Tazemetostat
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omid Afkhami-Ardakani
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Overview
Tazemetostat is a Histone Methyltransferase Inhibitor that is FDA approved 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. and also Adult patients with relapsed or refractory follicular lymphoma whose tumors are EZH2-mutation positive (as detected by an FDA-approved test), and who have received at least two prior systemic therapies or have no satisfactory alternative treatment options.. Common adverse reactions include Fatigue, pain, nausea, decreased appetite, vomiting, and constipation..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
The recommended dosage is 800 mg orally twice daily with or without food.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Tazemetostat in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Tazemetostat in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Tazemetostat is approved for use in pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection. The recommended dosage is 800 mg orally twice daily with or without food.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Tazemetostat in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Tazemetostat in pediatric patients.
Contraindications
There is limited information regarding Tazemetostat Contraindications in the drug label.
Warnings
Secondary Malignancies: Tazemetostat increases the risk of developing secondary malignancies, including T-cell lymphoblastic lymphoma, myelodysplastic syndrome, and acute myeloid leukemia. Monitor patients long-term for the development of secondary malignancies.
Embryo-Fetal Toxicity: Tazemetostat can cause fetal harm. Advise patients of potential risk to a fetus and to use effective non-hormonal contraception.
Adverse Reactions
Clinical Trials Experience
General: Fatigue, pain.
Gastrointestinal: Nausea, decreased appetite, vomiting, constipation.
Postmarketing Experience
There is limited information regarding Tazemetostat Postmarketing Experience in the drug label.
Drug Interactions
Strong and moderate CYP3A inhibitors may increase tazemetostat plasma concentrations.
Strong and moderate CYP3A inducers may decrease tazemetostat plasma concentrations.
Tazemetostat may induce CYP3A and CYP2B6, which could decrease plasma concentrations of drugs metabolized by these enzymes.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Tazemetostat in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Tazemetostat in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Tazemetostat during labor and delivery.
Nursing Mothers
It is unknown whether tazemetostat is excreted in human milk; breastfeeding is not recommended during treatment and for one week after the final dose.
Pediatric Use
Safety and effectiveness have been established in pediatric patients aged 16 years and older.
Geriatic Use
There is no FDA guidance on the use of Tazemetostat in geriatric settings.
Gender
There is no FDA guidance on the use of Tazemetostat with respect to specific gender populations.
Race
There is no FDA guidance on the use of Tazemetostat with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Tazemetostat in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Tazemetostat in patients with hepatic impairment.
Females of Reproductive Potential and Males
Advise females of reproductive potential to use effective non-hormonal contraception during treatment and for six months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment and for three months after the final dose.
Immunocompromised Patients
There is no FDA guidance one the use of Tazemetostat in patients who are immunocompromised.
Administration and Monitoring
Administration
Administer orally twice daily with or without food.
Swallow tablets whole; do not cut, crush, or chew.
If a dose is missed or vomiting occurs after taking tazemetostat, do not take an additional dose; continue with the next scheduled dose.
Monitoring
Monitor patients long-term for the development of secondary malignancies.
Monitor for signs and symptoms of embryo-fetal toxicity in females of reproductive potential.
IV Compatibility
Not applicable
Overdosage
There is limited information regarding Tazemetostat overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Tazemetostat Pharmacology in the drug label.
Mechanism of Action
Tazemetostat is a selective inhibitor of EZH2 (enhancer of zeste homolog 2), a histone methyltransferase involved in the epigenetic regulation of gene expression. Inhibition reduces trimethylation of histone H3 at lysine 27 (H3K27me3), reactivating silenced tumor suppressor genes and suppressing cancer cell growth.
Structure
There is limited information regarding Tazemetostat Structure in the drug label.
Pharmacodynamics
In vitro, tazemetostat reduces H3K27me3 levels and inhibits cell proliferation in EZH2-mutant cancer cell lines.
Pharmacokinetics
Absorption: Peak plasma concentration (Tmax) ~2 hours after oral administration.
Distribution: Volume of distribution ~1,240 L; highly protein-bound (~88%).
Metabolism: Primarily metabolized by CYP3A enzymes.
Elimination: Half-life ~3.1 hours; ~15% excreted in urine, ~79% in feces.
Nonclinical Toxicology
Carcinogenicity: Not fully assessed.
Genotoxicity: Negative in standard assays.
Reproductive toxicity: Embryo-fetal toxicity observed in animal studies.
Clinical Studies
There is limited information regarding Tazemetostat Clinical Studies in the drug label.
How Supplied
Form: Oral tablet.
Strength: 200 mg per tablet.
Packaging: Bottles of 120 tablets.
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).
Keep in original container to protect from moisture.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
Advise patients:
To take tazemetostat exactly as prescribed (twice daily, with or without food).
Not to crush, chew, or split the tablets.
To use effective contraception during treatment and for the required post-treatment period.
About the risk of secondary cancers and to report any unusual symptoms.
To notify their healthcare provider if they miss a dose or vomit after taking a dose—do not take extra doses.
Precautions with Alcohol
Alcohol-Tazemetostat interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
Tazverik®
Manufactured by Epizyme, Inc.
Look-Alike Drug Names
There is limited information regarding Tazemetostat Look-Alike Drug Names in the drug label.
Price
References
The contents of this FDA label are provided by the National Library of Medicine.