Management and follow-up of patients prescribed glecaprevir + pibrentasvir

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

Initiating treatment in primary care

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: https://pharmac.govt.nz/news-and-resources/consultations-and-decisions/decision-to-fund-a-new-hepatitis-c-treatment-maviret-and-to-widen-access-to-adalimumab-humira-for-psoriasis/

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:

• [email protected] or
• Phone 0800 222 843

For further information on prescribing and distribution, see: https://pharmac.govt.nz/medicine-funding-and-supply/make-an-application/special-access-medicines/

During treatment

If patients miss a dose

They should:¹

• 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 effects.⁸

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 regimen.

Follow-up after treatment is completed

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.