Temozolomide (Temodal) is a chemotherapeutic medicine that is activated in the body. The active metabolite of temozolomide is cytotoxic to the tumor cells. It causes DNA breaks by alkylating them.

It is used to treat the following conditions:

• Anaplastic astrocytoma (refractory):

  • It is used in the treatment of refractory anaplastic astrocytoma (refractory to a regimen containing a nitrosourea and procarbazine) in adults

• Glioblastoma multiforme (newly diagnosed):

  • It is used in  Treatment of newly-diagnosed glioblastoma multiforme in adults (initially in combination with radiotherapy, then as maintenance treatment)

• Off Label Use of Temozolomide in Adults:

  • It is used in:

    • Anaplastic gliomas;

    • Astrocytoma (low-grade)/oligodendroglioma (low grade);

    • CNS metastases (from solid tumors);

    • Cutaneous T-cell lymphomas (mycosis fungoides and Sézary syndrome), advanced;

    • Ewing sarcoma (recurrent or progressive);

    • Glioblastoma multiforme (recurrent, relapsed, or progressive);

    • Melanoma, metastatic malignant;

    • Pancreatic neuroendocrine tumors (advanced);

    • Pediatric CNS tumors (anaplastic astrocytoma, brain stem glioma, or medulloblastoma), relapsed or refractory;

    • Primary CNS lymphoma, relapsed or refractory;

    • Soft tissue sarcomas, advanced;

    • Soft tissue sarcoma, hemangiopericytoma/solitary fibrous tumor

Temozolomide (Temodal) Dose in Adults

Temozolomide (Temodal) Dose in the treatment of Anaplastic astrocytoma (refractory):

• Oral or intravenous dose: Initial dose:
• 150 mg/m² once daily given for 5 consecutive days of a 28-day treatment cycle.
• If ANC ≥1,500/mm³ and platelets ≥100,000/mm³, on day 1 of subsequent cycles, it may increase to 200 mg/m² once daily for 5 consecutive days of a 4-week treatment cycle.
• May continue until disease progression.

• Dosage modification for toxicity:

  • ANC <1,000/mm³ or platelets <50,000/mm³ on day 22 or day 29 (day 1 of next cycle)

    • Withhold therapy until ANC >1,500/mm³ and platelets >100,000/mm³
    • reduce dose by 50 mg/m² /day (but not below 100 mg/m ) for subsequent cycle

  • ANC 1,000 to 1,500/mm³ or platelets 50,000 to 100,000/mm³ on day 22 or day 29 (day 1 of next cycle)

    • Postpone therapy until ANC >1,500/mm³ and platelets >100,000/mm³ ; maintain initial dose

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Temozolomide (Temodal) Dose in the treatment of Anaplastic gliomas (off-label):

• 200 mg/m² orally once daily given on days 1 to 5 of a 28-day treatment cycle for 8 cycles

or

• 200 mg/m² once daily given on days 1 to 5 of a 28-day treatment cycle for 6 cycles

or

• (in patients with chromosome 1p/19q loss) 150 mg/m² once daily given for five days of a 28-day treatment cycle in cycles 1 and 2. This is followed by 200 mg/m² once daily for 5 days of subsequent 28-day treatment cycles.

or

• (in patients without chromosome 1p/19q loss) 150 mg/m² once daily given  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

or

• 75 mg/m² once daily given 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

or

• 150 to 200 mg/m² once daily given for 5 days of a 28-day treatment cycle for a maximum of 12 cycles in patients with a complete response or until the progression of the disease.

---

Temozolomide (Temodal) Dose in the treatment of Astrocytoma (low-grade)/oligodendroglioma (low grade) (off-label):

• 75 mg/m² orally once daily given 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

or

• (protracted single-agent therapy) 75 mg/m² once daily given for 21 days of a 28-day treatment cycle for 12 to 15 cycles.

---

Temozolomide (Temodal) Dose in the treatment of CNS metastases from solid tumors (off-label):

• 150 mg/m² (200 mg/m² in chemotherapy-naïve patients) orally once daily given for 5 days of a 28-day treatment cycle until disease progression or unacceptable toxicity up to a maximum of 1 year

or

• 150 mg/m² (200 mg/m² in chemotherapy-naïve patients) once daily given for 5 days of a 28-day treatment cycle until disease progression or unacceptable toxicity

or

• 150 mg/m² once daily given for 5 days of a 28-day treatment cycle until disease progression or unacceptable toxicity

or

• 150 mg/m² once daily given  days 1 to 7 and days 15 to 21 of a 28-day or 35day treatment cycle until disease progression or unacceptable toxicity

or

• 150 mg/m² once daily given 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 four cycles after stable partial response, six cycles after stable disease, or until unacceptable toxicity.

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Temozolomide (Temodal) Dose in the treatment of Cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome), advanced:

• 200 mg/m² orally once daily given for 5 days every 28 days for up to 1 year

---

Temozolomide (Temodal) Dose in the treatment of Ewing sarcoma, recurrent or progressive:

• Oral: 100 mg/m² /dose given  on days 1 to 5 every 21 days (in combination with irinotecan)

---

Temozolomide (Temodal) Dose in the treatment of Glioblastoma multiforme (newly diagnosed, high-grade glioma):

• Concomitant phase:

  • 75 mg/m² once daily given for 42 days (in combination with focal radiotherapy of 60 Gy administered in 30 fractions).
  • Continue at 75 mg/m² once a day throughout the 42-day concomitant phase (up to 49 days) until ANC ≥1,500/mm³, platelet count ≥100,000/mm³, and nonhematologic toxicity ≤ grade 1 (excludes alopecia, nausea/vomiting)

• Dosage modification for toxicity:

  • ANC ≥500/mm but <1,500/mm or platelet count ≥10,000/mm but <100,000/mm or grade 2 nonhematologic toxicity (excludes alopecia, nausea/vomiting):

    • Interrupt therapy

  • ANC <500/mm or platelet count <10,000/mm or grade 3/4 nonhematologic toxicity (excludes alopecia, nausea/vomiting):

    • Discontinue therapy

• Maintenance phase (consists of 6 treatment cycles):

  • • Start 4 weeks after concomitant phase completion.

  • Cycle 1:

    • 150 mg/m² once daily given for 5 days of a 28-day treatment cycle

  • Cycles 2 to 6:

    • May increase to 200 mg/m² once daily for 5 days
    • The dose is repeated 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 the dose was not increased at the onset of cycle 2, do not increase for cycles 3 to 6.

• Maintenance phase dosage modification for toxicity:

  • Monitor blood CP within 48 hours of day 22
  • Withhold next cycle and monitor CBC weekly until ANC >1,500/mm³ and platelet count >100,000/mm³
  • dosing modification should be based on the lowest blood counts and worst non-hematologic toxicity during the previous cycle.

• ANC <1,000/mm³ , platelet count <50,000/mm³ , or grade 3 nonhematologic toxicity (excludes alopecia, nausea/vomiting) during previous cycle:

  • Decrease dose by 1 dose level (by 50 mg/m² /day for 5 days), unless dose has already been lowered to 100 mg/m² /day, then stop therapy.

• If dose reduction <100 mg/m² /day is required or grade 4 nonhematologic toxicity (excludes alopecia, nausea/vomiting), or if the same grade 3 nonhematologic toxicity occurs after dose reduction:

  • Stop therapy

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Temozolomide (Temodal) Dose in the treatment of Glioblastoma multiforme, recurrent, relapsed, or progressive (off-label):

• 200 mg/m² orally once daily given for 5 days every 28 days
• if previously treated with chemotherapy, start 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

or

• 200 mg/m² once daily for 5 days every 28 days for up to 9 cycles or until disease progression

or

• 150 mg/m² once daily given  on days 1 to 7 and days 15 to 21 of a 28-day treatment cycle for a maximum of 12 cycles

or

• 50 mg/m² once daily for a maximum of 12 months or until disease progression

or

• 50 mg/m² once daily until disease progression

---

Temozolomide (Temodal) Dose in the treatment of Melanoma, metastatic malignant:

• 200 mg/m² orally once daily given for 5 days every 28 days (for up to 12 cycles in the absence of disease progression or unacceptable toxicity).
• Reduce the dose by one-fourth in subsequent cycles for grade 3/4 hematologic toxicity and reduce the dose by half for grade 3/4 nonhematologic toxicity

---

Temozolomide (Temodal) Dose in the treatment of advanced pancreatic neuroendocrine tumors:

• 150 mg/m² once daily given for 7 days every 14 days (in combination with bevacizumab) until disease progression or unacceptable toxicity

or

• 150 mg/m² once daily given  for 7 days every 14 days (in combination with everolimus) for 6 months

or

• 150 mg/m² once daily given  for 7 days every 14 days (in combination with thalidomide) until disease progression or unacceptable toxicity

or

• 200 mg/m² once daily given (at bedtime) days 10 to 14 (5 days) of a 28-day treatment cycle (in combination with capecitabine)

or

• (single-agent therapy) 100 to 150 mg/m² once daily given for 5 days of a 28-day treatment cycle in cycle 1, followed by 100 to 200 mg/m once daily for 5 days of subsequent 28-day treatment cycles.

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Temozolomide (Temodal) Dose in the treatment of primary CNS lymphoma, relapsed or refractory (off-label; based on limited data):

• 150 mg/m² orally once daily given for 5 days every 28 days, initially in combination with rituximab (for 4 cycles)
• It is followed by temozolomide monotherapy:
• 150 mg/m² once daily given  for 5 days every 28 days for 8 cycles

  OR

• 150 mg/m² once daily given 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 of 150 mg/m² once daily given  for 5 days every 28 days

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Temozolomide (Temodal) Dose in the treatment of advanced Soft tissue sarcomas:

• 75 mg/m² orally once daily given for 6 weeks

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Temozolomide (Temodal) Dose in the treatment of Soft tissue sarcoma, hemangiopericytoma/solitary fibrous tumor:

• 150 mg/m² orally once daily given days 1 to 7 and days 15 to 21 of a 28-day treatment cycle (in combination with bevacizumab)

Temozolomide (Temodal) Dose in Childrens

Temozolomide (Temodal) Dose in the treatment of Ewing sarcoma, recurrent or progressive: 

• Children ≥2 years and Adolescents:
  • 100 mg/m² /dose orally once daily given  for 5 days, repeat cycle every 21 days (in combination with irinotecan
  • Give 1 hour prior to irinotecan

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Temozolomide (Temodal) Dose in the treatment of Neuroblastoma, relapsed or refractory: 

• Irinotecan regimen:

  • 100 mg/m²/dose once daily given for 5 days, repeat cycle every 21 days for up to 6 cycles; in combination with irinotecan
  • Give 1 hour prior to irinotecan.

• Topotecan regimen (TOTEM):

  • 150 mg/m²/dose given  on days 1 to 5 every 28 days; in combination with topotecan
  • Give prior to the topotecan
  • continue until toxicity develops or the disease progresses up to a maximum of 12 months

• Single-agent:

  • Administer doses on days 1 to 5 every 21 to 28 days
  • continue it until disease progression or unacceptable toxicity up to a maximum of 24 cycles

• No prior craniospinal irradiation:

  • 215 mg/m² /day given

• Dose in Previous craniospinal irradiation or relapse after bone marrow transplant:

  • 180 mg/m² /day given

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Temozolomide (Temodal) Dose in the treatment of Solid tumors, relapsed or refractory (including but not limited to brain tumor [astrocytomas, gliomas, medulloblastoma], neuroblastoma, and sarcomas): 

• 200 to 215 mg/m /dose given  on days 1 to 5 every 21 to 28 days

Temozolomide (Temodal) Pregnancy Risk Factor D

• In animal reproduction studies, adverse events were observed.
• If administered to pregnant women, it can cause fetal harm. Female and male patients should use effective contraception to prevent pregnancy while taking temozolomide.
• Based on data from animals, it may affect male fertility.

Use of Temozolomide (Temodal), during lactation

• It is unknown if breast milk contains temozolomide.
• The manufacturer recommends that the infant be stopped breastfeeding and discontinue taking temozolomide. This is in consideration of the possibility of serious adverse reactions.

Temozolomide (Temodal) dose in kidney disease:

• CrCl >=36mL/minute/m2

  • The manufacturer's labeling does not contain any dosage adjustments.
  • However, it is unlikely that dosage adjustment will be required since there was no evidence of temozolomide clearance.

• Severe renal impairment (CrCl = 36 mL/minute/m2

  • The manufacturer's labeling does not contain any dosage adjustments. Use with caution (hasn't been studied).

• Dialysis patients:

  • The manufacturer's labeling does not contain any dosage adjustments (hasn't been studied).

Temozolomide (Temodal) dose in liver disease:

• Mild to moderate impairment:

  • There are no dosage adjustments given in the manufacturer’s labeling; however, pharmacokinetics are similar to patients with normal hepatic function.

• Severe hepatic impairment:

  • There are no dosage adjustments given in the manufacturer’s labeling; use with caution (has not been studied).

Side Effects of Temozolomide (Temodal):

• Cardiovascular:

  • Peripheral Edema

• Central Nervous System:

  • Fatigue
  • Headache
  • Seizure
  • Hemiparesis
  • Dizziness
  • Ataxia

• Dermatologic:

  • Alopecia
  • Skin Rash

• Gastrointestinal:

  • Nausea
  • Vomiting
  • Constipation
  • Anorexia
  • Diarrhea

• Hematologic & Oncologic:

  • Lymphocytopenia
  • Thrombocytopenia
  • Neutropenia
  • Leukopenia

• Infection:

  • Viral Infection

• Neuromuscular & Skeletal:

  • Weakness

• Miscellaneous:

  • Fever

Less Common Side Effects of Temozolomide:

• Central Nervous System:

  • Amnesia
  • Insomnia
  • Drowsiness
  • Paresthesia
  • Paresis
  • Anxiety
  • Memory Impairment
  • Abnormal gait
  • Depression
  • Confusion

• Dermatologic:

  • Pruritus
  • Xeroderma
  • Erythema

• Endocrine & Metabolic:

  • Hypercorticoidism
  • Weight Gain

• Gastrointestinal:

  • Stomatitis
  • Abdominal Pain
  • Dysphagia
  • Dysgeusia

• Genitourinary:

  • Urinary Incontinence
  • Urinary Tract Infection
  • Mastalgia
  • Urinary Frequency

• Hematologic & Oncologic:

  • Anemia

• Hypersensitivity:

  • Hypersensitivity Reaction

• Neuromuscular & Skeletal:

  • Back Pain
  • Arthralgia
  • Myalgia

• Ophthalmic:

  • Blurred Vision
  • Diplopia
  • Visual Disturbance

• Respiratory:

  • Pharyngitis
  • Upper Respiratory Tract Infection
  • Cough
  • Sinusitis
  • Dyspnea

• Miscellaneous:

  • Radiation Injury

Contraindications to Temozolomide (Temodal):

•  

  • Hypersensitivity (allergic reaction to temozolomide, any part of the formulation, anaphylaxis or Stevens-Johnson syndrome; toxic epidermal necrolysis)
  • Hypersensitivity to dacarbazine (both drugs can be metabolized to MTIC).
  • Patients with severe myelosuppression

Warnings and precautions

• Suppression of bone marrow

  • Myelosuppression is possible
  • You may need to interrupt treatment, reduce doses or discontinue medication; keep track of your blood count.
  • Geriatric and female patients have been affected by an increased risk of hematologic toxicities.
  • Aplastic anemia can be caused by prolonged pancytopenia.
  • The development of aplastic encephalopathy may be obscured by concurrent use of temozolomide and medications that are associated with it (eg, co-trimoxazole or carbamazepine).
  • Before treatment, ANC should be at least 1,500/mm and platelets at least 100,000/mm.

• Gastrointestinal toxicities:

  • Temozolomide has moderate emetic properties.
  • Antiemetics are used to prevent nausea or vomiting.

• Hepatotoxicity

  • Hepatotoxicity has been reported; it can be fatal or severe.
  • At baseline, halfway through each cycle and after each subsequent cycle, monitor liver function.
  • Hepatotoxicity has been reported in postmarketing reports as liver function abnormalities and hepatitis.

• Hypersensitivity

  • Temozolomide has been associated with allergic reactions, including anaphylaxis.

• Pneumocystis pneumonia

  • The possibility of pneumocystis pneumonia jirovecii (PCP), can occur. This is more common in people who are taking steroids or have temozolomide longer-term treatment.
  • All patients should be monitored for PCP, especially if they are also taking corticosteroids.
  • Patients with newly diagnosed glioblastoma are eligible for PCP prophylaxis. This is done in conjunction with radiotherapy and the 42-day regimen of temozolomide.

• Secondary malignancies

  • There have been cases of myelodysplastic Syndrome and secondary malignancies including myeloid Leukemia.

• Hepatic impairment

  • Patients with severe hepatic impairment should be cautious.

• Renal impairment

  • Patients with severe renal impairment should be cautious; it has not been tested in patients on dialysis.

Temozolomide: Drug Interaction

Risk Factor C (Monitor therapy)
Chloramphenicol (Ophthalmic)	May enhance the adverse/toxic effect of Myelosuppressive Agents.
CloZAPine	Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased.
Coccidioides immitis Skin Test	Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test.
Denosumab	May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
Mesalamine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Ocrelizumab	May enhance the immunosuppressive effect of Immunosuppressants.
Pidotimod	Immunosuppressants may diminish the therapeutic effect of Pidotimod.
Promazine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Siponimod	Immunosuppressants may enhance the immunosuppressive effect of Siponimod.
Trastuzumab	May enhance the neutropenic effect of Immunosuppressants.
Valproate Products	May enhance the adverse/toxic effect of Temozolomide. Valproate Products may increase the serum concentration of Temozolomide.
Risk Factor D (Consider therapy modification)
Baricitinib	Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted.
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.
Echinacea	May diminish the therapeutic effect of Immunosuppressants.
Fingolimod	Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections).
Leflunomide	Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly.
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.
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.
Nivolumab	Immunosuppressants may diminish the therapeutic effect of Nivolumab.
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.
Roflumilast	May enhance the immunosuppressive effect of Immunosuppressants.
Sipuleucel-T	Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy.
Tofacitinib	Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants.
Vaccines (Inactivated)	Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation.
Risk Factor X (Avoid combination)
BCG (Intravesical)	Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical).
BCG (Intravesical)	Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical).
Cladribine	May enhance the immunosuppressive effect of Immunosuppressants.
Cladribine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Dipyrone	May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased
Natalizumab	Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.
Pimecrolimus	May enhance the adverse/toxic effect of Immunosuppressants.
Tacrolimus (Topical)	May enhance the adverse/toxic effect of Immunosuppressants.
Vaccines (Live)	Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants.

Monitor:

• CBC with differential and platelets
  • prior to each cycle;
  • weekly during glioma concomitant phase treatment;
  • at or within 48 hours of day 22 and weekly until ANC >1,500/mm and platelets >100,000/mm for glioma maintenance and astrocytoma treatment.
• 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.

How to administer Temozolomide (Temodal)?

• Temozolomide is associated with a moderate emetic potential
• antiemetics are given to prevent nausea and vomiting.

Oral administration:

• Swallow capsules whole with a glass of water
• do not open or chew.
• It should be administered consistently either with or without food.
• May be administered on an empty stomach and/or at bedtime to reduce nausea and vomiting.
• The dose should not be repeated if vomiting occurs after the dose is administered
• wait until the next scheduled dose.
• Avoid contact with skin or mucous membranes of open or damaged capsules.

Intravenous administration:

• Administer over 90 minutes.
• Flush the line before and after administration.
• May be given through the same IV line as sodium chloride 0.9%
• Other solutions or medications should not be administered through the same intravenous line.

Mechanism of action of Temozolomide (Temodal):

• Temozolomide, a prodrug that is quickly and non-enzymatically transformed to the active alkylating metabolism MTIC ((methyl-triazene-1 yl)-imidazole-4 -carboxamide), is quickly and easily converted
• This conversion occurs spontaneously, without enzymes, in all tissues it is distributed in.
• MTIC can cause cytotoxic effects by alkylation (methylation), of DNA at the O6 and N7 guanine positions. This causes DNA double strand breakage and apoptosis.
• Temozolomide, a non-cell cycle-specific drug, is available

Absorption: Oral:

• It is Rapid and complete

Distribution: V : Parent drug:

• 0.4 L/kg; penetrates blood-brain barrier; CSF levels are ~35% to 39% of plasma levels

Protein binding:

• 15%

Metabolism:

• Prodrug is hydrolyzed to the active form, MTIC
• MTIC is eventually eliminated as CO 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:

• Empty stomach: 1 hour & with food (high-fat meal): 2.25 hours

Excretion:

• Via Urine (~38%; parent drug 6%) & feces <1%
• Clearance: 5.5 L/hour/m & women have a ∼5% lower clearance than men (adjusted for body surface area)

International Brands of Temozolomide:

• ACH-Temozolomide
• ACT Temozolomide
• TARO-Temozolomide
• Temodal
• Accotim
• Advecit
• Astrodal
• Astromide
• Blastomat
• Chemtheraz
• Dralitem
• Emzolam-100
• Niman
• Rubrum ASF
• Temo
• Temobela
• Temodal
• Temodal IV
• Temolde
• Temomedac
• Temonix
• Temoro
• Temotec
• Temotero
• Temovex
• Temozam
• Temozol
• Zolomide
• Zolotem-250

Temozolomide Brand Names in Pakistan:

No Brands Available in Pakistan.