FARYDAK

Clinical safety rating: caution

Comprehensive clinical and safety monograph for FARYDAK (FARYDAK).

How it works

Panobinostat is a histone deacetylase (HDAC) inhibitor that inhibits the enzymatic activity of HDACs, leading to accumulation of acetylated histones and other proteins, resulting in cell cycle arrest and apoptosis in cancer cells.

What the body does with it

Metabolism	Extensively metabolized via multiple pathways including reduction, hydrolysis, oxidation (CYP3A4), glucuronidation (UGT1A1, UGT1A3, UGT1A9), and glutathione conjugation.
Excretion	Primarily hepatic metabolism via CYP3A4, with <5% excreted unchanged in urine and <1% in feces.
Half-life	Terminal elimination half-life is approximately 50 hours (range 31-67 hours), supporting once-weekly dosing.
Protein binding	>99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Volume of distribution is approximately 1000 L (>14 L/kg), indicating extensive tissue distribution.
Bioavailability	Not applicable; only available as intravenous formulation; oral bioavailability is negligible (<2% due to extensive first-pass metabolism).
Onset of Action	Intravenous: Clinical effects observed within first week of administration; maximal pan-HDAC inhibition occurs within 1-2 hours post-dose.
Duration of Action	Duration of pharmacodynamic effect (histone acetylation) persists for at least 7 days post-dose, consistent with weekly schedule.

Classification & Brands

Dosing & administration

20 mg orally once daily on days 1, 8, and 15 of a 28-day cycle.

Dosage form	CAPSULE
Renal impairment	No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or ESRD; avoid use.
Liver impairment	Child-Pugh A: 15 mg orally once daily on days 1, 8, and 15 of a 28-day cycle. Child-Pugh B: 10 mg orally once daily on days 1, 8, and 15 of a 28-day cycle. Child-Pugh C: not recommended.
Pediatric use	Safety and efficacy in pediatric patients have not been established.
Geriatric use	No specific dose adjustment recommended; patients ≥65 years may experience increased toxicity (e.g., diarrhea, fatigue); monitor closely.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for FARYDAK (FARYDAK).

Breastfeeding

It is unknown if panobinostat is excreted in human milk. Due to potential for serious adverse reactions in nursing infants (e.g., hematologic toxicity, growth impairment), breastfeeding should be discontinued during treatment and for at least 3 weeks after the last dose. M/P ratio not available.

Teratogenic Risk

FARYDAK (panobinostat) is contraindicated in pregnancy. Based on its mechanism of action (histone deacetylase inhibitor) and animal studies, it is teratogenic. First trimester: High risk of major congenital malformations including neural tube defects, cardiac anomalies, and skeletal abnormalities. Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and fetal death. Embryofetal toxicity observed in rats and rabbits at doses below the human therapeutic dose.

Warnings & precautions

■ FDA Black Box Warning

Severe diarrhea, severe cardiac ischemic events, and severe arrhythmias have been reported.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Severe hepatic impairment (Child-Pugh class C)","History of severe cardiac ischemic events or arrhythmias"]

Clinical Precautions

Precautions

["Diarrhea","Cardiac toxicity (ischemic events, arrhythmias, QT prolongation)","Myelosuppression","Hemorrhage","Hepatotoxicity","Embryo-fetal toxicity"]

Clinical Tips & Counseling

Drug interactions

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FARYDAK

Clinical safety rating: caution

Comprehensive clinical and safety monograph for FARYDAK (FARYDAK).

How it works

What the body does with it

Metabolism	Extensively metabolized via multiple pathways including reduction, hydrolysis, oxidation (CYP3A4), glucuronidation (UGT1A1, UGT1A3, UGT1A9), and glutathione conjugation.
Excretion	Primarily hepatic metabolism via CYP3A4, with <5% excreted unchanged in urine and <1% in feces.
Half-life	Terminal elimination half-life is approximately 50 hours (range 31-67 hours), supporting once-weekly dosing.
Protein binding	>99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Volume of distribution is approximately 1000 L (>14 L/kg), indicating extensive tissue distribution.
Bioavailability	Not applicable; only available as intravenous formulation; oral bioavailability is negligible (<2% due to extensive first-pass metabolism).
Onset of Action	Intravenous: Clinical effects observed within first week of administration; maximal pan-HDAC inhibition occurs within 1-2 hours post-dose.
Duration of Action	Duration of pharmacodynamic effect (histone acetylation) persists for at least 7 days post-dose, consistent with weekly schedule.

Classification & Brands

Dosing & administration

20 mg orally once daily on days 1, 8, and 15 of a 28-day cycle.

Dosage form	CAPSULE
Renal impairment	No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or ESRD; avoid use.
Liver impairment	Child-Pugh A: 15 mg orally once daily on days 1, 8, and 15 of a 28-day cycle. Child-Pugh B: 10 mg orally once daily on days 1, 8, and 15 of a 28-day cycle. Child-Pugh C: not recommended.
Pediatric use	Safety and efficacy in pediatric patients have not been established.
Geriatric use	No specific dose adjustment recommended; patients ≥65 years may experience increased toxicity (e.g., diarrhea, fatigue); monitor closely.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for FARYDAK (FARYDAK).

Breastfeeding

Teratogenic Risk

Warnings & precautions

■ FDA Black Box Warning

Severe diarrhea, severe cardiac ischemic events, and severe arrhythmias have been reported.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Severe hepatic impairment (Child-Pugh class C)","History of severe cardiac ischemic events or arrhythmias"]

Clinical Precautions

Precautions

["Diarrhea","Cardiac toxicity (ischemic events, arrhythmias, QT prolongation)","Myelosuppression","Hemorrhage","Hepatotoxicity","Embryo-fetal toxicity"]

Clinical Tips & Counseling

Drug interactions

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