Tazemetostat is an EZH2 histone methyltransferase inhibitor. It 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. Tazemetostat is also indicated for the treatment of relapsed or refractory follicular lymphoma in adult patients with EZH2 mutation-positive disease who have received at least 2 prior therapies or who have no satisfactory alternative treatment options. Monitor patients who receive tazemetostat for the development of a new primary malignancy.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Emetic Risk
-Minimal/Low
-Administer prn antiemetics as necessary.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-Tazemetostat may be taken with or without food.
-Avoid eating grapefruit or drinking grapefruit juice during treatment.
-Swallow tablets whole; do not crush, chew, or cut tablets.
-If a dose is missed or vomiting occurs after a dose, skip that dose and resume therapy at the next scheduled time.
In a pooled analysis of clinical trials (n = 758), a new primary malignancy (i.e., myelodysplastic syndrome, acute myelogenous leukemia, or B-cell acute lymphoblastic leukemia) occurred in 1.7% of adult patients who received tazemetostat. One pediatric patient developed T-cell lymphoblastic lymphoma. Monitor patients for the development of secondary malignancies long-term after tazemetostat therapy.
Pain was reported in 52% of patients (age range, 16 to 79 years) with metastatic or locally advanced epithelioid sarcoma who received tazemetostat (n = 62) in a clinical trial; grade 3 or 4 pain occurred in 7% of these patients. The term pain included tumor/cancer pain, extremity pain, noncardiac chest pain, flank pain, back pain, arthralgia, bone pain, musculoskeletal pain, myalgia, and neck pain. In pooled results from 2 single-arm cohorts (n = 99) of a clinical study, musculoskeletal pain occurred in 22% (grade 3 or 4, 1%) of adult patients with relapsed or refractory follicular lymphoma who received tazemetostat. The term musculoskeletal pain included back pain, limb discomfort, musculoskeletal/non-cardiac chest pain, musculoskeletal discomfort, myalgia, neck pain, extremity pain, jaw pain, and spinal pain.
Fatigue/asthenia was reported in 47% of patients (age range, 16 to 79 years) with metastatic or locally advanced epithelioid sarcoma who received tazemetostat (n = 62) in a clinical trial; grade 3 or 4 fatigue/asthenia occurred in 1.6% of these patients. In pooled results from 2 single-arm cohorts (n = 99) of a clinical study, fatigue/asthenia occurred in 36% (grade 3 or 4, 5%) of adult patients with relapsed or refractory follicular lymphoma who received tazemetostat.
Gastrointestinal adverse events including nausea (36%), decreased appetite/anorexia (26%; grade 3 or 4, 4.8%), vomiting (24%), constipation (21%), diarrhea (16%), and abdominal pain (13%; grade 3 or 4, 1.6%) were reported in patients (age range, 16 to 79 years) with metastatic or locally advanced epithelioid sarcoma who received tazemetostat (n = 62) in a clinical trial. In pooled results from 2 single-arm cohorts (n = 99) of a clinical study, nausea (24%; grade 3 or 4, 1%), abdominal pain (20%; grade 3 or 4, 3%), diarrhea (18%), and vomiting (12%; grade 3 or 4, 1%) occurred in adult patients with relapsed or refractory follicular lymphoma who received tazemetostat.
Bleeding (18%; grade 3 or 4, 4.8%) and prolonged bleeding time (i.e., increased partial thromboplastin time (PTT) levels) (15%; grade 3 or 4, 5%) were reported in patients (age range, 16 to 79 years) with metastatic or locally advanced epithelioid sarcoma who received tazemetostat (n = 62) in a clinical trial. The term bleeding included rectal hemorrhage, pulmonary hemorrhage, intracranial bleeding, cerebral hemorrhage, and hemoptysis.
Weight loss was reported in 16% of patients (age range, 16 to 79 years) with metastatic or locally advanced epithelioid sarcoma who received tazemetostat (n = 62) in a clinical trial; grade 3 or 4 weight loss occurred in 7% of these patients.
Headache was reported in 18% of patients (age range, 16 to 79 years) with metastatic or locally advanced epithelioid sarcoma who received tazemetostat (n = 62) in a clinical trial. In pooled results from 2 single-arm cohorts (n = 99) of a clinical study, headache was reported in 13% of adult patients with relapsed or refractory follicular lymphoma who received tazemetostat. The term headache included migraine.
Respiratory adverse events including cough (18%) and dyspnea (16%; grade 3 or 4, 4.8%) were reported in patients (age range, 16 to 79 years) with metastatic or locally advanced epithelioid sarcoma who received tazemetostat (n = 62) in a clinical trial. Additionally, pleural effusion and respiratory distress were reported in 3% or more patients in this trial. In pooled results from 2 single-arm cohorts (n = 99) of a clinical study, cough was reported in 17% of adult patients with relapsed or refractory follicular lymphoma who received tazemetostat.
Increased triglyceride level/hypertriglyceridemia was worsened from baseline in 36% of patients (age range, 16 to 79 years) with metastatic or locally advanced epithelioid sarcoma who received tazemetostat (n = 62) in a clinical trial; grade 3 or 4 hypertriglyceridemia occurred in 3.3% of these patients.
Increased glucose levels/hyperglycemia (33%; grade 3 or 4, 1.6%) and decreased glucose levels/hypoglycemia (16%) were worsened from baseline in patients (age range, 16 to 79 years) with metastatic or locally advanced epithelioid sarcoma who received tazemetostat (n = 62) in a clinical trial. In pooled results from 2 single-arm cohorts (n = 99) of a clinical study, hyperglycemia was worsened from baseline in 53% (grade 3 or 4, 10%) of adult patients with relapsed or refractory follicular lymphoma who received tazemetostat.
Decreased sodium levels/hyponatremia (30%; grade 3 or 4, 1.7%), decreased phosphate levels/hypophosphatemia (28%; grade 3 or 4, 1.7%), decreased potassium levels/hypokalemia (20%; grade 3 or 4, 1.7%), decreased calcium levels/hypocalcemia (16%), and increased potassium levels/hyperkalemia (12%) were worsened from baseline in patients (age range, 16 to 79 years) with metastatic or locally advanced epithelioid sarcoma who received tazemetostat (n = 62) in a clinical trial.
Elevated hepatic enzymes including increased AST levels (18%; grade 3 or 4, 3.5%), increased ALT levels (14%; grade 3 or 4, 3.4%), and increased alkaline phosphatase levels (23%; grade 3 or 4, 1.7%) and decreased albumin levels/hypoalbuminemia (23%) were worsened from baseline in patients (age range, 16 to 79 years) with metastatic or locally advanced epithelioid sarcoma who received tazemetostat (n = 62) in a clinical trial. In pooled results from 2 single-arm cohorts (n = 99) of a clinical study, increased AST (24%), ALT (21%; grade 3 or 4, 2.3%), and alkaline phosphatase (18%; grade 3 or 4, 1%) levels were worsened from baseline in adult patients with relapsed or refractory follicular lymphoma who received tazemetostat.
Nephrotoxicity, specifically increased serum creatinine level, was worsened from baseline in 12% of patients (age range, 16 to 79 years) with metastatic or locally advanced epithelioid sarcoma who received tazemetostat (n = 62) in a clinical trial. In pooled results from 2 single-arm cohorts (n = 99) of a clinical study, increased serum creatinine level was worsened from baseline in 17% of adult patients with relapsed or refractory follicular lymphoma who received tazemetostat.
Myelosuppression has been reported with tazemetostat therapy. Monitor complete blood counts prior to and periodically during therapy. Interruption of therapy, a dose reduction, or permanent discontinuation of therapy may be necessary in patients who develop severe hematologic toxicity. Decreased hemoglobin levels/anemia (49%; grade 3 or 4, 15%), decreased lymphocyte levels/lymphopenia (36%; grade 3 or 4, 13%), and decreased white blood cell (WBC) count/leukopenia (19%) were worsened from baseline in patients with metastatic or locally advanced epithelioid sarcoma who received tazemetostat (n = 62) in a clinical trial. In pooled results from 2 single-arm cohorts (n = 99) of a clinical study, lymphopenia (57%; grade 3 or 4, 18%), anemia (50%; grade 3 or 4, 8%), decreased platelet count/thrombocytopenia (50%; grade 3 or 4, 7%), decreased WBC count/leukopenia (41%; grade 3 or 4, 9%), and decreased neutrophil count/neutropenia (20%; grade 3 or 4, 7%) were worsened from baseline in adult patients with relapsed or refractory follicular lymphoma.
Skin infection was reported in 3% or more of patients (age range, 16 to 79 years) with metastatic or locally advanced epithelioid sarcoma who received tazemetostat (n = 62) in a clinical trial. In pooled results from 2 single-arm cohorts (n = 99) of a clinical study, upper respiratory tract infection (30%), lower respiratory tract infection (17%), urinary tract infection (11%; grade 3 or 4, 2%), sepsis (2%), pneumonia (2%), and herpes zoster (2%) occurred in adult patients with relapsed or refractory follicular lymphoma who received tazemetostat. The upper respiratory tract infection term included laryngitis, nasopharyngitis, pharyngitis, rhinitis, and sinusitis; the lower respiratory tract infection term included bronchitis and tracheobronchitis; and the urinary tract infection term included cystitis.
Fever occurred in 10% of adult patients with relapsed or refractory follicular lymphoma who received tazemetostat in pooled results from 2 single-arm cohorts (n = 99) of a clinical study.
In pooled results from 2 single-arm cohorts (n = 99) of a clinical study, alopecia (17%) and rash (15%) occurred in adult patients with relapsed or refractory follicular lymphoma who received tazemetostat. The term rash included erythema, erythematous rash, maculopapular rash, pruritic rash, pustular rash, and skin exfoliation.
Tazemetostat may increase the risk of developing a new primary malignancy (e.g., myelodysplastic syndrome, acute myelogenous leukemia, B-cell acute lymphoblastic leukemia, T-cell lymphoblastic lymphoma). Monitor patients for the development of secondary malignancies during and long-term after tazemetostat therapy.
Myelosuppression (e.g., anemia, neutropenia, and thrombocytopenia) may occur with tazemetostat therapy. Monitor complete blood counts prior to and periodically during therapy. Interruption of therapy, a dose reduction, or permanent discontinuation of therapy may be necessary in patients who develop severe hematologic toxicity.
Tazemetostat may cause fetal harm when administered to a pregnant woman, based on its mechanism of action and findings from animal studies. Advise females of reproductive potential to avoid pregnancy during tazemetostat therapy. Discuss the potential hazard to the fetus if tazemetostat is used during pregnancy. Embryo-fetal toxicities including skeletal malformations and variations were observed when tazemetostat was administered to pregnant rabbits and rats during organogenesis at doses resulting in exposures of approximately 1.5-times and 2-times the exposure in humans (at the recommended dose).
Counsel patients about the reproductive risk and contraception requirements during tazemetostat treatment. Pregnancy testing prior to starting tazemetostat therapy is recommended for females of reproductive potential. These patients should avoid pregnancy and use effective non-hormonal contraception during therapy and for 6 months after the last tazemetostat dose. Discuss the potential hazard to the fetus if a patient becomes pregnant while taking tazemetostat. Concomitant use of tazemetostat and hormonal contraceptives may decrease the effectiveness of hormonal contraceptives. Due to the risk of male-mediated teratogenicity, men with female partners of reproductive potential should use effective contraception during and for 3 months after the last tazemetostat dose.
It is not known if tazemetostat is secreted in human milk or if it has effects on the breast-fed infant or on milk production. Because there is a potential for adverse reactions in a nursing child from tazemetostat, women should discontinue breast-feeding during tazemetostat therapy and for 1 week after the last dose.
For the treatment of soft-tissue sarcoma (STS):
NOTE: Tazemetostat is designated as an orphan drug by the FDA for this indication.
-for the treatment of metastatic or locally advanced epithelioid STS in patients not eligible for complete resection:
Oral dosage:
Adults: 800 mg orally twice daily until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Interruption of therapy, a dose reduction, or permanent discontinuation of therapy may be necessary in patients who develop severe toxicity. The overall response rate was 15% (complete response rate, 1.6%) in patients (median age, 34 years; range, 16 to 79 years) with histologically confirmed, metastatic or locally advanced epithelioid sarcoma who received tazemetostat in an open-label, single-arm cohort (n = 62) of a multi-center trial (EZH-202 trial). At a median follow-up of 13.8 months, the median time to response was 3.9 months and the median duration of response had not been reached. Additionally, the median progression-free survival and overall survival times were 5.5 and 19 months, respectively. In this trial, 77% of patients had received prior surgery and 61% of patients had received prior systemic chemotherapy(median lines of prior therapy, 1; range, 0 to 2).
Adolescents 16 years and older: 800 mg orally twice daily until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Interruption of therapy, a dose reduction, or permanent discontinuation of therapy may be necessary in patients who develop severe toxicity. The efficacy of tazemetostat in pediatric patients aged 16 years and older with advanced epithelioid sarcoma is supported by evidence from well-controlled adult studies including studies that included 3 adolescent patients who were 16 years of age.
For the treatment of non-Hodgkin's lymphoma (NHL):
NOTE: Tazemetostat has been designated an orphan drug by the FDA for the treatment of follicular lymphoma.
-for the treatment of relapsed or refractory EZH2 mutation-positive follicular lymphoma in patients who have received at least 2 prior systemic therapies:
NOTE: Evaluate patients for the presence of EZH2 mutation of codons Y646, A682, or A692 as detected by an FDA-approved test (www.fda.gov/CompanionDiagnostics).
Oral dosage:
Adults: 800 mg orally twice daily until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Interruption of therapy, a dose reduction, or permanent discontinuation of therapy may be necessary in patients who develop severe toxicity. Tazemetostat was evaluated in relapsed or refractory follicular lymphoma patients (age range, 36 to 87 years) who had previously received 2 or more prior systemic therapies in a multicenter (E7438-G000-101) trial (n = 99). At a median follow-up of 22 months (range, 3 to 44 months), the overall response rate was 69% (95% CI, 53% to 82%) in patients with EZH2 mutation-positive follicular lymphoma (n = 45; median of 2 prior therapies; range, 1 to 11 therapies). In responding patients with EZH2 mutation-positive disease, the median time to response was 3.7 months (range, 1.6 to 10.9 months) and the median duration of response was 10.9 months (range, 0 to more than 22.1 months). The median progression-free survival time was 13.8 months and the median overall survival time had not been reached.
-for the treatment of relapsed or refractory follicular lymphoma in patients who have no satisfactory alternative treatment options:
Oral dosage:
Adults: 800 mg orally twice daily until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Interruption of therapy, a dose reduction, or permanent discontinuation of therapy may be necessary in patients who develop severe toxicity. Tazemetostat was evaluated in relapsed or refractory follicular lymphoma patients (age range, 36 to 87 years) who had previously received 2 or more prior systemic therapies in a multicenter (E7438-G000-101) trial (n = 99). The overall response rates were 69% (95% CI, 53% to 82%) and 35% (95% CI, 23% to 49%) in patients with EZH2 mutation-positive (n = 45; median of 2 prior therapies) and wild-type (n = 54; median of 3 prior therapies) relapsed or refractory follicular lymphoma, respectively. The time to response was 3.7 months in both cohorts; the median durations of response were 10.9 months and 13 months in the EZH2 mutation-positive and wild-type follicular lymphoma arms, respectively. The median progression-free survival time was 13.8 months in the EZH2 mutation-positive arm and 11.1 months in the EZH2 wild-type arm; the median overall survival time had not been reached in either arm.
Therapeutic Drug Monitoring:
Management of Treatment-Related Toxicity
Recommended Dose Reductions
First dose reduction: 600 mg PO twice daily.
Second dose reduction: 400 mg PO twice daily; permanently discontinue therapy in patients unable to tolerate 400 mg PO twice daily.
Hematologic Adverse Reactions
Neutropenia (neutrophil count less than 1 x 109 cells/L)
First occurrence: Hold tazemetostat until the neutrophil count is 1 x 109 cells/L or greater or at baseline; resume therapy at the same dose.
Second and third occurrence: Hold tazemetostat until the neutrophil count is 1 x 109 cells/L or greater or at baseline; resume therapy at a reduced dose.
Fourth occurrence: Permanently discontinue therapy.
Thrombocytopenia (platelet count less than 50 x 109 cells/L)
First and second occurrence: Hold tazemetostat until the platelet count is 75 x 109 cells/L or greater or at baseline; resume therapy at a reduced dose.
Third occurrence: Permanently discontinue therapy.
Anemia (hemoglobin level less than 8 g/dL)
Hold tazemetostat until anemia improves to grade 1 or less or to baseline; resume therapy at the same or a reduced dose.
Other Adverse Reactions
Grade 3 toxicity: Hold tazemetostat until toxicity improves to grade 1 or less or to baseline. For first or second occurrence, resume therapy at a reduced dose. Permanently discontinue therapy after the third occurrence.
Grade 4 toxicity: Hold tazemetostat until toxicity improves to grade 1 or less or to baseline. For the first occurrence, resume therapy at a reduced dose. Permanently discontinue therapy after the second occurrence.
Maximum Dosage Limits:
-Adults
1,600 mg/day PO.
-Geriatric
1,600 mg/day PO.
-Adolescents
16 years and older: 1,600 mg/day PO.
Less than 16 years: Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No tazemetostat dosage adjustments are necessary in patients with baseline mild hepatic impairment (total bilirubin level of greater than 1 to 1.5 times the upper limit of normal (ULN) or AST level greater than ULN). Tazemetostat has not been evaluated in patients with baseline moderate (total bilirubin level greater than 1.5 to 3 times the ULN) or severe (total bilirubin level greater than 3 times the ULN) hepatic impairment.
Patients with Renal Impairment Dosing
No tazemetostat dosage adjustments are necessary in patients with baseline renal impairment or end-stage renal disease.
*non-FDA-approved indication
Acetaminophen; Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with tazemetostat is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If tazemetostat is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Tazemetostat is a weak CYP3A4 inducer. Concomitant use with tazemetostat can increase norcodeine levels via increased CYP3A4 metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Acetaminophen; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with tazemetostat is necessary; consider increasing the dose of hydrocodone as needed. If tazemetostat is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and tazemetostat is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Adagrasib: (Major) Avoid coadministration of tazemetostat with adagrasib as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor increased tazemetostat exposure by 3.1-fold.
Alfentanil: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with tazemetostat is necessary. If tazemetostat is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak CYP3A4 inducer like tazemetostat with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Amobarbital: (Major) Avoid coadministration of tazemetostat with amobarbital as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and amobarbital is a moderate CYP3A4 inducer.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of tazemetostat with clarithromycin as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Apalutamide: (Major) Avoid coadministration of tazemetostat with apalutamide as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer.
Aprepitant, Fosaprepitant: (Major) Avoid coadministration of tazemetostat with a multi-day regimen of aprepitant, fosaprepitant as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If aprepitant, fosaprepitant is discontinued, wait at least 3 half-lives of aprepitant, fosaprepitant before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor. Single oral and IV doses have not been shown to alter concentrations of CYP3A4 substrates Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Aspirin, ASA; Butalbital; Caffeine: (Major) Avoid coadministration of tazemetostat with butalbarbital as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and butalbarbital is a moderate CYP3A4 inducer.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with tazemetostat is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If tazemetostat is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Tazemetostat is a weak CYP3A4 inducer. Concomitant use with tazemetostat can increase norcodeine levels via increased CYP3A4 metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Atazanavir: (Major) Avoid coadministration of tazemetostat with atazanavir as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Atazanavir; Cobicistat: (Major) Avoid coadministration of tazemetostat with atazanavir as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold. (Major) Avoid coadministration of tazemetostat with cobicistat as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Atogepant: (Major) Avoid use of atogepant and tazemostat when atogepant is used for chronic migraine. Use an atogepant dose of 30 or 60 mg PO once daily for episodic migraine if coadministered with tazemostat. Concurrent use may decrease atogepant exposure and reduce efficacy. Atogepant is a CYP3A substrate and tazemostat is a weak CYP3A inducer. Coadministration with a weak CYP3A inducer resulted in a 25% reduction in atogepant overall exposure and a 24% reduction in atogepant peak concentration.
Berotralstat: (Major) Avoid coadministration of tazemetostat with berotralstat as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If berotralstat is discontinued, wait at least 3 half-lives of berotralstat before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and berotralstat is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Bexarotene: (Major) Avoid coadministration of tazemetostat with bexarotene as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer.
Bosentan: (Major) Avoid coadministration of tazemetostat with bosentan as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and bosentan is a moderate CYP3A4 inducer.
Butalbital; Acetaminophen: (Major) Avoid coadministration of tazemetostat with butalbarbital as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and butalbarbital is a moderate CYP3A4 inducer.
Butalbital; Acetaminophen; Caffeine: (Major) Avoid coadministration of tazemetostat with butalbarbital as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and butalbarbital is a moderate CYP3A4 inducer.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid coadministration of tazemetostat with butalbarbital as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and butalbarbital is a moderate CYP3A4 inducer. (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with tazemetostat is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If tazemetostat is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Tazemetostat is a weak CYP3A4 inducer. Concomitant use with tazemetostat can increase norcodeine levels via increased CYP3A4 metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Avoid coadministration of tazemetostat with butalbarbital as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and butalbarbital is a moderate CYP3A4 inducer. (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with tazemetostat is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If tazemetostat is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Tazemetostat is a weak CYP3A4 inducer. Concomitant use with tazemetostat can increase norcodeine levels via increased CYP3A4 metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Carbamazepine: (Major) Avoid coadministration of tazemetostat with carbamazepine as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
Cariprazine: (Major) Coadministration of cariprazine with tazemetostat is not recommended as the net effect of CYP3A4 induction on cariprazine and its metabolites is unclear. Cariprazine is a CYP3A4 substrate and tazemetostat is a weak CYP3A4 inducer. Coadministration of cariprazine with CYP3A4 inducers has not been evaluated.
Celecoxib; Tramadol: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with tazemetostat is necessary; consider increasing the dose of tramadol as needed. If tazemetostat is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A4 substrate and tazemetostat is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Cenobamate: (Major) Avoid coadministration of tazemetostat with cenobamate as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and cenobamate is a moderate CYP3A4 inducer.
Ceritinib: (Major) Avoid coadministration of tazemetostat with ceritinib as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Chloramphenicol: (Major) Avoid coadministration of tazemetostat with chloramphenicol as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Chlorpheniramine; Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with tazemetostat is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If tazemetostat is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Tazemetostat is a weak CYP3A4 inducer. Concomitant use with tazemetostat can increase norcodeine levels via increased CYP3A4 metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Chlorpheniramine; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with tazemetostat is necessary; consider increasing the dose of hydrocodone as needed. If tazemetostat is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and tazemetostat is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Ciprofloxacin: (Major) Avoid coadministration of tazemetostat with ciprofloxacin as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If ciprofloxacin is discontinued, wait at least 3 half-lives of ciprofloxacin before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and ciprofloxacin is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Clarithromycin: (Major) Avoid coadministration of tazemetostat with clarithromycin as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Cobicistat: (Major) Avoid coadministration of tazemetostat with cobicistat as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with tazemetostat is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If tazemetostat is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Tazemetostat is a weak CYP3A4 inducer. Concomitant use with tazemetostat can increase norcodeine levels via increased CYP3A4 metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Codeine; Guaifenesin: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with tazemetostat is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If tazemetostat is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Tazemetostat is a weak CYP3A4 inducer. Concomitant use with tazemetostat can increase norcodeine levels via increased CYP3A4 metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with tazemetostat is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If tazemetostat is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Tazemetostat is a weak CYP3A4 inducer. Concomitant use with tazemetostat can increase norcodeine levels via increased CYP3A4 metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Codeine; Phenylephrine; Promethazine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with tazemetostat is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If tazemetostat is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Tazemetostat is a weak CYP3A4 inducer. Concomitant use with tazemetostat can increase norcodeine levels via increased CYP3A4 metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Codeine; Promethazine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with tazemetostat is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If tazemetostat is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Tazemetostat is a weak CYP3A4 inducer. Concomitant use with tazemetostat can increase norcodeine levels via increased CYP3A4 metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Conivaptan: (Major) Avoid coadministration of tazemetostat with conivaptan as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If conivaptan is discontinued, wait at least 3 half-lives of conivaptan before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased tazemetostat exposure by 3.1-fold.
Conjugated Estrogens: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination.
Conjugated Estrogens; Bazedoxifene: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination.
Conjugated Estrogens; Medroxyprogesterone: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Crizotinib: (Major) Avoid coadministration of tazemetostat with crizotinib as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If crizotinib is discontinued, wait at least 3 half-lives of crizotinib before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and crizotinib is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Cyclosporine: (Major) Avoid coadministration of tazemetostat with cyclosporine as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Additionally, concurrent use may decrease cyclosporine exposure resulting in decreased efficacy. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If cyclosporine is discontinued, wait at least 3 half-lives of cyclosporine before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and cyclosporine is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Dabrafenib: (Major) Avoid coadministration of tazemetostat with dabrafenib as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer.
Danazol: (Major) Avoid coadministration of tazemetostat with danazol as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If danazol is discontinued, wait at least 3 half-lives of danazol before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Darunavir: (Major) Avoid coadministration of tazemetostat with darunavir as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Darunavir; Cobicistat: (Major) Avoid coadministration of tazemetostat with cobicistat as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold. (Major) Avoid coadministration of tazemetostat with darunavir as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid coadministration of tazemetostat with cobicistat as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold. (Major) Avoid coadministration of tazemetostat with darunavir as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Delavirdine: (Major) Avoid coadministration of tazemetostat with delavirdine as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Desogestrel; Ethinyl Estradiol: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Dienogest; Estradiol valerate: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Diltiazem: (Major) Avoid coadministration of tazemetostat with diltiazem as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If diltiazem is discontinued, wait at least 3 half-lives of diltiazem before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and diltiazem is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Doravirine: (Minor) Concurrent administration of doravirine and tazemetostat may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; tazemetostat is a weak CYP3A4 inducer.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Minor) Concurrent administration of doravirine and tazemetostat may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; tazemetostat is a weak CYP3A4 inducer.
Dronedarone: (Major) Avoid coadministration of tazemetostat with dronedarone as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If dronedarone is discontinued, wait at least 3 half-lives of dronedarone before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and dronedarone is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Drospirenone: (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Drospirenone; Estetrol: (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Drospirenone; Estradiol: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Drospirenone; Ethinyl Estradiol: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Duvelisib: (Major) Avoid coadministration of tazemetostat with duvelisib as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If duvelisib is discontinued, wait at least 3 half-lives of duvelisib before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Efavirenz: (Major) Avoid coadministration of tazemetostat with efavirenz as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and efavirenz is a moderate CYP3A4 inducer.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of tazemetostat with efavirenz as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and efavirenz is a moderate CYP3A4 inducer.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of tazemetostat with efavirenz as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and efavirenz is a moderate CYP3A4 inducer.
Elagolix: (Major) Avoid coadministration of tazemetostat with elagolix as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer.
Elagolix; Estradiol; Norethindrone acetate: (Major) Avoid coadministration of tazemetostat with elagolix as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid coadministration of tazemetostat with cobicistat as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of tazemetostat with cobicistat as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Encorafenib: (Major) Avoid coadministration of tazemetostat with encorafenib as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A substrate and encorafenib is a strong CYP3A inducer.
Enzalutamide: (Major) Avoid coadministration of tazemetostat with enzalutamide as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer.
Erythromycin: (Major) Avoid coadministration of tazemetostat with erythromycin as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If erythromycin is discontinued, wait at least 3 half-lives of erythromycin before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Eslicarbazepine: (Major) Avoid coadministration of tazemetostat with eslicarbazepine as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer.
Esterified Estrogens: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination.
Esterified Estrogens; Methyltestosterone: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination.
Estradiol: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination.
Estradiol; Levonorgestrel: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Estradiol; Norethindrone: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Estradiol; Norgestimate: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Estradiol; Progesterone: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Estrogens affected by CYP3A inducers: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination.
Estropipate: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination.
Ethinyl Estradiol; Norelgestromin: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Ethinyl Estradiol; Norethindrone Acetate: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Ethinyl Estradiol; Norgestrel: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Ethynodiol Diacetate; Ethinyl Estradiol: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Etonogestrel: (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Etonogestrel; Ethinyl Estradiol: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Etravirine: (Major) Avoid coadministration of tazemetostat with etravirine as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer.
Fedratinib: (Major) Avoid coadministration of tazemetostat with fedratinib as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If fedratinib is discontinued, wait at least 3 half-lives of fedratinib before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and fedratinib is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Fentanyl: (Moderate) Consider an increased dose of fentanyl and monitor for evidence of opioid withdrawal if coadministration with tazemetostat is necessary. If tazemetostat is discontinued, consider reducing the fentanyl dosage and monitor for evidence of respiratory depression. Coadministration of a weak CYP3A4 inducer like tazemetostat with fentanyl, a CYP3A4 substrate, may decrease exposure to fentanyl resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to fentanyl. Fentanyl plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Fluconazole: (Major) Avoid coadministration of tazemetostat with fluconazole as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If fluconazole is discontinued, wait at least 3 half-lives of fluconazole before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and fluconazole is a moderate CYP3A4 inhibitor. Coadministration of fluconazole increased tazemetostat exposure by 3.1-fold.
Fluvoxamine: (Major) Avoid coadministration of tazemetostat with fluvoxamine as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If fluvoxamine is discontinued, wait at least 3 half-lives of fluvoxamine before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and fluvoxamine is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Fosamprenavir: (Major) Avoid coadministration of tazemetostat with fosamprenavir as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If fosamprenavir is discontinued, wait at least 3 half-lives of fosamprenavir before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased tazemetostat exposure by 3.1-fold.
Fosphenytoin: (Major) Avoid coadministration of tazemetostat with fosphenytoin as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and fosphenytoin is a strong CYP3A4 inducer.
Grapefruit juice: (Major) Advise patients to avoid coadministration of tazemetostat with grapefuit juice as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and grapefuit juice is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Homatropine; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with tazemetostat is necessary; consider increasing the dose of hydrocodone as needed. If tazemetostat is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and tazemetostat is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with tazemetostat is necessary; consider increasing the dose of hydrocodone as needed. If tazemetostat is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and tazemetostat is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Hydrocodone; Ibuprofen: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with tazemetostat is necessary; consider increasing the dose of hydrocodone as needed. If tazemetostat is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and tazemetostat is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Idelalisib: (Major) Avoid coadministration of tazemetostat with idelalisib as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Imatinib: (Major) Avoid coadministration of tazemetostat with imatinib as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If imatinib is discontinued, wait at least 3 half-lives of imatinib before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Indinavir: (Major) Avoid coadministration of tazemetostat with indinavir as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and indinavir is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Isavuconazonium: (Major) Avoid coadministration of tazemetostat with isavuconazonium as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If isavuconazonium is discontinued, wait at least 3 half-lives of isavuconazonium before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and isavuconazonium is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of tazemetostat with rifampin as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of tazemetostat with rifampin as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
Isradipine: (Minor) Monitor for decreased efficacy of isradipine if coadministration with tazemetostat is necessary. Concomitant use may decrease isradipine exposure. Isradipine is a CYP3A4 substrate and tazemetostat is a weak CYP3A4 inducer.
Itraconazole: (Major) Avoid coadministration of tazemetostat with itraconazole as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and itraconazole is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Ketoconazole: (Major) Avoid coadministration of tazemetostat with ketoconazole as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of tazemetostat with clarithromycin as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Lefamulin: (Major) Avoid coadministration of tazemetostat with oral lefamulin as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If lefamulin is discontinued, wait at least 3 half-lives of lefamulin before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Lenacapavir: (Major) Avoid coadministration of tazemetostat with lenacapavir as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If lenacapavir is discontinued, wait at least 3 half-lives of lenacapavir before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased tazemetostat exposure by 3.1-fold.
Letermovir: (Major) Avoid coadministration of tazemetostat with letermovir as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use of tazemetostat and letermovir WITHOUT cyclosporine is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If letermovir is discontinued, wait at least 3 half-lives of letermovir before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Leuprolide; Norethindrone: (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Levoketoconazole: (Major) Avoid coadministration of tazemetostat with ketoconazole as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Levonorgestrel: (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Levonorgestrel; Ethinyl Estradiol: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Lonafarnib: (Major) Avoid coadministration of tazemetostat with lonafarnib as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Lopinavir; Ritonavir: (Major) Avoid coadministration of tazemetostat with ritonavir as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Lorlatinib: (Major) Avoid coadministration of tazemetostat with lorlatinib as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and lorlatinib is a moderate CYP3A4 inducer.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of tazemetostat with lumacaftor; ivacaftor as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and lumacaftor; ivacaftor is a strong CYP3A4 inducer.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of tazemetostat with lumacaftor; ivacaftor as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and lumacaftor; ivacaftor is a strong CYP3A4 inducer.
Lumateperone: (Major) Avoid coadministration of lumateperone and tazemetostat as concurrent use may decrease lumateperone exposure which may reduce efficacy. Lumateperone is a CYP3A substrate; tazemetostat is a weak CYP3A inducer.
Mavacamten: (Major) Avoid coadministration of tazemetostat with mavacamten as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Medroxyprogesterone: (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Mefloquine: (Moderate) Use mefloquine with caution if coadministration with tazemetostat is necessary as concurrent use may decrease mefloquine exposure and efficacy. Mefloquine is a CYP3A4 substrate and tazemetostat is a weak CYP3A4 inducer.
Methadone: (Moderate) Monitor for reduced efficacy of methadone and signs of opioid withdrawal if coadministration with tazemetostat is necessary. Consider increasing the dose of methadone as needed. If tazemetostat is discontinued, consider a dose reduction of methadone and frequently monitor for signs of respiratory depression and sedation. Methadone is a substrate of CYP3A4; tazemetostat is a weak CYP3A4 inducer. Concomitant use can decrease methadone exposure resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Methohexital: (Major) Avoid coadministration of tazemetostat with methohexital as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and methohexital is a moderate CYP3A4 inducer.
Midazolam: (Moderate) Monitor for reduced efficacy of midazolam if coadministration with tazemetostat is necessary as concurrent use may decrease midazolam exposure. Midazolam is a sensitive CYP3A4 substrate; tazemetostat is a weak CYP3A4 inducer. Coadministration of tazemetostat with oral midazolam decreased midazolam exposure by 40%.
Mifepristone: (Major) Avoid coadministration of tazemetostat with mifepristone as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Mitotane: (Major) Avoid coadministration of tazemetostat with mitotane as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and mitotane is a strong CYP3A4 inducer.
Modafinil: (Major) Avoid coadministration of tazemetostat with modafinil as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and modafinil is a moderate CYP3A4 inducer.
Nafcillin: (Major) Avoid coadministration of tazemetostat with nafcillin as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and nafcillin is a moderate CYP3A4 inducer.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with tazemetostat is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and tazemetostat is a weak CYP3A4 inducer.
Nanoparticle Albumin-Bound Sirolimus: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with tazemostat. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and tazemostat is a weak CYP3A inducer.
Nefazodone: (Major) Avoid coadministration of tazemetostat with nefazodone as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and nefazodone is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Nelfinavir: (Major) Avoid coadministration of tazemetostat with nelfinavir as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and nelfinavir is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Netupitant, Fosnetupitant; Palonosetron: (Major) Avoid coadministration of tazemetostat with netupitant as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If netupitant is discontinued, wait at least 3 half-lives of netupitant before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and netupitant is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Nilotinib: (Major) Avoid coadministration of tazemetostat with nilotinib as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If nilotinib is discontinued, wait at least 3 half-lives of nilotinib before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and nilotinib is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Nimodipine: (Moderate) Monitor for decreased efficacy of nimodipine if coadministration with tazemetostat is necessary as concomitant use may decrease plasma concentrations of nimodipine. Nimodipine is a CYP3A4 substrate and tazemetostat is a weak CYP3A4 inducer.
Nirmatrelvir; Ritonavir: (Major) Avoid coadministration of tazemetostat with ritonavir as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold. (Moderate) Monitor for a diminished response to nirmatrelvir if concomitant use of tazemostat is necessary. Concomitant use of nirmatrelvir and tazemostat may reduce the therapeutic effect of nirmatrelvir. Nirmatrelvir is a CYP3A substrate and tazemostat is a weak CYP3A inducer.
Nirogacestat: (Major) Avoid coadministration of tazemetostat with nirogacestat as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If nirogacestat is discontinued, wait at least 3 half-lives of nirogacestat before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A substrate and nirogacestat is a moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased tazemetostat exposure by 3.1-fold.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with tazemetostat as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and tazemetostat is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Norethindrone: (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Norethindrone; Ethinyl Estradiol: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Norgestimate; Ethinyl Estradiol: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Norgestrel: (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid coadministration of tazemetostat with rifabutin as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and rifabutin is a moderate CYP3A4 inducer.
Pexidartinib: (Major) Avoid coadministration of tazemetostat with pexidartinib as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
Phenobarbital: (Major) Avoid coadministration of tazemetostat with phenobarbital as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of tazemetostat with phenobarbital as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer.
Phenytoin: (Major) Avoid coadministration of tazemetostat with phenytoin as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and phenytoin is a strong CYP3A4 inducer.
Posaconazole: (Major) Avoid coadministration of tazemetostat with posaconazole as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Primidone: (Major) Avoid coadministration of tazemetostat with primidone as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and primidone is a strong CYP3A4 inducer.
Progesterone: (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Progestins: (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Relugolix; Estradiol; Norethindrone acetate: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Repotrectinib: (Major) Avoid coadministration of tazemetostat with repotrectinib as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A substrate and repotrectinib is a moderate CYP3A inducer.
Ribociclib: (Major) Avoid coadministration of tazemetostat with ribociclib as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Ribociclib; Letrozole: (Major) Avoid coadministration of tazemetostat with ribociclib as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Rifabutin: (Major) Avoid coadministration of tazemetostat with rifabutin as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and rifabutin is a moderate CYP3A4 inducer.
Rifampin: (Major) Avoid coadministration of tazemetostat with rifampin as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
Rifapentine: (Major) Avoid coadministration of tazemetostat with rifapentine as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Ritlecitinib: (Major) Avoid coadministration of tazemetostat with ritlecitinib as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If ritlecitinib is discontinued, wait at least 3 half-lives of ritlecitinib before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased tazemetostat exposure by 3.1-fold.
Ritonavir: (Major) Avoid coadministration of tazemetostat with ritonavir as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Saquinavir: (Major) Avoid coadministration of tazemetostat with saquinavir as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and saquinavir is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Secobarbital: (Major) Avoid coadministration of tazemetostat with secobarbital as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and secobarbital is a moderate CYP3A4 inducer.
Segesterone Acetate; Ethinyl Estradiol: (Major) Women taking both estrogens and tazemetostat should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 6 months after discontinuation of tazemetostat. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on tazemetostat, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and tazemetostat is a CYP3A4 inducer. Concurrent administration may increase estrogen elimination. (Major) Women taking both progestins and tazemetostat should report breakthrough bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed tazemetostat. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of tazemetostat. For patients on hormone replacement treatments (HRT) with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Progestins are CYP3A4 substrates and tazemetostat is a weak CYP3A4 inducer.
Sildenafil: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with tazemetostat is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A4 substrate and tazemetostat is a weak CYP3A4 inducer. Population pharmacokinetic analysis indicates an approximately 3-fold increase in sildenafil clearance with concomitant use of weak CYP3A4 inducers.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of tazemostat. Concomitant use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A substrate and tazemostat is a weak CYP3A inducer.
Sotorasib: (Major) Avoid coadministration of tazemetostat with sotorasib as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and sotorasib is a moderate CYP3A4 inducer.
St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of tazemetostat with St. John's Wort as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and St. John's Wort is a strong CYP3A4 inducer.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if tazemetostat must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with tazemetostat is necessary; consider increasing the dose of sufentanil injection as needed. If tazemetostat is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and tazemetostat is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Tacrolimus: (Moderate) Monitor tacrolimus serum concentrations as appropriate if coadministration with tazemetostat is necessary; a tacrolimus dose adjustment may be needed. Concurrent administration may decrease tacrolimus concentrations. Tacrolimus is a sensitive CYP3A4 substrate with a narrow therapeutic range; tazemetostat is a weak CYP3A4 inducer.
Tipranavir: (Major) Avoid coadministration of tazemetostat with tipranavir as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and tipranavir is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Tramadol: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with tazemetostat is necessary; consider increasing the dose of tramadol as needed. If tazemetostat is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A4 substrate and tazemetostat is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Tramadol; Acetaminophen: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with tazemetostat is necessary; consider increasing the dose of tramadol as needed. If tazemetostat is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A4 substrate and tazemetostat is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Trandolapril; Verapamil: (Major) Avoid coadministration of tazemetostat with verapamil as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If verapamil is discontinued, wait at least 3 half-lives of verapamil before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and verapamil is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Tucatinib: (Major) Avoid coadministration of tazemetostat with tucatinib as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Ubrogepant: (Major) Increase the initial and second dose of ubrogepant to 100 mg if coadministered with tazemetostat as concurrent use may decrease ubrogepant exposure and reduce its efficacy. Ubrogepant is a CYP3A4 substrate; tazemetostat is a weak CYP3A4 inducer.
Verapamil: (Major) Avoid coadministration of tazemetostat with verapamil as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If verapamil is discontinued, wait at least 3 half-lives of verapamil before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and verapamil is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of tazemetostat with clarithromycin as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Voriconazole: (Major) Avoid coadministration of tazemetostat with voriconazole as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Voxelotor: (Major) Avoid coadministration of tazemetostat with voxelotor as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If voxelotor is discontinued, wait at least 3 half-lives of voxelotor before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased tazemetostat exposure by 3.1-fold.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with tazemetostat is necessary as concurrent use may decrease the exposure of warfarin leading to reduced efficacy. Tazemetostat is a CYP3A4 inducer and the R-enantiomer of warfarin is a CYP3A4 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
Tazemetostat is an inhibitor of enhancer of zeste homolog-2 (EZH2) histone methyltransferase; it also inhibits EZH1 to a lesser extent. EZH2 is the catalytic subunit of EZH2 polycomb repressive complex 2 (PRC2); it catalyzes the trimethylation of lysine 27 of histone H3 leading to transcriptional repression of genes associated with cell cycle arrest. SWItch/Sucrose Non-Fermentable (SWI/SNF) complexes can antagonize PRC2 function in the regulation of some gene expression. Preclinical studies have shown that aberrant activation of EZH2 or loss of function mutations in the SWI/SNF complex (e.g., mutations of INI1 and SMARCA4) may occur in some tumors, including epithelioid sarcoma. In vitro, tazemetostat suppressed lymphoma B-cell proliferation; antitumor activity was also demonstrated against B-cells in mouse xenograft models.
Tazemetostat is administered orally. In vitro, it is 88% bound to human plasma proteins, with a blood-to-plasma ratio of 0.73. Following oral administration of tazemetostat, the steady-state mean apparent volume of distribution (Vd) was 1,230 L (coefficient of variance (CV), 46%), mean terminal elimination half-life was 3.1 hours (CV, 14%), and apparent total clearance was 274 L/hour (CV, 49%). Tazemetostat is metabolized via CYP3A to form the inactive metabolites M5 (EPZ-6930) and M3 (EPZ006931); M5 is also metabolized by CYP3A. Following a radiolabeled dose of tazemetostat, 79% of the dose was recovered in the feces and 15% of the dose was recovered in the urine within 12 days.
Affected cytochrome P450 isoenzymes and transporters: CYP3A
Tazemetostat is a substrate of CYP3A. Avoid the coadministration of strong or moderate CYP3A inhibitors and inducers with tazemetostat. If coadministration of moderate CYP3A inhibitors cannot be avoided, reduce the tazemetostat dose. When tazemetostat 800 mg twice daily was administered with repaglinide (a sensitive CYP2C8 substrate) and omeprazole (a sensitive CYP2C19 substrate), the repaglinide AUC(0-8h) value increased by 80% and there was no effect on the exposure of omeprazole. In vitro, tazemetostat a substrate of p-glycoprotein (P-gp) and an inhibitor of MATE1 and multidrug and toxin extrusion transporter 2-K (MATE2-K).
-Route-Specific Pharmacokinetics
Oral Route
The mean absolute bioavailability of tazemetostat is approximately 33% and the median time to peak concentration (Tmax) is 1 to 2 hours. Food consisting of a high-fat, high-calorie meal did not significantly influence tazemetostat exposure. Following tazemetostat 800 mg PO twice daily, the mean Cmax level was 829 ng/mL (coefficient of variance (CV), 56%) and the mean AUC(0-12h) value was 3,340 ng x hour/mL (CV, 49%) at steady state (achieved within 15 days). The AUC values increased proportionally over a dosage range of 200 mg to 1,600 mg twice daily. The mean accumulation ratio (using AUC) was 0.58.
-Special Populations
Hepatic Impairment
Mild hepatic impairment (total bilirubin level of greater than 1 to 1.5 times the upper limit of normal (ULN) or AST level greater than the ULN) had no clinically significant impact on the pharmacokinetic (PK) parameters of tazemetostat. It is not known if moderate or severe hepatic impairment influences the PK parameters of tazemetostat.
Renal Impairment
Any degree of renal impairment or end-stage renal disease had no clinically significant impact on the pharmacokinetic parameters of tazemetostat.
Geriatric
Age (range, 16 to 91 years) had no clinically significant impact on the pharmacokinetic parameters of tazemetostat.
Gender Differences
Gender had no clinically significant impact on the pharmacokinetic parameters of tazemetostat.
Ethnic Differences
Race (Caucasian, Black, or Asian ethnicity) had no clinically significant impact on the pharmacokinetic parameters of tazemetostat.
Obesity
Body weight (range, 37.3 kg to 173 kg) had no clinically significant impact on the pharmacokinetic parameters of tazemetostat.