Key Practice Points
- Patients should take three tablets of glecaprevir + pibrentasvir in the morning with food, for eight weeks
- Dose reductions are not required for patients with an eGFR between 30 to 50 mL/min/1.73 m2; referral
to or discussion with a gastroenterologist is recommended for patients with an eGFR < 30 mL/min/1.73 m2
- Headache and fatigue are the most common adverse effects
- Measure HCV RNA levels or HCV core antigen four weeks after treatment has finished to determine if treatment has been
successful; > 99% of patients treated with glecaprevir + pibrentasvir can be expected to have undetectable
HCV RNA at this point
- Patients without cirrhosis and with normal liver function tests following treatment do not require further follow-up
- Patients with cirrhosis should undergo monitoring, ideally every six months, for the development of hepatocellular
carcinoma and where appropriate, oesophageal varices
How to prescribe glecaprevir + pibrentasvir
Treatment with glecaprevir + pibrentasvir is once daily; patients should be instructed to take three tablets in the
morning with food.1 Glecaprevir + pibrentasvir is mainly excreted in faeces and dose reductions based on
renal function are not necessary.1
Provide patients with a prescription; distribution forms a no longer required
Treatment with Viekira Pak regimens required clinicians to submit a distribution form directly to PHARMAC. However,
this is not the case for prescriptions of glecaprevir + pibrentasvir and patients can be provided with a prescription
to present at an approved pharmacy.
Dispensing of glecaprevir + pibrentasvir occurs at enrolled pharmacies
Only enrolled pharmacies can dispense subsidised glecaprevir + pibrentasvir, similar to the previous arrangements
which were in place for Viekira Pak regimens.
From 1 February, 2019, a list and map of enrolled pharmacies will be available at: www.maviret.co.nz
Instructions for pharmacies that wish to become enrolled to dispense glecaprevir + pibrentasvir and further information
on distribution arrangements is available from PHARMAC; see:
Alternatives are available for patients unable to access an enrolled pharmacy
On the rare occasion that your patient cannot access an enrolled pharmacy for Maviret, the prescriber can contact Healthcare Logistics (HCL) to ask for the alternative distribution form:
For further information on prescribing and distribution, see:
If patients miss a dose
- Take the missed dose if less than 18 hours have passed since the previous dose
- Skip the dose if more than 18 hours have passed since the previous dose
In either case, patients should take the subsequent dose at the normal time.
Mild adverse effects occur in some patients but treatment can be continued
The most common adverse effects experienced by patients taking glecaprevir + pibrentasvir are:2
- Headache, occurring in 17% of patients
- Fatigue, occurring in 14% of patients
- Diarrhoea in 6% of patients
In a placebo-controlled clinical trial, adverse effects typically occurred at the same rate in participants taking placebo
tablets or glecaprevir + pibrentasvir, with the exception of nausea, which was reported by 7% of participants taking glecaprevir
+ pibrentasvir, compared to 3% of participants taking placebo tablets.3 Less than 1% of patients discontinue
treatment due to adverse effects.2
Treatment with glecaprevir + pibrentasvir is better tolerated than treatment with the previously subsidised Viekira
Pak regimens, which resulted in fatigue, headache or nausea in 24-46% of patients.4–6
Patients may drink up to two standard alcoholic drinks per day while taking glecaprevir + pibrentasvir, however, those
with evidence of severe fibrosis or cirrhosis should be advised to avoid alcohol before, during and after treatment.7
Monitoring patient safety
A follow-up visit after four weeks of treatment is recommended to discuss whether patients are experiencing any adverse
In patients without cirrhosis treated in primary care, no blood tests are needed for monitoring safety or efficacy during
glecaprevir + pibrentasvir treatment.7 HCV RNA assays during treatment are not usually necessary; most patients should achieve undetectable HCV RNA levels during treatment.8
Patients treated with the previously subsidised HCV medicine Viekira Pak-RBV required full blood count tests during
treatment, in order to detect reductions in haemoglobin levels caused by ribavirin. Full blood count tests during treatment
are not required for patients taking glecaprevir + pibrentasvir treatment as ribavirin is not included in the treatment
Evaluating the success of treatment
The effectiveness of treatment in eradicating HCV infection is determined by conducting an HCV RNA assay or HCV core
antigen assay four weeks after treatment has finished (see: “Test for treatment success timing has changed”). Liver function tests can be ordered at the same time in order to
assess whether additional follow-up is required (see: “Follow-up testing of liver disease after treatment
of HCV infection”).
A negative HCV RNA assay (undetectable HCV RNA levels) or negative HCV core antigen assay four weeks after treatment has
finished indicates cure. Over 99% of patients treated with glecaprevir + pibrentasvir can be expected to test negative
four weeks after treatment. If the HCV RNA assay or HCV core antigen test at four weeks after treatment is positive,
patients should be discussed with a gastroenterologist.
Treatment improves quality of life, eliminates the risk of transmission and reduces the risk of HCV complications
Successful treatment of HCV infection results in patients experiencing improvements in their quality of life, general
wellbeing and improved physical health, with resolution of fatigue and low mood. Patients may begin to experience these
benefits during treatment.9 Treatment also eliminates the risk of transmitting HCV to others.
Following treatment, patients are likely to have improved liver function and a reduced risk of hepatic and non-hepatic
complications. In patients with advanced liver disease, reductions in portal hypertension and splenomegaly may occur,
as well as a 70% reduction in the risk of hepatocellular carcinoma and a 90% reduction in the risk of mortality from liver
disease.8, 10, 11 Treatment may also resolve or improve non-hepatic complications, such as cryoglobulinaemia,
porphyria cutanea tarda and non-Hodgkin lymphoma.8
Follow-up of patients who relapse after treatment
Approximately 3% of patients relapse after treatment with Viekira Pak regimens, and 1% after treatment with glecaprevir
+ pibrentasvir, due to viral resistance to these medicines.12, 13 Patients who remain infected after treatment
with Viekira Pak or glecaprevir + pibrentasvir should be referred to or discussed with a gastroenterologist. Further treatment
options are available, however, these are not currently subsidised.
Follow-up testing of liver disease after treatment of HCV infection
After successful treatment, patients with normal liver function tests and without cirrhosis do not require additional
follow-up.7 For patients without cirrhosis, but with ongoing raised liver function results, other causes
of elevated liver enzymes may need to be investigated. This could include other medicines, over-the-counter supplements,
alcohol or recreational drug use, non-alcoholic fatty liver disease or inherited conditions, e.g. haemochromatosis.7
Successful treatment of HCV infection in people with cirrhosis reduces, but does not abolish, the risk of hepatocellular
carcinoma.14 Therefore, following successful treatment long-term monitoring for the development of hepatocellular
carcinoma is recommended in all patients with cirrhosis, with six monthly with measurement of serum alpha fetoprotein
(AFP) levels and liver ultrasounds.15 If an ultrasound result is unreliable, e.g. due to liver nodularity,
discuss the use of a CT or MRI scan for surveillance with a gastroenterologist.16 Patients with cirrhosis
with low platelet counts or evidence of portal hypertension on ultrasound should also have a baseline endoscopy to assess
for oesophageal varices.17 If no varices are present and the patient has no other underlying risk factors
for disease progression such as heavy alcohol intake or obesity, then no further endoscopic surveillance is required.18
Post-treatment monitoring for patients at high risk of re-infection
Patients who continue to use injectable drugs or have other ongoing risk factors should be monitored for HCV infection
with annual HCV RNA or HCV core antigen assays.7 In patients who have been successfully treated for HCV infection,
serology cannot be used to test for re-infection as the majority of patients remain seropositive for years following successful
treatment.19 The presence of HCV antibodies, however, does not confer immunity to re-infection. Discussion
with a gastroenterologist is recommended if patients become re-infected.
Test for treatment success timing has changed
The check for treatment success was previously recommended at 12 weeks post-treatment,2 however, more recent evidence by Gane et al (2021) indicates almost all patients (> 99%) who receive an eight-week course of glecaprevir + pibrentasvir will have a sustained virologic response at four weeks post-treatment. N.B. Sustained virological response is calculated as the number of patients with HCV RNA below the lower limit of quantification divided by the total number of patients in the intention-to-treat population.
In this study, the positive predictive value of this four-week check for achieving a sustained virologic response at 12-weeks post-treatment was also > 99% (i.e. > 99% of patients who were “successfully treated” at four weeks post-treatment had the same outcome at 12-weeks). One hundred percent of patients who did not achieve a sustained virologic response at four weeks did not achieve one at 12 weeks.
For further information, see: Gane E, de Ledinghen V, Dylla DE, et al. Positive predictive value of sustained virologic response 4 weeks posttreatment for achieving sustained virologic response 12 weeks posttreatment in patients receiving glecaprevir/pibrentasvir in Phase 2 and 3 clinical trials. J Viral Hepat 2021;28:1635–1642. https://dx.doi.org/10.1111/jvh.13600
- AbbVie Limited. Maviret. New Zealand Data Sheet. 2018. Available from:
http://www.medsafe.govt.nz/profs/datasheet/m/mavirettab.pdf (Accessed Jan, 2019).
- Puoti M, Foster GR, Wang S, et al. High SVR12 with 8-week and 12-week glecaprevir/pibrentasvir therapy: An integrated
analysis of HCV genotype 1-6 patients without cirrhosis. J Hepatol 2018;69:293–300.
- Asselah T, Kowdley KV, Zadeikis N, et al. Efficacy of glecaprevir/pibrentasvir for 8 or 12 weeks in patients with
hepatitis C virus genotype 2, 4, 5, or 6 infection without cirrhosis. Clin Gastroenterol Hepatol 2018;16:417–26.
- Ferenci P, Bernstein D, Lalezari J, et al. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N
Engl J Med 2014;370:1983–92. http://dx.doi.org/10.1056/NEJMoa1402338
- Feld JJ, Kowdley KV, Coakley E, et al. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N
Engl J Med 2014;370:1594–603. http://dx.doi.org/10.1056/NEJMoa1315722
- Andreone P, Colombo MG, Enejosa JV, et al. ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97% and 100% sustained
virologic response with or without ribavirin in treatment-experienced patients with HCV genotype 1b infection. Gastroenterology
- Hepatitis C Virus Infection Consensus Statement Working Group. Australian recommendations for the management of hepatitis
C virus infection: a consensus statement. Melbourne: Gastroenterological Society of Australia 2018. Available from:
http://www.asid.net.au/documents/item/1208 (Accessed Jan, 2019).
- American Association for the Study of Liver Diseases (AASLD), Infectious Diseases Society of America (IDSA). HCV guidance:
recommendations for testing, managing and treating and hepatitis C. 2018. Available from:
http://www.hcvguidelines.org (Accessed Jan, 2019).
- Younossi ZM, Stepanova M, Henry L, et al. An in-depth analysis of patient-reported outcomes in patients with chronic
hepatitis C treated with different anti-viral regimens. Am J Gastroenterol 2016;111:808–16. http://dx.doi.org/10.1038/ajg.2016.99
- van der Meer AJ, Veldt BJ, Feld JJ, et al. Association between sustained virological response and all-cause mortality
among patients with chronic hepatitis c and advanced hepatic fibrosis. JAMA 2012;308:2584–93.
- Morgan RL, Baack B, Smith BD, et al. Eradication of hepatitis C virus infection and the development of hepatocellular
carcinoma. A meta-analysis of observational studies. Ann Intern Med 2013;158:329–37.
- Wedemeyer H, Craxí A, Zuckerman E, et al. Real-world effectiveness of ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin
in patients with hepatitis C virus genotype 1 or 4 infection: A meta-analysis. J Viral Hepat 2017;24:936–43.
- Forns X, Lee SS, Valdes J, et al. Glecaprevir plus pibrentasvir for chronic hepatitis C virus genotype 1, 2, 4, 5,
or 6 infection in adults with compensated cirrhosis (EXPEDITION-1): a single-arm, open-label, multicentre phase 3 trial.
Lancet Infect Dis 2017;17:1062–8.
- Jacobson IM, Lim JK, Fried MW. American Gastroenterological Association Institute clinical practice update - expert
review: care of patients who have achieved a sustained virologic response after antiviral therapy for chronic hepatitis
C infection. Gastroenterology 2017;152:1578–87.
- Heimbach JK, Kulik LM, Finn RS, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology
- Expert Panel on Gastrointestinal Imaging, Horowitz JM, Kamel IR, et al. ACR appropriateness criteria: chronic liver
disease. J Am Coll Radiol 2017;14:S391–405.
- World Health Organisation (WHO). Guidelines for the screening, care and treatment of persons with chronic hepatitis
C infection. Geneva: WHO 2016. Available from:
http://www.who.int/hepatitis/publications/hepatitis-c-guidelines-2016/en/ (Accessed Jan, 2019).
- European Association for Study of the Liver (EASL). EASL recommendations on treatment of hepatitis C 2018. 2018. Available
http://www.easl.eu/medias/cpg/2018/EASL%20Recommendations%20on%20Treatment%20of%20Hepatitis%20C%202018/English-report.pdf (Accessed Jan, 2019).
- Kee K-M, Wang J-H, Hung C-H, et al. Decreased anti-hepatitis C virus titer and associated factors in chronic hepatitis
C patients after sustained virological response: a prospective study. J Gastroenterol Hepatol 2012;27:1106–11.