Amanda Binkley, PharmD, AAHIVP

 (HCV) treatment has changed drastically in the past 20 years. In the early 1990s, treatment included interferon monotherapy for 48 weeks, resulting in an approximate 10% sustained virologic response (SVR) rates for genotype 1.

In 1998, ribavirin was added to interferon to reduce the duration of treatment and to increase SVR rates to about 30%. Many toxicities were associated with this regimen, however, which made many patients ineligible for treatment and completing treatment challenging. By the early 2000s, pegylated interferon formulations had been developed to reduce toxicities and increase SVR rates to about 50%. The first protease inhibitors were approved in 2011 for treatment, leading to SVR rates of about 60% to 80% but also decreasing treatment duration to 24 to 28 weeks. In 2013, the FDA approved the first direct-acting antivirals (DAAs), simeprevir (SIM) and sofosbuvir (SOF). The advent of these agents allowed for interferon-free regimens, reduced the duration of treatment to as little as 12 weeks, and led to SVR rates of about 90%.

There are now 8 FDA-approved medications for HCV treatment, all of which bypass the use of interferon. The use of each medication varies based on HCV genotype, prior treatment exposure, presence of cirrhosis, HCV polymorphism, patient comorbidities, and drug—drug interactions (DDIs). Here is an overview of each FDA-approved HCV medication and its use as recommended by the American Association for the Study of Liver Diseases (AASLD).

Elbasvir/grazoprevir (EBR/GZR [Zepatier])3 is FDA-approved for the treatment of HCV genotypes 1 and 4. Baseline nonstructural protein 5A polymorphism testing is required in patients who are being treated for genotype 1a to determine the need for ribavirin and the duration of treatment. EBR/GZR are CYP3A (cytochrome P450, family 3, subfamily A) and P-glycoprotein substrates, though GZR weakly inhibits CYP3A. The effects of EBR/ GZR on other transporters are listed in TABLE 1

. Recommendations for other DDIs can be found in (TABLE 2)

. EBR/GZR can be taken with or without food, and no dosage adjustments are needed in patients with renal impairment or undergoing hemodialysis. EBR/GZR is contraindicated in patients with Child-Pugh scores B and C because of the lack of data and increases in GZR concentrations, respectively. The overall duration of therapy for EBR/GZR ranges from 12 to 16 weeks.

Ledipasvir (LDV)/SOF (Harvoni)4 is FDA approved for the treatment of HCV genotypes 1 and 4 through 6. Ribavirin may be required in combination with LDV/SOF for patients with decompensated cirrhosis or for patients who have received a liver transplant. LDV/SOF medications are not substrates, inhibitors, or inducers of the CYP enzymes. The effects on other transporters are listed in TABLE 1

. Food intake minimally affects LDV/SOF concentrations; however, acid-suppression medications have been shown to decrease LDV concentrations. Therefore, antacids should be taken 4 hours apart from the LDV/SOF dose.

-antagonists should be given simultaneously or 12 hours apart from LDV/SOF, and doses should not exceed famotidine 40 mg twice daily or its equivalent. Proton pump inhibitors (PPIs) can be given simultaneously if a patient is fasting and the dose does not exceed omeprazole 20 mg/day or its equivalent. Other serious DDIs include amiodarone, which has resulted in symptomatic bradycardia; concomitant therapy is not recommended. LDV/SOF should not be used in patients with an estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m2 or those undergoing hemodialysis because of the lack of published studies.

LDV/SOF can be used in patients with any degree of hepatic impairment. The duration of therapy is always 12 weeks unless the patient has HCV genotype 1, is treatment naïve, is not cirrhotic, is not co-infected with HIV, and has a pretreatment HCV RNA less than 6 million IU/mL; 8 weeks of therapy is sufficient in these populations.

OMBITASVIR/PARITAPREVIR/RITONAVIR AND DASABUVIR 

Ombitasvir/paritaprevir/ritonavir and dasabuvir (OMB/PTV/ RTV and DBV [Viekira Pak and Viekira XR])

 are FDA approved for HCV genotype 1; OMB/PTV/RTV (Technivie)is approved for genotype 4 because DBV is not active against genotype 4. Ribavirin is routinely recommended for use with all 3 combination products unless Viekira Pak or Viekira XR is being used for the treatment of genotype 1b. Although it is not required that Technivie, Viekira XR, and Viekira Pak be taken with food, if prescribed with ribavirin, this is the recommendation because concentrations of ribavirin increase 70% when taken with a high-fat meal.

PTV and RTV are substrates of CYP3A4. RTV is a strong inhibitor of CYP3A4 and leads to numerous DDIs (TABLE 2

). For example, RTV can induce the metabolism of PPIs such as omeprazole. Study results have shown a 54% decrease in the area under the concentration time curve (AUC) of omeprazole, requiring higher doses of the drug.

 There are no dosage requirements for patients with renal impairment or those undergoing hemodialysis; however, the use of these drugs is contraindicated in patients with Child-Pugh scores B and C. Treatment duration is typically 12 weeks unless the patient is treated with Viekira Pak or Viekira XR for genotype 1a with compensated cirrhosis; in these cases, treatment is 24 weeks.

TABLE 2. DRUG—DRUG INTERACTIONS WITH ANTIRETROVIRALS

Articles

There are now 8 FDA approved medications for HCV treatment, all of which bypass the use of interferon.