Direct Acting Antivirals (DAAs)

This guide has been developed as part of a Risk Management Plan (RMP) for prescribers involved in the care of patients treated with DAAs, to provide further information about some new safety issues associated with their use.

This guide is complementary to the full prescribing information of each product, please refer to it for further information and additional details.

DAAs are several oral regimens from different families [NS5B nucleotide inhibitors, NS5B non-nucleoside inhibitors, NS5A replication complex inhibitors and NS3/4A protease inhibitors (PI)] indicated for the treatment of chronic hepatitis C.

These regimens result in an increase in sustained virological response (SVR) rates to above 90% and reduce the duration of treatment to 12 weeks or less.

Since drug-resistant variants have rapidly developed in response to monotherapy with almost all DAAs for HCV, the need for combination therapies to effectively eradicate the virus from infected patients is clear.

EPVC is supporting the additional monitoring program which assign a list of products to be monitored even more intensively than other medicines, the labelling information of  these products contain the symbol of inverted black triangle ().

Reporting Suspected Adverse Reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in the product information.

EPVC encourages HealthCare Professionals (HCPs) to report any suspected adverse reaction with any suspected drug however EPVC has special interest to receive reports on some products including Direct Acting Antivirals (DAAs).

New Safety Issues associated with the use of DAAs

1.      HBV Reactivation in some patients treated with DAA for Hepatitis C

Background info:

In HBV/HCV co-infected patients, treatment with DAAs targeting specific HCV non-structural proteins without anti-HBV activity may result in disruption of viral replication and HBV reactivation. Cases of HBV reactivation have been reported during treatment with HCV DAAs in HBV/HCV co-infected patients.


2.      Drug interaction between DAA and Vitamin K antagonists leading to a reduced international normalized ratio (INR)

Background info:

A signal of a potential drug interaction leading to a reduced INR has recently been identified with co-administration of DAAs and vitamin K antagonists. The case reports on which the signal was based were reviewed by the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC).


3.      Possible effects of DAAs on blood glucose control when used in patients with type 2 diabetes

Background info:

New Zealand's Medsafe was alerted to a case of improved blood glucose control and decreased hemoglobin A1C (HbA1C) in a Type 2 diabetic patient 8 weeks after Initiation of DAA. There were no literature reports linking hypoglycemia to DAA regimens among diabetic patients with HCV Infection treated with DAA regimens. Instead, identified literature articles described improved glycemic control, or hemoglobin A1C reduction with no mention of hypoglycemia. There are also some case reports of increases in blood glucose levels.


4.      DAA regimens and liver failure

Background Info:

In New Zealand, 5 post-marketing reports of liver failure in patients receiving or post-treatment completion of DAA-therapy for HCV were identified.

Marketing Authorization Holders of products containing DAA continues to monitor all post-marketing adverse event reports that may impact the risk-benefit profile for use of their DAA products in all HCV-treated patients.


There are restrictions on which DAA regimens can be used in patients with liver impairment depending on whether the impairment is mild, moderate or severe. In patients with cirrhosis who are being treated with DAA treatment, HCPs should:

5.      The potential risk of liver cancer recurrence with the use of DAAs

Background Info:

On 27 April 2017, Health Canada issued a notification regarding use of all DAAs used to treat chronic hepatitis C virus (HCV) infection in adult patients and the potential risk of liver cancer recurrence based upon spontaneous reports of HCC recurrence and a recently published reference (Reig M et al “Unexpected early tumor recurrence in patients with hepatitis C virus -related hepatocellular carcinoma undergoing interferon-free therapy: a note of caution” J Hepatology 2016) which suggested this potential risk. Other published data from larger cohorts did not support these findings. There was not enough information to establish a link between DAAs and liver cancer recurrence.



Call for reporting

To enhance patient care and patient safety in relation to the use of medicines, if you receive any Adverse Event, please report to:

21 Abd Elaziz Al Souad st. – Manial El-Roda – Cairo, PO Box: 11451

Tel:  +202 – 25354100 +202 – 23684288 +202 – 23648046 +202 – 23640368 +202 – 23640369          Extension (Tel):1303              Fax: +202 23684194