Version July 2025
Epithelioid sarcoma, metastatic or locally advanced: Adolescents ≥16 years: Oral: 800 mg twice daily until disease progression or unacceptable toxicity.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosage adjustment for toxicity:
Dose reductions:
First dose reduction: Oral: Tazemetostat 600 mg twice daily.
Second dose reduction: Oral: Tazemetostat 400 mg twice daily.
Note: Discontinue permanently if unable to tolerate tazemetostat 400 mg twice daily.
Dosage adjustment for neutropenia (neutrophil count <1 x 109/L): Hold tazemetostat until neutrophil count ≥1 x 109/L or baseline, then resume as follows:
If first occurrence: Resume tazemetostat at same dose.
For second or third occurrence: Resume tazemetostat at reduced dose.
After fourth occurrence: Permanently discontinue tazemetostat.
Dosage adjustment for thrombocytopenia (platelet count <50 x 109/L): Hold tazemetostat until platelet count ≥75 x 109/L or baseline, then resume as follows:
For first and second occurrence: Resume tazemetostat at reduced dose.
After third occurrence: Permanently discontinue tazemetostat.
Dosage adjustment for anemia (hemoglobin <8 g/dL): Hold tazemetostat until improved to least grade 1 or baseline, then resume at the same or reduced dose.
Dosage adjustment for other grade 3 adverse reactions: Hold tazemetostat until improved to at least grade 1 or baseline, then resume as follows:
For first and second occurrence: Resume tazemetostat at reduced dose.
After third occurrence: Permanently discontinue tazemetostat.
Dosage adjustment for other grade 4 adverse reactions: Hold tazemetostat until improved to at least grade 1 or baseline, then resume as follows:
For first occurrence: Resume tazemetostat at reduced dose.
After second occurrence: Permanently discontinue tazemetostat.
Adolescents ≥16 years:
Mild to severe impairment: No dosage adjustment needed.
End-stage renal disease: No dosage adjustment needed.
Adolescents ≥16 years:
Mild impairment (total bilirubin >1 to 1.5 x ULN or AST > ULN): No dosage adjustment necessary.
Moderate (total bilirubin >1.5 to 3 x ULN) or severe (total bilirubin >3 x ULN) impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
(For additional information see "Tazemetostat: Drug information")
Epithelioid sarcoma, metastatic or locally advanced: Oral: 800 mg twice daily until disease progression or unacceptable toxicity (Ref).
Follicular lymphoma, relapsed/refractory, EZH2 mutation positive: Oral: 800 mg twice daily until disease progression or unacceptable toxicity (Ref).
Follicular lymphoma, relapsed/refractory, salvage therapy: Oral: 800 mg twice daily until disease progression or unacceptable toxicity (Ref).
Missed dose: If a dose is missed or vomited, do not take an additional dose; continue with the next scheduled dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary.
Mild impairment (total bilirubin >1 to 1.5 times ULN or AST > ULN): No dosage adjustment necessary.
Moderate (total bilirubin >1.5 to 3 times ULN) or severe (total bilirubin >3 times ULN) impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Tazemetostat may cause dose-limiting bone marrow suppression; decreased hemoglobin (including anemia), decreased neutrophils, decreased platelet count, decreased white blood cell count, and lymphocytopenia have been reported. Hematologic effects may be reversible following dosage modification, interruption of therapy, and/or discontinuation.
Mechanism: Dose-related; exact mechanism is unknown.
Onset: May occur at any time during treatment (Ref).
Tazemetostat may increase the risk of developing secondary malignancies. Myelodysplastic syndromes, acute myelocytic leukemia, and B-cell acute lymphocytic leukemia have been reported.
Mechanism: Time-related. Exact mechanism is unknown; impact of disease process and concurrent medications must be considered.
Onset: Delayed; myelodysplastic syndrome and acute myelocytic leukemia were reported after >1 year of treatment with tazemetostat in one clinical trial (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Dermatologic: Alopecia, skin rash
Endocrine & metabolic: Decreased serum albumin, decreased serum calcium, decreased serum glucose, decreased serum phosphate, decreased serum potassium, decreased serum sodium, increased serum glucose, increased serum potassium, increased serum triglycerides, weight loss
Gastrointestinal: Abdominal pain, constipation, decreased appetite, diarrhea, nausea, vomiting
Genitourinary: Urinary tract infection
Hematologic & oncologic: Decreased hemoglobin (including anemia), decreased neutrophils, decreased platelet count, decreased white blood cell count, hemorrhage (including cerebral hemorrhage, hemoptysis, pulmonary hemorrhage, rectal hemorrhage, wound hemorrhage), lymphocytopenia, prolonged partial thromboplastin time
Hepatic: Increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase
Nervous system: Fatigue (including asthenia), headache, pain
Neuromuscular & skeletal: Musculoskeletal pain
Renal: Increased serum creatinine
Respiratory: Cough, dyspnea, lower respiratory tract infection, upper respiratory tract infection
1% to 10%:
Dermatologic: Skin infection
Hematologic & oncologic: Acute lymphocytic leukemia (B-cell), acute myelocytic leukemia, myelodysplastic syndrome
Infection: Herpes zoster infection, sepsis
Respiratory: Pleural effusion, pneumonia, respiratory distress
Miscellaneous: Fever
<1%: Hematologic & oncologic: T-cell lymphoma
There are no contraindications listed in the manufacturer's labeling.
Other warnings/precautions:
• Appropriate use: Select patients for tazemetostat treatment of relapsed/refractory follicular lymphoma (excluding salvage therapy) based on the presence of EZH2 mutation of codons Y646, A682, or A692 in tumor specimens. Information on approved tests is available at http://www.fda.gov/CompanionDiagnostics.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Tazverik: 200 mg
No
Tablets (Tazverik Oral)
200 mg (per each): $103.88
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Tazemetostat is available through a specialty pharmacy and specialty distributors. For further information, contact 833-437-4669 or https://www.tazverik.com/Content/pdf/ordering-and-distribution-sheet.pdf.
Oral: Swallow tablet whole; do not cut, crush, or chew. Administer without regard to food. Do not administer an additional dose for a missed dose or for vomiting; resume with next scheduled dose.
Oral: May administer with or without food. Swallow tablets whole; do not cut, crush, or chew.
This medication is not on the NIOSH (2024) list; however, it may meet the criteria for a hazardous drug. Tazemetostat may cause carcinogenicity and teratogenicity.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Do not store above 30°C (86°F).
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Tazverik: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/211723s004lbl.pdf#page=17
Treatment of metastatic or locally advanced epithelioid sarcoma not eligible for complete resection (FDA approved in ages ≥16 years and adults); treatment of relapsed or refractory follicular lymphoma in patients whose tumors are positive for an EZH2 mutation (as detected by an approved test) and who have received at least 2 prior systemic therapies (FDA approved in adults); treatment of relapsed or refractory follicular lymphoma in patients who have no satisfactory alternative treatment options (FDA approved in adults).
Note: Indication approved under accelerated approval based on overall response rate and duration of response; continued approval may be contingent upon confirmatory trials.
Tazemetostat may be confused with belinostat, panobinostat, vorinostat.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of CYP3A4 (Major with inhibitors), CYP3A4 (Minor with inducers), P-glycoprotein (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C8 (Weak); Induces CYP3A4 (Weak);
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Atogepant: CYP3A4 Inducers (Weak) may decrease serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with CYP3A4 inducers. When used for treatment of chronic migraine, use of atogepant with CYP3A4 inducers should be avoided. Risk D: Consider Therapy Modification
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Miscellaneous Oncologic Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Tazemetostat. Risk X: Avoid
CYP3A4 Inducers (Strong): May decrease serum concentration of Tazemetostat. Risk X: Avoid
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Tazemetostat. Management: Avoid when possible. If combined, reduce tazemetostat dose from 800 mg twice daily to 400 mg twice daily, from 600 mg twice daily to 400 mg in AM and 200 mg in PM, or from 400 mg twice daily to 200 mg twice daily. Risk D: Consider Therapy Modification
CYP3A4 Inhibitors (Strong): May increase serum concentration of Tazemetostat. Risk X: Avoid
Daprodustat: CYP2C8 Inhibitors (Weak) may increase serum concentration of Daprodustat. Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Grapefruit Juice: May increase serum concentration of Tazemetostat. Risk X: Avoid
Hormonal Contraceptives: Tazemetostat may decrease serum concentration of Hormonal Contraceptives. Management: Individuals of childbearing potential should use a non-hormonal contraceptive method during treatment with tazemetostat and for 6 months after. Males with partners of childbearing potential should use contraception during treatment and for 3 months after. Risk D: Consider Therapy Modification
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Mumps- Rubella- or Varicella-Containing Live Vaccines may increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
NiMODipine: CYP3A4 Inducers (Weak) may decrease serum concentration of NiMODipine. Risk C: Monitor
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Repaglinide: CYP2C8 Inhibitors (Weak) may increase serum concentration of Repaglinide. Risk C: Monitor
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Selpercatinib: CYP3A4 Inducers (Weak) may decrease serum concentration of Selpercatinib. Risk C: Monitor
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sirolimus (Conventional): CYP3A4 Inducers (Weak) may decrease serum concentration of Sirolimus (Conventional). Risk C: Monitor
Sirolimus (Protein Bound): CYP3A4 Inducers (Weak) may decrease serum concentration of Sirolimus (Protein Bound). Risk C: Monitor
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor
Tacrolimus (Systemic): CYP3A4 Inducers (Weak) may decrease serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Ubrogepant: CYP3A4 Inducers (Weak) may decrease serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a weak CYP3A4 inducer. Risk D: Consider Therapy Modification
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Evaluate pregnancy status prior to use in females of reproductive potential. Females of reproductive potential should use effective nonhormonal contraception during therapy and for 6 months after the last tazemetostat dose. Males with female partners of reproductive potential should use effective contraception during therapy and for at least 3 months after the last dose of tazemetostat.
Based on the mechanism of action, and data from animal reproduction studies, in utero exposure to tazemetostat may cause fetal harm.
Baseline: Pregnancy status prior to use in females of reproductive potential, total bilirubin, liver function tests.
During treatment: CBC with differential; monitor (long-term) for development of secondary malignancies.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), total Ig or IgG, and antibody to hepatitis B surface antigen (anti-HBs) prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Tazemetostat is a potent and selective inhibitor of histone methyltransferase EZH2 (enhancer of zeste homolog 2); it also inhibits some EZH2 gain-of-function mutations (including Y646X and A687V), as well as EZH1. EZH2 is overexpressed or mutated in many cancer types and plays a role in tumor proliferation. SWItch/Sucrose Non-Fermentable (SWI/SNF) complex aids in facilitating gene expression and terminal differentiation; altered EZH2 upregulation and loss-of-function mutations in SWI/SNF are oncogenic in many human cancers; tazemetostat has antitumor activity in EZH2-mutant cell lines (Italiano 2018). Tazemetostat suppressed B-cell lymphoma cell lines proliferation in vitro, and showed antitumor activity in an animal model of B-cell lymphoma with or without EZH2 gain-of-function mutations; tazemetostat demonstrated increased inhibition of lymphoma cell line proliferation with mutant EZH2.
Distribution: Vss/F: 1,230 L.
Protein binding: 88%.
Metabolism: Via CYP3A to form the inactive major metabolites M5 (EPZ-6930) and M3 (EPZ006931); M5 is further metabolized by CYP3A.
Bioavailability: ~33%.
Half-life elimination: 3.1 hours.
Time to peak: 1 to 2 hours.
Excretion: Feces: 79%; urine: 15%.
Clearance: 274 L/hour.
