TEMODAR

Other Alkylating Agents

Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 1
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure.
Avoid contact with temozolomide powder. If capsules or vials open, avoid inhalation or contact with skin or mucous membranes.
Emetic Risk
Pediatrics:
Oral Doses 200 mg/m2: Low
Administer prn antiemetics as necessary.
Adults:
Oral Doses: Moderate/High
Administer routine antiemetic prophylaxis prior to treatment.

Take temozolomide at the same time each day consistently either with or without food.
Swallow capsules whole with a glass of water; do not open, chew, or dissolve the contents of the capsules.
To reduce nausea and vomiting, take on an empty stomach or at bedtime.

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Reconstitution:
Allow the lyophilized powder vial to acclimate to room temperature prior to reconstitution.
Add 41 mL of Sterile Water for injection to the 100-mg vial for a final vial concentration of 2.5 mg/mL.
Gently swirl the vial to dissolve the powder; do not shake.
Withdraw the appropriate amount (up to 40 mL per vial) from the reconstituted vial and add to an empty 250 mL infusion bag; do not dilute further.
Storage following reconstitution: store at room temperature (25 degrees C; 77 degrees F) for up to 14 hours (includes infusion time).
Intravenous Infusion:
Administer IV over 90 minutes via an infusion pump; flush the IV line prior to and after the infusion.
Temozolomide may be administered in the same IV line with 0.9% Sodium Chloride injection; do not administer in the same IV line with other fluids, additives, or medications.

lymphopenia / Delayed / 0-55.0
thrombocytopenia / Delayed / 0-19.0
neutropenia / Delayed / 0-14.0
leukopenia / Delayed / 0-11.0
nausea / Early / 1.0-10.0
fatigue / Early / 4.0-9.0
vomiting / Early / 0-6.0
headache / Early / 2.0-6.0
asthenia / Delayed / 0-6.0
seizures / Delayed / 3.0-5.0
anemia / Delayed / 0-4.0
amnesia / Delayed / 0-4.0
diarrhea / Early / 0-2.0
constipation / Delayed / 0-1.0
anorexia / Delayed / 0-1.0
aplastic anemia / Delayed / 0-1.0
pancytopenia / Delayed / 0-1.0
Stevens-Johnson syndrome / Delayed / 0-1.0
rash / Early / 0-1.0
erythema multiforme / Delayed / 0-1.0
toxic epidermal necrolysis / Delayed / 0-1.0
dizziness / Early / 0-1.0
pulmonary fibrosis / Delayed / 0-1.0
peripheral edema / Delayed / 0-1.0
anaphylactoid reactions / Rapid / 0-1.0
diabetes insipidus / Delayed / 0-1.0
new primary malignancy / Delayed / Incidence not known
teratogenesis / Delayed / Incidence not known
spontaneous fetal abortion / Delayed / Incidence not known

stomatitis / Delayed / 0-10.0
erythema / Early / 0-10.0
Cushing's syndrome / Delayed / 0-10.0
ataxia / Delayed / 0-10.0
dysphagia / Delayed / 0-10.0
paresis / Delayed / 0-10.0
dyspnea / Early / 0-10.0
blurred vision / Early / 0-10.0
urinary incontinence / Early / 0-10.0
depression / Delayed / 0-10.0
confusion / Early / 0-10.0
memory impairment / Delayed / 0-10.0
hyperbilirubinemia / Delayed / 0-1.0
cholestasis / Delayed / 0-1.0
hepatitis / Delayed / 0-1.0
elevated hepatic enzymes / Delayed / 0-1.0
pneumonitis / Delayed / 0-1.0
hematoma / Early / Incidence not known

alopecia / Delayed / 0-69.0
infection / Delayed / 0-11.0
abdominal pain / Early / 0-10.0
dysgeusia / Early / 0-10.0
xerosis / Delayed / 0-10.0
pruritus / Rapid / 0-10.0
back pain / Delayed / 0-10.0
arthralgia / Delayed / 0-10.0
myalgia / Early / 0-10.0
drowsiness / Early / 0-10.0
paresthesias / Delayed / 0-10.0
gait disturbance / Delayed / 0-10.0
cough / Delayed / 0-10.0
sinusitis / Delayed / 0-10.0
pharyngitis / Delayed / 0-10.0
weakness / Early / 0-10.0
diplopia / Early / 0-10.0
weight gain / Delayed / 0-10.0
mastalgia / Delayed / 0-10.0
increased urinary frequency / Early / 0-10.0
anxiety / Delayed / 0-10.0
insomnia / Early / 0-10.0
skin irritation / Early / Incidence not known
petechiae / Delayed / Incidence not known
injection site reaction / Rapid / Incidence not known
fever / Early / Incidence not known

TEMODAR

Rx

Alkylating agent
Used for the treatment of adults with glioblastoma multiforme and anaplastic astrocytoma
Severe hematologic toxicity and hepatotoxicity have been reported

75 mg/m2 orally once daily for 42 to 49 days with concomitant focal radiotherapy (to the tumor bed or resection site with a 2 to 3 cm margin). Administer Pneumocystis carinii pneumonia (PCP) prophylaxis during the concomitant therapy period; continue PCP prophylaxis in patients who develop lymphopenia. Temozolomide therapy interruption or discontinuation may be necessary in patients who develop toxicity during the concomitant treatment phase. At 4 weeks after completing the concomitant treatment phase, begin 6 cycles of maintenance therapy with temozolomide 150 mg/m2 orally once daily on days 1, 2, 3, 4, and 5 repeated every 28 days. Starting in cycle 2, the temozolomide dosage may be increased to 200 mg/m2 orally once daily for 5 days per cycle if no therapy interruptions or discontinuation was needed in cycle 1. If the dosage is not increased in cycle 2, do not increase the dosage in cycles 3 to 6. Interruption, dosage reduction, or discontinuation of maintenance therapy may be necessary in patients who develop toxicity. In a multicenter, randomized trial of 573 patients with newly diagnosed glioblastoma, the addition of oral temozolomide to radiotherapy followed by adjuvant temozolomide therapy significantly prolonged the median overall survival time compared with radiotherapy alone (14.6 months vs. 12.1 months; hazard ratio = 0.63; 95%CI, 0.52 to 0.75; p less than 0.001).

75 mg/m2 IV daily for 42 to 49 days with concomitant focal radiotherapy (to the tumor bed or resection site with a 2 to 3 cm margin). Administer Pneumocystis carinii pneumonia (PCP) prophylaxis during the concomitant therapy period; continue PCP prophylaxis in patients who develop lymphopenia. Temozolomide therapy interruption or discontinuation may be necessary in patients who develop toxicity during the concomitant treatment phase. At 4 weeks after completing the concomitant treatment phase, begin 6 cycles of maintenance therapy with temozolomide 150 mg/m2 IV once daily on days 1, 2, 3, 4, and 5 repeated every 28 days. Starting in cycle 2, the temozolomide dosage may be increased to 200 mg/m2 IV once daily for 5 days per cycle if no therapy interruptions or discontinuation occurred in cycle 1. If the dosage is not increased in cycle 2, do not increase the dosage in cycles 3 to 6. Interruption, dosage reduction, or discontinuation of maintenance therapy may be necessary in patients who develop toxicity.

200 mg/m2 orally daily for 5 days repeated every 28 days (150 mg/m2 orally daily for 5 days repeated every 28 days in patients with prior chemotherapy) significantly improved median progression-free survival (PFS) time (12.4 weeks vs. 8.32 weeks; p = 0.0063), 6-month PFS rate (21% vs. 8%; p = 0.008), and 6-month overall survival (OS) rate (60% vs. 44%; p = 0.019) compared with procarbazine in 225 patients with glioblastoma (GBM) in first relapse in a phase 2 study. Treatment with temozolomide (200 mg/m2 orally daily for 5 days or 100 mg/m2 orally daily for 21 days repeated every 28 days for up to 9 cycles) did not significantly improve OS compared with the procarbazine, lomustine, and vincristine (PCV) regimen (hazard ratio = 0.95; 95% CI, 0.75 to 1.19) in 277 chemotherapy-naive patients with recurrent GBM in another randomized clinical trial. Additionally, continuous, low-dose oral temozolomide (50mg/m2 orally daily) produced a 6-month PFS rate of 23.9% and a median OS time of 9.3 months in 91 patients with recurrent or progressive GBM after standard initial therapy for newly diagnosed GBM in a multicenter, phase 2 study (the RESCUE study).

150 mg/m2 orally once daily on days 1, 2, 3, 4, and 5 repeated every 28 days until disease progression. Increase the temozolomide dosage to 200 mg/m2 orally once daily for 5 days per cycle if the absolute neutrophil count is 1.5 X 109 cells/L or greater and the platelet count is 100 X 109 cells/L or greater at both the nadir and on day 1 of the next cycle. Therapy interruption, dosage reduction, or discontinuation may be necessary in patients who develop toxicity. In 54 patients with refractory anaplastic astrocytoma, the overall response rate was 22% (complete response rate, 9%) and the median duration of response was 50 weeks (range, 16 to 114 weeks). Additionally, the median progression-free survival (PFS) time was 4.4 months and the 6- and 12-month PFS rates were 45% and 29%, respectively. The median overall survival (OS) time was 15.9 months and the 6- and 12-month OS rates were 74% and 65%, respectively.

150 mg/m2 IV once daily on days 1, 2, 3, 4, and 5 repeated every 28 days until disease progression. Increase the temozolomide dosage to 200 mg/m2 IV once daily for 5 days per cycle of therapy if the absolute neutrophil count is 1.5 X 109 cells/L or greater and the platelet count is 100 X 109 cells/L or greater at both the nadir and on day 1 of the next cycle. Therapy interruption, dosage reduction, or discontinuation may be necessary in patients who develop toxicity.

150 mg/m2 orally once daily on days 1, 2, 3, 4, and 5 repeated every 28 days for 12 cycles starting 4 weeks after the completion of radiotherapy. Starting in cycle 2, increase the temozolomide dosage to 200 mg/m2 orally once daily for 5 days per cycle if there is no or minimal toxicity experienced in cycle 1. If the dosage is not increased in cycle 2, do not increase the dosage in subsequent cycles. Interruption, dosage reduction, or discontinuation of maintenance therapy may be necessary in patients who develop toxicity. The median overall survival time was significantly improved (not reached vs. 41.1 months; hazard ratio = 0.65; 99% to 145% CI, 0.45 to 0.93) in patients with newly diagnosed anaplastic astrocytoma who received adjuvant temozolomide (n = 373) compared with no adjuvant therapy (n = 372) in a planned interim analysis of a randomized, phase 3 (CATNON) trial.

90 mg/m2 orally daily for 42 days plus radiotherapy (RT) followed by adjuvant temozolomide 200 mg/m2 orally daily for 5 days repeated every 28 days for up to 10 cycles starting 4 weeks after RT led to a 3-year event-free survival rate of 11% and a 3-year overall survival (OS) rate of 22% in 90 pediatric patients with newly diagnosed high-grade glioma in a phase 2 trial. In a multicenter study in 31 pediatric patients with newly diagnosed high-grade glioma, adjuvant temozolomide 200 mg/m2 orally daily for 5 days repeated every 28 days for 6 cycles started 4 weeks after RT resulted in 1- and 2-year progression-free survival (PFS) rates of 43% and 11%, respectively, and 1- and 2-year OS rates of 63% and 21%, respectively. Patients in both trials received Pneumocystis jiroveci pneumonia prophylaxis. In 34 pediatric patients with relapsed or progressive, high-grade glioma, treatment with temozolomide 200 mg/m2 orally daily for 5 days repeated every 28 days resulted in an overall response rate of 12% and a median OS time of 4.8 months in a phase 2 trial. Temozolomide 200 mg/m2 orally 3-times daily for 5 days repeated every 28 days led to an ORR of 0%, a median PFS time of 3 months, and a median OS time of 4 months in 24 pediatric patients with recurrent high-grade glioma in a multicenter, phase 2 trial; additionally, the 6-month PFS and OS rates were 33% and 37.5%, respectively. Patients in both trials were receiving a stable corticosteroid dose prior to study entry.

90 mg/m2 orally daily for 42 days plus radiotherapy (RT) followed by adjuvant temozolomide 200 mg/m2 orally daily for 5 days repeated every 28 days up to 10 cycles starting 4 weeks after RT led to a 1-year event-free survival rate of 14%, a 1-year overall survival (OS) rate of 40%, and a median time to progression (TTP) of 6.1 months in 58 pediatric patients with newly diagnosed diffuse intrinsic pontine glioma in a phase 2 trial. In a multicenter study in 33 pediatric patients with newly diagnosed diffuse brainstem glioma, adjuvant temozolomide 200 mg/m2 orally daily for 5 days repeated every 28 days for 6 cycles starting 4 weeks after RT resulted in a median TTP of 8.8 months and a median OS time of 12 months; additionally, 1- and 2-year progression-free survival rates were 27% and 0%, respectively, and the 1-year OS rate was 48%.

200 mg/m2 PO daily for 5 days repeated every 28 days has been studied in clinical trials. Treatment with temozolomide led to a nonsignificantly improved median overall survival (OS) time (7.7 months vs. 6.4 months) and overall response rate (ORR) (13.5% vs. 12.1%) and a significantly improved median progression-free survival (PFS) time (1.9 vs. 1.5 months; p = 0.012) compared with dacarbazine in a multicenter, phase 3 trial in 305 patients with metastatic melanoma. Although combination therapy with temozolomide plus interferon alfa-2b significantly increased ORR compared with temozolomide alone (24.1% vs  13.4%; p = 0.036), the median OS (9.7 months vs. 8.4 months) and PFS (3.3 months vs. 2.4 months) times were not significantly different between the study arms in a multicenter, phase 3 trial in 282 patients with metastatic melanoma. Additionally, combination therapy with temozolomide plus cisplatin did not significantly improve ORR (29% vs. 26%), median OS time (12 months vs. 11.5 months), or median time to progression (5.8 months vs. 3.8 months) compared with temozolomide alone in a phase 2 trial in 127 patients.

†Indicates off-label use

Mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment: Dosage adjustment not necessary.Severe hepatic impairment (Child-Pugh class C): Specific guidelines are not available for dosage adjustments in patients with baseline severe hepatic impairment; temozolomide has not been evaluated in these patients.

Creatinine clearance (CrCl) of 36 mL/min/m2 or more: Dosage adjustment not necessary.CrCl less than 36 mL/min/m2 OR end-stage renal disease requiring dialysis: Specific guidelines are not available; temozolomide use has not been evaluated in these patients.

Acetaminophen; Ibuprofen: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Amlodipine; Celecoxib: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Bacillus Calmette-Guerin Vaccine, BCG: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Bupivacaine; Meloxicam: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Celecoxib: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Celecoxib; Tramadol: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Chikungunya Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
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.
Cyclosporine: (Minor) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Concurrent use of temozolomide with other agents that cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
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.
Diclofenac: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diclofenac; Misoprostol: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diflunisal: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Diphenhydramine; Ibuprofen: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diphenhydramine; Naproxen: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Etodolac: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Febuxostat: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi.
Fenoprofen: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Flurbiprofen: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Hydrocodone; Ibuprofen: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Famotidine: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Oxycodone: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Pseudoephedrine: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Indomethacin: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Intranasal Influenza Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Ketoprofen: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ketorolac: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Live Vaccines: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles/Mumps/Rubella Vaccines, MMR: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Meclofenamate Sodium: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Mefenamic Acid: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Meloxicam: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Methotrexate: (Minor) Concurrent use of temozolomide with other agents that cause bone marrow or immune suppression such as methotrexate may result in additive effects.
Mycophenolate: (Minor) Concurrent use of temozolomide with other agents that cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Nabumetone: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen; Esomeprazole: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen; Pseudoephedrine: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Nonsteroidal antiinflammatory drugs: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Oxaprozin: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Pegfilgrastim: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert their toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Piroxicam: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Rotavirus Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
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.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Smallpox Vaccine, Vaccinia Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Sulindac: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Sumatriptan; Naproxen: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Tacrolimus: (Minor) Concurrent use of temozolomide with other agents that cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Tolmetin: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Typhoid Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Valproic Acid, Divalproex Sodium: (Moderate) Valproic acid decreases the oral clearance of temozolomide. The clinical implication of this effect is not known.
Varicella-Zoster Virus Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Yellow Fever Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.

TEMODAR Intravenous Inj Pwd F/Sol: 100mg
TEMODAR/Temozolomide Oral Cap: 5mg, 20mg, 100mg, 140mg, 180mg, 250mg

75 mg/m2 PO/IV daily with concomitant radiation therapy OR 200 mg/m2 PO/IV daily for 5 days per 28-day cycle.

75 mg/m2 PO/IV daily with concomitant radiation therapy OR 200 mg/m2 PO/IV daily for 5 days per 28-day cycle.

Safety and efficacy not established.

Safety and efficacy not established.

Safety and efficacy not established.

Temozolomide is an imidazotetrazine derivative prodrug that undergoes rapid nonenzymatic conversion at physiologic pH to the reactive compound 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide (MTIC). It is a second-generation DNA alkylating agent that causes crosslinking of double-stranded DNA resulting in calcium-dependent apoptosis and cell death. Alkylation via methylation occurs primarily at the O6 and N7 positions of guanine and cycle arrest usually occurs between the G2- and M-phases. Temozolomide is a lipophilic molecule that crosses the blood-brain barrier and effectively penetrates into glioma cells. A mechanism of temozolomide resistance includes the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT), which is expressed in glioma cells; loss of DNA mismatch repair appears to be another resistance mechanism. Temozolomide exhibits synergy with radiotherapy.

Temozolomide is administered orally and intravenously. It is minimally bound to plasma proteins (15%) and has a mean apparent Vd of 0.4 L/kg (coefficient of variation, 13%), an overall clearance of 5.5 L/hour/m2, and a mean elimination half-life of 1.8 hours. Temozolomide exhibits linear kinetics over a daily dose range of 75 to 250 mg/m2. It is spontaneously hydrolyzed at physiologic pH to an active metabolite, 3-methyl-(triazen-1-yl)imidazole-4-carboxamide (MTIC) and to temozolomide acid. MTIC is further hydrolyzed to 5-amino-imidazole-4-carboxamide (AIC) and methylhydrazine, the active alkylating substance. AIC is known to be an intermediate in purine and nucleic acid biosynthesis. Relative to temozolomide, the exposure of MTIC and AIC is 2.4% and 23%, respectively. Temozolomide and MTIC are not significantly metabolized via CYP450 enzymes. About 38% of a radioactive dose of temozolomide was recovered after 7 days, 37.7% in urine and 0.8% in feces. Most of the radioactivity in urine is unchanged temozolomide (6%), AIC (12%), temozolomide acid metabolite (2.3%), and unidentified polar metabolites (17%).

Temozolomide is rapidly absorbed following oral administration; it has a systemic bioavailability of nearly 100%. Following a single oral dose of temozolomide 150 mg/m2, the mean Cmax values for temozolomide and MTIC were 7.68 (coefficient of variation (CV), 19%) and 0.33 (CV, 62%) micrograms (mcg)/mL, respectively, and the mean AUC(0 to inf) values were 23.6 (CV, 15%) and 1 (CV, 60%) mcg X hour/mL, respectively. The Tmax was reached at a median of 1 (range, 0.25 to 2) hour.
Effects of food: When temozolomide was given after a modified high-fat breakfast (587 total calories), the mean Cmax and AUC values decreased by 32% and 9%, respectively; additionally, the median Tmax increased from 1 to 2.25 hours.

Administering temozolomide 150 mg/m2 orally or as a 90-minute IV infusion met exposure equivalence criteria for Cmax and AUC values for both temozolomide and the active metabolite, 3-methyl-(triazen-1-yl)imidazole-4-carboxamide (MTIC) in a pharmacokinetic study in 19 subjects. Following a single IV dose of temozolomide 150 mg/m2, the mean Cmax values for temozolomide and MTIC were 7.44 (coefficient of variation (CV), 21%) and 0.32 (CV, 61%) micrograms (mcg)/mL, respectively, and the mean AUC(0 to inf) values were 25 (CV, 16%) and 1 (CV, 54%) mcg X hour/mL, respectively.

Temozolomide may cause fetal harm when administered during pregnancy, based on its mechanism of action, animal studies, and limited data in humans. Discuss the potential hazard to the fetus if temozolomide is used during pregnancy. Spontaneous abortion and congenital malformations including central nervous system, facial, cardiac, skeletal, and genitourinary system anomalies have been reported in postmarketing surveillance of temozolomide-exposed pregnant women. Similar adverse developmental outcomes have been observed in animal studies with temozolomide doses that were less than the maximum human dose (based on body surface area).

It is not known if temozolomide or its metabolites are secreted in human milk or if it has effects on the breast-fed child or on milk production. Due to the risk of serious adverse reactions (e.g., myelosuppression) in breast-fed children, advise patients against breast-feeding during temozolomide therapy and for 1 week after the last dose.