevi and will be part of the next fixed-dose combination from Gilead, for the treatment of all HCV genotypes.

DRUG CLASS
glecaprevir: NS3/4A protease inhibitor; pibrentasvir: NS5A inhibitor

Genotype
1 2 3 4 5 6

HIV/HCV co-infection
Approved use

Manufacturer
AbbVie

AWP
$16,332 / month

Dosage

Take three glecaprevir/pibrentasvir 100 mg/40 mg tablets once daily for a total of 300 mg/120 mg. Take it with food. Take your missed dose as soon as possible, unless it is closer to the time of your next dose. Never double your dose.

Black Box Warning

Before starting treatment with any DAA, including Mavyret, patients should take a blood test to check for hepatitis B (HBV) infection. HBV infection could get worse or reactivate again during or after DAA treatment, potentially leading to serious liver problems including liver failure or death. Patients with HBV or some with past infection should be monitored during HCV DAA treatment, and some may need to take HBV treatment. For more information, see HBV Reactivation; consult your medical provider.

What are the potential side effects and adverse events?

Mavyret is a very well-tolerated medication with minimal side effects. Only headaches and fatigue were reported by clinical trial participants at rates higher than 10% (16 and 11% respectively), with even fewer reporting nausea or diarrhea. There were no serious lab abnormalities, and very few people stopped treatment because of side effects.

What are the potential drug interactions?

Be sure to tell your medical provider or pharmacist about all the medications, supplements, and herbs you take, whether they are prescribed, over-the-counter, or illicit, before starting this regimen, and inform them of any changes as they happen. It cannot be taken with St. John’s wort. It is not recommended to take Mavyret with the HIV antivirals  atazanavir, darunavir, lopinavir, ritonavir, or efavirenz. There are no dose adjustments needed when taken with the following HIV antivirals: elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide, abacavir, dolutegravir, or lamivudine.

More information

Mavyret marks an exciting development in HCV treatment: It’s the first pan-genotypic regimen that cures people with 8 weeks of treatment without ribavirin. It has very high cure rates: The overall cure rate (sustained virologic response, or SVR) across
all genotypes was 97.5%, but when you remove genotype 3, that number improves to 99% (GT 3 still achieves a 95% SVR). It also appears to be an excellent regimen for people with kidney disease, curing 98% of patients with severe kidney disease with 12 weeks of treatment. This regimen also appears to be an excellent choice for patients post-liver or kidney transplant, having cured 99% of people in one study. See below for summary of treatment durations.

Treatment-naïve patients

If you’ve never taken HCV treatment before, you’ll take it as follows:

Treatment-experienced patients

If you have taken HCV treatment before, you’ll take it as follows:

DRUG CLASS
Nucleoside analog

Genotype
1 2 3 4 5 6

HIV/HCV co-infection
Approved use

Manufacturer
Copegus: Genentech
Moderiba: AbbVie
Ribasphere: Kadmon

AWP
$1,390 / month for generic, based on 1,200 mg/day Copegus: $5,589/month

Dosage

Ribavirin dosage depends upon the brand, and is given in either fixed doses or in doses related to weight (weight-based). The dose range is 800 mg to 1,400 mg per day taken in two divided doses. Depending upon the manufacturer, tablets are available in 200 mg, 400 mg, 500 mg, and 600 mg. A liquid dose is also available. Must be taken with food. Ribavirin should never be taken by itself. Take your missed dose as soon as possible, unless it’s too close to your next dose. Never double dose.

Generic available.

What are the potential side effects and adverse events?

There are two very serious potential side effects associated with ribavirin: Anemia, and birth defects or fetal death. The anemia can be very severe and can happen very quickly, usually within the first 1–2 weeks of starting treatment. The anemia can cause severe fatigue, dizziness, headaches, and shortness of breath; routine blood testing to look for anemia, neutropenia, and other blood conditions is recommended. The anemia may also cause or worsen cardiac conditions. The other major side effect is birth defects or fetal death in pregnant women. Pregnant women or women who are trying to become pregnant cannot take ribavirin; women of childbearing age and their male sexual partners must use two forms of birth control throughout treatment and for six months post-treatment. It is unknown if ribavirin passes through breast milk or the impact it could have on breastfeeding babies. Other side effects that have been reported with ribavirin include rash and itching, and there is a small risk of pancreatitis. If you experience any symptoms related to pancreatitis (severe stomach pain that radiates to your back, nausea, vomiting, and/or diarrhea) you should call your advice nurse (when applicable) or go to an emergency department for evaluation. If you have renal (kidney) disease, talk with your medical provider about potential dosage adjustments as the levels of ribavirin can be increased dramatically. Some people who are taking ribavirin experience what is commonly called “riba-rage,” that is they get easily irritated and get angry easier.

What are the potential drug interactions?

Ribavirin cannot be used with didanosine (Videx-EC, Videx, ddI) as this combination can lead to potentially fatal levels of ddI; similarly, azathioprine (an immunosuppressive) cannot be used. Ribavirin is okay to take with other HIV antivirals, but check closely for anemia.

More information

It’s not entirely understood how ribavirin works against HCV, but along with interferon, it’s been a major part of HCV treatment for years, and while interferon is no longer used, ribavirin continues to play a role in some treatments and patient populations. That said, we are in the ribavirin-free era with many of the current HCV DAAs.

If you need to take it, the side effects can be difficult. If you become anemic while on ribavirin, your medical provider may be able to adjust the dose accordingly. The anemia often happens quickly, so get blood tests to monitor it early in your treatment. “Riba-rage” is not a common occurrence, but it’s good to be aware and (if disclosing HCV status is not an issue) telling the people around you about it so you can get the support you need to minimize its impact.