2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dosing
Second-Line Advanced RCC
When INLYTA is used as a single agent, the recommended starting oral dose is 5 mg twice daily. Administer INLYTA doses approximately 12 hours apart with or without food.
2.2 Dose Modification Guidelines
Dose increase or reduction is recommended based on individual safety and tolerability.
|Dose Modification||Dose Regimen|
|Recommended starting dosage||5 mg twice daily|
|First dose increase||7 mg twice daily|
|Second dose increase||10 mg twice daily|
|First dose reduction†||3 mg twice daily|
|Second dose reduction||2 mg twice daily|
|Adverse Reaction||Severity||Dosage Modifications for INLYTA|
|Hypertension [see Warnings and Precautions (5.1)]||SBP > 150 mmHg or DBP > 100 mmHg despite antihypertensive treatment|
|SBP > 160 mmHg or DBP > 105 mmHg|
|Grade 4 or hypertensive crisis|
|Hemorrhage [see Warnings and Precautions (5.4)]||Grade 3 or 4|
|Cardiac failure [see Warnings and Precautions (5.5)]||Asymptomatic cardiomyopathy (left ventricular ejection fraction greater than 20% but less than 50% below baseline or below the lower limit of normal if baseline was not obtained)|
|Clinically manifested congestive heart failure|
|Impaired wound healing [see Warnings and Precautions (5.8)]||Any Grade|
|Reversible Posterior Leukoencephalopathy Syndrome [see Warnings and Precautions (5.9)]||Any Grade|
|Proteinuria [see Warnings and Precautions (5.10)]||2 or more grams proteinuria per 24 hours|
|Other Adverse Reactions||Grade 3|
|Treatment||Adverse Reaction||Severity*||Dosage Modifications for INLYTA|
|ALT = alanine aminotransferase, AST = aspartate aminotransferase, ULN = upper limit normal|
|INLYTA in combination with avelumab OR pembrolizumab||Liver enzyme elevations†||ALT or AST at least 3 times ULN but less than 10 times ULN without concurrent total bilirubin at least 2 times ULN|
|ALT or AST increases to more than 3 times ULN with concurrent total bilirubin at least 2 times ULN or ALT or AST at least 10 times ULN|
|INLYTA in combination with avelumab||Major Adverse Cardiovascular Events (MACE)||Grade 3 or 4|
2.3 Dosage Modification for Drug Interactions
Strong CYP3A4/5 Inhibitors
The concomitant use of strong CYP3A4/5 inhibitors should be avoided (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole). Selection of an alternate concomitant medication with no or minimal CYP3A4/5 inhibition potential is recommended. Although INLYTA dose adjustment has not been studied in patients receiving strong CYP3A4/5 inhibitors, if a strong CYP3A4/5 inhibitor must be co-administered, a dose decrease of INLYTA by approximately half is recommended, as this dose reduction is predicted to adjust the axitinib area under the plasma concentration vs time curve (AUC) to the range observed without inhibitors. The subsequent doses can be increased or decreased based on individual safety and tolerability. If co-administration of the strong inhibitor is discontinued, the INLYTA dose should be returned (after 3 – 5 half-lives of the inhibitor) to that used prior to initiation of the strong CYP3A4/5 inhibitor [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
2.4 Dosage Modification for Hepatic Impairment
No starting dose adjustment is required when administering INLYTA to patients with mild hepatic impairment (Child-Pugh class A). Based on the pharmacokinetic data, the INLYTA starting dose should be reduced by approximately half in patients with baseline moderate hepatic impairment (Child-Pugh class B). The subsequent doses can be increased or decreased based on individual safety and tolerability. INLYTA has not been studied in patients with severe hepatic impairment (Child-Pugh class C) [see Warnings and Precautions (5.12), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].