Drug Safety-related Labeling Changes (SrLC)

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Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

TAZVERIK (NDA-211723)

(TAZEMETOSTAT HYDROBROMIDE)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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08/13/2024 (SUPPL-5)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

…

Table 4 presents adverse reactions in patients with epithelioid sarcoma in Cohort 5 of Study EZH-202.

Table 4. Adverse Reactions (greater than or equal to 10%) in Patients with Epithelioid Sarcoma Who Received TAZVERIK in Cohort 5 of Study EZH-202

Please refer to label to view Table 4

…

Table 5 summarizes select laboratory abnormalities in patients with epithelioid sarcoma in Cohort 5 of Study EZH-202.

Please refer to label to view Table 5

…

Relapsed or Refractory Follicular Lymphoma

The safety of TAZVERIK was evaluated in two cohorts (Cohorts 4 and 5) of Study E7438-G000-101 that enrolled patients with relapsed or refractory follicular lymphoma [see Clinical Studies (14.2)]. Patients received TAZVERIK 800 mg orally twice daily (n=99). Among patients who received TAZVERIK, 68% were exposed for 6 months or longer, 39% were exposed for 12 months or longer, and 21% were exposed for 18 months or longer.

The median age was 62 years (range 36 to 87 years), 54% were male, and 95% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. The median number of prior therapies was 3 (range 1 to 11). Patients were required to have a creatinine clearance greater than or equal to 40 mL/min per the Cockcroft and Gault formula.

Serious adverse reactions occurred in 30% of patients who received TAZVERIK. Serious adverse reactions in greater than or equal to 2% of patients who received TAZVERIK were general physical health deterioration, abdominal pain, pneumonia, sepsis, and anemia.

Permanent discontinuation due to an adverse reaction occurred in 8% of patients who received TAZVERIK. Adverse reaction resulting in permanent discontinuation in greater than or equal to 2% of patients was second primary malignancy.

Dosage interruptions due to an adverse reaction occurred in 28% of patients who received TAZVERIK. Adverse reactions requiring dosage interruptions in greater than or equal to 3% of patients were thrombocytopenia and fatigue.

Dose reduction due to an adverse reaction occurred in 9% of patients who received TAZVERIK.

The most common adverse reactions (greater than or equal to 20%) were fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain.

…

Clinically relevant adverse reactions occurring in <10% of patients who received TAZVERIK included:

Infection: sepsis (2%), pneumonia (2%), and herpes zoster (2%)

…

7 Drug Interactions

7.1 Effect of Other Drugs on TAZVERIK

Additions and/or revisions underlined:

Strong or Moderate CYP3A Inhibitors

Coadministration of TAZVERIK with a strong or moderate CYP3A inhibitor increases tazemetostat plasma concentrations [see Clinical Pharmacology (12.3)], which may increase the frequency or severity of adverse reactions. Avoid coadministration of strong or moderate CYP3A inhibitors with TAZVERIK. If coadministration of strong or moderate CYP3A inhibitors cannot be avoided, reduce TAZVERIK dose [see Dosage and Administration (2.4)].

Strong or Moderate CYP3A Inducers

Coadministration of TAZVERIK with a strong CYP3A inducer decreases tazemetostat plasma concentrations [see Clinical Pharmacology (12.3)], and coadministration of TAZVERIK with a moderate CYP3A inducer may also decrease tazemetostat plasma concentrations. The decrease in tazemetostat plasma concentration may decrease the efficacy of TAZVERIK. Avoid coadministration of moderate or strong CYP3A inducers with TAZVERIK.

11/16/2023 (SUPPL-4)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Secondary Malignancies

Additions and/or revisions underlined:

The risk of developing secondary malignancies is increased following treatment with TAZVERIK. Across clinical trials of 758 adults who received TAZVERIK 800 mg twice daily as monotherapy, myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), or B-cell acute lymphoblastic leukemia (B-ALL) occurred in 1.7% of patients. One pediatric patient developed T-cell lymphoblastic lymphoma (T-LBL). Monitor patients long-term for the development of secondary malignancies.

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

…

Relapsed or Refractory Follicular Lymphoma

The median age was 62 years (range 36 to 87 years), 54% were male, and 95% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. The median number of prior therapies was 3 (range 1 to 11). Patients were required have a creatinine clearance greater than or equal to 40 mL/min per the Cockcroft and Gault formula.

Dose reduction due to an adverse reaction occurred in 9% of patients who received TAZVERIK.

The most common adverse reactions (greater than or equal to 20%) were fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain.

Table 6 presents adverse reactions in patients with relapsed or refractory follicular lymphoma in Cohorts 4 and 5 of Study E7438-G000-101.

Please refer to label to view Table 6.

…

Clinically relevant adverse reactions occurring in <10% of patients who received TAZVERIK included:

Infection: sepsis (2%), pneumonia (2%), and herpes zoster (2%)

Table 7 summarizes select laboratory abnormalities in patients with follicular lymphoma in Cohorts 4 and 5 of Study E7438-G000-101.

Please refer to label to view Table 7.

8 Use in Specific Populations

8.5 Geriatric Use

Additions and/or revisions underlined:

Clinical studies of TAZVERIK did not include sufficient numbers of patients with epithelioid sarcoma or relapsed or refractory follicular lymphoma aged 65 and over to determine whether they respond differently from younger subjects.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

…

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)].

…

MEDICATION GUIDE

Additions and/or revisions underlined:

…

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.
…
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 follicular lymphoma include:

tiredness
bone and muscle pain
cold-like symptoms (upper respiratory infection)
nausea
stomach (abdominal) pain
…