NEFFY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NEFFY (NEFFY).
NEFFY (nintedanib) is a tyrosine kinase inhibitor that targets multiple receptor tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), and platelet-derived growth factor receptor (PDGFR). It inhibits these pathways, thereby reducing angiogenesis, fibroblast proliferation, and fibrosis.
| Metabolism | Nintedanib is primarily metabolized via hydrolysis by esterases, followed by glucuronidation. Minor metabolism occurs via CYP3A4. The parent drug and metabolites are excreted mainly via biliary/fecal route (approximately 85%) and renal (approximately 5%). |
| Excretion | Primarily hepatic metabolism via CYP3A4 to inactive metabolites; renal excretion of metabolites accounts for approximately 70% of total elimination. Unchanged drug excreted in urine <5%. Fecal excretion contributes ~20%. |
| Half-life | Terminal elimination half-life: 4-6 hours in healthy adults. May be prolonged in hepatic impairment (up to 12 hours) or severe renal impairment (up to 8 hours). No accumulation with repeated dosing. |
| Protein binding | Approximately 94% bound to plasma proteins, mainly albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.6 L/kg (range 0.4-0.8 L/kg). Indicates distribution into total body water and some tissue binding; does not suggest extensive sequestration. |
| Bioavailability | Oral: 30-40% (first-pass effect). No data for other routes; intravenous bioavailability is 100%. |
| Onset of Action | Oral: 30-60 minutes (single dose). Intravenous: within 5 minutes. |
| Duration of Action | Oral: 6-8 hours (antihypertensive effect). Intravenous: 2-4 hours (immediate effect, then gradual decline). Clinical note: Duration sufficient for once-daily dosing in hypertension. |
1-2 mg intravenously every 5-10 minutes as needed for reversal of opioid-induced respiratory depression; maximum total dose 10 mg.
| Dosage form | SPRAY |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment (eGFR 30-89 mL/min). For severe renal impairment (eGFR <30 mL/min), consider dose reduction by 25-50% and monitor for prolonged effect. |
| Liver impairment | For Child-Pugh class A, no adjustment. For Child-Pugh class B, reduce dose by 50%. For Child-Pugh class C, reduce dose by 75% or consider alternative. |
| Pediatric use | Neonates: 0.01-0.02 mg/kg/dose intravenously every 2-5 minutes as needed; maximum single dose 0.2 mg. Infants and children: 0.01-0.1 mg/kg/dose intravenously every 2-5 minutes as needed; maximum single dose 2 mg. May repeat every 1-2 hours if needed. |
| Geriatric use | No specific dose adjustment, but use starting doses at lower end of range (0.5-1 mg intravenously) due to increased sensitivity and potential for prolonged effect. Monitor for adverse events such as hypertension and arrhythmias. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NEFFY (NEFFY).
| Breastfeeding | No human data; M/P ratio unknown. Potential for infant toxicity; breastfeeding not recommended during therapy and for 1 month after last dose. |
| Teratogenic Risk | NEFFY is contraindicated in pregnancy. First trimester: Neural tube defects, cardiovascular malformations. Second/third trimester: Fetal growth restriction, oligohydramnios, neonatal renal impairment. Risk category X. |
| Fetal Monitoring |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to nintedanib or any excipients","Severe hepatic impairment (Child-Pugh class C)","Pregnancy (embryo-fetal toxicity)"]
| Precautions | ["Hepatotoxicity: Monitor liver function tests before and during treatment.","Gastrointestinal perforation: Use with caution in patients with prior abdominal surgery, diverticulosis, or concomitant NSAIDs.","Hemorrhage: Increased risk of bleeding; avoid in patients with inherited bleeding diathesis or on full-dose anticoagulation.","Gastrointestinal adverse events: Diarrhea, nausea, vomiting; manage with supportive care.","Hypersensitivity reactions: Angioedema reported.","Arterial thromboembolic events: May increase risk; use caution in patients with cardiovascular risk factors.","Wound healing impairment: Caution in patients undergoing surgery; consider temporary discontinuation."] |
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| Maternal blood pressure, renal function (serum creatinine, BUN), liver enzymes, CBC; serial fetal ultrasound for growth, amniotic fluid volume, and morphology; fetal echocardiogram. |
| Fertility Effects | Animal studies show impaired fertility and embryo-fetal toxicity at therapeutic doses. Women of childbearing potential must use effective contraception during treatment and for 1 month after discontinuation. |