Tyrosine kinase inhibitors
Brand names: Nintedanib Dr. Reddys, Ofev, Vargatef, Nintedanib Zentiva
Updated · Methodology
First line
First-line IPF therapy per ATS/ERS/JRS/ALAT 2022 and Spanish SEPAR 2023 – on par with pirfenidone. Dose 150 mg twice daily. INPULSIS-1 and INPULSIS-2 (NEJM 2014) reduced FVC decline by 50% (~100 mL/year vs 200 mL). Direct mortality benefit not proven, but meta-analyses show a downward trend. Duration – lifelong until intolerance or lung transplantation.
Sources
ICD-10: J84.1 · ICD-11: CB03.4
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Nintedanib is a tyrosine kinase inhibitor. It is prescribed for idiopathic pulmonary fibrosis and other interstitial lung diseases with progressive fibrosis (AEMPS Ficha Técnica, INPULSIS 2014). In alt-anti-aging circles, nintedanib is occasionally promoted to suppress fibrosis of aging in healthy people. In healthy adults, no clinical studies of such use exist. The drug has serious risks: hepatotoxicity up to severe liver injury, GI disturbances (severe diarrhea in 60% of patients), elevated bleeding risk (especially on anticoagulants), hypertension, and thromboembolic events. If nintedanib was recommended to a healthy person, seek a second opinion immediately.
Small molecule – multi-kinase inhibitor of VEGFR-1/2/3, FGFR-1/2/3, PDGFR-α/β receptor tyrosine kinases. These signals are critical for fibroblast proliferation, angiogenesis, and inflammation in lung fibrosis pathogenesis. Slows IPF progression but does not halt it. Also used in systemic sclerosis with interstitial lung disease (SSc-ILD) and metastatic non-small cell lung cancer (only oncology form – Vargatef).
AEMPS summary of product characteristics (section 4.6): there is no information on nintedanib use in pregnant women, but preclinical animal studies have shown reproductive toxicity, and nintedanib may cause fetal harm in humans too. It should not be used during pregnancy, and pregnancy tests are done before and during treatment as appropriate. Women of childbearing potential use highly effective contraception from the start of treatment until at least 3 months after the last dose. Vomiting, diarrhoea or other conditions affecting absorption may reduce the efficacy of oral hormonal contraceptives, and in that case an alternative highly effective method is used. If pregnancy occurs during treatment, nintedanib is stopped and the patient is informed of the potential risk to the fetus.
No milk excretion data. Discontinue breastfeeding.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Verbatim lines from the interaction sections, in the language of the label
«P-glycoprotein (P-gp) and CYP3A4 Inhibitors and Inducers: Nintedanib is a substrate of P-gp and, to a minor extent, CYP3A4 [see Clinical Pharmacology (12.3) ] . Coadministration with oral doses of a…»FDA, section 7 · Open on DailyMed
«P-glycoprotein (P-gp) and CYP3A4 Inhibitors and Inducers: Nintedanib is a substrate of P-gp and, to a minor extent, CYP3A4 [see Clinical Pharmacology (12.3) ] . Coadministration with oral doses of a…»FDA, section 7 · Open on DailyMed
«P-glycoprotein (P-gp) and CYP3A4 Inhibitors and Inducers: Nintedanib is a substrate of P-gp and, to a minor extent, CYP3A4 [see Clinical Pharmacology (12.3) ] . Coadministration with oral doses of a…»FDA, section 7 · Open on DailyMed
«P-glycoprotein (P-gp) and CYP3A4 Inhibitors and Inducers: Nintedanib is a substrate of P-gp and, to a minor extent, CYP3A4 [see Clinical Pharmacology (12.3) ] . Coadministration with oral doses of a…»FDA, section 7 · Open on DailyMed
«P-glycoprotein (P-gp) and CYP3A4 Inhibitors and Inducers: Nintedanib is a substrate of P-gp and, to a minor extent, CYP3A4 [see Clinical Pharmacology (12.3) ] . Coadministration with oral doses of a…»FDA, section 7 · Open on DailyMed
«P-glycoprotein (P-gp) and CYP3A4 Inhibitors and Inducers: Nintedanib is a substrate of P-gp and, to a minor extent, CYP3A4 [see Clinical Pharmacology (12.3) ] . Coadministration with oral doses of a…»FDA, section 7 · Open on DailyMed
«Perforaciones gastrointestinales y colitis isquémica: En los ensayos clínicos en pacientes adultos, la frecuencia de los casos de perforación fue de hasta el 0,3 % en ambos grupos de tratamiento…»AEMPS, section 4.4 · Open on CIMA
«Anticoagulants: Nintedanib is a VEGFR inhibitor and may increase the risk of bleeding. Monitor patients on full anticoagulation therapy closely for bleeding and adjust anticoagulation treatment as…»FDA, section 7 · Open on DailyMed
«Glicoproteína-P (gp-P): Nintedanib es un sustrato de la gp-P (ver sección 5.2). La administración conjunta con ketoconazol, un potente inhibidor de la gp-P, aumentó la exposición a nintedanib 1,61…»AEMPS, section 4.5 · Open on CIMA
«Perforaciones gastrointestinales y colitis isquémica: En los ensayos clínicos en pacientes adultos, la frecuencia de los casos de perforación fue de hasta el 0,3 % en ambos grupos de tratamiento…»AEMPS, section 4.4 · Open on CIMA
«DRUG INTERACTIONS: Coadministration of P-gp and CYP3A4 inhibitors may increase nintedanib exposure. Monitor patients closely for tolerability of Nintedanib Capsules. ( 7.1 )»FDA, section 7 · Open on DailyMed
«Glicoproteína-P (gp-P): Nintedanib es un sustrato de la gp-P (ver sección 5.2). La administración conjunta con ketoconazol, un potente inhibidor de la gp-P, aumentó la exposición a nintedanib 1,61…»AEMPS, section 4.5 · Open on CIMA
«Glicoproteína-P (gp-P): Nintedanib es un sustrato de la gp-P (ver sección 5.2). La administración conjunta con ketoconazol, un potente inhibidor de la gp-P, aumentó la exposición a nintedanib 1,61…»AEMPS, section 4.5 · Open on CIMA
«Glicoproteína-P (gp-P): Nintedanib es un sustrato de la gp-P (ver sección 5.2). La administración conjunta con ketoconazol, un potente inhibidor de la gp-P, aumentó la exposición a nintedanib 1,61…»AEMPS, section 4.5 · Open on CIMA
«Administración conjunta con otros medicamentos: La administración conjunta de nintedanib con anticonceptivos hormonales orales no alteró la farmacocinética de los anticonceptivos hormonales orales de…»AEMPS, section 4.5 · Open on CIMA
«Glicoproteína-P (gp-P): Los inductores potentes de la gp-P (por ejemplo, rifampicina, carbamazepina, fenitoína y la hierba de San Juan) pueden disminuir la exposición a nintedanib. En este caso se…»AEMPS, section 4.5 · Open on CIMA
«Glicoproteína-P (gp-P): Los inductores potentes de la gp-P (por ejemplo, rifampicina, carbamazepina, fenitoína y la hierba de San Juan) pueden disminuir la exposición a nintedanib. En este caso se…»AEMPS, section 4.5 · Open on CIMA
«Pirfenidone: In a multiple-dose study conducted to assess the pharmacokinetic effects of concomitant treatment with nintedanib and pirfenidone, the coadministration of nintedanib with pirfenidone did…»FDA, section 7 · Open on DailyMed
«Agentes antineoplásicos: Alitretinoína (oral), Bortezomib, Brentuximab vedotina, Erlotinib, Idelalisib, Imatinib, Nintedanib, Panobinostat, Ponatinib, Ruxolitinib, Sonidegib, Tretinoína (oral)»AEMPS, section 4.5 · Open on CIMA
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Nintedanib is evaluated for the following indications with varying evidence strength: Idiopathic pulmonary fibrosis (evidence tier A), Anti-aging and longevity (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Nintedanib (≥ 1 in 100): Diarrhea (60–70%), Nausea, Vomiting, Abdominal pain, Weight loss, ALT/AST elevation. See the Safety section for uncommon and serious reactions.
AEMPS summary of product characteristics (section 4.6): there is no information on nintedanib use in pregnant women, but preclinical animal studies have shown reproductive toxicity, and nintedanib may cause fetal harm in humans too. It should not be used during pregnancy, and pregnancy tests are done before and during treatment as appropriate. Women of childbearing potential use highly effective contraception from the start of treatment until at least 3 months after the last dose. Vomiting, diarrhoea or other conditions affecting absorption may reduce the efficacy of oral hormonal contraceptives, and in that case an alternative highly effective method is used. If pregnancy occurs during treatment, nintedanib is stopped and the patient is informed of the potential risk to the fetus.
No milk excretion data. Discontinue breastfeeding.
Nintedanib is contraindicated in: Hypersensitivity; Pregnancy; Severe hepatic impairment Child-Pugh B-C; Age under 18 (except specific pediatric indications). Full list in the Safety section.
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