Overview
11 DESCRIPTION INLYTA (axitinib) is a kinase inhibitor. Axitinib has the chemical name N-methyl-2-[3-((E)-2-pyridin-2-yl-vinyl)-1H-indazol-6-ylsulfanyl]-benzamide. The molecular formula is C22H18N4OS and the molecular weight is 386.47 Daltons. The chemical structure is: Axitinib is a white to light-yellow powder with a pKa of 4.8. The solubility of axitinib in aqueous media over the range pH 1.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Axitinib has been shown to inhibit receptor tyrosine kinases including vascular endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3 at therapeutic plasma concentrations. These receptors are implicated in pathologic angiogenesis, tumor growth, and cancer progression. VEGF-mediated endothelial cell proliferation and survival were inhibited by axitinib in vitro and in mouse models. Axitinib was shown to inhibit tumor growth and phosphorylation of VEGFR-2 in tumor xenograft mouse models. 12.2 Pharmacodynamics The effect of a single oral dose of INLYTA (5 mg) in the absence and presence of 400 mg ketoconazole on the QTc interval was evaluated in a randomized, single-blinded, two-way crossover study in 35 healthy subjects.
Indications
- 1 INDICATIONS AND USAGE INLYTA is a kinase inhibitor indicated: • in combination with avelumab, for the first-line treatment of patients with advanced renal cell carcinoma (RCC). ( 1.1 ) • in combination with pembrolizumab, for the first-line treatment of patients with advanced RCC. ( 1.1 ) • as a single agent, for the treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy. ( 1.2 ) 1.1 First-Line Advanced Renal Cell Carcinoma INLYTA in combination with avelumab is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).
Common Doses
- 5 mg
- 800 mg
- 200 mg
- 400 mg
Dosage
2 DOSAGE AND ADMINISTRATION • INLYTA 5 mg orally twice daily with avelumab 800 mg every 2 weeks. ( 2.1 ) • INLYTA 5 mg orally twice daily with pembrolizumab 200 mg every 3 weeks or 400 mg every 6 weeks. ( 2.1 ) • INLYTA as a single agent the starting dose is 5 mg orally twice daily. ( 2.1 ) • Dose adjustments can be made based on individual safety and tolerability. ( 2.2 ) • Administer INLYTA dose approximately 12 hours apart with or without food. ( 2.1 ) • INLYTA should be swallowed whole with a glass of water. ( 2.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed elsewhere in the labeling [see Warnings and Precautions (5) ] : • Hypertension [see Warnings and Precautions (5.1) ] • Arterial thromboembolic events [see Warnings and Precautions (5.2) ] • Venous thromboembolic events [see Warnings and Precautions (5.3) ] • Hemorrhage [see Warnings and Precautions (5.4) ] • Cardiac failure [see Warnings and Precautions (5.5) ] • Gastrointestinal perforation and fistula formation [see Warnings and Precautions (5.6) ] • Thyroid dysfunction [see Warnings and Precautions (5.
Interactions
- 7 DRUG INTERACTIONS • Avoid strong CYP3A4/5 inhibitors. If unavoidable, reduce the INLYTA dose. ( 2.2 , 7.1 ) • Avoid strong CYP3A4/5 inducers. ( 7.2 ) 7.1 CYP3A4/5 Inhibitors Co-administration of ketoconazole, a strong inhibitor of CYP3A4/5, increased the plasma exposure of axitinib in healthy volunteers. Co-administration of INLYTA with strong CYP3A4/5 inhibitors should be avoided. Grapefruit or grapefruit juice may also increase axitinib plasma concentrations and should be avoided. Selection of concomitant medication with no or minimal CYP3A4/5 inhibition potential is recommended.