Note: Temozolomide is associated with a low or moderate emetic potential depending on dose (POGO [Dupuis 2011]; POGO [Paw Cho Sing 2019]); antiemetics may be recommended to prevent nausea and vomiting. Prior to dosing, ANC should be ≥1,500/mm3 and platelets ≥100,000/mm3. Dose, frequency, number of doses, and start date may vary by protocol and treatment phase. Refer to individual protocols.
Ewing sarcoma, recurrent or progressive: Limited data available: Children ≥2 years and Adolescents: Oral: 100 mg/m2/dose once daily for 5 days, repeat cycle every 21 days (in combination with irinotecan; administer 1 hour prior to irinotecan) (Casey 2009); dosing based on a retrospective review.
Neuroblastoma , relapsed or refractory: Limited data available:
Irinotecan regimen: Infants, Children, and Adolescents: Oral: 100 mg/m2/dose once daily for 5 days, repeat cycle every 21 days for up to 6 cycles; in combination with irinotecan; administer 1 hour prior to irinotecan (Bagatell 2011). Note: Temozolomide doses were rounded to the nearest capsule size.
Topotecan regimen (TOTEM): Infants ≥6 months, Children, and Adolescents: Oral: 150 mg/m2/dose on days 1 to 5 every 28 days; in combination with topotecan; administer prior to the topotecan; continue until disease progression or unacceptable toxicity up to a maximum of 12 months; doses were reduced for hematologic toxicity (Di Giannatale 2014).
Single agent: Children ≥3 years and Adolescents: Oral: Administer doses on days 1 to 5 every 21 to 28 days; continue until disease progression or unacceptable toxicity up to a maximum of 24 cycles; doses were reduced by 25% for grade 4 thrombocytopenia or neutropenia, and grade 3 or 4 mucositis, documented sepsis, pulmonary distress/infiltrate, or seizures requiring prophylaxis (De Sio 2006).
No prior craniospinal irradiation: Oral: 215 mg/m2/day.
Previous craniospinal irradiation or relapse after bone-marrow transplant: Oral: 180 mg/m2/day.
Solid tumors, relapsed or refractory (including but not limited to brain tumor [astrocytomas, gliomas, medulloblastoma], neuroblastoma, and sarcomas): Limited data available; efficacy results variable: Infants, Children, and Adolescents: Oral: 200 to 215 mg/m2/dose days 1 to 5 every 21 to 28 days; dose was decreased to 180 mg/m2/dose for patients who received prior craniospinal irradiation or relapsed after bone marrow transplant (De Sio 2006; Nicholson 2007); in other trials, lower doses of 160 to 200 mg/m2/dose once daily for 5 days every 28 days were used in patients 3 to 18 years of age (manufacturer labeling).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no pediatric specific recommendations; refer to individual protocols if available. Based on experience in adult patients with mild to moderate renal impairment, no effect on temozolomide clearance was demonstrated; in severe impairment and dialysis, use with caution; has not been adequately studied.
There are no pediatric specific recommendations; refer to individual protocols if available. Based on experience in adult patients, use with caution; has not been adequately studied.
(For additional information see "Temozolomide: Drug information")
Note: Temozolomide is associated with a moderate or high emetic potential (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]); antiemetics are recommended to prevent nausea and vomiting. Pneumocystis jirovecii pneumonia prophylaxis is required during concomitant phase (with radiation therapy) and should continue in patients who develop lymphocytopenia until lymphocyte recovery to ≤ grade 1. ANC should be ≥1,500/mm3 and platelets ≥100,000/mm3 prior to administration.
Anaplastic astrocytoma (refractory): Oral, IV: Initial dose: 150 mg/m2 once daily on days 1 to 5 every 28 days. If ANC ≥1,500/mm3 and platelets ≥100,000/mm3 at the nadir and on day 1 of the next cycle, increase dose to 200 mg/m2 on days 1 to 5 every 28 days and continue until disease progression or unacceptable toxicity (in the clinical trial, temozolomide could be continued for up to a maximum of 2 years, although the optimal treatment duration is unknown).
Dosage modification for toxicity:
Monitor CBC on day 22 and then weekly until ANC >1,500/mm3 and platelet count >100,000/mm3; do not initiate the next cycle until ANC >1,500/mm3 and platelets >100,000/mm3.
ANC <1,000/mm3 or platelets <50,000/mm3 during any cycle: Reduce temozolomide dose for the next cycle by 50 mg/m2/day. Permanently discontinue if unable to tolerate a dose of 100 mg/m2/day.
Anaplastic gliomas (off-label use): Oral: 200 mg/m2 once daily on days 1 to 5 of a 28-day treatment cycle for 8 cycles (Wick 2009) or 200 mg/m2 once daily on days 1 to 5 of a 28-day treatment cycle for 6 cycles (Gan 2010) or (in patients with chromosome 1p/19q loss) 150 mg/m2 once daily for 5 days of a 28-day treatment cycle in cycles 1 and 2, followed by 200 mg/m2 once daily for 5 days of subsequent 28-day treatment cycles (Mikkelsen 2009) or (in patients without chromosome 1p/19q loss) 150 mg/m2 once daily for 5 days of a 28-day treatment cycle in cycles 1 and 2, followed by 200 mg/m2 once daily for 5 days for up to two 28-day cycles, followed by 75 mg/m2 once daily during radiation therapy, and then followed by post-radiation temozolomide treatment (Mikkelsen 2009) or 75 mg/m2 once daily for a maximum of 7 weeks during radiation therapy and then (adjuvant therapy) 150 mg/m2 once daily for 5 days of a 28-day treatment cycle in cycle 1, followed by 200 mg/m2 once daily for 5 days of subsequent 28-day treatment cycles for up to a total of 12 adjuvant cycles (van den Bent 2017) or 150 to 200 mg/m2 once daily for 5 days of a 28-day treatment cycle for a maximum of 12 cycles in patients with a complete response or until disease progression in patients with partial response or stable disease (Brandes 2006).
Astrocytoma (low-grade)/oligodendroglioma (low grade) (off-label use): Oral: 75 mg/m2 once daily during radiation therapy and then (adjuvant therapy) 150 to 200 mg/m2 once daily for 5 days of a 28-day treatment cycle for up to 12 cycles (Fisher 2015) or (protracted single-agent therapy) 75 mg/m2 once daily for 21 days of a 28-day treatment cycle for 12 to 15 cycles (Pouratian 2007).
CNS metastases from solid tumors (off-label use): Oral: 150 mg/m2 (200 mg/m2 in chemotherapy-naïve patients) once daily for 5 days of a 28-day treatment cycle until disease progression or unacceptable toxicity up to a maximum of 1 year (Agarwala 2004) or 150 mg/m2 (200 mg/m2 in chemotherapy-naïve patients) once daily for 5 days of a 28-day treatment cycle until disease progression or unacceptable toxicity (Abrey 2001) or 150 mg/m2 once daily for 5 days of a 28-day treatment cycle until disease progression or unacceptable toxicity (Christodoulou 2001) or 150 mg/m2 once daily on days 1 to 7 and days 15 to 21 of a 28-day or 35-day treatment cycle until disease progression or unacceptable toxicity (Siena 2010) or 150 mg/m2 once daily on days 1 to 7 and days 15 to 21 of a 28-day treatment cycle for a maximum of 2 cycles after complete response, until disease progression or for 4 cycles after stable partial response, 6 cycles after stable disease, or until unacceptable toxicity (Trudeau 2006).
Cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome), advanced (off-label use; based on limited data): Oral: 200 mg/m2 once daily for 5 days every 28 days for up to 1 year (Querfeld 2011).
Ewing sarcoma, recurrent or progressive (off-label use; based on limited data): Oral: 100 mg/m2/dose on days 1 to 5 every 21 days (in combination with irinotecan) (Casey 2009).
Glioblastoma (newly diagnosed, high-grade glioma):
Concomitant phase: Oral, IV: 75 mg/m2 once daily for 42 days (in combination with focal radiotherapy of 60 Gy administered in 30 fractions).
Continue at 75 mg/m2 once daily throughout the 42-day concomitant phase (up to 49 days) as long as ANC ≥1,500/mm3, platelet count ≥100,000/mm3, and nonhematologic toxicity ≤ grade 1 (excludes alopecia, nausea/vomiting).
Dosage modification for toxicity:
ANC ≥500/mm3 but <1,500/mm3 or platelet count ≥10,000/mm3 but <100,000/mm3 or grade 2 nonhematologic toxicity (excludes alopecia, nausea/vomiting): Interrupt temozolomide therapy; resume temozolomide when ANC ≥1,500/mm3, platelet count ≥100,000/mm3, and nonhematologic toxicity is resolved to ≤ grade 1.
ANC <500/mm3 or platelet count <10,000/mm3 or grade 3 or 4 nonhematologic toxicity (excludes alopecia, nausea/vomiting): Discontinue therapy.
Maintenance phase (consists of 6 treatment cycles): Begin 4 weeks after concomitant phase completion.
Cycle 1: Oral, IV: 150 mg/m2 once daily on days 1 to 5 of a 28-day treatment cycle.
Cycles 2 to 6: Oral, IV: May increase to 200 mg/m2 once daily on days 1 to 5; repeat every 28 days (if ANC ≥1,500/mm3, platelets ≥100,000/mm3, and nonhematologic toxicities for cycle 1 are ≤ grade 2 [excludes alopecia, nausea/vomiting]). If dose was not escalated at the onset of cycle 2, do not increase for cycles 3 to 6.
Maintenance phase dosage modification for toxicity:
Monitor CBC on day 22 and then weekly until ANC >1,500/mm3 and platelet count >100,000/mm3.
ANC <1,000/mm3, platelet count <50,000/mm3, or grade 3 nonhematologic toxicity (excludes alopecia, nausea/vomiting) during previous cycle: Interrupt temozolomide therapy; when ANC >1,500/mm3, platelet count >100,000/mm3, and nonhematologic toxicity is resolved to ≤ grade 1, resume temozolomide at a reduced dose for the next cycle. If temozolomide is withheld, decrease dose by 50 mg/m2/day. Permanently discontinue if unable to tolerate a dose of 100 mg/m2/day.
Duration of therapy: A retrospective analysis of 4 randomized studies in patients with newly diagnosed glioblastoma who were progression free following 6 cycles of adjuvant temozolomide therapy determined that continued administration beyond 6 cycles did not demonstrate improvement in overall survival (Blumenthal 2017). In a randomized study in patients with stable disease after 6 cycles, those randomized to a total of 12 temozolomide cycles had similar progression free and overall survival as the patients who stopped after 6 cycles; however, toxicities, including lymphopenia, thrombocytopenia, and nausea/vomiting, were higher in the patients who continued temozolomide beyond 6 months (Balana 2020).
Glioblastoma, recurrent, relapsed, or progressive (off-label use): Oral: 200 mg/m2 once daily for 5 days every 28 days; if previously treated with chemotherapy, initiate at 150 mg/m2 once daily for 5 days every 28 days and increase to 200 mg/m2 once daily for 5 days every 28 days with cycle 2 if no hematologic toxicity (Brada 2001; Yung 2000) or 200 mg/m2 once daily for 5 days every 28 days for up to 9 cycles or until disease progression (Brada 2010) or 150 mg/m2 once daily on days 1 to 7 and days 15 to 21 of a 28-day treatment cycle for a maximum of 12 cycles (Wick 2007) or 50 mg/m2 once daily for a maximum of 12 months or until disease progression (Perry 2010) or 50 mg/m2 once daily until disease progression (Omuro 2013).
Melanoma, metastatic malignant (off-label use): Oral: 200 mg/m2 once daily for 5 days every 28 days (for up to 12 cycles in the absence of disease progression or unacceptable toxicity). Reduce the dose by 25% in subsequent cycles for grade 3/4 hematologic toxicity and reduce the dose by 50% for grade 3/4 nonhematologic toxicity (Middleton 2000).
Pancreatic neuroendocrine tumors, advanced (off-label use): Oral: 150 mg/m2 once daily for 7 days every 14 days (in combination with bevacizumab) until disease progression or unacceptable toxicity (Chan 2012) or 150 mg/m2 once daily for 7 days every 14 days (in combination with everolimus) for 6 months (Chan 2013) or 150 mg/m2 once daily for 7 days every 14 days (in combination with thalidomide) until disease progression or unacceptable toxicity (Kulke 2006) or 200 mg/m2 once daily (at bedtime) on days 10 to 14 (5 days) of a 28-day treatment cycle (in combination with capecitabine) (Kunz 2018; Strosberg 2011) or (single-agent therapy) 100 to 150 mg/m2 once daily for 5 days of a 28-day treatment cycle in cycle 1, followed by 100 to 200 mg/m2 once daily for 5 days of subsequent 28-day treatment cycles (Ekeblad 2007).
Primary CNS lymphoma, newly diagnosed (off-label use; based on limited data): Oral: Induction: 150 mg/m2 once daily on days 7 to 11 each month for 5 months (in combination with 14-day cycles of high-dose methotrexate, leucovorin, and rituximab; temozolomide is administered during odd cycles), followed by consolidation therapy with etoposide and cytarabine; refer to protocol for details (Rubenstein 2013).
Primary CNS lymphoma, relapsed or refractory (off-label use; based on limited data): Oral: 150 mg/m2 once daily for 5 days every 28 days, initially in combination with rituximab (for 4 cycles), followed by temozolomide monotherapy: 150 mg/m2 once daily for 5 days every 28 days for 8 cycles (Wong 2004) or 150 mg/m2 once daily on days 1 to 7 and 15 to 21 every 28 days (initially in combination with rituximab for 1 or 2 cycles), followed by temozolomide maintenance monotherapy: 150 mg/m2 once daily for 5 days every 28 days (Enting 2004).
Soft tissue sarcomas, advanced (off-label use): Oral: 75 mg/m2 once daily for 6 weeks (Garcia del Muro 2005).
Soft tissue sarcoma, hemangiopericytoma/solitary fibrous tumor (off-label use; based on limited data): Oral: 150 mg/m2 once daily on days 1 to 7 and days 15 to 21 of a 28-day treatment cycle (in combination with bevacizumab) (Park 2011).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥36 mL/minute/m2: No dosage adjustment necessary.
CrCl <36 mL/minute/m2: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Dialysis patients: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Mild to moderate impairment (Child-Pugh classes A and B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Temodar: 5 mg [DSC] [contains fd&c blue #2 (indigotine)]
Temodar: 20 mg [DSC], 100 mg
Temodar: 140 mg [contains fd&c blue #2 (indigotine)]
Temodar: 180 mg, 250 mg
Generic: 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, 250 mg
Solution Reconstituted, Intravenous [preservative free]:
Temodar: 100 mg (1 ea) [pyrogen free; contains polysorbate 80]
May be product dependent
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Temodal: 5 mg [contains fd&c blue #2 (indigotine)]
Temodal: 20 mg, 100 mg [contains alcohol, usp]
Temodal: 140 mg [contains fd&c blue #2 aluminum lake]
Temodal: 250 mg [contains alcohol, usp]
Generic: 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, 250 mg
Temozolomide is associated with a low or moderate emetic potential depending on dose (POGO [Dupuis 2011]; POGO [Paw Cho Sing 2019]); antiemetics may be recommended to prevent nausea and vomiting.
Oral: Swallow capsule intact with a glass of water; do not chew; per manufacturer's labeling, capsules should not be opened. However, capsules are large and often cannot be swallowed by pediatric patients; if patient is unable to swallow capsule, open capsule and dissolve in acidic juice (eg, orange juice, apple juice) or applesauce, taking precautions to avoid exposure to the cytotoxic agent (De Sio 2006; Wagner 2013); an extemporaneously prepared oral solution or suspension may also be used. Administer temozolomide on an empty stomach or at bedtime to reduce the incidence of nausea and vomiting; absorption is affected by food; may administer with food as long as food intake and administration are performed at the same time each day to ensure consistent bioavailability. Do not repeat if vomiting occurs after dose is administered; wait until the next scheduled dose.
Temozolomide is associated with a moderate or high emetic potential (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]); antiemetics are recommended to prevent nausea and vomiting.
Oral: Swallow capsules whole with a full glass of water; do not open or chew. Administer consistently with respect to food (either consistently fasting or nonfasting). Administer on an empty stomach and/or at bedtime to reduce nausea and vomiting. Do not repeat dose if vomiting occurs after dose is administered; wait until the next scheduled dose. If capsules are accidently opened or damaged, avoid inhalation or contact with skin or mucous membranes.
Note: In some glioblastoma studies of temozolomide with concurrent radiation therapy, temozolomide was administered in a fasted state, 1 hour prior to radiotherapy (on radiotherapy days), and either in the morning or per institutional protocol on nonradiotherapy days (Perry 2017; Stupp 2002).
IV: Infuse over 90 minutes (shorter or longer infusion times may result in suboptimal dosing). Flush line before and after administration. May be administered through the same IV line as sodium chloride 0.9%; do not administer other solutions or medications through the same IV line.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Capsule: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Injection: Store intact vials at 2°C to 8°C (36°F to 46°F). Reconstituted vials may be stored for up to 14 hours at room temperature of 25°C (77°F); infusion must be completed within 14 hours of reconstitution.
Treatment of refractory anaplastic astrocytoma with progression after initial therapy with a nitrosourea and procarbazine (FDA approved in adults); treatment of newly-diagnosed glioblastoma multiforme (initially in combination with radiotherapy, then as maintenance treatment) (FDA approved in adults); has also been used in neuroblastoma (relapsed or refractory), Ewing sarcoma (recurrent or progressive), and solid tumors (relapsed or refractory)
Temodar may be confused with Tambocor
Temozolomide may be confused with temsirolimus
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. With CNS malignancies, it may be difficult to distinguish between CNS adverse events caused by temozolomide versus the effects of progressive disease.
>10%:
Cardiovascular: Peripheral edema (11%)
Dermatologic: Alopecia (55%), skin rash (8% to 13%)
Gastrointestinal: Nausea (49% to 53%), vomiting (29% to 42%), constipation (22% to 33%), anorexia (9% to 27%), diarrhea (10% to 16%)
Hematologic & oncologic: Lymphocytopenia (grades 3/4: 55%), thrombocytopenia (8%; grades 3/4: 4% to 19%), decreased neutrophils (grades 3/4: 14%), leukopenia (grades 3/4: 11%)
Infection: Viral infection (11%)
Nervous system: Fatigue (34% to 61%), headache (23% to 41%), seizure (6% to 23%), hemiparesis (18%), dizziness (5% to 12%), ataxia (8% to 11%)
Neuromuscular & skeletal: Asthenia (7% to 13%)
Miscellaneous: Fever (13%)
1% to 10%:
Dermatologic: Pruritus (5% to 8%), xeroderma (5%), erythema of skin (1%)
Endocrine & metabolic: Hypercorticoidism (8%), weight gain (5%)
Gastrointestinal: Stomatitis (9%; grades ≥3: 1%), abdominal pain (5% to 9%), dysphagia (7%), dysgeusia (5%)
Genitourinary: Urinary incontinence (8%), urinary tract infection (8%), mastalgia (females: 6%), urinary frequency (6%)
Hematologic & oncologic: Decreased hemoglobin (grades 3/4: 4%)
Hypersensitivity: Hypersensitivity reaction (3%)
Nervous system: Amnesia (10%), insomnia (4% to 10%), drowsiness (9%), paresthesia (9%), paresis (8%), anxiety (7%), memory impairment (7%), abnormal gait (6%), depression (6%), confusion (5%)
Neuromuscular & skeletal: Back pain (8%), arthralgia (6%), myalgia (5%)
Ophthalmic: Blurred vision (5% to 8%), diplopia (5%), visual disturbance (visual deficit/vision changes: 5%)
Respiratory: Pharyngitis (8%), upper respiratory tract infection (8%), cough (5% to 8%), sinusitis (6%), dyspnea (5%)
Frequency not defined:
Hematologic & oncologic: Anemia, myelodysplastic syndrome, secondary acute myelocytic leukemia
Respiratory: Pneumonia due to Pneumocystis jirovecii
<1%, postmarketing, and/or case reports: Anaphylaxis, aplastic anemia, cholestasis, diabetes insipidus, erythema multiforme, hematoma, hepatitis, hepatotoxicity, hyperbilirubinemia, increased liver enzymes, injection site reaction (erythema, irritation, pain, pruritus, swelling, warmth), interstitial pneumonitis, opportunistic infection, pancytopenia (may be prolonged), petechia, pneumonitis, pulmonary alveolitis, pulmonary fibrosis, Stevens-Johnson syndrome, toxic epidermal necrolysis
Hypersensitivity to temozolomide or any component of the formulation; hypersensitivity to dacarbazine (both drugs are metabolized to [methyl-triazene-1-yl]-imidazole-4-carboxamide).
Canadian labeling: Additional contraindications (not in the US labeling): Not recommended in patients with severe myelosuppression.
Concerns related to adverse effects:
• Bone marrow suppression: Myelosuppression (including leukopenia, anemia, and pancytopenia), some with fatal outcomes, may occur. Hematologic toxicity may require treatment interruption, dose reduction, and/or discontinuation. An increased risk of hematologic toxicity has been reported in geriatric and female patients. ANC should be ≥1,500/mm3 and platelets ≥100,000/mm3 prior to treatment.
• Hepatotoxicity: Hepatotoxicity has been reported; may be severe or fatal. Postmarketing reports of hepatotoxicity have included liver function abnormalities, hepatitis, hepatic failure, cholestasis, hepatitis cholestasis, jaundice, cholelithiasis, hepatic steatosis, hepatic necrosis, hepatic lesion, and hepatic encephalopathy (Sarganas 2012).
• Hypersensitivity: Allergic reactions (including anaphylaxis) have been observed with temozolomide.
• Pneumocystis pneumonia: Pneumocystis jirovecii pneumonia (PCP) may occur in patients receiving temozolomide; risk is increased in those receiving corticosteroids or with longer temozolomide treatment regimens. Provide PCP prophylaxis to all patients with newly diagnosed glioblastoma receiving concomitant phase radiotherapy; continue in patients with lymphopenia until lymphopenia resolves to ≤ grade 1.
• Secondary malignancies: Cases of myelodysplastic syndromes and secondary malignancies, including myeloid leukemia, have been reported following treatment with temozolomide.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with severe hepatic impairment.
• Renal impairment: Use with caution in patients with severe renal impairment; has not been studied in dialysis patients.
Special populations:
• Elderly: Patients ≥70 years of age experienced a higher incidence of grade 4 neutropenia and thrombocytopenia in cycle 1 (compared to younger patients).
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Other warnings/precautions:
• Administration schedule: Administration schedule (intermittent versus continuous) varies based on indication.
• Temozolomide resistance: Increased O-6-methylguanine-DNA methyltransferase (MGMT) activity/levels within tumor tissue is associated with temozolomide resistance. Glioblastoma patients with decreased levels (due to methylated MGMT promoter) may be more likely to benefit from the combination of radiation therapy and temozolomide (Hegi 2008; Stupp 2009). Determination of MGMT status may be predictive for response to alkylating agents.
None known.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: In the US, after receipt of the single dose COVID-19 adenovirus vector vaccine (Janssen), administer an additional 2nd dose using an mRNA COVID-19 vaccine, at least 28 days after the primary vaccine dose, in patients taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Consider administration of a 3rd dose of COVID-19 vaccine, at least 28 days after completion of the primary 2-dose series, in patients 5 years of age and older taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider avoiding echinacea in patients receiving therapeutic immunosuppressants, such cytotoxic chemotherapy. If combined, monitor for reduced efficacy of cytotoxic chemotherapy. Risk D: Consider therapy modification
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Valproate Products: May enhance the adverse/toxic effect of Temozolomide. Valproate Products may increase the serum concentration of Temozolomide. Risk C: Monitor therapy
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Food reduces rate and extent of absorption. Management: Administer consistently either with food or without food (was administered in studies under fasting and nonfasting conditions).
Evaluate pregnancy status prior to use in females of reproductive potential. Females of reproductive potential should use effective contraception during treatment and for at least 6 months after the last temozolomide dose. Males with pregnant partners or with female partners of reproductive potential should use condoms during treatment and for at least 3 months after the last temozolomide dose.
Males should not donate semen during treatment and for at least 3 months after the last temozolomide dose.
Temozolomide may impair fertility; limited data indicate changes in sperm parameters during temozolomide treatment; however, there is no information in duration or reversibility of sperm changes.
Based on the mechanism of action and findings in animal reproduction studies, in utero exposure to temozolomide may cause fetal harm.
Refer to pediatric-specific protocols. CBC with differential and platelets (prior to each cycle; at or within 48 hours of day 22 and weekly until ANC >1,500/mm3 and platelets >100,000/mm3. Monitor liver function tests at baseline, halfway through the first cycle, prior to each subsequent cycle, and at ~2 to 4 weeks after the last dose. Monitor for signs/symptoms of pneumocystis pneumonia. Monitor adherence.
Temozolomide is a prodrug which is rapidly and nonenzymatically converted to the active alkylating metabolite MTIC [(methyl-triazene-1-yl)-imidazole-4-carboxamide]; this conversion is spontaneous, nonenzymatic, and occurs under physiologic conditions in all tissues to which it distributes (Marchesi 2007; Villano 2009). The cytotoxic effects of MTIC are manifested through alkylation (methylation) of DNA at the O6, N7 guanine positions which lead to DNA double strand breaks and apoptosis (Villano 2009). Temozolomide is noncell cycle specific (Marchesi 2007).
Absorption: Oral: Rapid and complete.
Distribution: Vd: Parent drug: 0.4 L/kg. Temozolomide penetrates blood-brain barrier; cerebrospinal fluid levels are ~35% to 39% of plasma levels (Yung 1999).
Protein binding: 15%.
Metabolism: Prodrug, hydrolyzed to the active form, (methyl-triazene-1-yl)-imidazole-4-carboxamide (MTIC); MTIC is eventually eliminated as CO2 and 5-aminoimidazole-4-carboxamide (AIC), a natural constituent in urine; CYP isoenzymes play only a minor role in metabolism (of temozolomide and MTIC).
Bioavailability: Oral: 100% (on a mg-per-mg basis, IV temozolomide, infused over 90 minutes, is bioequivalent to an oral dose).
Half-life elimination: Mean: Parent drug: Children: 1.7 hours; Adults: 1.8 hours.
Time to peak: Oral: Median: 1 hour; with food (high-fat meal): 2.25 hours.
Excretion: Urine (~38%; parent drug 6%; AIC 12%); feces <1%.
Clearance: 5.5 L/hour/m2; pediatric subjects 3 to 17 years have similar temozolomide clearance as adults.
Gender: Females may have an ~5% lower temozolomide clearance (adjusted for body surface area) than males.
To minimize the risk of a wrong dose error, each strength of temozolomide must be packaged and dispensed in a separate vial or in its original glass bottle. Label each container with the appropriate number of capsules to be taken each day.
1.25 mg/mL Oral Solution
Reconstitute temozolomide powder for injection according to the manufacturer's labeling, resulting in a concentration of 2.5 mg/mL; further dilute 1:1 with distilled water, resulting in a final concentration of 1.25 mg/mL. Stable for 13 weeks refrigerated. Prior to administration, dose may be mixed with a small amount of apple juice or cola if needed.
10 mg/mL Oral Suspension
A 10 mg/mL temozolomide oral suspension may be compounded in a vertical flow hood. Mix the contents of ten 100 mg capsules and 500 mg of povidone K-30 powder in a glass mortar; add 25 mg anhydrous citric acid dissolved in 1.5 mL purified water and mix to a uniform paste; mix while adding 50 mL Ora-Plus in incremental proportions. Transfer to an amber plastic bottle, rinse mortar 4 times with small portions of either Ora-Sweet or Ora-Sweet SF, and add quantity of Ora-Sweet or Ora-Sweet SF sufficient to make 100 mL. Store in plastic amber prescription bottles; label "shake well" and "refrigerate"; include the beyond-use date. Stable at room temperature for 7 days (Ora-Sweet) or 14 days (Ora-Sweet SF), or for 60 days refrigerated (preferred).
Capsules (Temodar Oral)
100 mg (per each): $546.72
140 mg (per each): $765.41
180 mg (per each): $984.10
250 mg (per each): $1,366.80
Capsules (Temozolomide Oral)
5 mg (per each): $12.52 - $14.83
20 mg (per each): $50.46 - $57.56
100 mg (per each): $252.29 - $287.76
140 mg (per each): $353.21 - $402.87
180 mg (per each): $454.13 - $517.97
250 mg (per each): $630.91 - $719.60
Solution (reconstituted) (Temodar Intravenous)
100 mg (per each): $1,203.73
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