Drug reference

pibrentasvir

NS5A inhibitor · Antiviral, Hepatitis C agent

NS5A inhibitorAntiviral, Hepatitis C agent

CDSCO approved

EXCRETION

—

not curated

INTERACTIONS

5 major

SEVERE in our sources

PREGNANCY

—

not curated

Top interactionssee all 9 →

CyclosporineSevereTextbookG&G 14e · p1241
Hiv Protease InhibitorsSevereTextbookG&G 14e · p1241
Potent Cyp3a InducersSevereTextbookG&G 14e · p1241, p1242
Potent Oatp1b1 InhibitorsSevereTextbookG&G 14e · p1241, p1242

Mechanism

Pibrentasvir is an inhibitor of the non-structural protein 5A (NS5A) of the hepatitis C virus, which plays a critical role in viral RNA replication and virion assembly.

Indications

All HCV genotypes (pangenotypic) for treatment-naïve individuals (as part of fixed-dose combination with glecaprevir)Treatment-experienced patients with prior NS3 protease and NS5A failures (as part of fixed-dose combination with glecaprevir)HCV in patients with chronic kidney disease (preferred treatment in renal impairment)Children aged >12 years or ≥45 kg (as part of fixed-dose combination with glecaprevir)Children aged ≥3 years (weight-based dosing of film-coated pellets, as part of fixed-dose combination with glecaprevir)

Dosing

Adult: 120 mg (as part of three fixed-dose combination tablets with glecaprevir) once daily for 8 weeks
Pediatric: 100 mg (as part of GLE/PIB) for children weighing ≥30 kg to <45 kg; 80 mg for children weighing ≥20 kg to <30 kg; 60 mg for children weighing 12 kg to <20 kg
Renal adjustment: Preferred treatment in renal impairment, though exposures are elevated in ESRD

Pharmacokinetics

Half-life

13 h

Protein binding

Highly protein-bound

Excretion

Largely via biliary-fecal route (>92%); renal excretion less than 1%

Contraindications

Decompensated cirrhosis
Advanced liver disease
Concomitant use with potent P-gp, CYP3A inducers (antiepileptics, St. John’s wort, rifampin, efavirenz)
Concomitant use with HIV protease inhibitors or cyclosporine (due to increased GLE exposures and potential hepatotoxicity)
Concomitant use with ethinyl estradiol-containing hormonal contraception (during and for 2 weeks after treatment)

Side effects

Common

HeadacheFatigueNausea

Drug interactions

Cyclosporine

Severe

Textbook

Increased pibrentasvir exposures, potentially predisposing to hepatotoxicity (implicitly, as part of GLE/PIB).

Should not be used with GLE/PIB.

Source: G&G 14e · p1241

Hiv Protease Inhibitors

Severe

Textbook

Increased pibrentasvir exposures, potentially predisposing to hepatotoxicity (implicitly, as part of GLE/PIB).

Should not be used with GLE/PIB.

Source: G&G 14e · p1241

Potent Cyp3a Inducers

Severe

Textbook

Reduced pibrentasvir concentrations and efficacy.

Potent inducers (e.g., antiepileptics, St. John’s wort, rifampin, efavirenz) are not recommended. Do not use with potent CYP3A inducers.

Source: G&G 14e · p1241, p1242

Potent Oatp1b1 Inhibitors

Severe

Textbook

Increased pibrentasvir exposures.

Potent OATP1B1 inhibitors are not recommended. Do not use with potent OATP1B1 inhibitors.

Source: G&G 14e · p1241, p1242

Potent P Gp Inducers

Severe

Textbook

Reduced pibrentasvir concentrations and efficacy.

Potent inducers (e.g., antiepileptics, St. John’s wort, rifampin, efavirenz) are not recommended. Do not use with potent P-gp inducers.

Source: G&G 14e · p1241, p1242

Bcrp Substrates

Moderate

Textbook

Increased concentrations of co-administered drugs that are BCRP substrates.

No specific management stated, but likely requires monitoring and potential dose adjustment.

Source: Harrison 22e · unknown

Ethinyl Estradiol Containing Hormonal Contraception

Moderate

Textbook

Liver enzyme elevations and potential hepatotoxicity.

Should not be used during and for 2 weeks after GLE/PIB. Avoid ethinyl estradiol-containing hormonal contraception during and for 2 weeks after treatment due to potential hepatotoxicity.

Source: G&G 14e · p1241, p1242

Oatp1 Substrates

Moderate

Textbook

Increased concentrations of co-administered drugs that are OATP1 substrates.

No specific management stated, but likely requires monitoring and potential dose adjustment.

Source: Harrison 22e · unknown

P Glycoprotein Substrates

Moderate

Textbook

Increased concentrations of co-administered drugs that are P-glycoprotein substrates.

No specific management stated, but likely requires monitoring and potential dose adjustment.