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. |
| Molecular Weight | 386.5 |
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 | Axitinib is contraindicated in pregnancy. Based on its mechanism of action (VEGF receptor inhibitor) and animal studies showing teratogenicity, embryotoxicity, and fetal loss, axitinib should not be used during the first trimester. Adequate contraception is recommended for women of childbearing potential. |
| 2nd trimester | Same contraindication as first trimester. Axitinib can cause fetal harm when administered to pregnant women. There are no adequate and well-controlled studies in pregnant women. If used during pregnancy, or if patient becomes pregnant while taking this drug, apprise of potential hazard to the fetus. |
| 3rd trimester | Contraindicated during third trimester due to risk of fetal harm and potential interference with normal fetal development. Avoid use in pregnant women. Advise women of childbearing potential to avoid pregnancy during treatment and for at least 1 week after the final dose. |
Clinical note
Comprehensive clinical and safety monograph for INLYTA (INLYTA).
| Placental transfer | Axitinib is a small molecule (molecular weight 386.5 Da) that likely crosses the placenta. In animal studies, axitinib was teratogenic and embryotoxic, consistent with placental transfer. No human studies on placental transfer are available, but given its molecular weight and lipophilicity, placental transfer is expected. |
■ FDA Black Box Warning
None.
| Serious Effects |
History of hypersensitivity to axitinib or any excipients in the formulationPregnancy
| 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 |
| Food/Dietary | Avoid grapefruit and grapefruit juice. Take with or without food consistently. |
| Clinical Pearls |
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| Breastfeeding | It is not known whether axitinib is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from axitinib, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. The manufacturer recommends that breastfeeding be avoided during therapy and for at least 2 weeks after the last dose. |
| Lactation Rating | L5 (Contraindicated) |
| 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). |
| 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. |
| Monitor blood pressure weekly during first 4 weeks and then monthly; manage hypertension aggressively. Assess thyroid function before and periodically during treatment. Dose reduction or interruption may be required for moderate to severe hepatotoxicity. Avoid strong CYP3A4/5 inducers and inhibitors; adjust dose with moderate CYP3A4 inhibitors. Check for proteinuria before each cycle. |
| Patient Advice | Take Inlyta twice daily about 12 hours apart with or without food. · Swallow tablet whole; do not crush, chew, or split. · Do not consume grapefruit or grapefruit juice while on this medication. · Report severe diarrhea, nausea, vomiting, or weight loss immediately. · Notify your doctor if you experience unusual bleeding, chest pain, or shortness of breath. · Use effective contraception during treatment and for 1 week after last dose. · Avoid pregnancy and breastfeeding while taking Inlyta. |