Published: 3 September 2020

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Spotlight on Maviret – De-liver-ing treatment in patients with hepatitis C

Published: 3 September 2020
Prescriber Update 41(3): 58–59
September 2020

Key Messages

  • Maviret is a combination of two direct-acting antivirals (glecaprevir + pibrentasvir) and is used for the treatment of chronic hepatitis C.
  • Glecaprevir and pibrentasvir are metabolised in the liver. Therefore, patients with impaired liver function will be exposed to increased levels of these antivirals, increasing the risk of adverse reactions.
  • Assess the severity of liver disease before starting treatment:
    • Maviret can be used in patients with mild liver impairment (Child-Pugh A)
    • Maviret is not recommended in patients with moderate liver impairment (Child-Pugh B) and is contraindicated in patients with severe liver impairment (Child-Pugh C).


The Spotlight series continues with this article on Maviret, a combination direct-acting antiviral (DAA) medicine used for the treatment of chronic hepatitis C.

Background

In August 2019, the United States Food and Drug Administration (FDA) warned about the rare occurrence of serious liver injury with use of hepatitis C medicines, including Maviret, in some patients with advanced liver disease.1 The hepatitis C medicines implicated are all direct-acting antivirals (DAAs) that include a protease inhibitor.

The Medicines Adverse Reactions Committee reviewed the risk of serious liver injury in patients taking Maviret to determine the impact for New Zealand prescribers and patients.2,3 The review highlighted the importance of only prescribing Maviret in patients with mild liver impairment as recommended in the data sheet.

What is Maviret?

Maviret is a combination of the DAAs glecaprevir and pibrentasvir. It is indicated for the treatment of chronic hepatitis C infection due to any of the hepatitis C virus (HCV) genotypes.

DAAs disrupt viral replication and infection by targeting specific viral proteins. More than one target can be attacked if different groups of DAAs are combined.4 Maviret contains the protease inhibitor glecaprevir and the protein NS5A inhibitor pibrentasvir.

Patients with liver impairment

Before starting treatment, check the patient’s liver function.

The data sheet states that:5

  • Maviret can be used in patients with mild liver impairment (Child-Pugh A)
  • Maviret is not recommended for patients with moderate liver impairment (Child-Pugh B)
  • Maviret is contraindicated in patients with severe liver impairment (Child-Pugh C).

These prescribing recommendations are based on the increased exposure to the two DAAs, especially glecaprevir, in patients with impaired liver function. The increased exposure increases the risk of adverse reactions.

In clinical studies using the standard dose of Maviret, the glecaprevir area under the curve (AUC) was 33 percent higher in patients with Child-Pugh A cirrhosis, 100 percent (two-fold) higher in patients with Child-Pugh B, and 11-fold higher in patients with Child-Pugh C compared to study participants without HCV and with normal hepatic function.5 The pibrentasvir AUC was also increased in patients with Child-Pugh B or C, but not to the same extent as glecaprevir.5

Similarly, population pharmacokinetic analysis showed glecaprevir exposure was increased by two-fold in patients with HCV and compensated cirrhosis compared to patients with HCV and no cirrhosis, while pibrentasvir exposure was similar for both patient groups.5

Reported cases of liver injury

New Zealand

The Centre for Adverse Reactions Monitoring (CARM) has not received any reports of liver-related adverse reactions in association with Maviret.

United States1

The FDA’s warning was based on 63 reported cases of worsening liver function associated with DAA treatment (Maviret, Zepatier and Vosevi), sometimes leading to liver failure and death.

  • In many of the reported liver failure cases, patients had signs and symptoms of moderate to severe liver impairment (Child-Pugh B or C) or other serious liver problems prior to starting treatment with one of the DAAs. These patients should not have been treated with these medicines.
  • Some patients were incorrectly classified as being Child-Pugh A, despite having evidence of a previous decompensation event, portal hypertension or decreased platelets at baseline.
  • Some patients had other significant pre-existing risk factors, such as alcohol abuse or concomitant illness or were taking medicines associated with serious liver problems.

References

  1. Food and Drug Administration. 2019. FDA warns about rare occurrence of serious liver injury with use of hepatitis C medicines Mavyret, Zepatier, and Vosevi in some patients with advanced liver disease 28 August 2019. URL: fda.gov/drugs/drug-safety-and-availability/fda-warns-about-rare-occurrence-serious-liver-injury-use-hepatitis-c-medicines-mavyret-zepatier-and (accessed 25 June 2020).
  2. Medsafe. 2020. Protease inhibitors for Hepatitis C and Risk of Serious Liver Injury. Presented at the 182th Medicines Adverse Reaction Committee meeting, 11 June 2020. URL: medsafe.govt.nz/committees/MARC/reports/182-3.2.4ProteasInhibitorsHepatitisC.pdf (accessed 4 August 2020).
  3. Medsafe. 2020. Minutes of the 182th Medicines Adverse Reactions Committee Meeting. URL: medsafe.govt.nz/profs/adverse/Minutes182.htm (accessed 4 August 2020).
  4. Pockros PJ. 2019. Direct-acting antivirals for the treatment of hepatitis C virus infection. In: UpToDate 12 December 2019. URL: uptodate.com/contents/direct-acting-antivirals-for-the-treatment-of-hepatitis-c-virus-infection (accessed 1 July 2020).
  5. AbbVie Limited. 2020. Maviret New Zealand Data Sheet April 2020. URL: medsafe.govt.nz/profs/Datasheet/m/mavirettab.pdf (accessed 25 June 2020).
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