Lucius Version of Tazemetostat: Dosage and Administration, Indications, Precautions

Lucius Version of Tazemetostat: Dosage and Administration, Indications, Precautions

Indications

Tazemetostat is a methyltransferase inhibitor indicated for the treatment of:

Adult and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma who are not eligible for complete resection.

Adult patients with relapsed or refractory follicular lymphoma that is positive for EZH2 mutations (detected by an FDA-approved test) and who have received at least 2 lines of systemic therapy.

Adult patients with relapsed or refractory follicular lymphoma for whom no satisfactory alternative treatment options are available.

Dosage and Administration

The recommended dosage is 800 mg orally twice daily, which can be taken with or without food.

Use in Specific Populations

1. Pregnancy

Based on findings from animal studies and its mechanism of action, tazemetostat can cause fetal harm when administered to pregnant women. There are no available data on the use of tazemetostat in pregnant women to inform drug-related risks. Administration of tazemetostat to pregnant rats and rabbits during organogenesis resulted in a dose-dependent increase in skeletal developmental abnormalities in both species, starting at a maternal exposure [AUC₀₋₄₅h] approximately 1.5 times the exposure in adults receiving 800 mg twice daily. Inform pregnant women of the potential risk to the fetus.

2. Lactation

There are no animal or human data regarding the presence of tazemetostat in human milk, or its effects on breastfed children or milk production. Due to the potential risk of serious adverse reactions in breastfed children, women are advised not to breastfeed during treatment with tazemetostat and for one week after the last dose.

3. Males and Females of Reproductive Potential

Pregnancy Testing

Verify the pregnancy status of females of reproductive potential prior to initiating tazemetostat.

Risk Summary

Tazemetostat can cause fetal harm when administered to pregnant women.

Contraception

Females: Advise females of reproductive potential to use effective non-hormonal contraceptive methods during treatment with tazemetostat and for 6 months after the last dose. Tazemetostat may render certain hormonal contraceptives ineffective [see "Drug Interactions"].

Males: Advise males with female partners of reproductive potential to use effective contraceptive methods during treatment with tazemetostat and for at least 3 months after the last dose.

4. Pediatric Use

The safety and effectiveness of TAZVERIK (tazemetostat) have been established in pediatric patients aged 16 years and older (adolescents) with metastatic or locally advanced epithelioid sarcoma. Evidence from adequate and well-controlled studies in adults, including 3 adolescent patients aged 16 years, supports the use of tazemetostat for this indication [see "Adverse Reactions"]. The safety and effectiveness of tazemetostat in pediatric patients younger than 16 years have not been established.

Juvenile Animal Toxicity Data

In a 13-week juvenile rat toxicology study, animals were dosed daily from postnatal day 7 to day 97 (roughly equivalent to neonate to adulthood). Tazemetostat caused:

T-LBL effects at doses ≥ 50 mg/kg (approximately 2.8 times the adult exposure at 800 mg twice daily)

Increased trabecular bone at doses ≥ 100 mg/kg (approximately 10 times the adult exposure at 800 mg twice daily)

Increased body weight at doses ≥ 50 mg/kg (approximately equivalent to the adult exposure at 800 mg twice daily)

Testicular dilatation in males at doses ≥ 50 mg/kg (approximately equivalent to the adult exposure at 800 mg twice daily)

5. Geriatric Use

Clinical studies of tazemetostat did not include a sufficient number of patients aged 65 years and older with epithelioid sarcoma or relapsed or refractory follicular lymphoma to determine whether their response differs from that of younger subjects.

6. Renal Impairment

No dosage adjustment of tazemetostat is recommended for patients with mild to severe renal impairment or end-stage renal disease.

7. Hepatic Impairment

No dosage adjustment is recommended for patients with mild hepatic impairment (total bilirubin > 1 to 1.5 times the upper limit of normal [ULN] or AST > ULN). Tazemetostat 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.

Warnings and Precautions

Secondary Malignancies: Tazemetostat increases the risk of developing secondary malignancies, including T-cell lymphoblastic lymphoma, myelodysplastic syndromes, and acute myeloid leukemia. Monitor patients long-term for the development of secondary malignancies.

Embryo-Fetal Toxicity: May cause fetal harm. Advise patients of the potential risk to the fetus and to use effective non-hormonal contraception.

Drug Interactions

1. Effects of Other Drugs on Tazemetostat

a. Strong and Moderate CYP3A Inhibitors

Concomitant use of tazemetostat with a strong or moderate CYP3A inhibitor increases the plasma concentration of tazemetostat, which may increase the frequency or severity of adverse reactions. Avoid concomitant use of strong or moderate CYP3A inhibitors with tazemetostat. If concomitant use of a moderate CYP3A inhibitor cannot be avoided, reduce the dosage of tazemetostat [see "Dosage and Administration"].

b. Strong and Moderate CYP3A Inducers

Concomitant use of TAZVERIK (tazemetostat) with a strong or moderate CYP3A inducer may decrease the plasma concentration of tazemetostat, which may reduce the efficacy of tazemetostat. Avoid concomitant use of moderate and strong CYP3A inducers with tazemetostat.

2. Effects of Tazemetostat on Other Drugs

CYP3A Substrates

Concomitant use of tazemetostat with CYP3A substrates (including hormonal contraceptives) results in decreased concentrations and reduced efficacy of CYP3A substrates [see "Use in Specific Populations"].

Adverse Reactions

The most common (≥ 20%) adverse reactions in patients with epithelioid sarcoma are pain, fatigue, nausea, decreased appetite, vomiting, and constipation.

The most common (≥ 20%) adverse reactions in patients with follicular lymphoma are fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain.

Contraindications

Not yet specified.

Dosage Form

Tablets.

Storage

Store at 20°C to 25°C (68°F to 77°F); short-term transport between 15°C and 30°C (59°F and 86°F) is permitted. Protect from moisture.