Names and pronunciation
(glek-a′pre vir/pi-brent′as-vir) Mavyret
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Drug reference
(glek-a′pre vir/pi-brent′as-vir) Mavyret
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Func. class.: Antiviral
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Chem. class.: HCV MS3/4A protease inhibitor/HCV NSSA inhibitor
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Do not confuse: Mavyret/Mavik
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ACTION: Glecaprevir is an inhibitor of hepatitis C virus (HCV) NS3/4A protease, necessary for the proteolytic cleavage of the HCV- encoded polyprotein and is essential for viral replication Pibrentasvir is an inhibitor of HCV NS5A, essential for viral RNA replication
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USES: Chronic hepatitis C (HCV monoinfected or HCV/HIV co-infected patients): With- out cirrhosis or with compensated cir- rhosis (Child-Pugh class A)
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CONTRAINDICATIONS Moderate or severe hepatic impairment (Child-Pugh class B or C); hepatic decom- pensation; coadministration with atazanavir or rifampin
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Black Box Warning: HBV reactivation/ exacerbation PRECAUTIONS Pregnancy, children, breastfeeding, immunosuppressants, chemotherapy Black Box Warning: Hepatitis B surface antigen (HBsAg) and hepatitis B core an- tibody (anti-HBc) prior to initiation Black Box Warning: Serologic evidence of hepatitis B virus (HBV) infection, mon- itor for clinical and laboratory signs of hepa- titis flare or HBV reactivation during treat- ment and during post-treatment follow-up • Diabetes, monitor blood glucose and G for signs/symptoms of hypoglycemia • Monitor for treatment failure; if de- compensation occurs, discontinue treat- ment • Pregnancy/breastfeeding: Avoid use in pregnancy and breastfeeding
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INTERACTIONS Increase: effect of—afatinib, aliskiren, alpelisib, asunaprevir, atorvastatin, betrixa- ban, bilastine, celiprolol, cladribine, CYP1A2 inhibitors, colchicine, dabigatran, dofetilide, doxorubicin, edoxaban, elagolix, digoxin, eluxadoline, etoposide, everolimus, grazo- previr, HMG-CoA reductase inhibitors Increase: hypoglycemic effect— antidiabetics Increase effect of glecaprevir/pibrentas- vir—atazanavir, cobicistat, cyclosporine, darunavir, P-glycoprotein inhibitors (except cyclosporine) Decrease: effect of glecaprevir/pibren- tasvir—carBAMazepine, CYP3A4 induc- ers, efavirenz, fosphenytoin, rifamycins Eltrombopag: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/ 1B3) substrates. Monitor therapy Eltrombopag: May increase the serum concentration of BCRP/ABCG2 substrates. Monitor therapy Increase: adverse reactions of glecapre- vir/pibrentasvir—ethinyl Drug/Herb Decrease: effect of glecaprevir/pibrentas vir, avoid using together—St. John’s Wort Drug/Lab Test Increase: bilirubin
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DOSAGE AND ROUTES • Adult/child >45 kg: PO 3 tablets with food • Child 12-17: PO 6 packets daily with food × 8 wk • Child 3-11, >45 kg: PO 6 packets daily with food × 8 wk • Child 3-11, 30-44 kg: PO 5 packets daily with food × 8 wk • Child 3-11, 20-29 kg: PO 4 packets daily with food × 8 wk • Child 3-11 <20 kg: PO 3 packets daily with food × 8 wk Duration: Therapy-naive: HCV genotype 1, 2, 3, 4, 5, 6: No cirrhosis: 8 wk; compensated cirrhosis (Child-Pugh A): 8 wk Therapy-experienced: HCV genotype 1 (prior therapy with regimen con- taining an NS5A inhibitor without prior therapy with an NS3/4A prote- ase inhibitor): No cirrhosis: 16 wk; compensated cirrhosis (Child-Pugh A): 16 wk HCV genotype 1 (prior therapy with an NS3/4A protease inhibitor without prior therapy with an NS5A inhibi- tor): No cirrhosis: 12 wk; compensated cirrhosis (Child-Pugh A): 12 wk HCV genotype 1, 2, 4, 5, 6 (prior therapy with PRS): No cirrhosis: 8 wk; compensated cirrhosis (Child-Pugh A): 12 wk HCV genotype 3 (prior therapy with PRS): No cirrhosis: 16 wk; compensated cirrhosis (Child-Pugh A): 16 wk
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Available forms: Tablet: glecaprevir 100 mg/pibrentasvir 40 mg; oral pellets 50 mg/20 mg
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Administer: • Give with food • If dose is missed, give as soon as remembered if within 18 hr, then normal dosing; if >18 hr, skip • Store at room temperature
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Assess: • Baseline (within 12 wk prior to starting antiviral therapy) CBC, INR, hepatic function panel (albumin, total and direct bilirubin, ALT, AST, and alkaline phosphatase), and calculated GFR; repeat CBC, serum creatinine, calculated GFR, and LFTs panel after 4 wk of therapy and as clinically indicated • Baseline (at any time prior to starting therapy) hepatitis C virus (HCV) genotype and subtype and quanti- tative HCV viral load; repeat quantitative HCV viral load testing (after 4 wk of therapy and at 12 wk after completion of therapy). If quantitative HCV viral load is detectable at treatment wk 4, repeat test- ing after 2 additional wk of treatment (treatment week 6)
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Evaluate: • Therapeutic response: hepatitis C RNA reduction
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To report side effects to the prescriber • To notify all providers of product use, many drug interactions; do not take with St. John’s wort • To take at the same time each day, to use for full course even if feeling better, to take missed doses when re- membered on the same day; not to double doses • That the product will not decrease transmission of infection in others • Pregnancy/breastfeeding: To notify provider if pregnancy is planned or sus- pected, or if breastfeeding HIGH ALERT
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PHARMACOKINETICS Peak 5 hr, half-life: glecaprevir 6 hr; pibrentasvir 13 hr
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• Adult/child >45 kg: PO 3 tablets with food
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• Child 12-17: PO 6 packets daily with food × 8 wk
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• Child 3-11, >45 kg: PO 6 packets daily with food × 8 wk
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• Child 3-11, 30-44 kg: PO 5 packets daily with food × 8 wk
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• Child 3-11, 20-29 kg: PO 4 packets daily with food × 8 wk
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• Child 3-11 <20 kg: PO 3 packets daily with food × 8 wk Duration: Therapy-naive: HCV genotype 1, 2, 3, 4, 5, 6: No cirrhosis: 8 wk; compensated cirrhosis (Child-Pugh A): 8 wk Therapy-experienced: HCV genotype 1 (prior therapy with regimen con- taining an NS5A inhibitor without prior therapy with an NS3/4A prote- ase inhibitor): No cirrhosis: 16 wk; compensated cirrhosis (Child-Pugh A): 16 wk HCV genotype 1 (prior therapy with an NS3/4A protease inhibitor without prior therapy with an NS5A inhibi- tor): No cirrhosis: 12 wk; compensated cirrhosis (Child-Pugh A): 12 wk HCV genotype 1, 2, 4, 5, 6 (prior therapy with PRS): No cirrhosis: 8 wk; compensated cirrhosis (Child-Pugh A): 12 wk HCV genotype 3 (prior therapy with PRS): No cirrhosis: 16 wk; compensated cirrhosis (Child-Pugh A): 16 wk
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