OFEV
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OFEV (OFEV).
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.
| 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. |
| Molecular Weight | 539.5 |
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. |
| 1st trimester | Contraindicated due to teratogenicity (embryofetal toxicity, including malformations and fetal death in animal studies). |
| 2nd trimester | Contraindicated due to risk of oligohydramnios, fetal renal impairment, and fetal death. |
| 3rd trimester | Contraindicated due to risk of oligohydramnios, fetal renal impairment, and fetal death. |
Clinical note
Comprehensive clinical and safety monograph for OFEV (OFEV).
| Placental transfer | Evidence of placental transfer in animal studies; likely crosses human placenta based on molecular weight and animal data. |
| Breastfeeding | No human data; based on molecular weight and animal studies, excretion into breast milk is likely. Avoid breastfeeding due to potential for serious adverse reactions in the infant. |
■ FDA Black Box Warning
None
| Common Effects | Nausea Headache Dizziness Itching Insomnia difficulty in sleeping Rash Genital itching Vaginal inflammation Phlebitis Injection site reactions pain swelling redness |
| Serious Effects |
PregnancyHypersensitivity to nintedanib or any excipient
| 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) |
| Food/Dietary |
Loading safety data…
| Lactation Rating |
| L5 (Contraindicated) |
| 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. |
| Fetal Monitoring | During pregnancy: Monitor for fetal growth restriction, oligohydramnios, and structural anomalies via ultrasound. Monitor liver function tests (ALT, AST, bilirubin) monthly due to risk of hepatotoxicity. Monitor blood pressure and renal function. In neonates: Assess for hypothyroidism and skeletal abnormalities if exposure occurred. |
| Fertility Effects | Nintedanib may impair fertility in females. Animal studies show reduced fertility, increased preimplantation loss, and decreased ovarian and uterine weights. Males: May cause reduced sperm count and motility. Advise patients of potential reversible impact on fertility. |
| Avoid grapefruit and grapefruit juice as they may increase nintedanib exposure. Take with a meal to improve tolerability and reduce GI side effects. |
| Clinical Pearls | Monitor liver function tests (ALT, AST, bilirubin) monthly for first 3 months, then every 3 months. GI adverse effects (diarrhea, nausea) are common; consider antiemetics and antidiarrheals. Avoid use in severe hepatic impairment (Child-Pugh C). Nintedanib is a tyrosine kinase inhibitor with anticoagulant effects; monitor for bleeding especially in patients on anticoagulants. |
| Patient Advice | Take with food to reduce nausea and diarrhea. · Do not break, crush, or chew capsules; swallow whole. · Report any signs of bleeding (unusual bruising, black/tarry stools, blood in urine) promptly. · Avoid grapefruit juice during treatment. · Use effective contraception during treatment and for at least 3 months after stopping. · Do not take St. John's wort with OFEV. |