INLYTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INLYTA (INLYTA).
Axitinib is a tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, and VEGFR-3), which are involved in pathologic angiogenesis, tumor growth, and metastatic progression of cancer.
| Metabolism | Primarily metabolized by CYP3A4/5; minor contribution from CYP1A2, CYP2C19, and UGT1A1. |
| Excretion | Primarily hepatic metabolism via CYP3A4 and subsequent biliary-fecal elimination (approximately 61% of dose recovered in feces, 23% in urine as metabolites; <10% excreted unchanged in urine or feces). |
| Half-life | Terminal elimination half-life is approximately 13–17 hours in patients, supporting twice-daily dosing. |
| Protein binding | 99.8% bound to plasma proteins (primarily albumin and alpha-1 acid glycoprotein). |
| Volume of Distribution | Apparent volume of distribution (Vd/F) is approximately 160–260 L (2.3–3.7 L/kg for a 70 kg patient), indicating extensive distribution into tissues. |
| Bioavailability | Absolute oral bioavailability is approximately 50% (range 30–70%), with food reducing peak concentration and AUC (administer on empty stomach). |
| Onset of Action | Time to maximum plasma concentration (Tmax) is 1.5–4 hours after oral administration; clinical effect (VEGF inhibition) occurs within hours of first dose. |
| Duration of Action | Duration of VEGF inhibition persists for at least 12 hours, consistent with twice-daily dosing; continuous exposure required for sustained effect. |
5 mg orally twice daily, approximately 12 hours apart, with or without food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to severe renal impairment (creatinine clearance ≥15 mL/min). For end-stage renal disease (CrCl <15 mL/min), no clinical data available; use with caution. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): no adjustment. Moderate hepatic impairment (Child-Pugh B): reduce dose to 2 mg orally twice daily. Severe hepatic impairment (Child-Pugh C): not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no recommended dose. |
| Geriatric use | No specific dose adjustment recommended solely for age. Monitor renal function and blood pressure closely, as elderly patients may have increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for INLYTA (INLYTA).
| Breastfeeding | No human data; INLYTA is excreted in milk in animal studies. M/P ratio unknown. Breastfeeding is contraindicated during therapy and for at least 2 weeks after last dose. |
| Teratogenic Risk | Based on its mechanism of action (VEGF receptor tyrosine kinase inhibitor) and animal studies, INLYTA is embryotoxic and teratogenic. There are no adequate human studies. First trimester exposure carries risk of major congenital malformations; second and third trimester exposure may cause fetotoxicity (e.g., oligohydramnios, renal impairment, intrauterine growth restriction). |
■ FDA Black Box Warning
None.
| Serious Effects |
None.
| Precautions | ["Hypertension including hypertensive crisis","Arterial thromboembolic events (e.g., myocardial infarction, stroke)","Venous thromboembolic events","Hemorrhage including fatal events","Cardiac failure","Gastrointestinal perforation and fistula","Hypothyroidism","Wound healing complications","Reversible posterior leukoencephalopathy syndrome (RPLS)","Proteinuria","Hepatic impairment","Fetal harm"] |
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| Fetal Monitoring |
| Monitor blood pressure, proteinuria, liver enzymes, and thyroid function monthly. Fetal ultrasound for growth, amniotic fluid volume, and renal development every 4-6 weeks. Assess for signs of preeclampsia. |
| Fertility Effects | In animal studies, INLYTA impaired male and female fertility. In humans, may cause menstrual irregularities, anovulation, and spermatogenesis impairment. Recommend fertility preservation counseling prior to treatment. |