TAZVERIK SIDE EFFECTS
- Generic Name: tazemetostat tablets
- Brand Name: Tazverik
- Drug Class: EZH2 Inhibitors
SIDE EFFECTS
The following clinically significant adverse reactions are described elsewhere in labeling:
- Secondary Malignancies
Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Epithelioid Sarcoma
The safety of TAZVERIK was evaluated in a cohort (Cohort 5) of Study EZH-202 that enrolled patients with epithelioid sarcoma. Patients received TAZVERIK 800 mg orally twice daily (n=62). Among patients who received TAZVERIK, 44% were exposed for 6 months or longer and 24% were exposed for greater than one year.
Serious adverse reactions occurred in 37% of patients who received TAZVERIK. Serious adverse reactions in ≥3% of patients who received TAZVERIK were hemorrhage, pleural effusion, skin infection, dyspnea, pain, and respiratory distress.
One patient (2%) permanently discontinued TAZVERIK due to an adverse reaction of altered mood.
Dosage interruptions due to an adverse reaction occurred in 34% of patients who received TAZVERIK. The most frequent adverse reactions requiring dosage interruptions in ≥3% were hemorrhage, increased alanine aminotransferase (ALT), and increased aspartate aminotransferase (AST).
Dose reduction due to an adverse reaction occurred in one (2%) patient who received TAZVERIK; the dose was reduced in this patient for decreased appetite.
The most common adverse reactions (≥20%) were pain, fatigue, nausea, decreased appetite, vomiting, and constipation.
Table 1 presents adverse reactions in patients with epithelioid sarcoma in Cohort 5 of Study EZH-202.
Table 1: Adverse Reactions (≥10%) in Patients with Epithelioid Sarcoma Who Received TAZVERIK in Cohort 5 of Study EZH-202
| Adverse Reaction | TAZVERIK N=62 |
|
| All Grades (%) | Grade 3 or 4 (%) | |
| General | ||
| Paina | 52 | 7 |
| Fatigueb | 47 | 1.6 |
| Gastrointestinal | ||
| Nausea | 36 | 0 |
| Vomiting | 24 | 0 |
| Constipation | 21 | 0 |
| Diarrhea | 16 | 0 |
| Abdominal painc | 13 | 1.6 |
| Metabolism and nutrition | ||
| Decreased appetite | 26 | 4.8 |
| Respiratory, thoracic and mediastinal | ||
| Cough | 18 | 0 |
| Dyspnead | 16 | 4.8 |
| Vascular | ||
| Hemorrhagee | 18 | 4.8 |
| Nervous system | ||
| Headache | 18 | 0 |
| Investigations | ||
| Weight decreased | 16 | 7 |
| a Includes tumor pain, pain in extremity, non-cardiac chest pain, flank pain, back pain, arthralgia, bone pain, cancer pain, musculoskeletal pain, myalgia, neck pain b Includes fatigue and asthenia c Includes abdominal pain, gastrointestinal pain, abdominal pain lower d Includes dyspnea and dyspnea exertional e Includes wound hemorrhage, rectal hemorrhage, pulmonary hemorrhage, hemorrhage intracranial, cerebral hemorrhage, hemoptysis |
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Table 2 summarizes select laboratory abnormalities in patients with epithelioid sarcoma in Cohort 5 of Study EZH-202.
Table 2: Select Laboratory Abnormalities (≥ 10%) Worsening from Baseline in Patients with Epithelioid Sarcoma Who Received TAZVERIK in Cohort 5 of Study EZH-202
| Laboratory Abnormality | TAZVERIK* | |
| All Grades (%) | Grade 3 or 4 (%) | |
| Hematology | ||
| Decreased hemoglobin | 49 | 15 |
| Decreased lymphocytes | 36 | 13 |
| Decreased white blood cell count | 19 | 0 |
| Chemistry | ||
| Increased triglycerides | 36 | 3.3 |
| Increased glucose | 33 | 1.6 |
| Decreased sodium | 30 | 1.7 |
| Decreased phosphate | 28 | 1.7 |
| Decreased albumin | 23 | 0 |
| Increased alkaline phosphatase | 23 | 1.7 |
| Decreased potassium | 20 | 1.7 |
| Increased aspartate aminotransferase | 18 | 3.5 |
| Decreased calcium | 16 | 0 |
| Decreased glucose | 16 | 0 |
| Increased partial thromboplastin time | 15 | 5 |
| Increased alanine aminotransferase | 14 | 3.4 |
| Increased creatinine | 12 | 0 |
| Increased potassium | 12 | 0 |
| *The denominator used to calculate the rate varied from 39 to 61 based on the number of patients with a baseline value and at least one post-treatment value. | ||
Relapsed Or Refractory Follicular Lymphoma
The safety of TAZVERIK was evaluated in two cohorts (Cohorts 4 and 5) of Study E7438-G000-101 that enrolled patients with relapsed or refractory follicular lymphoma. Patients received TAZVERIK 800 mg orally twice daily (n=99). Among patients who received TAZVERIK, 68% were exposed for 6 months or longer, 39% were exposed for 12 months or longer, and 21% were exposed for 18 months or longer.
The median age was 62 years (range 36 to 87 years), 54% were male, and 95% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. The median number of prior therapies was 3 (range 1 to 11). Patients were required have a creatinine clearance ≥40 mL/min per the Cockcroft and Gault formula.
Serious adverse reactions occurred in 30% of patients who received TAZVERIK. Serious adverse reactions in ≥2% of patients who received TAZVERIK were general physical health deterioration, abdominal pain, pneumonia, sepsis, and anemia.
Permanent discontinuation due to an adverse reaction occurred in 8% of patients who received TAZVERIK. Adverse reaction resulting in permanent discontinuation in ≥2% of patients was second primary malignancy.
Dosage interruptions due to an adverse reaction occurred in 28% of patients who received TAZVERIK. Adverse reactions requiring dosage interruptions in ≥3% of patients were thrombocytopenia and fatigue.
Dose reduction due to an adverse reaction occurred in 9% of patients who received TAZVERIK.
The most common adverse reactions (≥20%) were fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain.
Table 3 presents adverse reactions in patients with relapsed or refractory follicular lymphoma in Cohorts 4 and 5 of Study E7438-G000-101.
Table 3: Adverse Reactions (≥10%) in Patients with Relapsed or Refractory Follicular Lymphoma Who Received TAZVERIK in Cohorts 4 and 5 of Study E7438-G000-101
| Adverse Reaction | TAZVERIK N=99 |
|
| All Grades (%) | Grade 3 or 4 (%) | |
| General | ||
| Fatiguea | 36 | 5 |
| Pyrexia | 10 | 0 |
| Infections | ||
| Upper respiratory tract infectionb | 30 | 0 |
| Lower respiratory tract infectionc | 17 | 0 |
| Urinary tract infectiond | 11 | 2 |
| Gastrointestinal | ||
| Nausea | 24 | 1 |
| Abdominal paine | 20 | 3 |
| Diarrhea | 18 | 0 |
| Vomiting | 12 | 1 |
| Musculoskeletal and connective tissue | ||
| Musculoskeletal painf | 22 | 1 |
| Skin and subcutaneous tissue | ||
| Alopecia | 17 | 0 |
| Rashg | 15 | 0 |
| Respiratory and mediastinal system | ||
| Coughh | 17 | 0 |
| Nervous system | ||
| Headachei | 13 | 0 |
| a Includes fatigue and asthenia b Includes laryngitis, nasopharyngitis, pharyngitis, rhinitis, sinusitis, upper repiratory tract infection, viral upper respiratory tract infection c Includes bronchitis, lower respiratory tract infection, tracheobronchitis d Includes cystitis, urinary tract infection, urinary tract infection staphylococcal e Includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper f Includes back pain, limb discomfort, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, pain in extremity, pain in jaw, spinal pain g Includes erythema, rash, rash erythematous, rash generalized, rash maculo-papular, rash pruritic, rash pustular, skin exfoliation h Includes cough and productive cough i Includes headache, migraine, sinus headache |
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Clinically relevant adverse reactions occurring in <10% of patients who received TAZVERIK included:
- Infection: sepsis (2%), pneumonia (2%), and herpes zoster (2%)
Table 4 summarizes select laboratory abnormalities in patients with follicular lymphoma in Cohorts 4 and 5 of Study E7438-G000-101.
Table 4: Select Laboratory Abnormalities (≥10%) Worsening from Baseline in Patients with Relapsed or Refractory Follicular Lymphoma Who Received TAZVERIK in Cohorts 4 and 5 of Study E7438-G000-101
| Laboratory Abnormality | TAZVERIK* | |
| All Grades (%) | Grade 3 or 4 (%) | |
| Hematology | ||
| Decreased lymphocytes | 57 | 18 |
| Decreased hemoglobin | 50 | 8 |
| Decreased platelets | 50 | 7 |
| Decreased white blood cells | 41 | 9 |
| Decreased neutrophils | 20 | 7 |
| Chemistry | ||
| Increased glucose | 53 | 10 |
| Increased aspartate aminotransferase | 24 | 0 |
| Increased alanine aminotransferase | 21 | 2.3 |
| Increased alkaline phosphatase | 18 | 1.0 |
| Increased creatinine | 17 | 0 |
| *The denominator used to calculate the rate varied from 88 to 96 based on the number of patients with a baseline value and at least one post-treatment value. | ||
SRC: NLM .