Tazverik (tazemetostat hydrobromide)

Dosage of tazemetostat hydrobromide is expressed in terms of tazemetostat.

If adverse reactions occur during tazemetostat therapy, temporary interruption of therapy, dosage reduction, and/or discontinuance of the drug may be necessary. If dosage reduction is required, the dosage of tazemetostat should be reduced as described in Table 1.

Table 1: Recommended Dosage Reduction for Tazemetostat Toxicity

Dose Reduction Level Dosage Reduction after Recovery from Toxicity (Initial Dosage = 800 mg twice daily) First Resume at 600 mg twice daily Second Resume at 400 mg twice daily Third Permanently discontinue drug

The following Recommended Dosage Modification for Tazemetostat Toxicity table indicates the recommended dosage modification (i.e., temporary interruption of therapy, dosage reduction, discontinuance of therapy) for adverse effects according to severity.

Table 2. Recommended Dosage Modification for Tazemetostat Toxicity

Adverse Reaction and Toxicity Occurrence Dosage Modification Severity Neutropenia Absolute neutrophil First Withhold therapy; when count (ANC) <1000/mm3 ANC improves to baseline or >=1000/mm3, resume therapy at same dosage Second or third Withhold therapy; when ANC improves to baseline or >=1000/mm3, resume therapy at a reduced dosage Fourth Permanently discontinue therapy Thrombocytopenia Platelet count First or second Withhold therapy; when <50,000/mm3 platelet count improves to baseline or >=75,000/mm3, resume therapy at a reduced dosage Third Permanently discontinue therapy Anemia Hemoglobin concentration Any Withhold therapy; when <8 g/dL anemia improves to grade 1 or less or to baseline, resume therapy at same or reduced dosage Other Toxicity Grade 3 First or second Withhold therapy; when toxicity improves to grade 1 or less or to baseline, resume therapy at a reduced dosage Third Permanently discontinue therapy Grade 4 First Withhold therapy; when toxicity improves to grade 1 or less or to baseline, resume therapy at a reduced dosage Second Permanently discontinue therapy

Tazemetostat is administered orally twice daily without regard to meals. The tablets should be swallowed whole; they should not be cut, chewed, or crushed.

If a dose of tazemetostat is missed or vomited after administration, an additional dose should not be administered to replace the missed or vomited dose. The next dose should be administered at the next scheduled time.

Tazemetostat tablets should not be stored above 30degreesC.

No dosing information is available for this tab.

No dosing information is available for this tab.

Tazemetostat is metabolized principally by cytochrome P-450 (CYP) isoenzyme 3A.

In vitro, tazemetostat does not inhibit CYP isoenzymes 1A2, 2B6, 2C9, or 2D6 at clinically relevant concentrations.

In vitro studies also suggest that tazemetostat is a substrate of P-glycoprotein (P-gp), but is not a substrate of breast cancer resistance protein (BCRP), organic cation transporter (OCT) 2, organic anion transporter (OAT) 3, multidrug and toxin extrusion (MATE) transporter 1, organic anion transporting polypeptide (OATP) 1B1, and OATP1B3.

In vitro, tazemetostat inhibits MATE1 and MATE2K, but does not inhibit P-gp, BCRP, OATP1B1, OATP1B3, OCT1, OCT2, OAT1, OAT3, or bile salt export pump (BSEP) at clinically relevant concentrations.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*None.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

Adverse effects reported in 20% or more of patients receiving tazemetostat for the treatment of epithelioid sarcoma include pain, fatigue, nausea, decreased appetite, vomiting, and constipation. Grade 3 or 4 laboratory abnormalities reported in 10% or more of patients receiving tazemetostat include anemia and lymphocytopenia.

Adverse effects reported in 20% or more of patients receiving tazemetostat for the treatment of follicular lymphoma include fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain. Grade 3 or 4 laboratory abnormalities reported in 5% or more of patients receiving tazemetostat include lymphocytopenia, hyperglycemia, leukopenia, neutropenia, thrombocytopenia, and anemia.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

Safety and efficacy of tazemetostat have not been established in adolescents younger than 16 years of age.

Safety and efficacy of tazemetostat for the treatment of metastatic or locally advanced epithelioid sarcoma in adolescents 16 years of age or older have been established in clinical studies evaluating tazemetostat in adults and 3 adolescent patients 16 years of age.

T-LBL, weight gain, and distended testicles have been observed in immature rats receiving tazemetostat from postnatal day 7-97 at exposure levels approximately equal to the adult human exposure at the recommended dosage, and increased trabecular bone was observed at exposure levels approximately 10 times the adult human exposure at the recommended dosage.

Tazemetostat may cause fetal harm if administered to pregnant women based on animal findings.

It is not known whether tazemetostat is distributed into human milk or if the drug has any effect on milk production or the nursing infant. Because of the potential for serious adverse reactions to tazemetostat in nursing infants, women should be advised to discontinue nursing during tazemetostat therapy and for 1 week after the last dose.

The manufacturer makes no specific dosage recommendations for geriatric patients.

Experience with tazemetostat in patients 65 years of age or older with epithelioid sarcoma or follicular lymphoma is insufficient to determine whether geriatric patients respond differently than younger individuals.