These Relatively Recent Direct-Acting Antivirals Are Increasingly Popular For Treating Chronic Hepatitis C, But There Could Be Serious Side Effects In Addition To The High Costs
In April 2016 Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) discussed its ongoing safety review of the direct-acting antivirals class of drugs used for treating long-term, or chronic, hepatitis C.
From this April 15 EMA News item, "Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 11-14 April 2016" we get an overview of this still emerging drug safety issue:
At its previous meeting in March, the Committee had initiated a review following cases of hepatitis B re-activation in patients who have been infected with hepatitis B and C viruses, and who were treated with direct-acting antivirals for hepatitis C.
In April 2016, data from a study became available regarding the risk of liver cancer (hepatocellular carcinoma) coming back in patients who were treated with these medicines. The study suggested that these patients were at risk of their cancer coming back earlier than patients with hepatitis C who were not treated with direct-acting antivirals. The scope of the ongoing review has therefore been extended to also assess the risk of liver cancer with these medicines.
We get additional details from this press release about the matter, "EMA reviews direct-acting antivirals for hepatitis C":
- The following direct-acting antivirals have been approved in the EU for treating chronic hepatitis C: Daklinza (daclatasvir), Exviera (dasabuvir), Harvoni (sofosbuvir / ledipasvir), Olysio (simeprevir), Sovaldi (sofosbuvir) and Viekirax (ombitasvir / paritaprevir / ritonavir).
- The review was triggered by reports of hepatitis B re-activation in patients who have been infected with hepatitis B and C viruses, and who were treated with direct-acting antivirals for hepatitis C. Hepatitis B re-activation refers to a return of active infection in a patient whose hepatitis B infection had been inactive. The review will assess the extent of hepatitis B re-activation in patients treated with direct-acting antivirals for hepatitis C and evaluate whether any measures are needed to optimise the treatment.
- In addition, in April 2016 data from a study [Unexpected early tumor recurrence in patients with hepatitis C virus -related hepatocellular carcinoma undergoing interferon-free therapy: a note of caution, Journal of Hepatology (2016)] became available regarding the risk of liver cancer (hepatocellular carcinoma) coming back in patients who were treated with direct-acting antivirals for hepatitis C. The study suggested that these patients were at risk of their cancer coming back earlier than patients with hepatitis C who were not treated with direct-acting antivirals. The scope of the ongoing review has therefore been extended to also assess the risk of liver cancer with these medicines.
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As for what this development means for US patients and physicians, Harvoni, Sovaldi, Daklinza, and Olysio -- as well as Technivie (not listed above but with the same composition as Viekirax) -- are the implicated direct-acting antivirals currently approved by the FDA.
In addition, Viekira Pak (dasabuvir and ombitasvir and paritaprevir and ritonavir) -- which is available for use here -- seems to be a "combination-product" of the Exviera and Viekirax drugs which are listed in the EMA press release, above.
We have written in the past about Technivie and Viekira Pak side effects in this October 2015 article, "Hepatitis C Drugs Viekira Pak And Technivie Require Warnings Label Changes Due To Liver Injury Reports".
The current EMA Timetable for this PRAC safety review of Harvoni, Sovaldi, and the other new "hep-c" drugs has the current process coming to an end this summer.
The April 2016 EMA press release details what will happen at that time:
The PRAC recommendations will then be forwarded to the Committee for Medicinal Products for Human Use (CHMP), responsible for questions concerning medicines for human use, which will adopt a final opinion. The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable in all EU Member States.
Of course, we will be watching for results of safety review and report those out, here, when available.