Published: 8 December 2016
Prescriber Update 37(4): 50-51
Direct-acting antivirals (DAAs) are recently approved medicines indicated for the treatment of hepatitis C infection. The World Health Organization (WHO) now recommends DAA regimens for the treatment of persons with hepatitis C infection, rather than regimens with pegylated interferon and ribavirin1. The NZ Society of Gastroenterology HCV Treatment Guidelines and PHARMAC funding have been updated to align with the WHO recommendations2,3.
DAAs are used for the treatment of hepatitis C infection with the goal of curing the patient. DAAs work by blocking the action of hepatitis C virus proteins required for viral replication.
Treatment regimens with DAAs have a short treatment duration (usually 12 weeks), are administered orally and are very effective (sustained virological response rates of ≥ 90%)1.
There are a number of DAAs approved in New Zealand. This article focuses on Viekira Pak, Viekira Pak-RBV and Harvoni, which are funded by PHARMAC.
Viekira Pak contains ombitasvir, ritonavir and paritaprevir in a combination tablet packaged together with dasabuvir tablets. Viekira Pak-RBV also contains ribavirin in the same package.
Harvoni is a combination tablet containing ledipasvir and sofosbuvir.
In some countries DAAs are marketed under different brand names and in different combinations. Be aware that patients who have been importing DAA products from overseas may be taking a different combination from those funded in New Zealand.
Prior to starting the treatment, determine the hepatitis C virus genotype and measure the viral load, as this will direct the choice of DAA and the treatment duration (Table 1).
DAAs are known to interact and postulated to interact with a substantial list of medicines. These interactions may be severe. Comorbidities are common in patients with hepatitis C so it is important to know what other medicines the patient is taking. Be careful when prescribing DAAs with medicines metabolised or transported by4,5,6:
The University of Liverpool provides an online interactions tool that is quick and easy to use (see below).
Hepatitis B reactivation has also been reported in temporal association with DAA treatment. The Medicines Adverse Reactions Committee (MARC) recently reviewed the information on this possible risk. Although patients may get flares of hepatitis B at any time, the MARC considered that patients who are being prescribed DAAs should be assessed, tested and closely monitored for hepatitis B (www.medsafe.govt.nz/profs/adverse/Minutes167.htm#3.2.4).
Advise patients to report any signs and symptoms of hepatotoxicity with Viekira Pak or Viekira Pak-RBV to their healthcare professionals. Patients who develop evidence of hepatic decompensation with the use of Viekira Pak or Viekira Pak-RBV should discontinue treatment4,5.
|Viekira Pak||Viekira Pak-RBV||Harvoni|
|Genotypes||Genotype 1b||Genotype 1a||All genotypes|
|Contraindications||Hypersensitivity to any component|
|Severe hepatic impairment|
|Patients taking other medicines with significant interactions|
|Pregnant women or patients with a pregnant partner|
|Severe pre-existing cardiac disease|
|Main adverse effects||Fatigue, nausea, itchy skin, insomnia, anaemia||Fatigue, nausea, headache, rash|
|Hypersensitivity reactions including tongue and lip swelling||Symptomatic bradycardia when co-administered with amiodarone|
|Hepatic decompensation and hepatic failure|
Please report any adverse reactions with DAAs, including interactions, to the Centre for Adverse Reactions Monitoring (CARM). These are new medicines, and the safety profile has not yet been fully identified. Reports can be submitted on paper or electronically (https://nzphvc.otago.ac.nz/). These reports will help CARM and Medsafe identify any trends or patterns in New Zealand that may require action to ensure DAAs continue to be used safely.
Links to some useful resources are provided below.