TEMOZOLOMIDE
Generic: TEMOZOLOMIDE
Basic Information
Manufacturer
Rising Pharma Holdings, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
70996a9d-4a4f-4ed1-ab07-130486aa14ab
Indications & Usage
1 INDICATIONS AND USAGE Temozolomide is an alkylating drug indicated for the treatment of adults with: Newly diagnosed glioblastoma concomitantly with radiotherapy and then as maintenance treatment.
( 1.1 ) Anaplastic astrocytoma.
( 1.2 ) Adjuvant treatment of adults with newly diagnosed anaplastic astrocytoma.
( 1.2 ) Treatment of adults with refractory anaplastic astrocytoma.
( 1.2 ) 1.1 Newly Diagnosed Glioblastoma Temozolomide capsules are indicated for the treatment of adults with newly diagnosed glioblastoma, concomitantly with radiotherapy and then as maintenance treatment.
1.2 Anaplastic Astrocytoma Temozolomide capsules are indicated for the: adjuvant treatment of adults with newly diagnosed anaplastic astrocytoma; treatment of adults with refractory anaplastic astrocytoma.
( 1.1 ) Anaplastic astrocytoma.
( 1.2 ) Adjuvant treatment of adults with newly diagnosed anaplastic astrocytoma.
( 1.2 ) Treatment of adults with refractory anaplastic astrocytoma.
( 1.2 ) 1.1 Newly Diagnosed Glioblastoma Temozolomide capsules are indicated for the treatment of adults with newly diagnosed glioblastoma, concomitantly with radiotherapy and then as maintenance treatment.
1.2 Anaplastic Astrocytoma Temozolomide capsules are indicated for the: adjuvant treatment of adults with newly diagnosed anaplastic astrocytoma; treatment of adults with refractory anaplastic astrocytoma.
Adverse Reactions
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Myelosuppression [see Warnings and Precautions (5.1) ] Hepatotoxicity [see Warnings and Precautions (5.2) ] Pneumocystis Pneumonia [see Warnings and Precautions (5.3) ] Secondary Malignancies [see Warnings and Precautions (5.4) ] The most common adverse reactions (≥20%) are: alopecia, fatigue, nausea, vomiting, headache, constipation, anorexia, and convulsions.
( 6.1 ) The most common Grade 3 to 4 hematologic laboratory abnormalities (≥10%) in patients with anaplastic astrocytoma are: decreased lymphocytes, decreased platelets, decreased neutrophils, and decreased leukocytes.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharma Holdings, Inc.
at 1-844-874-7464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials 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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Newly Diagnosed Glioblastoma The safety of temozolomide was evaluated in study MK-7365-051 [see Clinical Studies (14.1) ] .
Severe or life-threatening adverse reactions occurred in 49% of patients treated with temozolomide; the most common were fatigue (13%), convulsions (6%), headache (5%), and thrombocytopenia (5%).
The most common adverse reactions (≥20%) in patients treated with temozolomide were alopecia, fatigue, nausea, anorexia, headache, constipation, and vomiting.
Table 3 summarizes the adverse reactions in MK-7365-051.
Clinically relevant adverse reactions in <10% of patients are presented below: Central & Peripheral Nervous System: memory impairment, confusion Eye: vision blurred Gastrointestinal System: stomatitis, abdominal pain General: weakness, dizziness Immune System: allergic reaction Injury: radiation injury not otherwise specified Musculoskeletal System: arthralgia Platelet, Bleeding, & Clotting: thrombocytopenia Psychiatric: insomnia Respiratory System: coughing, dyspnea Special Senses Other: taste perversion Skin & Subcutaneous Tissue: dry skin, pruritus, erythema When laboratory abnormalities and adverse reactions were combined, Grade 3 or Grade 4 neutrophil abnormalities including neutropenic reactions were observed in 8% of patients, and Grade 3 or Grade 4 platelet abnormalities including thrombocytopenic reactions were observed in 14% of patients.
Newly Diagnosed Anaplastic Astrocytoma The safety of temozolomide for the adjuvant treatment of adults with newly diagnosed anaplastic astrocytoma was derived from published literature [see Clinical Studies (14.2)] .
The safety of temozolomide for the adjuvant treatment of patients with newly diagnosed anaplastic astrocytoma was consistent with the known safety profile of temozolomide.
Refractory Anaplastic Astrocytoma The safety of temozolomide was evaluated in study MK-7365-006 [see Clinical Studies (14.2) ] .
The most common adverse reactions (≥20%) were nausea, vomiting, headache, fatigue, constipation, and convulsions.
Tables 4 and 5 summarize the adverse reactions and hematological laboratory abnormalities in MK-7365-006.
Clinically relevant adverse reactions in <10% of patients are presented below: Central and Peripheral Nervous System: paresthesia, somnolence, paresis, urinary incontinence, ataxia, dysphasia, convulsions local, gait abnormal, confusion Endocrine: adrenal hypercorticism Gastrointestinal System: abdominal pain, anorexia General: back pain Metabolic: weight increase Musculoskeletal System: myalgia Psychiatric: anxiety, depression Reproductive Disorders: breast pain female Respiratory System: upper respiratory tract infection, pharyngitis, sinusitis, coughing Skin & Appendages: rash, pruritus Urinary System: urinary tract infection, micturition increased frequency Vision: diplopia, vision abnormal* * This term includes blurred vision; visual deficit; vision changes; and vision troubles.
Hematological Toxicities for Advanced Gliomas In clinical trial experience with 110 to 111 females and 169 to 174 males (depending on measurements), females experienced higher rates of Grade 4 neutropenia (ANC <0.5 x 10 9 /L) and thrombocytopenia (<20 x 10 9 /L) than males in the first cycle of therapy (12% vs.
5% and 9% vs.
3%, respectively).
In the entire safety database for which hematologic data exist (N=932), 7% (4/61) and 10% (6/63) of patients >70 years experienced Grade 4 neutropenia or thrombocytopenia in the first cycle, respectively.
For patients ≤70 years, 7% (62/871) and 6% (48/879) experienced Grade 4 neutropenia or thrombocytopenia in the first cycle, respectively.
Pancytopenia, leukopenia, and anemia also occurred.
temozolomide-table3 temozolomide-table4 temozolomide-table5 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of temozolomide.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the drug exposure.
Dermatologic: Toxic epidermal necrolysis and Stevens-Johnson syndrome.
Immune System: Hypersensitivity reactions, including anaphylaxis.
Erythema multiforme, which resolved after discontinuation of temozolomide and, in some cases, recurred upon rechallenge.
Hematopoietic: Prolonged pancytopenia, which may result in aplastic anemia and fatal outcomes.
Hepatobiliary: Fatal and severe hepatotoxicity, elevation of liver enzymes, hyperbilirubinemia, cholestasis, and hepatitis.
Infections: Serious opportunistic infections, including some cases with fatal outcomes, with bacterial, viral (primary and reactivated), fungal, and protozoan organisms.
Pulmonary: Interstitial pneumonitis, pneumonitis, alveolitis, and pulmonary fibrosis.
Endocrine: Diabetes insipidus.
( 6.1 ) The most common Grade 3 to 4 hematologic laboratory abnormalities (≥10%) in patients with anaplastic astrocytoma are: decreased lymphocytes, decreased platelets, decreased neutrophils, and decreased leukocytes.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharma Holdings, Inc.
at 1-844-874-7464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials 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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Newly Diagnosed Glioblastoma The safety of temozolomide was evaluated in study MK-7365-051 [see Clinical Studies (14.1) ] .
Severe or life-threatening adverse reactions occurred in 49% of patients treated with temozolomide; the most common were fatigue (13%), convulsions (6%), headache (5%), and thrombocytopenia (5%).
The most common adverse reactions (≥20%) in patients treated with temozolomide were alopecia, fatigue, nausea, anorexia, headache, constipation, and vomiting.
Table 3 summarizes the adverse reactions in MK-7365-051.
Clinically relevant adverse reactions in <10% of patients are presented below: Central & Peripheral Nervous System: memory impairment, confusion Eye: vision blurred Gastrointestinal System: stomatitis, abdominal pain General: weakness, dizziness Immune System: allergic reaction Injury: radiation injury not otherwise specified Musculoskeletal System: arthralgia Platelet, Bleeding, & Clotting: thrombocytopenia Psychiatric: insomnia Respiratory System: coughing, dyspnea Special Senses Other: taste perversion Skin & Subcutaneous Tissue: dry skin, pruritus, erythema When laboratory abnormalities and adverse reactions were combined, Grade 3 or Grade 4 neutrophil abnormalities including neutropenic reactions were observed in 8% of patients, and Grade 3 or Grade 4 platelet abnormalities including thrombocytopenic reactions were observed in 14% of patients.
Newly Diagnosed Anaplastic Astrocytoma The safety of temozolomide for the adjuvant treatment of adults with newly diagnosed anaplastic astrocytoma was derived from published literature [see Clinical Studies (14.2)] .
The safety of temozolomide for the adjuvant treatment of patients with newly diagnosed anaplastic astrocytoma was consistent with the known safety profile of temozolomide.
Refractory Anaplastic Astrocytoma The safety of temozolomide was evaluated in study MK-7365-006 [see Clinical Studies (14.2) ] .
The most common adverse reactions (≥20%) were nausea, vomiting, headache, fatigue, constipation, and convulsions.
Tables 4 and 5 summarize the adverse reactions and hematological laboratory abnormalities in MK-7365-006.
Clinically relevant adverse reactions in <10% of patients are presented below: Central and Peripheral Nervous System: paresthesia, somnolence, paresis, urinary incontinence, ataxia, dysphasia, convulsions local, gait abnormal, confusion Endocrine: adrenal hypercorticism Gastrointestinal System: abdominal pain, anorexia General: back pain Metabolic: weight increase Musculoskeletal System: myalgia Psychiatric: anxiety, depression Reproductive Disorders: breast pain female Respiratory System: upper respiratory tract infection, pharyngitis, sinusitis, coughing Skin & Appendages: rash, pruritus Urinary System: urinary tract infection, micturition increased frequency Vision: diplopia, vision abnormal* * This term includes blurred vision; visual deficit; vision changes; and vision troubles.
Hematological Toxicities for Advanced Gliomas In clinical trial experience with 110 to 111 females and 169 to 174 males (depending on measurements), females experienced higher rates of Grade 4 neutropenia (ANC <0.5 x 10 9 /L) and thrombocytopenia (<20 x 10 9 /L) than males in the first cycle of therapy (12% vs.
5% and 9% vs.
3%, respectively).
In the entire safety database for which hematologic data exist (N=932), 7% (4/61) and 10% (6/63) of patients >70 years experienced Grade 4 neutropenia or thrombocytopenia in the first cycle, respectively.
For patients ≤70 years, 7% (62/871) and 6% (48/879) experienced Grade 4 neutropenia or thrombocytopenia in the first cycle, respectively.
Pancytopenia, leukopenia, and anemia also occurred.
temozolomide-table3 temozolomide-table4 temozolomide-table5 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of temozolomide.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the drug exposure.
Dermatologic: Toxic epidermal necrolysis and Stevens-Johnson syndrome.
Immune System: Hypersensitivity reactions, including anaphylaxis.
Erythema multiforme, which resolved after discontinuation of temozolomide and, in some cases, recurred upon rechallenge.
Hematopoietic: Prolonged pancytopenia, which may result in aplastic anemia and fatal outcomes.
Hepatobiliary: Fatal and severe hepatotoxicity, elevation of liver enzymes, hyperbilirubinemia, cholestasis, and hepatitis.
Infections: Serious opportunistic infections, including some cases with fatal outcomes, with bacterial, viral (primary and reactivated), fungal, and protozoan organisms.
Pulmonary: Interstitial pneumonitis, pneumonitis, alveolitis, and pulmonary fibrosis.
Endocrine: Diabetes insipidus.