HIGHLIGHTS OF PRESCRIBING INFORMATION • Neutropenia: Monitor blood counts during treatment (5.2). These highlights do not include all the information needed to use • Diarrhea or Non-infectious colitis: Monitor for the development of diarrhea UKONIQ safely and effectively. See full prescribing information for or colitis and provide supportive care as appropriate (5.3). UKONIQ. • Hepatotoxicity: Monitor hepatic function (5.4). UKONIQ™ (umbralisib) tablets, for oral use • Severe cutaneous reactions: Withhold treatment, reduce dose, or Initial U.S. Approval: 2021 discontinue treatment depending on severity and persistence of severe cutaneous reaction (5.5). ___________________________INDICATIONS AND USAGE________________________________ • Allergic reactions due to inactive ingredient FD&C Yellow No. 5: UKONIQ is a kinase inhibitor indicated for the treatment of adult patients UKONIQ contains FD&C Yellow No. 5 (tartrazine) which may cause with: allergic-type reactions (5.6). • Relapsed or refractory marginal zone lymphoma (MZL) who have • Embryo-fetal toxicity: Can cause fetal harm. Advise patients of potential received at least one prior anti-CD20-based regimen (1.1). risk to a fetus and to use effective contraception (5.7, 8.1, 8.3). • Relapsed or refractory follicular lymphoma (FL) who have received at ____________________________ _____________________________________ least three prior lines of systemic therapy (1.2). ADVERSE REACTIONS The most common (≥15%) adverse reactions, including laboratory These indications are approved under accelerated approval based on overall abnormalities, were increased creatinine, diarrhea-colitis, fatigue, nausea, response rate. Continued approval for these indications may be contingent neutropenia, transaminase elevation, musculoskeletal pain, anemia, upon verification and description of clinical benefit in a confirmatory trial. thrombocytopenia, upper respiratory tract infection, vomiting, abdominal ________________________DOSAGE AND ADMINISTRATION_________________________ pain, decreased appetite, and rash (6.1). • Recommended dosage: 800 mg orally once daily with food (2.1). To report SUSPECTED ADVERSE REACTIONS, contact TG • Manage toxicity using treatment interruption, dose reduction, or Therapeutics at 1-877-848-9462 or FDA at 1-800-FDA-1088 or discontinuation (2.3). www.fda.gov/medwatch. ________________________DOSAGE FORMS AND STRENGTHS______________________ ___________________________USE IN SPECIFIC POPULATIONS_______________________ Tablets: 200 mg (3). Lactation: Advise not to breastfeed (8.2). ________________________CONTRAINDICATIONS________________________________________ See 17 for PATIENT COUNSELING INFORMATION and Medication None (4). Guide ________________________WARNINGS AND PRECAUTIONS__________________________ Revised: 02/2021 • Infections: Monitor for fever and any new or worsening signs and symptoms of infection. Evaluate promptly and treat as needed (5.1). FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE 8.3 Females and Males of Reproductive Potential 1.1 Marginal Zone Lymphoma 8.4 Pediatric Use 1.2 Follicular Lymphoma 8.5 Geriatric Use 2 DOSAGE AND ADMINISTRATION 8.6 Renal Impairment 2.1 Recommended Dosage 8.7 Hepatic Impairment 2.2 Recommended Prophylaxis 11 DESCRIPTION 2.3 Recommended Modifications for Adverse Reactions 12 CLINICAL PHARMACOLOGY 3 DOSAGE FORMS AND STRENGTHS 12.1 Mechanism of Action 4 CONTRAINDICATIONS 12.2 Pharmacodynamics 5 WARNINGS AND PRECAUTIONS 12.3 Pharmacokinetics 5.1 Infections 13 NONCLINICAL TOXICOLOGY 5.2 Neutropenia 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 5.3 Diarrhea or Non-Infectious Colitis 14 CLINICAL STUDIES 5.4 Hepatotoxicity 14.1 Marginal Zone Lymphoma 5.5 Severe Cutaneous Reactions 14.2 Follicular Lymphoma 5.6 Allergic Reactions Due to Inactive Ingredient FD&C Yellow No. 5 16 HOW SUPPLIED/STORAGE AND HANDLING 5.7 Embryo-Fetal Toxicity 17 PATIENT COUNSELING INFORMATION 6 ADVERSE REACTIONS 6.1 Clinical Trials Experience *Sections or subsections omitted from the full prescribing information are not 8 USE IN SPECIFIC POPULATIONS listed. 8.1 Pregnancy 8.2 Lactation 1 Reference ID: 4742425 FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE 1.1 Marginal Zone Lymphoma UKONIQ is indicated for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based regimen. This indication is approved under accelerated approval based on overall response rate [see Clinical Studies (14.1)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). 1.2 Follicular Lymphoma UKONIQ is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy. This indication is approved under accelerated approval based on overall response rate [see Clinical Studies (14.2)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosage The recommended dosage of UKONIQ is 800 mg taken orally once daily with food [see Clinical Pharmacology (12.3)] until disease progression or unacceptable toxicity. Advise patients of the following: • Swallow tablets whole. Do not crush, break, cut, or chew tablets. • Take UKONIQ at the same time each day. • If vomiting occurs, do not take an additional dose; continue with the next scheduled dose. • If a dose is missed, take a missed dose unless it is less than 12 hours until the next scheduled dose. 2.2 Recommended Prophylaxis Provide prophylaxis for Pneumocystis jirovecii pneumonia (PJP) during treatment with UKONIQ [see Warnings and Precautions (5.1)]. Consider prophylactic antivirals during treatment with UKONIQ to prevent cytomegalovirus (CMV) infection, including CMV reactivation [see Warnings and Precautions (5.1)]. 2.3 Dosage Modifications for Adverse Reactions Recommended dosage modifications of UKONIQ for adverse reactions are presented in Table 1 and the recommended dose reductions of UKONIQ for adverse reactions are presented in Table 2. 2 Reference ID: 4742425 Table 1: Recommended Dosage Modifications of UKONIQ for Adverse Reactions a Adverse Reactions Severity Dosage Modification Hematologic Adverse Reactions 9 Neutropenia ANC 0.5 to 1 ×10 /L • Maintain UKONIQ. 9 [see Warnings and • If ANC 0.5 to 1 × 10 /L recurs or is Precautions (5.2)] persistent, then withhold UKONIQ until 9 ANC 1 × 10 /L or greater, then resume at same dose. 9 ANC less than 0.5 × 10 /L • Withhold UKONIQ until ANC 0.5 × 9 10 /L or greater, then resume at same dose. • If recurrence, then resume at reduced dose. Thrombocytopenia Platelet count 25 to less than 50 × • Withhold UKONIQ until platelet count 9 10 /L with bleeding 25 × 109/L or greater and resolution of [see Adverse Reactions bleeding (if applicable), then resume at (6.1)] OR same dose. Platelet count less than 25 × 109/L • If recurrence, withhold until resolution and then resume at reduced dose. Nonhematologic Adverse Reactions Infection, including Grade 3 or 4 Withhold UKONIQ until resolved, then opportunistic infection resume at same or reduced dose. [see Warnings and PJP • For suspected PJP, withhold UKONIQ Precautions (5.1)] until evaluated. • For confirmed PJP, discontinue UKONIQ. CMV infection or viremia Withhold UKONIQ until infection or viremia resolves, then resume at same or reduced dose. ALT or AST Elevation AST or ALT greater than 5 to less Withhold UKONIQ until return to less than 3 [see Warnings and than 20 times ULN times ULN, then resume at reduced dose. Precautions (5.4)] AST or ALT greater than 20 times Discontinue UKONIQ. ULN Diarrhea or Non­ Mild or moderate diarrhea (up to 6 • If persistent, withhold UKONIQ until infectious Colitis stools per day over baseline) resolved, then resume at same or reduced dose. [see Warnings and OR Precautions (5.3)] • If recurrence, withhold until resolution Asymptomatic (Grade 1) colitis and then resume at reduced dose. 3 Reference ID: 4742425 Adverse Reactions Severitya Dosage Modification Severe diarrhea (greater than 6 stools • Withhold UKONIQ until resolved, then per day over baseline) resume at reduced dose. • For recurrent severe diarrhea or recurrent OR colitis of any grade, discontinue Abdominal pain, stool with mucus or UKONIQ. blood, change in bowel habits, peritoneal signs Life-threatening Discontinue UKONIQ. Severe Cutaneous Severe • Withhold UKONIQ until resolved, then Reactions [see resume at reduced dose or discontinue. Warnings and • If recurrence after re-challenge, Precautions (5.5)] discontinue UKONIQ. Life-threatening Discontinue UKONIQ. SJS, TEN, DRESS (any grade) Discontinue UKONIQ. Other Adverse Severe Withhold UKONIQ until resolved, then Reactions [see Adverse resume at the same or reduced dose. Reactions (6.1)] Life-threatening Discontinue UKONIQ. ALT, alanine aminotransferase; ANC, absolute neutrophil count; AST, aspartate aminotransferase; CMV, cytomegalovirus; PJP, Pneumocystis jirovecii pneumonia; ULN, upper limit of normal; SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis; DRESS, drug reaction with eosinophilia and systemic symptoms. aNational Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. Table 2: Recommended Dose Reductions of UKONIQ for Adverse Reactions Dose Reduction Dosage First 600 mg orally daily Second 400 mg orally daily Subsequent Permanently