Names and pronunciation
(soe-fos′bue-vir/vel-pat′as-vir) Epclusa
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Drug reference
(soe-fos′bue-vir/vel-pat′as-vir) Epclusa
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Func. class.: Antiviral, antihepatitis agent
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ACTION: Sofosbuvir: A nucleotide prodrug that prevents hepatitis C viral (HCV) replication by inhibiting the activ- ity of HCV NS5B RNA polymerase Velpatasvir: Inhibits the HCV NS5A pro- tein, which is required for viral replica- tion
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USES: Treatment of chronic hepatitis C infection, including genotypes 1, 2, 3, 4, 5, and 6, in those without cirrho- sis and in patients with compensated cirrhosis (Child-Pugh A); treatment of chronic hepatitis C infection in patients with decompensated cirrhosis (Child- Pugh B or C)
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CONTRAINDICATIONS: Hyper sensitivity Precautions: Breastfeeding, hepatitis C and HIV coinfection, male-mediated teratogenicity, pregnancy, renal failure/ impairment
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Black Box Warning: Hepatitis B exacer- bation Black Box Warning: Hepatitis B exac- erbation: monitor serum HCV-RNA base- line and periodically, monitor coinfected patients during and after treatment for signs of hepatitis B exacerbation (HBsAg, HBV DNA, hepatic enzymes, bilirubin), as- sess for signs of liver toxicity (yellow eyes or skin, fatigue, weakness, loss of appe- tite, nausea, vomiting, or light-colored stools); screen all potential recipients for current or prior HBV infection by testing HBsAg and anti-HBc concentrations. For those whose screening reveals evidence of HBV infection, a baseline HBV DNA should be obtained before starting sofos- buvir/velpatasvir; monitor LFTs • Heart rate, B/P; severe bradycardia may occur with amiodarone used con- currently • Severe renal disease/GFR <30 mL/ min/1.73 m2; monitor BUN, creatinine • Closer monitoring in geriatric patients; may develop renal, cardiac symptoms more rapidly • Anemia: Monitor HB/Hct if anemia is suspected • Pregnancy/breastfeeding: contra- indicated in pregnant women and in the male partners of women who are preg- nant; two reliable forms of effective contraception are needed during treat- ment and for 6 mo after use of these combination therapies. Pregnancy test immediately before initiation of therapy, monthly and for 6 mo post-therapy. To monitor maternal-fetal outcomes of pregnancies in female patients and fe- male partners of male patients exposed to ribavirin during treatment and for 6 mo following cessation of treatment, report any cases to the Ribavirin Preg- nancy Registry, 800-593-2214. For pa- tients who are also infected with HIV and taking concomitant antiretrovirals, an Antiretroviral Pregnancy Registry is S available at 800-258-4263; do not breastfeed Black Box Warning: Hepatitis exacer- bation: report to provider immediately signs of liver toxicity (yellow eyes or skin, fatigue, weakness, loss of appetite, nau- sea, vomiting, or light-colored stools)
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SIDE EFFECTS CNS: Fatigue, headache, insomnia, de- pression, irritability, asthenia GI: Nausea, diarrhea INTEG: Rash META: Hyperbilirubinemia HEMA: Anemia
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INTERACTIONS Increase: velpatasvir level—CYP3A4 inhibitors (aldesleukin, aliskiren, amLO- DIPine, clarithromycin, aprepitant, fosa- prepitant, atazanavir, bromocriptine, chloramphenicol, ciprofloxacin, cyclo- SPORINE, delavirdine, dasatinib, danazol, darunavir, diltiaZEM, dronedarone, erythromycin, fluconazole, FLUoxetine, fluvoxaMINE, idelalisib, imatinib, indina- vir, isavuconazonium, amprenavir, bocenavir, ketoconazole, itraconazole, dalfopristin/quinupristin, ritonavir, tip- ranavir, isoniazid, miconazole), P-gp inhibitors Increase: bradycardia—amiodarone; avoid using together Increase: myopathy, rhabdomyolysis— atorvastatin Increase: sofosbuvir level—carvedilol, cobicistat Increase: effect of both products—cla rithromycin, azithromycin, boceprevir, canagliflozin, carvedilol, crizotinib Decrease: velpatasvir level—CYP3A4 inducers (armodafinil, barbiturates, bex- arotene, bosentan, carBAMazepine, dexamethasone, efavirenz, enzalutamide, eslicarbazepine, ethanol, etravirine, fel bamate, flutamide, griseofulvin, lesinu- rad, modafinil, nafcillin, nevirapine, rifAMPin, rifapentine, rifabutin, phenyt- oin, PHENobarbital, pioglitazone, primi- done); antacids, PPIs separate by 4 hr Decrease: sofosbuvir level—P-glycopro- tein (P-gp) inducers (carBAMazepine, PHENobarbital, phenytoin, rifAMPin); OXcarbazepine, rifabutin, rifapentine, tipranavir; avoid concurrent use Decrease: levels of—ritonavir Drug/Herb Decrease: sofosbuvir level—St. John’s wort; do not use together
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DOSAGE AND ROUTES Chronic hepatitis C infection with- out cirrhosis and with compensated cirrhosis (Child-Pugh A) • Adult: PO 1 tablet (400 mg sofosbuvir; 100 mg velpatasvir) daily × 12 wk Chronic hepatitis C infection in pa- tients with decompensated cirrhosis (Child-Pugh B or C) • Adult/child/adolescent 3-17 yr and ≥30 kg: PO 1 tablet (400 mg sofosbuvir; 100 mg velpatasvir) daily plus ribavirin × 12 wk. The dose of ribavirin is based on weight as follows: <75 kg give 500 mg bid; ≥75 kg give 600 mg bid
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Available forms: Tabs 400 mg sofosbu- vir-100 mg velpatasvir; granules 150 mg/37.5 mg; 200 mg/50 mg pellets
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Administer: • Take without regard to food • If given with ribavirin, take ribavirin with food • Pellets: may be poured in the mouth and swallowed without chewing, water may be taken after swallowing the pellets or may be taken with soft food
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Evaluate: • Decreased symptoms of chronic hepa- titis C Patient and caregiver information: • That optimal duration of treatment is unknown; that product is not a cure, that transmission to others may still occur • To avoid use with other products un- less approved by prescriber • Not to stop abruptly unless directed, worsening of hepatitis may occur; to keep in original container • Pregnancy/breastfeeding: teach pa- tients that they and their partners are required to use two reliable forms of effec- tive contraception during treatment and for 6 mo after use; that pregnancy tests are needed immediately before, monthly during therapy, and for 6 mo post-therapy; not to breastfeed
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CLINICAL CONSIDERATIONS Assess
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PHARMACOKINETICS • Sofosbuvir: 61% to 65% protein bind- ing, converted in the liver from the nucleo- tide prodrug to active nucleoside analog triphosphate; elimination via kidneys 80%, feces 14%, expired air 2.5%, terminal elimination half-life of 25 hr, peak 0.5-1 hr, high-fat meal increases bioavailability • Velpatasvir: 99.5% protein binding, metabolized by CYP2B6, CYP2C8, and CYP3A4, excretion in bile 77% of the parent drug, 95% feces, 0.4% urine, ter- minal elimination half-life 15 hr, peak 3 hr, increased by high-fat meal
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• Adult: PO 1 tablet (400 mg sofosbuvir; 100 mg velpatasvir) daily × 12 wk Chronic hepatitis C infection in pa- tients with decompensated cirrhosis (Child-Pugh B or C)
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• Adult/child/adolescent 3-17 yr and ≥30 kg: PO 1 tablet (400 mg sofosbuvir; 100 mg velpatasvir) daily plus ribavirin × 12 wk. The dose of ribavirin is based on weight as follows: <75 kg give 500 mg bid; ≥75 kg give 600 mg bid
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