Glecaprevir/Pibrentasvir and the Expanding Role of Pharmacists in HCV Test-and-Treat Models

In a written interview with Pharmacy Times, Callan Bleick, PharmD, MSc, highlighted key aspects of hepatitis C virus (HCV) management—particularly with glecaprevir/pibrentasvir (Mavyret; AbbVie)—including risk factors, baseline assessments, dosing, and missed-dose protocols, as well as the importance of drug-drug interaction (DDI) screening.

Bleick emphasized the growing impact of shorter, simplified regimens, expanded HCV screening guidelines, and collaborative practice agreements, all of which can increase pharmacist-led care opportunities in community and ambulatory settings. Bleick also discussed how future label expansions, simplified regimens, and point-of-care diagnostics may further enhance pharmacy-based HCV test-and-treat models, improving access and cure rates, notably in underserved populations.

Pharmacy Times: What are certain risk factors that contribute to HCV infection?

Callan Bleick, PharmD, MSc: Risk factors for HCV infection include intravenous drug use, health care–related exposures, receiving blood products in the US before 1992 (or 1987 for certain blood products), long-term hemodialysis, needle stick injuries, and poor infection control practices. Other risk factors include incarceration, transmission from an infected mother to child, and percutaneous or parental exposure in unregulated settings. People with untreated HIV are also at increased risk. It is important to note that these risk factors can vary depending on geographic location and population. Pharmacists should remain vigilant about the most significant risks for HCV infection to ensure timely screening, prevention counseling, and linkage to care.¹

Pharmacy Times: What key administration counseling points should be provided to patients taking glecaprevir (300 mg)/pibrentasvir (120 mg), and what should be done if a patient misses a dose?

Bleick: This regimen is taken 3 times a day with food. If a dose is missed, it is advised that the patient take it as soon as they remember; however, it is important that they do not double up. Patients should always contact their pharmacist or health care provider if a dose or doses are missed, as treatment adjustments may be necessary. If it has been 18 hours or less from the usual dosage time, the missed dose can be taken as soon as possible, then the following dose can be taken at the usual time. If it has been more than 18 hours from the usual dosage time, [the patient should] skip the missed dose and take the next dose at usual dosage time.²

It is recommended that patients who are DAA [direct acting antiviral] naive and
eligible for simplified regimens adhere to the following guidelines¹:
• If a dose is missed within:
˚ Seven days or fewer: Restart immediately and finish the course as originally planned.
˚ Eight to 20 days: Restart immediately and contact a health care provider for
an HCV-RNA test. Treatment duration may need to be extended or restarted, depending on results, cirrhosis status, and genotype.
˚ Twenty-one days or more: Stop therapy and follow up to assess whether retreatment is needed.

Pharmacy Times: What baseline assessments, counseling, and preventive measures should be completed prior to initiating glecaprevir (300 mg)/pibrentasvir (120 mg) therapy? What key medication counseling points should pharmacists provide?

Bleick: Before starting glecaprevir/pibrentasvir, patients should receive education on liver disease prevention and HCV transmission, be screened for coinfections (eg, hepatitis B virus [HBV] and HIV), and undergo cirrhosis assessment and fibrosis staging (noninvasive or biopsy). Alcohol cessation interventions should be offered, and vaccinations should be updated appropriately (ie, hepatitis A vaccine, HBV, pneumococcal). Patients should be linked to knowledgeable providers for comprehensive care. Medication reconciliation and a thorough DDI review are essential, along with pretreatment laboratory tests. Genotype screening should be performed as it may influence treatment duration; in addition, the patient’s eligibility for simplified vs nonsimplified treatment course should be determined.¹

It is important for pharmacists to counsel patients on proper administration and what to do if they miss a dose, as well as to conduct a complete review of prescription drugs, OTC medications, and supplements. As pharmacists, we play a key role in making sure patients stay on track with their therapy. By continuously monitoring their progress, reinforcing adherence at every follow-up, and providing clear ongoing education, we can help maximize cure rates while minimizing risks throughout the entire course of treatment.

Pharmacy Times: What key DDIs should pharmacists watch for when starting a patient on glecaprevir/pibrentasvir? What free, reliable resources can they use to quickly check for these interactions?

Bleick: When initiating glecaprevir/pibrentasvir, pharmacists should carefully review clinically significant DDIs. Coadministration with certain drugs and/or supplements can often lead to reduced efficacy or increased toxicity. The University of Liverpool in England offers a free, user-friendly online tool for checking potential DDIs.³ In addition, the monitoring section of the updated HCV guidance includes a comprehensive DDI assessment table. Using these resources can significantly improve medication adherence, optimize therapy, and reduce the risk of adverse effects.^1,3

Examples of potential DDIs observed (not an exhaustive list) include the following³:

Contraindicated (avoid use):

• HIV antivirals: atazanavir, darunavir, lopinavir, ritonavir, efavirenz

• Statins: atorvastatin, simvastatin, lovastatin (Note: Coadministration with certain β-hydroxy-β-methylglutaryl-CoA statins may increase their concentration.)

• Anticonvulsants: carbamazepine, oxcarbazepine, phenytoin

• Other: rifampin, St John’s wort (Hypericum perforatum), red yeast rice, estradiol-containing products, irinotecan, certain chemotherapeutics (eg, doxorubicin, vincristine, topotecan)

Significant interactions (monitor or adjust):
• Statins: Limit rosuvastatin to 10 mg daily; reduce pravastatin dose by 50%
• Digoxin: Monitor serum levels; adjust dose as needed
• Warfarin: May decrease anticoagulant effect; monitor international normalized ratio closely

Other considerations:

• Benzodiazepines: Monitor for sedation or toxicity

• Proton pump inhibitors: May be used safely

• Levetiracetam: Safe antiepileptic choice with no significant interaction

Pharmacy Times: Can you discuss how renal or hepatic impairment affects the appropriateness of glecaprevir/pibrentasvir and how pharmacists should approach dosing or monitoring?

Bleick: When determining appropriateness, glecaprevir/pibrentasvir is primarily affected by hepatic rather than renal impairment. Because the drug is not significantly cleared renally, patients with renal impairment, including those with end-stage renal disease or on hemodialysis, do not require dose adjustments. Glecaprevir/pibrentasvir exposure can increase significantly, especially in patients with moderate or severe hepatic impairment, which raises the risk for hepatic decompensation; however, mild hepatic impairment does not require dose adjustment. Baseline liver function tests and Child-Pugh classification should be assessed and monitored closely. When possible, pharmacists should continue to monitor significant changes in kidney function and assess for the use of nephrotoxic medications. These dosing and monitoring parameters factors should be carefully considered to ensure safety and efficacy in patients and help maintain continuity of care throughout the HCV treatment course.^1,2

Pharmacy Times: How has the 8-week duration of therapy with glecaprevir/pibrentasvir influenced treatment uptake and adherence in real-world pharmacy settings?

Bleick: In my opinion, the relatively shortened 8-week regimen of glecaprevir/pibrentasvir in certain patient populations has been shown to have positive effects on treatment uptake and adherence. Due to the reduced duration of therapy (compared with longer durations, such as 12 weeks), the patient’s pill burden has decreased over time, improving patient convenience and minimizing treatment fatigue. The 8-week course can also align well with certain pharmacy-based models by streamlining medication dispensing, patient follow-up, and adherence monitoring. In general, the shortened course can influence a patient’s willingness to begin therapy, making it relatively easier to complete therapy without interruption while also reducing overall treatment costs. These pharmacy-based models can provide pharmacists with the ability to effectively maintain frequent contact with the patient and provide adherence support throughout the treatment duration, leading to improved sustained virologic response rates.

Pharmacy Times: How do the updated HCV screening guideline changes impact patient identification, treatment initiation, and care coordination in pharmacy-based models?

Bleick: Generally speaking, the hepatitis C guidance document provided by the AASLD-IDSA [American Association for the Study of Liver Diseases and Infectious Diseases Society of America] broadened the scope of screening, expanding the role and opportunities for pharmacy-based involvement.¹ More patients are now being diagnosed with HCV in earlier stages, including those without traditional risk factors, which has been linked to improved public and patient health outcomes.^4,5 HCV incidence has been increasing among particular high-risk patient populations, and routine testing has been shown to have a positive impact on cost-effectiveness, including the decrease in cost of highly effective DAA therapy. With the universal screening recommendation, this update can help identify patients who would otherwise be missed and can offer promising health care savings when reinfection risk requires testing.

Additionally, certain pharmacybased models can operate as accessible community screening sites to offer rapid HCV testing and linkage to care in their designated areas. With more individuals being identified with HCV due to the screening recommendation, there is a greater demand for pharmacist-based lead initiation and management of DAA therapy under collaborative practice agreements (CPAs). As a result, these efforts can lead to a steady patient flow, allowing pharmacies to develop a streamlined referral system to HCV specialists, infectious diseases care centers, or in-house treatment programs.

Although evidence is lacking regarding optimal testing frequency for individuals at ongoing risk of HCV exposure, current guidance recommends at least annual HCV RNA testing for people who inject drugs and men who have unprotected sex with HIV-infected men, with clinicians determining additional testing based on individual patient risk of infection or reinfection.¹

Pharmacy Times: How can pharmacists become more involved in HCV test-and-treat models, especially in community or ambulatory care settings?

Bleick: Pharmacists can leverage their accessibility to the public by offering routine HCV screening and education as part of broader health services, helping to identify undiagnosed cases and facilitate timely linkage to treatment under collaborative practice agreements where permitted. For instance, in an ambulatory care setting, pharmacists can manage patient therapy directly, including screening for drug-drug interactions, performing medication counseling, monitoring for adherence, and ordering and evaluating laboratory tests. Additionally, pharmacists can collaborate with public health agencies, primary care providers, and harm reduction programs to improve patient engagement, reduce barriers to care, and expand access to HCV treatment in underserved populations. Overall, we can leverage pharmacists’ medication expertise and accessibility to build trust within our communities and improve HCV cure rates.

Pharmacy Times: In your experience, how common are CPAs that allow pharmacists to initiate or adjust DAA therapy?

Bleick: In my opinion, CPAs—which authorize pharmacists to initiate or adjust direct-acting antiviral therapy—are becoming more common, but their availability still varies widely due to state regulations, institutional policies, and local provider partnerships. I think CPAs will become more common in certain states, especially those with progressive pharmacy practice laws and established test-and-treat models. However, we are still seeing, in many cases, limited roles for pharmacist intervention, such as screening, counseling, and recommending therapy rather than formally prescribing or adjusting treatment directly in other areas. I think it’s important that we continue to advocate and empower pharmacists to lead these efforts. Certain states with CPAs in place have already demonstrated positive outcomes.

Pharmacy Times: Do you anticipate further label expansions or simplified regimens that could shift more HCV care into pharmacy-led environments?

Bleick: Yes, I think that this is likely and could significantly increase the feasibility of pharmacy-led care. We know that treatment options currently available are already shorter in duration compared with older regimens and are highly effective and generally well tolerated. Ongoing research exploring pan-genotypic therapy with minimal monitoring requirements is still ongoing. Regulatory changes that broaden indications to include more patient populations, along with point-of-care diagnostic advancements, could further streamline initiation in pharmacy environments. As treatment regimens become simpler and monitoring demands decrease, pharmacies equipped with CPAs or prescriptive authority will be well positioned to initiate and manage HCV therapy.

REFERENCES

1. Bhattacharya D, Aronsohn A, Price J, Lo Re V; AASLD-IDSA HCV Guidance Panel. Hepatitis C guidance 2023 update: AASLD-IDSA recommendations for testing, managing, and treating hepatitis C virus infection. Clin Infect Dis. Published online May 25, 2023. doi:10.1093/cid/ciad319

2. Glecaprevir and pibrentasvir (oral route). Mayo Clinic. Accessed March 6, 2025. https://www.mayoclinic.org/drugs-supplements/glecaprevir-and-pibrentasvir-oralroute/description/drg-20406400

3. HEP drug interactions. University of Liverpool. Accessed March 6, 2025. https://www.hep-druginteractions.org/checker

4. Roudot-Thoraval F. Epidemiology of hepatitis C virus infection. Clin Res Hepatol Gastroenterol. 2021;45(3):101596. doi:10.1016/j.clinre.2020.101596

5. Stroffolini T, Stroffolini G. Prevalence and modes of transmission of hepatitis C virus infection: a historical worldwide review. Viruses. 2024;16(7):1115.doi:10.3390/v16071115