TEMOZOLOMIDE- temozolomide_capsule

Temozolomide is not directly active but undergoes rapid nonenzymatic conversion at physiologic pH to the reactive compound 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide (MTIC). The cytotoxicity of MTIC is thought to be primarily due to DNA alkylation, mainly at the O 6 7 Temozolomide exposure-response relationships and the time course of pharmacodynamic response are unknown. Following a single oral dose of 150 mg/m 2 max Following a single 90-minute intravenous infusion of 150 mg/m 2 max Temozolomide exhibits linear kinetics over the therapeutic dosing range of 75 mg/m 2 2 Absorption The median T max Effect of Food The mean C max max Distribution Temozolomide has a mean (CV%) apparent volume of distribution of 0. 4 L/kg (13%). The mean percent bound of drug-related total radioactivity is 15%. Elimination Clearance of temozolomide is approximately 5. 5 L/hr/m 2 Metabolism Temozolomide is spontaneously hydrolyzed at physiologic pH to the active species, MTIC and to temozolomide acid metabolite. MTIC is further hydrolyzed to 5-amino-imidazole-4-carboxamide (AIC), which is known to be an intermediate in purine and nucleic acid biosynthesis, and to methylhydrazine, which is believed to be the active alkylating species. Cytochrome P450 enzymes play a minor role in the metabolism of temozolomide and MTIC. Relative to the AUC of temozolomide, the exposure to MTIC and AIC is 2. 4% and 23%, respectively. Excretion Approximately 38% of the administered temozolomide total radioactive dose is recovered over 7 days: 38% in urine and 0. 8% in feces. The majority of the recovered radioactivity in urine is unchanged temozolomide (6%), AIC (12%), temozolomide acid metabolite (2. 3%), and unidentified polar metabolite(s) (17%). Specific Populations No clinically significant differences in the pharmacokinetics of temozolomide were observed based on age (range: 19-78 years), gender, smoking status (smoker vs. non-smoker), creatinine clearance (CLcr) of 36 to 130 mL/min/m 2 2 Drug Interaction Studies Clinical Studies and Model-Informed Approaches No clinically significant differences in the pharmacokinetics of temozolomide or MTIC were observed when co-administered with ranitidine.

Temozolomide is an alkylating drug indicated for the treatment of adults with: Newly diagnosed glioblastoma concomitantly with radiotherapy and then as maintenance treatment. 1 Anaplastic astrocytoma. 2 Adjuvant treatment of adults with newly diagnosed anaplastic astrocytoma. 2 Treatment of adults with refractory anaplastic astrocytoma. 2 Temozolomide Capsules are indicated for the treatment of adults with newly diagnosed glioblastoma, concomitantly with radiotherapy and then as maintenance treatment. Temozolomide capsules are indicated for the: adjuvant treatment of adults with newly diagnosed anaplastic astrocytoma; treatment of adults with refractory anaplastic astrocytoma.

Newly Diagnosed Glioblastoma 75 mg/m 2 2 2 2. 1 Provide Pneumocystis 2. 1 Adjuvant Treatment of Newly Diagnosed Anaplastic Astrocytoma: 2 2 2. 2 Refractory Anaplastic Astrocytoma: 2 2. 2 Prior to dosing, withhold Temozolomide until patients have an absolute neutrophil count (ANC) of 1. 5 x 10 9 9 For concomitant radiotherapy, obtain a complete blood count prior to initiation of treatment and weekly during treatment. For the 28-day treatment cycles, obtain a complete blood count prior to treatment on Day 1 and on Day 22 of each cycle. Perform complete blood counts weekly until recovery if the ANC falls below 1. 5 x 10 9 9 For concomitant use with focal radiotherapy, obtain a complete blood count weekly and as clinically indicated. Administer Temozolomide once daily for 42 to 49 consecutive days during the concomitant use phase with focal radiotherapy and then once daily on Days 1 to 5 of each 28-day cycle for 6 cycles during the maintenance use phase. Provide Pneumocystis [see Warnings and Precautions ( 5. 3 Concomitant Use Phase: The recommended dosage of Temozolomide is 75 mg/ m 2 Other administration schedules have been used. Obtain a complete blood count weekly. The recommended dosage modifications due to adverse reactions during concomitant use phase are provided in Table 1 TABLE 1: Dosage Modifications Due to Adverse Reactions During Concomitant Use Phase Adverse Reaction Interruption Discontinuation Absolute Neutrophil Count Withhold Temozolomide if ANC is greater than or equal to 0. 5 × 10 9 9 9 Discontinue Temozolomide if ANC is less than 0. 5 × 10 9 Platelet Count Withhold Temozolomide if platelet count is greater than or equal to 10 × 10 9 9 9 Discontinue Temozolomide if platelet count is less than 10 × 10 9 Non-hematological Adverse Reaction (except for alopecia, nausea, vomiting) Withhold Temozolomide if Grade 2 adverse reaction occurs. Discontinue Temozolomide if Grade 3 or 4 adverse reaction occurs. Single Agent Maintenance Use Phase: Beginning 4 weeks after concomitant use phase completion, administer Temozolomide once daily on Days 1 to 5 of each 28-day cycle for 6 cycles. The recommended dosage of Temozolomide in the maintenance use phase is: Cycle 1: 150 mg/ m 2 Cycles 2 to 6: May increase to 200 mg/m 2 do not Obtain a complete blood count on Day 22 and then weekly until the ANC is above 1. 5 x 10 9 9 The recommended dosage modifications due to adverse reactions during the the maintenance use phase are provided in Table 2 If Temozolomide is withheld, reduce the dose for the next cycle by 50 mg/m 2 2 TABLE 2: Dosage Modifications Due to Adverse Reactions During Maintenance and Adjuvant Treatment Adverse Reactions Interruption and Dose Reduction Discontinuation Absolute Neutrophil Count Withhold Temozolomide if ANC less than 1 × 10 9 When ANC is above 1. 5 × 10 9 Discontinue Temozolomide if unable to tolerate a dose of 100 mg/m 2 Platelet Count Withhold Temozolomide if platelet less than 50 × 10 9 When platelet count is above 100 × 10 9 Discontinue Temozolomide if unable to tolerate a dose of 100 mg/m 2 Nonhematological Adverse Reactions (except for alopecia, nausea, vomiting) Withhold Temozolomide if Grade 3 adverse reaction occurs. When resolved to Grade 1 or less, resume Temozolomide at reduced dose for the next cycle. Discontinue Temozolomide if recurrent Grade 3 adverse reaction occurs after dose reduction, if Grade 4 adverse reaction occurs, or if unable to tolerate a dose of 100 mg/m 2 Adjuvant Treatment of Newly Diagnosed Anaplastic Astrocytoma Beginning 4 weeks after the end of radiotherapy, administer Temozolomide orally in a single dose on days 1 to 5 of a 28-day cycle for 12 cycles. The recommended dosage of Temozolomide is: Cycle 1: 150 mg/m 2 Cycles 2 to 12: 200 mg/m 2 do not The recommended complete blood count testing and dosage modifications due to adverse reactions during adjuvant treatment are provided above and in Table 2 [see Dosage and Administration ( 2. 2 Refractory Anaplastic Astrocytoma The recommended initial dosage of Temozolomide is 150 mg/m 2 2 ANC is greater than or equal to 1. 5 x 10 9 Platelet count is greater than or equal to 100 x 10 9 Continue Temozolomide until disease progression or unacceptable toxicity. Obtain a complete blood count on Day 22 and then weekly until the ANC is above 1. 5 x 10 9 9 If the ANC is less than 1 x 10 9 9 2 2 Temozolomide is a hazardous drug. Follow applicable special handling and disposal procedures. 1 Temozolomide capsules Take Temozolomide at the same time each day. Administer Temozolomide consistently with respect to food (fasting vs. nonfasting) [see Clinical Pharmacology ( 12. 3 Swallow Temozolomide capsules whole with water. Advise patients not to open, chew, or dissolve the contents of the capsules. [see Warnings and Precautions ( 5. 6 If capsules are accidentally opened or damaged, take precautions to avoid inhalation or contact with the skin or mucous membranes. In case of powder contact, wash the affected area with water immediately.

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 [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. 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. 1 To report SUSPECTED ADVERSE REACTIONS, contact NextSource Pharma at 1-855-672-2468 or FDA at 1-800-FDA-1088 or www. gov/medwatch. 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 TABLE 3: Adverse Reactions (>=10%) in Patients with Newly Diagnosed Glioblastoma NOS = not otherwise specified. NOTE: *One patient who was randomized to radiation therapy-only arm received radiation therapy and TEMOZOLOMIDE. Adverse Reactions Concomiotant Use Phase Maintenance Use Phase Radiation Therapy and Temozolomide N=288* Radiation Therapy Alone N=285 Temozolomide N=224 All Grades (%) Grade >=3 (%) All Grades (%) Grades >=3 (%) All Grades (%) Grade >=3 (%) Skin and Subcutaneous Tissue Alopecia 69 0 63 0 55 0 Rash 19 1 15 0 13 1 General Fatigue 54 7 49 5 61 9 Anorexia 19 1 9 <1 27 1 Headache 19 2 17 4 23 4 Gastrointestinal System Nausea 36 1 16 <1 49 1 Vomiting 20 <1 6 <1 29 2 Constipation 18 1 6 0 22 0 Diarrhea 6 0 3 0 10 1 Central and Peripheral Nervous System Convulsions 6 3 7 3 11 3 Clinically relevant adverse reactions in <10% of patients are presented below: Central & Peripheral Nervous System: Eye: Gastrointestinal System: General: Immune System: Injury: Musculoskeletal System: Platelet, Bleeding, & Clotting: Psychiatric: Respiratory System: Special Senses Other: Skin & Subcutaneous Tissue: 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 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 5 TABLE 4: Adverse Reactions (>=10%) in Patients with Refactory Anaplastic Astrocytoma Adverse Reactions TEMOZOLOMIDE N=158 All Reactions (%) Grade 3-4 (%) Gastrointestinal System Nausea 53 10 Vomiting 42 6 Constipation 33 1 Diarrhea 16 2 General Headache 41 6 Fatigue 34 4 Asthenia 13 6 Fever 13 2 Central and Peripheral Nervous System Convulsions 23 5 Hemiparesis 18 6 Dizziness 12 1 Coordination abnormal 11 1 Amnesia 10 4 Insomnia 10 0 Cardiovascular Edema peripheral 11 1 Resistance Mechanism Infection viral 11 0 Clinically relevant adverse reactions in <10% of patients are presented below: Central and Peripheral Nervous System: Endocrine: Gastrointestinal System: General: Metabolic: Musculoskeletal System: Psychiatric: Reproductive Disorders: Respiratory System: Skin & Appendages: Urinary System: Vision: 1 1 TABLE 5: Grade 3 to 4 Hematologic Laboratory Abnormalities That Worsened from Baseline in Patients with Refractory Anaplastic Astrocytoma * Change from Grade 0 to 2 at baseline to Grade 3 or 4 during treatment. Ŧ Denominator range = 142, 158 TEMOZOLOMIDE *,Ŧ Decreased lymphocytes 55 Decreased platelets 19 Decreased neutrophils 14 Decreased leukocytes 11 Decreased hemoglobin 4 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 9 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. 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: Immune System Hematopoietic Hepatobiliary Infections Pulmonary Endocrine.

Temozolomide is contraindicated in patients with a history of serious hypersensitivity reactions to: temozolomide or any other ingredients in Temozolomide capsules; and dacarbazine, since both temozolomide and dacarbazine are metabolized to the same active metabolite 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide. Reactions to Temozolomide have included anaphylaxis [see Adverse Reactions ( 6. 2 History of serious hypersensitivity to temozolomide or any other ingredients in Temozolomide Capsules and dacarbazine.

Lactation: Advise not to breastfeed. 2 Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology ( 12. 1 ​see Data In the U. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Five consecutive days of oral administration of temozolomide at doses of 75 and 150 mg/m 2 2 2 2 There are no data on the presence of Temozolomide or its metabolites in human milk, the effects on a breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions, including myelosuppression from temozolomide in the breastfed children, advise women not to breastfeed during treatment with Temozolomide and for 1 week after the last dose. Temozolomide can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8. 1 Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating Temozolomide [see Use in Specific Populations ( 8. 1 Contraception Females Advise females of reproductive potential to use effective contraception during treatment with Temozolomide and for 6 months after the last dose. Males Because of the potential for embryofetal toxicity and genotoxic effects on sperm cells, advise male patients with pregnant partners or female partners of reproductive potential to use condoms during treatment with Temozolomide and for 3 months after the last dose [see Use in Specific Populations ( 8. 1 Infertility Temozolomide may impair male fertility [see Nonclinical Toxicology ( 13. 1 Safety and effectiveness of Temozolomide have not been established in pediatric patients. Safety and effectiveness of Temozolomide capsules were assessed, but not established, in 2 open-label studies in pediatric patients aged 3 to 18 years. In one study, 29 patients with recurrent brain stem glioma and 34 patients with recurrent high-grade astrocytoma were enrolled. In a second study conducted by the Children’s Oncology Group (COG), 122 patients were enrolled, including patients with medulloblastoma/PNET (29), high grade astrocytoma (23), low grade astrocytoma (22), brain stem glioma (16), ependymoma (14), other CNS tumors (9), and non-CNS tumors (9). The adverse reaction profile in pediatric patients was similar to adults. In MK-7365-051, 15% of patients with newly diagnosed glioblastoma were 65 years and older. This study did not include sufficient numbers of patients aged 65 years and older to determine differences in effectiveness from younger patients. No overall differences in safety were observed between patients >=65 years and younger patients. The CATNON trial did not include sufficient numbers of patients aged 65 years and older to determine differences in safety or effectiveness when compared to younger patients. In MK-7365-006, 4% of patients with refractory anaplastic astrocytoma were 70 years and older. This study did not include sufficient numbers of patients aged 70 years and older to determine differences in effectiveness from younger patients. Patients 70 years and older had a higher incidence of Grade 4 neutropenia (25%) and Grade 4 thrombocytopenia (20%) in the first cycle of therapy than patients less than 70 years of age [see Warnings and Precautions ( 5. 1 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. No dosage adjustment is recommended for patients with creatinine clearance (CLcr) of 36 to 130 mL/min/m 2 [see Clinical Pharmacology ( 12. 3 2 No dosage adjustment is recommended for patients with mild to moderate hepatic impairment (Child Pugh class A and B) [see Clinical Pharmacology ( 12.

OVERDOSAGE
Dose-limiting toxicity was myelosuppression and was reported with any dose but is expected to be more severe at higher doses. An overdose of 2000 mg per day for 5 days was taken by one patient and the adverse reactions reported were pancytopenia, pyrexia, multi-organ failure, and death. There are reports of patients who have taken more than 5 days of treatment (up to 64 days), with adverse reactions reported including myelosuppression, which in some cases was severe and prolonged, and infections and resulted in death. In the event of an overdose, monitor complete blood count and provide supportive measures as necessary.
NONCLINICAL TOXICOLOGY
Temozolomide is carcinogenic in rats at doses less than the maximum recommended human dose. Temozolomide induced mammary carcinomas in both males and females at doses 0. 63 times the maximum human dose (25 - 125 mg/m 2 Mammary tumors were also induced following 3 cycles of temozolomide at the maximum recommended daily dose. Temozolomide impairs male fertility. Temozolomide caused syncytial cells/immature sperm formation at doses of 50 and 125 mg/m 2 2 2 Toxicology studies in rats and dogs identified a low incidence of hemorrhage, degeneration, and necrosis of the retina at temozolomide doses equal to or greater than 125 mg/m 2 2.
CLINICAL STUDIES
The efficacy of Temozolomide was evaluated in study MK-7365-051 ( NCT00006353 2 2 2 A total of 573 patients were randomized, 287 to Temozolomide and radiation therapy and 286 to radiation therapy alone. At the time of disease progression, Temozolomide was administered as salvage therapy in 161 patients of the 282 (57%) in the radiation therapy alone arm and 62 patients of the 277 (22%) in the Temozolomide and radiation therapy arm. The addition of concomitant and maintenance Temozolomide to radiation therapy for the treatment of patients with newly diagnosed glioblastoma showed a statistically significant improvement in overall survival compared to radiotherapy alone ( Figure 1 P figure-1 Newly Diagnosed Anaplastic Astrocytoma The efficacy of TEMOZOLOMIDE for the adjuvant treatment of newly diagnosed anaplastic astrocytoma was derived from studies of TEMOZOLOMIDE in the published literature. TEMOZOLOMIDE was evaluated in CATNON ( NCT00626990 Refractory Anaplastic Astrocytoma The efficacy of Temozolomide was evaluated in Study MK-7365-006, a single-arm, multicenter trial. Eligible patients had anaplastic astrocytoma at first relapse and a baseline Karnofsky performance status (KPS) of 70 or greater. Patients had previously received radiation therapy and may also have previously received a nitrosourea with or without other chemotherapy. Fifty-four patients had disease progression on prior therapy with both a nitrosourea and procarbazine and their malignancy was considered refractory to chemotherapy (refractory anaplastic astrocytoma population). Temozolomide capsules were given on Days 1 to 5 of each 28-day cycle at a starting dose of 150 mg/m 2 9 9 2 In the refractory anaplastic astrocytoma population (n=54), the median age was 42 years (range:19 to 76); 65% were male; and 72% had a KPS of >80. Sixty-three percent of patients had surgery other than a biopsy at the time of initial diagnosis. Of those patients undergoing resection, 73% underwent a subtotal resection and 27% underwent a gross total resection. Eighteen percent of patients had surgery at the time of first relapse. The median time from initial diagnosis to first relapse was 13. 8 months (range: 4. 2 months to 6. In the refractory anaplastic astrocytoma population, the overall response rate (CR+PR) was 22% (12 of 54 patients) and the complete response rate was 9% (5 of 54 patients). The median duration of all responses was 50 weeks (range: 16 to 114 weeks) and the median duration of complete responses was 64 weeks (range: 52 to 114 weeks). In this population, progression-free survival at 6 months was 45% (95% CI: 31%, 58%) and progression-free survival at 12 months was 29% (95% CI: 16%, 42%). Median progression-free survival was 4. Overall survival at 6 months was 74% (95% CI: 62%, 86%) and 12-month overall survival was 65% (95% CI: 52%, 78%). Median overall survival was 15.
REFERENCES
1. “OSHA Hazardous Drugs.” OSHA
Patient Information
Temozolomide (tem" oh zol'' oh mide) Capsules, USP What is Temozolomide? Do not take TEMOZOLOMIDE if you: have had an allergic reaction to temozolomide or any of the other ingredients in TEMOZOLOMIDE. See the end of this leaflet for a list of ingredients in TEMOZOLOMIDE. Symptoms of an allergic reaction with TEMOZOLOMIDE may include: a red itchy rash, or a severe allergic reaction, such as trouble breathing, swelling of the face, throat, or tongue, or severe skin reaction. If you are not sure, ask your healthcare provider. have had an allergic reaction to dacarbazine (DTIC), another cancer medicine. Before taking or receiving TEMOZOLOMIDE, tell your healthcare provider about all of your medical conditions, including if you: have kidney problems have liver problems are pregnant or plan to become pregnant. TEMOZOLOMIDE can harm your unborn baby and cause birth defects. You should not become pregnant during treatment with TEMOZOLOMIDE. You should use an effective form of birth control (contraception) during treatment and for 6 months after your last dose of TEMOZOLOMIDE. Your healthcare provider should do a pregnancy test to make sure that you are not pregnant before you start taking TEMOZOLOMIDE. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with TEMOZOLOMIDE. Males with a female partner who is pregnant or who can become pregnant: Use a condom for birth control (contraception) during treatment and for 3 months after taking your last dose of TEMOZOLOMIDE. Do not are breastfeeding or plan to breastfeed. It is not known if TEMOZOLOMIDE passes into your breast milk. Do not breastfeed during treatment and for 1 week after your last dose of TEMOZOLOMIDE. Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine. How should I take TEMOZOLOMIDE? you may take TEMOZOLOMIDE by mouth as a capsule, Your healthcare provider will decide the best way for you to take TEMOZOLOMIDE. If your healthcare provider prescribes TEMOZOLOMIDE capsules for you, take the capsules exactly as prescribed. People with certain brain cancer tumors take or receive TEMOZOLOMIDE: 1 time each day for 42 to 49 days in a row, along with receiving radiation treatment. This is 1 cycle of treatment. This is a 28-day maintenance treatment cycle. People with certain other brain cancer tumors take or receive TEMOZOLOMIDE: 1 time each day for 5 days in a row only, and then stop taking it for the next 23 days. This is 1 cycle of treatment (28 days). Your healthcare provider will watch your progress on TEMOZOLOMIDE and decide how long you should take it. If your healthcare provider prescribes a treatment regimen that is different from the information in this leaflet, make sure you follow the instructions given to you by your healthcare provider. Your healthcare provider may change your dose of TEMOZOLOMIDE, or tell you to stop TEMOZOLOMIDE for a short period of time or permanently if you have certain side effects. Your healthcare provider will decide how many treatment cycles of TEMOZOLOMIDE that you will receive, depending on how you respond to and tolerate treatment. TEMOZOLOMIDE capsules: Take TEMOZOLOMIDE capsules exactly as your healthcare provider tells you to. TEMOZOLOMIDE capsules contain a white capsule body with a color cap and the colors vary based on the dosage strength. Your healthcare provider may prescribe more than 1 strength of TEMOZOLOMIDE capsules for you, so it is important that you understand how to take your medicine the right way. Be sure that you understand exactly how many capsules you need to take on each day of your treatment, and what strengths to take. This may be different whenever you start a new cycle. Do not take more TEMOZOLOMIDE than prescribed. Talk to your healthcare provider or pharmacist before taking your dose if you are not sure how much TEMOZOLOMIDE to take. This will help to prevent taking too many TEMOZOLOMIDE and decrease your chances of getting serious side effects. Take each day''s dose of TEMOZOLOMIDE capsules at one time, with a full glass of water. Take TEMOZOLOMIDE capsules at the same time each day. Take TEMOZOLOMIDE the same way each time, either with food or without food. Swallow TEMOZOLOMIDE capsules whole with water. Do not If TEMOZOLOMIDE capsules are accidentally opened or damaged, be careful not to breathe in (inhale) the powder from the capsules or get the powder on your skin or mucous membranes (for example, in your nose or mouth). If contact with any of these areas happens, wash the area with water right away. To help reduce nausea and vomiting, try to take TEMOZOLOMIDE on an empty stomach or at bedtime. Your healthcare provider may prescribe medicine to help prevent or treat nausea, or other medicines to reduce side effects with TEMOZOLOMIDE. See your healthcare provider regularly to check your progress. Your healthcare provider will check you for side effects. If you take more TEMOZOLOMIDE than prescribed, call your healthcare provider or get emergency medical help right away. What are the possible side effects of TEMOZOLOMIDE? TEMOZOLOMIDE can cause serious side effects, including: Decreased blood cell counts. Your healthcare provider will do blood tests regularly to check your blood cell counts before you start and during treatment with TEMOZOLOMIDE. Your healthcare provider may need to change the dose of TEMOZOLOMIDE or when you get it depending on your blood cell counts. People who are age 70 or older and women have a higher risk for developing decreased blood cell counts during treatment with TEMOZOLOMIDE. Liver problems. Liver problems can happen with TEMOZOLOMIDE and can sometimes be severe and lead to death. Pneumocystis People who are taking steroid medicines or who stay on TEMOZOLOMIDE for a longer period of time may have an increased risk of getting PCP infection. Anyone who takes TEMOZOLOMIDE will be watched carefully by their healthcare provider for low blood cell counts and this infection. Tell your healthcare provider if you have any of the following signs and symptoms of PCP infection: shortness of breath, or fever, chills, dry cough. Secondary Cancers. Common side effects of TEMOZOLOMIDE include: hair loss feeling tired nausea and vomiting headache constipation loss of appetite convulsions TEMOZOLOMIDE can affect fertility in males and may affect your ability to father a child. Talk with your healthcare provider if fertility is a concern for you. Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of TEMOZOLOMIDE. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store TEMOZOLOMIDE capsules? Store TEMOZOLOMIDE capsules at room temperature between 68°F to 77°F (20°C to 25°C). Keep TEMOZOLOMIDE and all medicines out of the reach of children. General information about the safe and effective use of TEMOZOLOMIDE. What are the ingredients in TEMOZOLOMIDE? TEMOZOLOMIDE capsules: Active ingredient: Inactive ingredients: The body of the capsules is made of gelatin and is opaque white. The cap is also made of gelatin, and the colors vary based on the dosage strength. The capsule body and cap are imprinted with pharmaceutical branding ink, which contains shellac, dehydrated alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, purified water, strong ammonia, and ferric oxide. TEMOZOLOMIDE 100 mg: The purple cap contains gelatin, titanium dioxide, and iron oxide red, and FD&C Blue #2. TEMOZOLOMIDE This Patient Information has been approved by the U.S. Food and Drug Administration Revised: 08/2024

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