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)

• 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. (2.1)
• See Full Prescribing Information for dosage modifications for adverse reactions. (2.2)
• If a strong CYP3A4/5 inhibitor is required, decrease the INLYTA dose by approximately half. (2.2)
• For patients with moderate hepatic impairment, decrease the starting dose by approximately half. (2.2)

1 mg and 5 mg tablets (3)

None. (4)

• Hypertension: Hypertension including hypertensive crisis has been observed. Blood pressure should be well-controlled prior to initiating INLYTA. Monitor for hypertension and treat as needed. Withhold and then dose reduce INLYTA or permanently discontinue based on severity of hypertension. (5.1)
• Arterial and Venous Thromboembolic Events: Arterial and venous thrombotic events have been observed and can be fatal. Use with caution in patients who are at increased risk for these events. Permanently discontinue INLYTA if an arterial thromboembolic event occurs during treatment. Withhold INLYTA and then resume at same dose or permanently discontinue based on severity of VTE. (5.2, 5.3)
• Hemorrhage: Hemorrhagic events, including fatal events, have been reported. INLYTA has not been studied in patients with evidence of untreated brain metastasis or recent active gastrointestinal bleeding and should not be used in those patients. Withhold and then dose reduce INLYTA or discontinue based on severity and persistence of hemorrhage. (5.4)
• Cardiac Failure: Cardiac failure has been observed and can be fatal. Monitor for signs or symptoms of cardiac failure throughout treatment with INLYTA. Management of cardiac failure may require dose reduction, dose interruption or permanent discontinuation of INLYTA. (5.5)
• Gastrointestinal Perforation and Fistula Formation: Gastrointestinal perforation and fistula, including death, have occurred. Use with caution in patients at risk for gastrointestinal perforation or fistula. (5.6)
• Hypothyroidism: Hypothyroidism requiring thyroid hormone replacement has been reported. Monitor thyroid function before initiation of, and periodically throughout, treatment with INLYTA. (5.7)
• Impaired Wound Healing: Withhold INLYTA for at least 2 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. Resume INLYTA at a reduced dose or discontinue based on severity and persistence of the impaired wound healing. The safety of resumption of INLYTA after resolution of wound healing complications has not been established. (5.8)
• Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS has been observed. Permanently discontinue INLYTA if signs or symptoms of RPLS occur. (5.9)
• Proteinuria: Monitor for proteinuria before initiation of, and periodically throughout, treatment with INLYTA. For moderate to severe proteinuria, withhold and then dose reduce INLYTA. (5.10)
• Hepatotoxicity: Liver enzyme elevation has occurred during treatment with INLYTA as a single agent. Monitor ALT, AST and bilirubin before initiation of, and periodically throughout, treatment with INLYTA. When used in combination with avelumab or pembrolizumab, higher frequencies of Grade 3 and 4 ALT and AST elevation may occur. Consider more frequent monitoring of liver enzymes. Withhold INLYTA and avelumab or pembrolizumab, initiate corticosteroid therapy as needed, and/or permanently discontinue the combination for severe or life-threatening hepatotoxicity. (5.11)
• Use in Patients with Hepatic Impairment: Decrease the starting dose of INLYTA if used in patients with moderate hepatic impairment. INLYTA has not been studied in patients with severe hepatic impairment. (2.2, 5.12)
• Major adverse cardiovascular events (INLYTA in combination with avelumab): Optimize management of cardiovascular risk factors. Permanently discontinue INLYTA in combination with avelumab for Grade 3–4 events. (5.13)
• Embryo-Fetal Toxicity: INLYTA can cause fetal harm. Advise patients of the potential risk to the fetus and to use effective contraception. (5.14, 8.1, 8.3)

Most common adverse reactions (≥20%) are:

INLYTA in combination with avelumab: diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain, and headache. (6.1)

INLYTA in combination with pembrolizumab: diarrhea, fatigue/asthenia, hypertension, hepatotoxicity, hypothyroidism, decreased appetite, palmar-plantar erythrodysesthesia, nausea, stomatitis/mucosal inflammation, dysphonia, rash, cough, and constipation. (6.1)

INLYTA as a single agent: diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, palmar-plantar erythrodysesthesia (hand-foot) syndrome, weight decreased, vomiting, asthenia, and constipation. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Avoid strong CYP3A4/5 inhibitors. If unavoidable, reduce the INLYTA dose. (2.2, 7.1)
• Avoid strong CYP3A4/5 inducers. (7.2)

Lactation: Advise not to breastfeed. (8.2)