Glecaprevir/pibrentasvir is an NS3/4A protease inhibitor/NS5A protein inhibitor combination.
Dose: Three tablets taken once a day, with food, for eight weeks (Mavyret, 2020).
Dosing/geriatric: No dosing adjustments are needed (Mavyret, 2020).
Dosing/hepatic impairment: Mavyret can be used in patients who have compensated cirrhosis, Child-Pugh score A, and no dosing adjustment is required (Mavyret, 2020). See Contraindications and Warnings and precautions for other information about Mavyret and hepatic impairment patients.
Dosing/renal impairment: No dosing adjustments are needed.
Contraindications: Glecaprevir 300 mg/pibrentasvir should not be taken by patients for whom ribavirin is contraindicated (Mavyret, 2020).
Mavyret is contraindicated in patients with moderate to severe hepatic impairment, Child-Pugh score B or C and in patients who have evidence of previous episodes of hepatic decompensation (Mavyret, 2020).
Child-Pugh Classification System
|The Child-Pugh classification system measures albumin, bilirubin, and prothrombin time or INR. It assigns a point score to each test result based on the numerical value of the result, and the total score can be used to determine the one-year survival rate in patients who have cirrhosis. The scores are divided into 3 categories: 5-6, category A, mild hepatic impairment; 7-9, category B, moderate; > 9, category C, severe. Patients who are category B or C have decompensated cirrhosis.|
This example illustrates how the system is used.
This patient has a Child-Pugh score of 10 and has category C, severe hepatic impairment
- Total bilirubin is > 50 mg/dL = 3 points
- Serum albumin is 2.8-3.5 g/dL = 2 points
- Prothrombin time is > 6.0 = 3 points
- Ascites is mild = 2 points
- Hepatic encephalopathy is absent = 0 points
US Boxed Warning: Hepatitis B virus reactivation has been reported in hepatitis C/hepatitis B coinfected patients who were undergoing or had completed treatment with hepatitis C direct-acting antivirals and were not receiving hepatitis B antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death (Mavyret, 2020).
Note: Treating patients who are infected with hepatitis B and C will be discussed later in the module.
Warnings and precautions: In August 2019, the FDA issued a safety warning about Mavyret and two other direct-acting antivirals (FDA, 2019).
"The Food and Drug Administration (FDA) has received reports that the use of Mavyret, Zepatier, or Vosevi to treat chronic hepatitis C in patients with moderate to severe liver impairment has resulted in rare cases of worsening liver function or liver failure. In most patients, symptoms resolved, or the worsening of liver function improved after stopping the medicine. In most cases, liver failure or decompensation typically occurred within the first four weeks of starting treatment (FDA, 2019)."
The safety warning notes that the majority of the patients who had severe outcomes had moderate or severe hepatic impairment (Child-Pugh B or C) before they took these drugs; some patients with mild hepatic impairment (Child-Pugh A) before antiviral therapy had had prior episodes of hepatic decompensation, and; there were rare cases of patients who did not have any degree of hepatic impairment but who had evidence of portal hypertension and who developed hepatic decompensation/liver failure (FDA, 2019). Also, some patients had risk factors for hepatic decompensation/liver failure like alcohol abuse or liver cancer (FDA, 2019).
The FDA recommended that healthcare professionals continue to use Mavyret, Zepatier, or Vosevi as indicated by the prescribing information, do a baseline assessment of liver function before starting antiviral therapy, and closely monitor patients for signs and symptoms of liver failure (Epclusa, 2020).
Adverse effects: During clinical trials, > 5% of patients had headache (13%), fatigue (11%) and nausea (8%) (Mavyret, 2020).
Drug interactions: The Lexicomp® Drug Interaction database lists 92 drug-drug interactions involving glecaprevir and pibrentasvir, and many of these involve commonly used drugs like antidiabetics antiepileptics, statin drugs, and warfarin.
Drug-drug interactions can be checked using the University of Liverpool drug interaction checker (Ghany et al., 2019). The website address is www.hep-druginteractions.org/checker. The AASLD/ISDA website has drug-drug interaction information, as well.
Monitoring: If there are no signs and symptoms of liver damage, there is no need to do laboratory testing during the treatment.
Twelve weeks or later, after the last dose, obtain a quantitative measurement of hepatitis C RNA and do a hepatic function panel: A hepatic panel should measure albumin, alkaline phosphatase, ALT, AST, and total direct bilirubin.
If SVR has been attained and the AST and ALT are normal, no further treatment or follow-up is needed (Ghany et al., 2019).
If an SVR has been attained, but the AST and ALT are elevated, the patient should be assessed for other causes of liver damage (Ghany et al., 2019).
If an SVR has not been attained, the patient should be referred to a specialist (Ghany et al., 2019).
Treatment failure will be discussed later in the module.
During clinical trials of glecaprevir/pibrentasvir, 99% of patients who had genotype 1 had an SVR. The SVR for the other genotypes was 98% (genotype 2), 93% (genotype 4), 95% (genotype 5), and 100% (genotype 6) (Mavyret, 2020). Patients who had genotype three were not included in these clinical trials.