Tazemetostat

Reviewed on 9/17/2021

What Is Tazemetostat Used For and How Does it Work?

Tazemetostat is used for metastatic or locally advanced epithelioid sarcoma not eligible for complete resection.

Tazemetostat is available under the following different brand names: Tazverik.

What Are the Dosages of Tazemetostat?

Dosages of Tazemetostat:

Dosage Forms and Strengths

Tablet

  • 200 mg

Dosage Considerations – Should be Given as Follows:

Epithelial Sarcoma

  • Indicated for metastatic or locally advanced epithelioid sarcoma not eligible for complete resection
  • Adults and children 16 years and older: 800 mg orally twice daily; continue until disease progression or unacceptable toxicity
  • Children under 16 years: Safety and efficacy not established

Dosage Modifications

Dose reduction schedule

  • First reduction: 600 mg orally twice daily
  • Second reduction: 400 mg orally twice daily
  • Permanently discontinue if unable to tolerate 400 mg twice daily

Neutropenia

  • Neutrophil count less than 1 x 109/L: Withhold until neutrophil count 1 x 109/L or greater or baseline
  • First occurrence: Resume at the same dose
  • Second and third occurrences: Resume at reduced dose
  • Permanently discontinue after the fourth occurrence

Thrombocytopenia

  • Platelet count less than 50 x 109/L: Withhold until platelet count 75 x 109/L or greater or baseline
  • First and second occurrences: Resume at reduced dose
  • Permanently discontinue after the third occurrence

Anemia

  • Hemoglobin less than 8 g/dL: Withhold until improvement to at least Grade 1 or baseline, then resume at same or reduced dose

Other adverse reactions

  • Grade 3
    • withhold until improvement to at least Grade 1 or baseline
    • First and second occurrences: Resume at reduced dose
    • Permanently discontinue after the third occurrence
  • Grade 4
    • Withhold until improvement to at least Grade 1 or baseline
    • First and second occurrences: Resume at reduced dose
    • Permanently discontinue after the second occurrence

Coadministration with CYP3A inhibitors

  • Strong CYP3A inhibitors: Avoid use
  • Moderate CYP3A inhibitors
    • Avoid use; if coadministration with a moderate CYP3A inhibitor cannot be avoided, reduce the dose
    • Current dose 800 mg twice daily: Reduce to 400 mg twice daily
    • Current dose 600 mg twice daily: Reduce to 400 mg for the first dose and 200 mg for the second dose
    • Current dose 400 mg twice daily: Reduce to 200 mg twice daily
    • After discontinuation of the moderate CYP3A inhibitor for 3 elimination half-lives, resume the tazemetostat dose that was taken before initiating the inhibitor

Renal impairment

Hepatic impairment

  • Mild (total bilirubin greater than 1-1.5 times ULN or AST greater than ULN): No dosage adjustment is necessary
  • Moderate-to-severe (total bilirubin greater than 1.5 times ULN): Not studied

SLIDESHOW

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What Are Side Effects Associated with Using Tazemetostat?

Common side effects of tazemetostat include:

  • Pain
  • Decreased hemoglobin
  • Fatigue
  • Decreased lymphocytes
  • Increased triglycerides
  • Nausea
  • Increased glucose
  • Decreased sodium
  • Decreased phosphate
  • Decreased appetite
  • Vomiting
  • Decreased albumin
  • Increased alkaline phosphatase
  • Increased AST
  • Decreased potassium
  • Constipation
  • Decreased white blood cell count
  • Cough
  • Hemorrhage
  • Headache
  • Decreased calcium
  • Anemia
  • Weight loss
  • Decreased glucose
  • Shortness of breath
  • Diarrhea
  • Increased partial thromboplastin time
  • Increased ALT
  • Abdominal pain
  • Increased creatinine
  • Increased potassium

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

What Other Drugs Interact with Tazemetostat?

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

  • Tazemetostat has no listed severe interactions with other drugs.
  • Tazemetostat has serious interactions with at least 91 different drugs.
  • Tazemetostat has moderate interactions with at least 392 different drugs.
  • Tazemetostat has no listed mild interactions with other drugs.

What Are Warnings and Precautions for Tazemetostat?

Warnings

  • This medication contains tazemetostat. Do not take Tazverik if you are allergic to tazemetostat or any ingredients contained in this drug.

Contraindications

  • None

Effects of Drug Abuse

  • No information is available.

Short-Term Effects

  • See "What Are Side Effects Associated with Using Tazemetostat?"

Long-Term Effects

  • See "What Are Side Effects Associated with Using Tazemetostat?"

Cautions

  • May increase the risk of developing secondary malignancies, including T-cell lymphoblastic lymphoma, myelodysplastic syndrome, and acute myeloid leukemia
  • Can cause fetal harm; advise patients of the potential risk to a fetus and to use effective nonhormonal contraception

Drug interaction overview

Tazemetostat is a CYP3A4 substrate and CYP3A4 inducer

  • Strong and moderate CYP3A inhibitors
    • Avoid coadministration
    • Coadministration increases tazemetostat plasma concentrations, which may increase the frequency or severity of adverse reactions
    • If unable to avoid coadministration with moderate CYP3A inhibitors, modify tazemetostat dose
  • Strong and moderate CYP3A inducers
    • Avoid coadministration
    • Coadministration with a strong or moderate CYP3A inducer may decrease tazemetostat plasma concentrations, which may decrease the efficacy of tazemetostat
  • CYP3A substrates
    • Coadministration with CYP3A substrates, including hormonal contraceptives, can result in decreased concentrations and reduced efficacy of CYP3A substrates

Pregnancy and Lactation

  • Based on findings from animal studies and its mechanism of action, fetal harm may occur when tazemetostat is administered to pregnant women. There are no data available on tazemetostat use in pregnant women to inform a drug-associated risk. Pregnant women should be advised of the potential risk to a fetus. The pregnancy status of females of reproductive potential should be verified before the use of tazemetostat.
  • Females of reproductive potential are advised to use effective nonhormonal contraception during treatment and for 6 months after the final dose; tazemetostat may render some hormonal contraceptives ineffective. Males with female partners of reproductive potential are advised to use effective contraception during treatment and for at least 3 months after the final dose.
  • There is no animal or human data on the presence of tazemetostat in human milk or on its effects on the breastfed child or milk production. Owing to the potential risk for serious adverse reactions from tazemetostat in the breastfed child, women are advised not to breastfeed during treatment with tazemetostat and for 1 week after the final dose.
References
https://reference.medscape.com/drug/tazverik-tazemetostat-1000089#3

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