TAZVERIK tazemetostat 200 mg Tablet, Film Coated, 240-count

1 INDICATIONS AND USAGE TAZVERIK is a methyltransferase inhibitor indicated for the treatment of: Adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection. ( 1.1 ) Adult patients with relapsed or refractory follicular lymphoma whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least 2 prior systemic therapies. ( 1.2 ) Adult patients with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options.

( 1.2 ) These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

1.1Epithelioid Sarcoma TAZVERIK is indicated for the treatment of adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection. This indication is approved under accelerated approval based on overall response rate and duration of response [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).

1.2Relapsed or Refractory Follicular Lymphoma TAZVERIK is indicated for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least 2 prior systemic therapies. TAZVERIK is indicated for the treatment of adult patients with R/R FL who have no satisfactory alternative treatment options. These indications are approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies ( 14.2 )].

Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

2 DOSAGE AND ADMINISTRATION Recommended dosage is 800 mg taken orally twice daily with or without food. ( 2.2 )

2.1Patient Selection Select patients with R/R FL for treatment with TAZVERIK based on the presence of EZH2 mutation of codons Y646, A682, or A692 in tumor specimens [see Clinical Studies ( 14.2 )] . Information on FDA-approved tests for the detection of EZH2 mutation in relapsed or refractory follicular lymphoma is available at: http://www.fda.gov/CompanionDiagnostics.

2.2Recommended Dosage The recommended dosage of TAZVERIK is 800 mg orally twice daily with or without food until disease progression or unacceptable toxicity. Swallow tablets whole. Do not cut, crush, or chew tablets. Do not take an additional dose if a dose is missed or vomiting occurs after TAZVERIK, but continue with the next scheduled dose.

2.3Dosage Modifications for Adverse Reactions Table 1 summarizes the recommended dose reductions, and Table 2 summarizes the recommended dosage modifications of TAZVERIK for adverse reactions. Table 1. Recommended Dose Reductions of TAZVERIK for Adverse Reactions *Permanently discontinue TAZVERIK in patients who are unable to tolerate 400 mg orally twice daily.

Dose Reduction Dosage First 600 mg orally twice daily Second 400 mg orally twice daily* Table 2. Recommended Dosage Modifications of TAZVERIK for Adverse Reactions Adverse Reaction Severity Dosage Modification Neutropenia [see Adverse Reactions ( 6.1 )] Neutrophil count less than 1 × 10 9 /L Withhold until neutrophil count is greater than or equal to 1 × 10 9 /L or baseline. For first occurrence, resume at same dose.

For second and third occurrence, resume at reduced dose. Permanently discontinue after fourth occurrence. Thrombocytopenia [see Adverse Reactions ( 6.1 )] Platelet count less than 50 × 10 9 /L Withhold until platelet count is greater than or equal to 75 × 10 9 /L or baseline.

For first and second occurrence, resume at reduced dose. Permanently discontinue after third occurrence. Anemia [see Adverse Reactions ( 6.1 )] Hemoglobin less than 8 g/dL Withhold until improvement to at least Grade 1 or baseline, then resume at same or reduced dose.

Other adverse reactions [see Adverse Reactions ( 6.1 )] Grade 3 Withhold until improvement to at least Grade 1 or baseline. For first and second occurrence, resume at reduced dose. Permanently discontinue after third occurrence.

Grade 4 Withhold until improvement to at least Grade 1 or baseline. For first occurrence, resume at reduced dose. Permanently discontinue after second occurrence.

2.4Dosage Modifications for Drug Interactions Strong or Moderate CYP3A Inhibitors Avoid coadministration of TAZVERIK with strong or moderate CYP3A inhibitors. If coadministration with a strong or moderate CYP3A inhibitor cannot be avoided, reduce the TAZVERIK dose as shown in Table 3 below. After discontinuation of the strong or moderate CYP3A inhibitor for 3 elimination half-lives, resume the TAZVERIK dose that was taken prior to initiating the inhibitor [see Drug Interactions ( 7.1 ), Clinical Pharmacology ( 12.3 )] .

Table 3. Recommended Dose Reductions of TAZVERIK for Strong or Moderate CYP3A Inhibitors Current Dosage Adjusted Dosage 800 mg orally twice daily 400 mg orally twice daily 600 mg orally twice daily 400 mg for first dose and 200 mg for second dose 400 mg orally twice daily 200 mg orally twice daily

3 DOSAGE FORMS AND STRENGTHS Tablets: 200 mg film-coated, red, round, biconvex shape and debossed with "EZM 200" on one side and plain on the other. Tablets: 200 mg ( 3 )

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Secondary Malignancies Advise patients of the increased risk of secondary hematologic malignancies. Advise patients to inform their healthcare provider if they experience fatigue, easy bruising, fever, bone pain, or paleness [see Warnings and Precautions ( 5.1 )] .

Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy [see Use in Specific Populations ( 8.1 )] . Advise females of reproductive potential to use effective non-hormonal contraception during treatment with TAZVERIK and for 6 months after the final dose [see Use in Specific Populations ( 8.3 )] .

Advise males with female partners of reproductive potential to use effective contraception during treatment with TAZVERIK and for 3 months after the final dose [see Use in Specific Populations ( 8.3 ), Nonclinical Toxicology ( 13.1 )]. Lactation Advise women not to breastfeed during treatment with TAZVERIK and for 1 week after the final dose [see Use in Special Populations ( 8.2 )]. Drug Interactions Advise patients and caregivers to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products.

Inform patients to avoid St. John's wort, grapefruit, and grapefruit juice while taking TAZVERIK [see Drug Interactions ( 7.1 )] . Manufactured for: Epizyme, Inc.

An Ipsen Company One Main St. Cambridge, MA 02142 ©2023, 2024 Epizyme, Inc.

This Medication Guide has been approved by the U.S. Food and Drug Administration. Issued: November/2023 MEDICATION GUIDE TAZVERIK ® (taz vayr′ ik) (tazemetostat) tablets What is the most important information I should know about TAZVERIK?

TAZVERIK can cause serious side effects, including: Risk of new cancers. An increase in new (second) cancers has happened in people who were treated with TAZVERIK. Talk with your healthcare provider about your risk of developing new cancers.

Your healthcare provider will monitor you for new cancers after your treatment with TAZVERIK. Tell your healthcare provider if you are more tired than usual, or have easy bruising, fever, bone pain, or paleness. See " What are the possible side effects of TAZVERIK " for more information about side effects.

What is TAZVERIK? TAZVERIK is a prescription medicine used to treat: adults and children aged 16 years and older with epithelioid sarcoma that has spread or grown and cannot be removed by surgery. adults with follicular lymphoma when the disease has come back or did not respond to treatment, whose tumors have an abnormal EZH2 gene, and who have been treated with at least two prior medicines. Your healthcare provider will perform a test to make sure TAZVERIK is right for you. adults with follicular lymphoma when the disease has come back or did not respond to treatment, who have no other satisfactory treatment options.

It is not known if TAZVERIK is safe and effective in children less than 16 years of age. Before taking TAZVERIK tell your healthcare provider about all of your medical conditions, including if you: are pregnant or plan to become pregnant. TAZVERIK can harm your unborn baby.

Your healthcare provider will give you a pregnancy test before you start treatment with TAZVERIK. Tell your healthcare provider right away if you become pregnant or think you may be pregnant. Females who are able to become pregnant should use effective non-hormonal birth control (such as condoms) during treatment and for 6 months after the final dose of TAZVERIK.

Birth control pills (oral contraceptives) and other hormonal forms of birth control may not be effective if used during treatment with TAZVERIK. Talk to your healthcare provider about birth control options that are right for you. Males with female partners who are able to become pregnant should use effective birth control during treatment and for 3 months after the final dose of TAZVERIK. are breastfeeding or plan to breastfeed.

It is not known if TAZVERIK passes into your breast milk. Do not breastfeed during treatment and for 1 week after the final dose of TAZVERIK. Tell your healthcare provider about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements.

TAZVERIK may affect the way other medicines work and other medicines may affect how TAZVERIK works. How should I take TAZVERIK? Take TAZVERIK exactly as your healthcare provider tells you.

Take TAZVERIK 2 times each day. Take TAZVERIK with or without food. Swallow TAZVERIK tablets whole.

Do not cut, crush, or chew tablets. If you miss a dose or vomit after taking your dose, just skip that dose and take the next dose at your regular time. Your healthcare provider may change your dose, temporarily stop, or completely stop treatment with TAZVERIK if you get certain side effects.

What should I avoid while taking TAZVERIK? Avoid eating grapefruit or drinking grapefruit juice during treatment with TAZVERIK. Avoid taking St.

John's wort during treatment with TAZVERIK. What are the possible side effects of TAZVERIK? TAZVERIK can cause serious side effects.

See "What is the most important information I should know about TAZVERIK?" The most common side effects of TAZVERIK in people with epithelioid sarcoma include: pain nausea vomiting tiredness decreased appetite constipation The most common side effects of TAZVERIK in people with follicular lymphoma include: tiredness bone and muscle pain cold-like sympt…