- Two new FDA warnings issued for simeprevir
- FDA grants new breakthrough therapy designation for grazoprevir and elbasvir
- Good adherence to Harvoni shown in two clinical trials
Two new warnings for simeprevir (Galexos) have been issued by the U.S. Food and Drug Administration (FDA) about:
- a drug interaction with amiodarone when simeprevir is taken with sofosbuvir (Sovaldi)
- a risk of liver decompensation and liver failure when taking simeprevir
Serious slowing of the heart rate (symptomatic bradycardia) can occur when the drug amiodarone, which is used to treat an irregular heartbeat, is taken with simeprevir in combination with sofosbuvir.
The FDA recommends that amiodarone not be prescribed with the combination of simeprevir and sofosbuvir. If there is no alternative to taking amiodarone, the FDA recommends for patients to be monitored appropriately by their doctor.
Related to the second warning, liver decompensation and liver failure have occurred when simeprevir was taken in combination with peg-interferon and ribavirin or sofosbuvir. Most cases occurred in people who already had moderate to severe liver injury.
Liver decompensation and failure is when the liver is no longer able to function normally and symptoms such as fluid build-up in the abdomen (ascites) and swelling or ruptured veins (varices) in the esophagus occur.
It is not recommended for people with moderate or severe liver injury (Child-Pugh Class B or C) to take simeprevir. (Healio.com, April 2015, in English)
The FDA has granted a breakthrough therapy designation for grazoprevir and elbasvir for the treatment people with genotype 1 virus and genotype 4 virus with end stage kidney disease who are on hemodialysis.
If a medication is designated as a breakthrough therapy the FDA will speed up the process of reviewing the medication.
Grazoprevir and elbasvir are both direct-acting antivirals (DAAs). DAAs are a group of medications that directly attack the ability of a virus to make copies of itself.
Grazoprevir and elbasvir are combined into one pill that is taken once per day. These drugs have activity against viral genotypes 1, 2 and 3. Elbasvir also has some activity against genotype 4 virus.
This combination has some side effects, including fatigue, headache, nausea and diarrhea, but they are generally mild. (Healio.com, April 2015, in English)
For more information on grazoprevir and elbasvir, see TreatmentUpdate 208, CATIE’s Hep C and HIV treatment digest.
Adherence rates ranged from 96% to 99% in two clinical trials of Harvoni with groups of participants considered “difficult to treat”, reported researchers at the 2015 Conference on Retroviruses and Opportunistic Infections (CROI).
The studies were conducted by the National Institute of Allergy and Infection Diseases (NIAID) with primarily low-income participants from Washington, D.C. One study included 20 participants with Hep C. The second study included 50 participants with HIV and Hep C.
Characteristics of the participants include:
- Three-quarters were men
- 80% were African American
- 70% had the harder to treat genotype 1a virus
- One-third had severe liver injury
- About one-third had a history of a psychiatric diagnosis
- 60% were unemployed
Participants were treatment for 12 weeks with Harvoni. All participants experienced rapid decline of their Hep C viral loads consistent with good adherence. 99% of participants were cured.
Adherence was measured by three methods: pill counts, participant self-reports and Medication Event Monitoring System (MEMS) caps, which record when a pill bottle is opened. All three measures reported high levels of adherence (96.6% to 99.8%). Adherence according to MEMs caps declined over the course of treatment.
“Adherence to the single daily tablet of ledipasvir/sofosbuvir was high in this urban population…,” the researchers concluded. “Adherence did significantly decline over time…, suggesting pill fatigue, and needs to be evaluated in larger patient population in real-life scenarios.” (HIVandhepatitis.com, April 2015, in English)