MAVYRET

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MAVYRET (MAVYRET).

How it works

Fixed-dose combination of glecaprevir (NS3/4A protease inhibitor) and pibrentasvir (NS5A inhibitor) that directly inhibits HCV viral replication by targeting viral proteins essential for polyprotein processing and RNA replication.

What the body does with it

Metabolism	Glecaprevir: metabolized mainly by CYP3A; pibrentasvir: minimal metabolism, primarily excreted unchanged in feces.
Excretion	Primarily fecal (92%) with unchanged drug (50.3% glecaprevir, 63.8% pibrentasvir); renal elimination is minimal (<1%).
Half-life	Glecaprevir: 6 hours; pibrentasvir: 13 hours; supports once-daily dosing.
Protein binding	≥97% bound to plasma proteins (primarily albumin) for both glecaprevir and pibrentasvir.
Volume of Distribution	Glecaprevir: 211 L; pibrentasvir: 248 L; indicates extensive tissue distribution.
Bioavailability	Glecaprevir: ~36% under fed conditions; pibrentasvir: ~9% under fed conditions; food increases absorption (administer with food).
Onset of Action	Rapid antiviral effect: HCV RNA decline observed within hours; maximal suppression by 2-4 weeks.
Duration of Action	Sustained virologic response (SVR) is achieved after 8-16 weeks of treatment; duration depends on HCV genotype, prior treatment, and cirrhosis status.

Classification & Brands

Dosing & administration

Three tablets (containing glecaprevir 100 mg and pibrentasvir 40 mg) taken orally once daily with food for 8 to 16 weeks depending on patient characteristics and prior treatment history.

Dosage form	TABLET
Renal impairment	No dose adjustment required for any degree of renal impairment including dialysis.
Liver impairment	Contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh B or C). No dose adjustment needed for mild hepatic impairment (Child-Pugh A).
Pediatric use	For patients aged ≥12 years or weighing ≥45 kg: three tablets (glecaprevir 100 mg/pibrentasvir 40 mg) once daily with food. For younger children and lower weights, weight-based dosing is used; e.g., for 3 to <12 years or weight 30 to <45 kg: two tablets (glecaprevir 200 mg/pibrentasvir 80 mg total) once daily; for weight 20 to <30 kg: one tablet (glecaprevir 100 mg/pibrentasvir 40 mg) plus one 50 mg/20 mg tablet; for weight 12 to <20 kg: two 50 mg/20 mg tablets once daily.
Geriatric use	No specific dose adjustment is required for elderly patients; clinical studies included patients aged ≥65 years with similar efficacy and safety compared to younger adults.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for MAVYRET (MAVYRET).

Breastfeeding	No data on presence in human milk, effects on breastfed infant, or milk production. Due to potential for adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for 30 days after last dose. M/P ratio unknown.
Teratogenic Risk	MAVYRET is contraindicated in pregnancy due to risk of fetal harm. Based on animal studies and mechanism of action (HCV RNA polymerase inhibitor), there is potential for teratogenicity. In pregnant women, exposure during first trimester may increase risk of congenital anomalies. Use effective contraception during treatment and for 30 days after last dose.

Warnings & precautions

■ FDA Black Box Warning

Risk of hepatitis B virus (HBV) reactivation in patients coinfected with HCV and HBV; test all patients for HBV before starting treatment and monitor during therapy.

Side Effect Profile

Serious Effects

Absolute Contraindications

Moderate to severe hepatic impairment (Child-Pugh B or C); coadministration with atazanavir, simvastatin, ethinyl estradiol-containing contraceptives, or rifampin.

Clinical Precautions

Precautions

Risk of HBV reactivation; elevated liver enzymes (ALT elevations); risk of hepatic decompensation in patients with moderate to severe cirrhosis (Child-Pugh B or C); drug interactions with strong CYP3A inducers or certain P-glycoprotein substrates.

Clinical Tips & Counseling

Drug interactions

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MAVYRET

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MAVYRET (MAVYRET).

How it works

What the body does with it

Metabolism	Glecaprevir: metabolized mainly by CYP3A; pibrentasvir: minimal metabolism, primarily excreted unchanged in feces.
Excretion	Primarily fecal (92%) with unchanged drug (50.3% glecaprevir, 63.8% pibrentasvir); renal elimination is minimal (<1%).
Half-life	Glecaprevir: 6 hours; pibrentasvir: 13 hours; supports once-daily dosing.
Protein binding	≥97% bound to plasma proteins (primarily albumin) for both glecaprevir and pibrentasvir.
Volume of Distribution	Glecaprevir: 211 L; pibrentasvir: 248 L; indicates extensive tissue distribution.
Bioavailability	Glecaprevir: ~36% under fed conditions; pibrentasvir: ~9% under fed conditions; food increases absorption (administer with food).
Onset of Action	Rapid antiviral effect: HCV RNA decline observed within hours; maximal suppression by 2-4 weeks.
Duration of Action	Sustained virologic response (SVR) is achieved after 8-16 weeks of treatment; duration depends on HCV genotype, prior treatment, and cirrhosis status.

Classification & Brands

Dosing & administration

Three tablets (containing glecaprevir 100 mg and pibrentasvir 40 mg) taken orally once daily with food for 8 to 16 weeks depending on patient characteristics and prior treatment history.

Dosage form	TABLET
Renal impairment	No dose adjustment required for any degree of renal impairment including dialysis.
Liver impairment	Contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh B or C). No dose adjustment needed for mild hepatic impairment (Child-Pugh A).
Pediatric use	For patients aged ≥12 years or weighing ≥45 kg: three tablets (glecaprevir 100 mg/pibrentasvir 40 mg) once daily with food. For younger children and lower weights, weight-based dosing is used; e.g., for 3 to <12 years or weight 30 to <45 kg: two tablets (glecaprevir 200 mg/pibrentasvir 80 mg total) once daily; for weight 20 to <30 kg: one tablet (glecaprevir 100 mg/pibrentasvir 40 mg) plus one 50 mg/20 mg tablet; for weight 12 to <20 kg: two 50 mg/20 mg tablets once daily.
Geriatric use	No specific dose adjustment is required for elderly patients; clinical studies included patients aged ≥65 years with similar efficacy and safety compared to younger adults.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for MAVYRET (MAVYRET).

Breastfeeding	No data on presence in human milk, effects on breastfed infant, or milk production. Due to potential for adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for 30 days after last dose. M/P ratio unknown.
Teratogenic Risk	MAVYRET is contraindicated in pregnancy due to risk of fetal harm. Based on animal studies and mechanism of action (HCV RNA polymerase inhibitor), there is potential for teratogenicity. In pregnant women, exposure during first trimester may increase risk of congenital anomalies. Use effective contraception during treatment and for 30 days after last dose.

Warnings & precautions

■ FDA Black Box Warning

Risk of hepatitis B virus (HBV) reactivation in patients coinfected with HCV and HBV; test all patients for HBV before starting treatment and monitor during therapy.

Side Effect Profile

Serious Effects

Absolute Contraindications

Moderate to severe hepatic impairment (Child-Pugh B or C); coadministration with atazanavir, simvastatin, ethinyl estradiol-containing contraceptives, or rifampin.