Tazverik
(tazemetostat)Dosage & Administration
By using PrescriberAI, you agree to the AI Terms of Use.
Tazverik Prescribing Information
Epithelioid 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 ]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Relapsed 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 ]. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Patient 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 ]. 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.
Recommended 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.
Dosage Modifications for Adverse Reactions
Table 1 summarizes the recommended dose reductions, and Table 2 summarizes the recommended dosage modifications 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* |
| Adverse Reaction | Severity | Dosage Modification |
|---|---|---|
| Neutropenia [see Adverse Reactions ] | Neutrophil count less than 1 × 109/L |
|
| Thrombocytopenia [see Adverse Reactions ] | Platelet count less than 50 × 109/L |
|
| Anemia [see Adverse Reactions ] | Hemoglobin less than 8 g/dL |
|
| Other adverse reactions [see Adverse Reactions ] | Grade 3 |
|
| Grade 4 |
|
Dosage 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 , Clinical Pharmacology ].
| 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 |
Tablets: 200 mg film-coated, red, round, biconvex shape and debossed with "EZM 200" on one side and plain on the other.
Pregnancy
Risk Summary
Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology ], TAZVERIK can cause fetal harm when administered to pregnant women. There are no available data on TAZVERIK use in pregnant women to inform the drug-associated risk. Administration of tazemetostat to pregnant rats and rabbits during organogenesis resulted in dose-dependent increases in skeletal developmental abnormalities in both species beginning at maternal exposures approximately 1.5 times the adult human exposure [AUC0-45h] at the 800 mg twice daily dose (see Data). Advise pregnant women of the potential risk to a fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Animal Data
In pregnant rats, once daily oral administration of tazemetostat during the period of organogenesis from gestation day (GD) 7 through 17 resulted in no maternal adverse effects at doses up to 100 mg/kg/day (approximately 6 times the adult human exposure at 800 mg twice daily). Skeletal malformations and variations occurred in fetuses at doses of ≥50 mg/kg (approximately 2 times the adult human exposure at the 800 mg twice daily dose). At 200 mg/kg (approximately 14 times the adult human exposure at the 800 mg twice daily dose), major findings included increased post implantation loss, missing digits, fused vertebrae, domed heads and fused bones of the skull, and reduced fetal body weights.
In pregnant rabbits, no adverse maternal effects were observed after once daily oral administration of 400 mg/kg/day tazemetostat (approximately 7 times the adult human exposure at the 800 mg twice daily dose) from GD 7 through 19. Skeletal variations were present at doses ≥100 mg/kg/day (approximately 1.5 times the adult human exposure at the 800 mg twice daily dose), with skeletal malformations at ≥200 mg/kg/day (approximately 5.6 times the adult human exposure at the 800 mg twice daily dose). At 400 mg/kg (approximately 7 times the adult human exposure at the 800 mg twice daily dose), major findings included increased post implantation loss and cleft palate and snout.
Lactation
Risk Summary
There are no animal or human data on the presence of tazemetostat in human milk or on its effects on the breastfed child or milk production. Because of the potential risk for serious adverse reactions from TAZVERIK in the breastfed child, advise women not to breastfeed during treatment with TAZVERIK and for one week after the final dose.
Females and Males of Reproductive Potential
Pregnancy Testing
Verify the pregnancy status of females of reproductive potential prior to initiating TAZVERIK [see Use in Specific Populations ].
Risk Summary
TAZVERIK can cause fetal harm when administered to pregnant women [see Use in Specific Populations ].
Contraception
Females
Advise females of reproductive potential to use effective non-hormonal contraception during treatment with TAZVERIK and for 6 months after the final dose. TAZVERIK can render some hormonal contraceptives ineffective [see Drug Interactions ].
Males
Advise males with female partners of reproductive potential to use effective contraception during treatment with TAZVERIK and for at least 3 months after the final dose.
Pediatric Use
The safety and effectiveness of TAZVERIK have been established in pediatric patients aged 16 years and older (adolescents) with metastatic or locally advanced epithelioid sarcoma. Use of TAZVERIK for this indication is supported by evidence from adequate and well-controlled studies in adults (including 3 adolescent patients aged 16 years) [see Adverse Reactions , Clinical Pharmacology , Clinical Studies ].
The safety and effectiveness of TAZVERIK in pediatric patients aged less than 16 years have not been established.
Juvenile Animal Toxicity Data
In a 13-week juvenile rat toxicology study, animals were dosed daily from post-natal day 7 to day 97 (approximately equivalent to neonate to adulthood). Tazemetostat resulted in:
- T-LBL at doses ≥50 mg/kg (approximately 2.8 times the adult human exposure at the 800 mg twice daily dose)
- Increased trabecular bone at doses ≥100 mg/kg (approximately 10 times the adult human exposure at the 800 mg twice daily dose)
- Increased body weight at doses ≥50 mg/kg (approximately equal to the adult human exposure at the 800 mg twice daily dose)
- Distended testicles in males at doses ≥50 mg/kg (approximately equal to the adult human exposure at the 800 mg twice daily dose)
Geriatric Use
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.
Renal Impairment
No dose adjustment of TAZVERIK is recommended for patients with mild to severe renal impairment or end stage renal disease [see Clinical Pharmacology ].
Hepatic Impairment
No dose adjustment of TAZVERIK is recommended for patients with mild hepatic impairment (total bilirubin > 1 to 1.5 times upper limit of normal [ULN] or AST > ULN). TAZVERIK has not been studied in patients with moderate (total bilirubin > 1.5 to 3 times ULN) or severe (total bilirubin > 3 times ULN) hepatic impairment [see Clinical Pharmacology ].
None.
Secondary Malignancies
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.
Embryo-Fetal Toxicity
Based on findings from animal studies and its mechanism of action, TAZVERIK can cause fetal harm when administered to pregnant women. There are no available data on TAZVERIK use in pregnant women to inform the drug-associated risk. Administration of tazemetostat to pregnant rats and rabbits during organogenesis resulted in dose-dependent increases in skeletal developmental abnormalities in both species beginning at maternal exposures approximately 1.5 times the adult human exposure (area under the plasma concentration time curve [AUC0-45h]) at the 800 mg twice daily dose.
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAZVERIK and for 6 months after the final dose. 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 ].