OFEV

Clinical safety rating: caution

Comprehensive clinical and safety monograph for OFEV (OFEV).

How it works

Nintedanib is a tyrosine kinase inhibitor that blocks the activity of fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR), thereby inhibiting fibroblast proliferation, migration, and transformation, and reducing extracellular matrix deposition.

What the body does with it

Metabolism	Primarily metabolized by esterases (hydrolysis) to free acid BIBF 1202; minor CYP3A4-mediated metabolism; biliary-fecal excretion.
Excretion	Primarily biliary/fecal (~93.4% of total radioactivity recovered in feces), renal excretion is minor (~0.6% unchanged in urine).
Half-life	Terminal elimination half-life is approximately 38 hours (range 30–48 hours) at steady state, supporting once-daily dosing.
Protein binding	Bound primarily to albumin and alpha-1-acid glycoprotein (AAG); total protein binding is approximately 99.8%.
Volume of Distribution	Volume of distribution is approximately 1.8 L/kg (range 1.0–2.5 L/kg) after oral administration, indicating extensive tissue distribution.
Bioavailability	Absolute bioavailability is ~30% (range 23–40%) after oral administration under fed conditions; food increases exposure by approximately 40%.
Onset of Action	Oral: Clinical effects on forced vital capacity (FVC) decline are observed after 2–4 weeks of continuous dosing.
Duration of Action	Duration of action is sustained over the 24-hour dosing interval; continuous treatment is required to maintain effect on slowing disease progression.

Classification & Brands

Dosing & administration

150 mg orally twice daily, taken with food.

Dosage form	CAPSULE
Renal impairment	No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). Not recommended for use in severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease.
Liver impairment	Contraindicated in severe hepatic impairment (Child-Pugh class C). For mild hepatic impairment (Child-Pugh class A), reduce dose to 100 mg twice daily. For moderate hepatic impairment (Child-Pugh class B), not recommended.
Pediatric use	Safety and efficacy not established in pediatric patients; no recommended dosing available.
Geriatric use	No specific dose adjustment required based on age alone; monitor for adverse effects due to potential decreased renal function.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for OFEV (OFEV).

Breastfeeding	No human data on excretion in breast milk. M/P ratio not available. Nintedanib is excreted in rat milk. Due to potential for adverse effects (e.g., diarrhea, vomiting, hepatotoxicity) in nursing infants, advise against breastfeeding during treatment and for at least 3 weeks after last dose.
Teratogenic Risk	FDA Pregnancy Category D. First trimester: Nintedanib is teratogenic in animal studies, causing embryofetal lethality, structural abnormalities, and reduced fetal weight. Avoid use; if exposure occurs, inform patient of risks. Second/third trimesters: Risk of oligohydramnios, fetal renal impairment, and skeletal malformations; use only if benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Common Effects	Nausea Headache Dizziness Itching Insomnia difficulty in sleeping Rash Genital itching Vaginal inflammation Phlebitis Injection site reactions pain swelling redness
Serious Effects

Absolute Contraindications

["Hypersensitivity to nintedanib or excipients","Moderate to severe hepatic impairment (Child-Pugh B or C)"]

Clinical Precautions

Precautions

["Hepatic impairment (elevated liver enzymes, drug-induced liver injury; monitor LFTs)","Gastrointestinal disorders (diarrhea, nausea, vomiting; manage with hydration and antiemetics)","Arterial thromboembolic events (use caution in high cardiovascular risk)","Bleeding risk (avoid in patients requiring full-dose anticoagulation)","Gastrointestinal perforation (discontinue if suspected)","Embryo-fetal toxicity (contraception required during and 1 month after therapy)"]

Clinical Tips & Counseling

Drug interactions

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OFEV

Clinical safety rating: caution

Comprehensive clinical and safety monograph for OFEV (OFEV).

How it works

What the body does with it

Metabolism	Primarily metabolized by esterases (hydrolysis) to free acid BIBF 1202; minor CYP3A4-mediated metabolism; biliary-fecal excretion.
Excretion	Primarily biliary/fecal (~93.4% of total radioactivity recovered in feces), renal excretion is minor (~0.6% unchanged in urine).
Half-life	Terminal elimination half-life is approximately 38 hours (range 30–48 hours) at steady state, supporting once-daily dosing.
Protein binding	Bound primarily to albumin and alpha-1-acid glycoprotein (AAG); total protein binding is approximately 99.8%.
Volume of Distribution	Volume of distribution is approximately 1.8 L/kg (range 1.0–2.5 L/kg) after oral administration, indicating extensive tissue distribution.
Bioavailability	Absolute bioavailability is ~30% (range 23–40%) after oral administration under fed conditions; food increases exposure by approximately 40%.
Onset of Action	Oral: Clinical effects on forced vital capacity (FVC) decline are observed after 2–4 weeks of continuous dosing.
Duration of Action	Duration of action is sustained over the 24-hour dosing interval; continuous treatment is required to maintain effect on slowing disease progression.

Classification & Brands

Dosing & administration

150 mg orally twice daily, taken with food.

Dosage form	CAPSULE
Renal impairment	No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). Not recommended for use in severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease.
Liver impairment	Contraindicated in severe hepatic impairment (Child-Pugh class C). For mild hepatic impairment (Child-Pugh class A), reduce dose to 100 mg twice daily. For moderate hepatic impairment (Child-Pugh class B), not recommended.
Pediatric use	Safety and efficacy not established in pediatric patients; no recommended dosing available.
Geriatric use	No specific dose adjustment required based on age alone; monitor for adverse effects due to potential decreased renal function.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for OFEV (OFEV).

Breastfeeding	No human data on excretion in breast milk. M/P ratio not available. Nintedanib is excreted in rat milk. Due to potential for adverse effects (e.g., diarrhea, vomiting, hepatotoxicity) in nursing infants, advise against breastfeeding during treatment and for at least 3 weeks after last dose.
Teratogenic Risk	FDA Pregnancy Category D. First trimester: Nintedanib is teratogenic in animal studies, causing embryofetal lethality, structural abnormalities, and reduced fetal weight. Avoid use; if exposure occurs, inform patient of risks. Second/third trimesters: Risk of oligohydramnios, fetal renal impairment, and skeletal malformations; use only if benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Common Effects	Nausea Headache Dizziness Itching Insomnia difficulty in sleeping Rash Genital itching Vaginal inflammation Phlebitis Injection site reactions pain swelling redness
Serious Effects

Absolute Contraindications

["Hypersensitivity to nintedanib or excipients","Moderate to severe hepatic impairment (Child-Pugh B or C)"]