Temozolomide is an oral chemotherapy drug used primarily in the treatment of brain tumors. It is classified as an alkylating agent and belongs to the class of medications known as nitrosoureas. Temozolomide is commonly prescribed for the management of glioblastoma multiforme, a type of aggressive brain cancer.

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

Note: Temozolomide is a medicine used to treat certain brain tumors. It can cause nausea and vomiting, so doctors may prescribe anti-nausea medications to prevent these side effects. When taken together with radiation therapy, patients may need to take medicine to prevent a type of pneumonia called Pneumocystis pneumonia (PCP). This medicine should be continued if the patient's lymphocyte count is low until it recovers. Before taking temozolomide, the patient's white blood cell count (ANC) should be at least 1,500/mm and platelet count should be at least 100,000/mm.

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

• In the treatment of refractory Anaplastic astrocytoma, the initial dose of Temozolomide is 150 mg/m once daily for 5 consecutive days in a 28-day treatment cycle.
• If the patient's absolute neutrophil count (ANC) is equal to or greater than 1,500/mm and platelet count is equal to or greater than 100,000/mm, the dose may be increased to 200 mg/m once daily for 5 consecutive days in subsequent cycles.
• The treatment can be continued until there is disease progression.

Dosage modification for toxicity:

• If the ANC drops below 1,000/mm or platelet count drops below 50,000/mm on day 22 or day 29 (day 1 of the next cycle), the therapy should be postponed until the ANC is above 1,500/mm and platelet count is above 100,000/mm. In subsequent cycles, the dose should be reduced by 50 mg/m per day (but not below 100 mg/m).
• If the ANC is between 1,000 and 1,500/mm or platelet count is between 50,000 and 100,000/mm on day 22 or day 29, the therapy should also be postponed until the ANC is above 1,500/mm and platelet count is above 100,000/mm, but the initial dose should be maintained.

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

Oral:

• 200 mg/m once daily for 5 days of a 28-day treatment cycle for 8 cycles (Wick 2009)
• 200 mg/m once daily for 5 days of a 28-day treatment cycle for 6 cycles (Gan 2010)
• 150 mg/m once daily for 5 days of a 28-day treatment cycle in cycles 1 and 2, followed by 200 mg/m once daily for 5 days of subsequent 28-day treatment cycles (Mikkelsen 2009)
• 150 mg/m once daily for 5 days of a 28-day treatment cycle in cycles 1 and 2, followed by 200 mg/m once daily for 5 days for up to two 28-day cycles, followed by 75 mg/m once daily during radiation therapy, and then followed by post-radiation temozolomide treatment (Mikkelsen 2009)
• 75 mg/m once daily for a maximum of 7 weeks during radiation therapy and then (adjuvant therapy) 150 mg/m once daily for 5 days of a 28-day treatment cycle in cycle 1, followed by 200 mg/m once daily for 5 days of subsequent 28-day treatment cycles for up to a total of 12 adjuvant cycles (van den Bent 2017)
• 150 to 200 mg/m 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).

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

Oral:

• During radiation therapy: 75 mg/m once daily
• Adjuvant therapy: 150 to 200 mg/m once daily for 5 days of a 28-day treatment cycle for up to 12 cycles (Fisher 2015)
• Protracted single-agent therapy: 75 mg/m once daily for 21 days of a 28-day treatment cycle for 12 to 15 cycles (Pouratian 2007).

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

• In the treatment of central nervous system (CNS) metastases from solid tumors (which is an off-label use), the recommended dose of Temozolomide is 150 mg/m (or 200 mg/m for patients who have not received chemotherapy before) once daily for 5 days in a 28-day treatment cycle.
• This treatment can be continued until there is disease progression or if the patient experiences severe side effects, for a maximum duration of 1 year.
• In some studies, the treatment duration may vary, such as continuing until disease progression or unacceptable side effects.
• Another approach is to administer 150 mg/m once daily for 5 days, with treatment cycles lasting for either 28 days or 35 days, until disease progression or unacceptable side effects.
• In certain cases, the treatment may involve administering 150 mg/m once daily for 7 days, followed by a break, and then repeating the cycle for a maximum of 2 cycles after a complete response, or for 4 cycles after a stable partial response, 6 cycles after stable disease, or until unacceptable side effects occur.

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

• In the treatment of advanced Cutaneous T-cell lymphoma, specifically mycosis fungoides and Sézary syndrome (which is an off-label use), the recommended dose of Temozolomide is 200 mg/m once daily for 5 days, repeated every 28 days.
• This treatment regimen can be continued for up to 1 year.
• However, it's important to note that this off-label use is based on limited data and should be carefully considered and monitored.

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

• In the treatment of recurrent or progressive Ewing sarcoma (which is an off-label use), the recommended dose of Temozolomide is 100 mg/m² per dose, administered orally, on days 1 to 5 of a 21-day treatment cycle.
• This dosage is usually used in combination with irinotecan.
• However, it's important to note that this off-label use is based on limited data and should be carefully considered and monitored.

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

In the treatment of newly diagnosed glioblastoma multiforme (a type of high-grade brain tumor), the use of Temozolomide involves two phases: the concomitant phase and the maintenance phase.

Concomitant phase:

• During the concomitant phase, Temozolomide is administered orally or intravenously at a dose of 75 mg/m² once daily for 42 days.
• This is done in combination with focal radiotherapy over the course of 60 Gy administered in 30 fractions.
• The Temozolomide treatment is continued at the same dose throughout the 42-day concomitant phase (up to 49 days) as long as certain conditions are met: the absolute neutrophil count (ANC) is equal to or greater than 1,500/mm³, the platelet count is equal to or greater than 100,000/mm³, and nonhematologic toxicity is less than or equal to grade 1 (excluding alopecia, nausea/vomiting).

Dosage modification for toxicity:

• • Dosage modifications are necessary if certain toxicities occur during treatment.
  • If the ANC is between 500 and 1,500/mm³ or the platelet count is between 10,000 and 100,000/mm³ or there is grade 2 nonhematologic toxicity (excluding alopecia, nausea/vomiting), the therapy should be temporarily interrupted.
  • If the ANC falls below 500/mm³ or the platelet count drops below 10,000/mm³ or there is grade 3 or 4 nonhematologic toxicity (excluding alopecia, nausea/vomiting), the therapy should be discontinued.therapy

Maintenance phase (consists of 6 treatment cycles):

• Following the completion of the concomitant phase, the maintenance phase begins after 4 weeks.
• It consists of 6 treatment cycles.
• In the first cycle, Temozolomide is administered orally at a dose of 150 mg/m² once daily for 5 days of a 28-day treatment cycle.
• For cycles 2 to 6, the dose may be increased to 200 mg/m² once daily for 5 days, repeated every 28 days, but only if certain conditions are met: the ANC is equal to or greater than 1,500/mm³, the platelet count is equal to or greater than 100,000/mm³, and the nonhematologic toxicities observed during cycle 1 are less than or equal to grade 2 (excluding alopecia, nausea/vomiting).
• If the dose was not escalated at the beginning of cycle 2, it should not be increased for cycles 3 to 6.

Maintenance phase dosage modification for toxicity:

• During the maintenance phase, dosage modifications may be necessary based on blood counts and nonhematologic toxicities.
• The complete blood count (CBC) should be monitored on or within 48 hours of day 22 of the cycle.
• If the ANC falls below 1,000/mm³, the platelet count drops below 50,000/mm³, or there is grade 3 nonhematologic toxicity (excluding alopecia, nausea/vomiting) during the previous cycle, the dose should be decreased by 1 dose level (by 50 mg/m² per day for 5 days) unless the dose has already been lowered to 100 mg/m² per day, in which case the therapy should be discontinued.
• If a dose reduction to less than 100 mg/m² per day is required, if there is grade 4 nonhematologic toxicity (excluding alopecia, nausea/vomiting), or if the same grade 3 nonhematologic toxicity occurs after dose reduction, the therapy should be discontinued.

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

• In the treatment of recurrent, relapsed, or progressive glioblastoma multiforme (a type of brain tumor), Temozolomide can be used off-label at different doses and schedules.
• The recommended oral dose is 200 mg/m² once daily for 5 days, repeated every 28 days.
• If the patient has previously received chemotherapy, the initial dose is usually 150 mg/m² once daily for 5 days every 28 days, and it may be increased to 200 mg/m² once daily for 5 days every 28 days starting from the second cycle if there are no hematologic toxicities.
• Another approach is to administer 200 mg/m² once daily for 5 days every 28 days for up to 9 cycles or until disease progression.
• Alternatively, Temozolomide can be given at a dose of 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.
• In some cases, a lower dose of 50 mg/m² once daily can be used, either for a maximum of 12 months or until disease progression.
• Another option is to continue the daily dose of 50 mg/m² until disease progression.

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

• In the treatment of metastatic malignant melanoma (which is an off-label use), Temozolomide can be administered orally at a dose of 200 mg/m² once daily for 5 days, repeated every 28 days.
• This treatment regimen can be continued for up to 12 cycles, as long as there is no disease progression or unacceptable toxicity.

Dose Modification of Toxicity:

• Dosage modifications are necessary in case of certain toxicities.
• If there is grade 3 or 4 hematologic toxicity, the dose should be reduced by 25% in subsequent cycles.
• Similarly, if there is grade 3 or 4 nonhematologic toxicity, the dose should be reduced by 50% in subsequent cycles.

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

In the treatment of advanced pancreatic neuroendocrine tumors (which is an off-label use), Temozolomide can be administered orally at different doses and schedules depending on the specific combination therapy or single-agent therapy.

• One option is to use Temozolomide at a dose of 150 mg/m² once daily for 7 days every 14 days, in combination with bevacizumab, until disease progression or unacceptable toxicity. Another combination involves Temozolomide at a dose of 150 mg/m² once daily for 7 days every 14 days, in combination with everolimus, for a duration of 6 months.
• Additionally, Temozolomide can be used at a dose of 150 mg/m² once daily for 7 days every 14 days, in combination with thalidomide, until disease progression or unacceptable toxicity. Another combination therapy involves Temozolomide at a dose of 200 mg/m² once daily (at bedtime) for days 10 to 14 (5 days) of a 28-day treatment cycle, in combination with capecitabine.
• As a single-agent therapy, Temozolomide can be used at a dose of 100 to 150 mg/m² once daily for 5 days of a 28-day treatment cycle in the first cycle, followed by 100 to 200 mg/m² 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):

• In the treatment of relapsed or refractory primary CNS lymphoma (an off-label use), Temozolomide can be administered orally at a dose of 150 mg/m² once daily for 5 days every 28 days. The treatment approach may involve combining Temozolomide with rituximab initially for a specific number of cycles, followed by temozolomide monotherapy.
• One option is to administer Temozolomide in combination with rituximab for 4 cycles. After completing the combination therapy, Temozolomide is continued as monotherapy at a dose of 150 mg/m² once daily for 5 days every 28 days for a total of 8 cycles.
• Another approach involves using Temozolomide initially in combination with rituximab for 1 or 2 cycles, followed by temozolomide maintenance monotherapy. During the maintenance phase, Temozolomide is given at a dose of 150 mg/m² once daily on days 1 to 7 and 15 to 21 of a 28-day cycle.

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

• In the treatment of advanced soft tissue sarcomas (which is an off-label use), Temozolomide can be administered orally at a dose of 75 mg/m² once daily for a duration of 6 weeks.

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

• In the treatment of soft tissue sarcoma, specifically hemangiopericytoma/solitary fibrous tumor (an off-label use), Temozolomide can be administered orally at a dose of 150 mg/m² once daily on days 1 to 7 and days 15 to 21 of a 28-day treatment cycle.
• This treatment regimen is used in combination with bevacizumab.

Temozolomide (Temodal) Dose in Childrens

Note: Temozolomide can cause moderate nausea and vomiting. To prevent these side effects, it is recommended to take antiemetic medications. Before taking temozolomide, your healthcare provider will check your ANC (a measure of white blood cells) which should be at least 1,500/mm, and your platelet count, which should be at least 100,000/mm. The specific dose, how often you take it, the number of doses, and when you start treatment may vary depending on the treatment plan and phase.

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

Children ≥2 years and Adolescents:

• In children aged 2 years and older, as well as adolescents, temozolomide is administered orally at a dose of 100 mg/m² once daily for 5 days.
• This treatment cycle is repeated every 21 days and is usually given in combination with irinotecan.
• Temozolomide should be taken one hour before irinotecan is administered.

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

There are different regimens depending on the combination with other medications or if temozolomide is used as a single agent.

Irinotecan regimen:

• Infants, children, and adolescents:
  • Temozolomide is administered orally at a dose of 100 mg/m² once daily for 5 days.
  • This treatment cycle is repeated every 21 days for up to 6 cycles.
  • Temozolomide should be taken one hour before irinotecan is administered.

Topotecan regimen (TOTEM):

• Infants ≥6 months, children, and adolescents:
  • Temozolomide is administered orally at a dose of 150 mg/m² on days 1 to 5 every 28 days.
  • This treatment is given in combination with topotecan and should be taken prior to the topotecan.
  • The treatment continues until disease progression or unacceptable toxicity, for a maximum of 12 months.
  • Doses may be reduced for hematologic toxicity.

Single agent:

• Children ≥3 years and adolescents:
  • Temozolomide is administered orally on days 1 to 5 every 21 to 28 days.
  • The treatment continues until disease progression or unacceptable toxicity, for a maximum of 24 cycles.
  • Doses may be reduced by 25% for specific grade 4 hematologic toxicities or grade 3 or 4 non-hematologic toxicities.
  • No prior craniospinal irradiation: The dose is 215 mg/m² per day.
  • Previous craniospinal irradiation or relapse after bone marrow transplant: The dose is 180 mg/m² per day.

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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): 

• For infants, children, and adolescents, the oral dose of temozolomide is typically in the range of 200 to 215 mg/m² per dose. This is administered on days 1 to 5 of a treatment cycle that lasts every 21 to 28 days. However, for patients who have received prior craniospinal irradiation or have relapsed after a bone marrow transplant, the dose is decreased to 180 mg/m² per dose.
• In other trials, lower doses of temozolomide, ranging from 160 to 200 mg/m² per dose, were used once daily for 5 days every 28 days in patients aged 3 to 18 years. It's important to note that the specific dosing may vary depending on the trial or individual patient characteristics.

Temozolomide (Temodal) Pregnancy Risk Factor D

• Animal reproduction studies have shown adverse events associated with the use of temozolomide.
• Therefore, it is possible that the drug may cause harm to the fetus when administered to pregnant females.
• To prevent pregnancy while receiving temozolomide, both male and female patients should use effective contraception methods.
• It's important to note that based on animal data, temozolomide may also have an impact on male fertility.

Use of Temozolomide (Temodal), during lactation

• The presence of temozolomide in breast milk is not known.
• As there is a potential for serious adverse reactions in breastfed infants, the manufacturer recommends that a decision be made whether to discontinue breastfeeding or to discontinue temozolomide treatment.
• This decision should consider the importance of the treatment to the mother.

Temozolomide (Temodal) dose in kidney disease:

• For patients with a creatinine clearance (CrCl) of 36 mL/minute/m² or higher, no dosage adjustments are recommended as temozolomide clearance is not affected in these individuals. The manufacturer's labeling does not provide specific dosage adjustments for this population.
• In cases of severe renal impairment with a CrCl less than 36 mL/minute/m², no specific dosage adjustments are provided in the manufacturer's labeling. However, temozolomide should be used with caution in these patients as its use has not been extensively studied in this population.
• For patients undergoing dialysis, no dosage adjustments are provided in the manufacturer's labeling, as the use of temozolomide in dialysis patients has not been studied extensively.

Temozolomide (Temodal) dose in liver disease:

• For patients with mild to moderate hepatic impairment, no specific dosage adjustments are provided in the manufacturer's labeling for temozolomide. The pharmacokinetics of temozolomide in patients with mild to moderate hepatic impairment are similar to those with normal liver function. Therefore, no dose modification is recommended in this population.
• In cases of severe hepatic impairment, there are no specific dosage adjustments provided in the manufacturer's labeling for temozolomide. The use of temozolomide in patients with severe hepatic impairment has not been extensively studied. Therefore, caution should be exercised when using temozolomide in this population.

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 reactions can range from mild allergic reactions, such as urticaria (hives), to severe reactions like anaphylaxis, Stevens-Johnson syndrome, or toxic epidermal necrolysis.
• It is important to note that temozolomide and dacarbazine are both metabolized to the same active compound called MTIC (methyl-triazeno-imidazole-carboxamide). Therefore, if a patient has a known hypersensitivity or allergy to dacarbazine, which is a related drug, they may also be at risk of hypersensitivity reactions to temozolomide.
• In the Canadian labeling, temozolomide is not recommended for use in patients with severe myelosuppression. Myelosuppression refers to a decrease in the production of blood cells (red blood cells, white blood cells, and platelets) in the bone marrow, leading to low blood cell counts. Severe myelosuppression can increase the risk of infections, bleeding, and other complications.

Warnings and precautions

Suppression of bone marrow

• Temozolomide can cause a decrease in the production of blood cells in the bone marrow, which is called myelosuppression.
• This may lead to low blood cell counts and can require treatment changes such as temporarily stopping or reducing the dose of temozolomide, or even stopping treatment altogether.
• Regular monitoring of blood counts is important.
• It's been observed that older adults and females may have a higher risk of experiencing blood-related side effects.
• Rare cases of severe myelosuppression resulting in aplastic anemia (a condition where the bone marrow doesn't produce enough new blood cells) have been reported, and this can be life-threatening.
• If temozolomide is used together with other medications known to cause aplastic anemia, such as carbamazepine, co-trimoxazole, or phenytoin, it may be harder to recognize the development of aplastic anemia.
• Before starting treatment with temozolomide, the absolute neutrophil count (ANC) should be at least 1,500/mm and platelet count should be at least 100,000/mm.

Gastrointestinal toxicities:

• Temozolomide can cause gastrointestinal side effects, including nausea and vomiting.
• It has a moderate potential to induce these symptoms.
• To prevent or reduce nausea and vomiting, doctors often prescribe antiemetic medications along with temozolomide.
• These medications help to prevent or alleviate these gastrointestinal side effects and improve the patient's comfort during treatment.

Hepatotoxicity

• Temozolomide can cause hepatotoxicity, which refers to liver damage.
• This side effect can be severe or even life-threatening.
• To monitor for liver function and detect any potential liver problems, doctors will conduct liver function tests before starting temozolomide, during the treatment cycles, and after the completion of treatment.
• These tests help assess the health of the liver and detect any abnormalities.
• Some reported cases of hepatotoxicity associated with temozolomide include liver function abnormalities, hepatitis (inflammation of the liver), hepatic failure (severe impairment of liver function), cholestasis (impaired bile flow), jaundice (yellowing of the skin and eyes), cholelithiasis (gallstones), hepatic steatosis (fatty liver), hepatic necrosis (death of liver cells), hepatic lesion (abnormality in the liver tissue), and hepatic encephalopathy (brain dysfunction due to liver failure).

Hypersensitivity

• Temozolomide can cause hypersensitivity reactions, which are allergic reactions that may include severe symptoms like anaphylaxis.
• It is important to be aware of the signs of hypersensitivity, such as rash, itching, swelling, difficulty breathing, or a severe allergic reaction, and seek immediate medical attention if any of these symptoms occur while taking temozolomide.

Pneumocystis pneumonia

• There is a risk of developing Pneumocystis jirovecii pneumonia (PCP) while taking temozolomide, especially in patients who are also receiving steroids or undergoing longer treatment with temozolomide.
• It is important to monitor all patients for the development of PCP, particularly if they are also receiving corticosteroids.
• For patients with newly diagnosed glioblastoma who are receiving radiotherapy in combination with the 42-day temozolomide regimen, PCP prophylaxis is necessary to prevent the infection.

Secondary malignancies

• There have been reported cases of myelodysplastic syndrome and secondary malignancies, including myeloid leukemia, in patients treated with temozolomide.
• It is important to be aware of the potential risk of developing these conditions and to monitor patients for any signs or symptoms of such malignancies during and after treatment with temozolomide.

Hepatic impairment

• Temozolomide should be used with caution in patients who have severe liver problems.
• Close monitoring and careful consideration of the potential risks and benefits are important in such cases.

Renal impairment

• In patients with severe kidney problems, temozolomide should be used with caution.
• There is limited information available regarding the use of temozolomide in these patients, and its effects have not been specifically studied in individuals undergoing dialysis.
• Close monitoring and careful assessment of renal function are recommended.

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.

Monitoring Parameter:

Complete Blood Count (CBC) with Differential and Platelets:

• Prior to each treatment cycle.
• Weekly during the concomitant phase treatment of glioma.
• At or within 48 hours of day 22 and weekly until Absolute Neutrophil Count (ANC) is >1,500/mm and platelets are >100,000/mm for glioma maintenance and astrocytoma treatment.

Liver Function Tests:

• Baseline assessment.
• Halfway through the first cycle.
• Prior to each subsequent cycle.
• ~2 to 4 weeks after the last dose.

Monitoring for Signs/Symptoms of Pneumocystis Pneumonia:

• Particularly important if corticosteroids are also being used.
• Promptly report any symptoms to the healthcare provider.

Adherence Monitoring:

• Ensure the patient is taking the medication as prescribed.
• Discuss any challenges or concerns related to adherence with the healthcare provider.

It is important to follow these monitoring guidelines to assess the patient's response to temozolomide treatment, detect any potential side effects, and ensure the best possible outcome.

How to administer Temozolomide (Temodal)?

Emetic Potential and Antiemetics:

• Temozolomide has a moderate potential to cause nausea and vomiting.
• To prevent these side effects, antiemetic medications are recommended.

Oral Administration:

• Swallow the capsules whole with a glass of water. Do not open or chew them.
• Temozolomide absorption is affected by food, so it's important to administer it consistently either with food or without food.
• Taking it on an empty stomach and/or at bedtime may help reduce nausea and vomiting.
• If vomiting occurs after taking a dose, do not repeat the dose. Wait until the next scheduled dose.

Handling of Capsules:

• Avoid contact of open or damaged capsules with the skin or mucous membranes.

Intravenous (IV) Administration:

• Temozolomide can be given via IV infusion over 90 minutes.
• Flush the IV line before and after administering the medication.
• It can be administered through the same IV line as sodium chloride 0.9%, but do not mix it with other solutions or medications in the same IV line.

Following these administration guidelines ensures the proper delivery of temozolomide and helps minimize the risk of adverse effects.

Mechanism of action of Temozolomide (Temodal):

• Temozolomide is a prodrug, meaning it undergoes a spontaneous and nonenzymatic conversion to its active form called MTIC (methyl-triazene-1-yl)-imidazole-4-carboxamide).
• This conversion occurs naturally in all tissues of the body that the drug reaches.
• Studies have shown that this conversion takes place under normal physiological conditions (Marchesi 2007; Villano 2009).
• The active metabolite, MTIC, exerts its cytotoxic effects by causing alkylation (methylation) of DNA at specific positions, particularly the O and N guanine positions.
• This DNA alkylation leads to the formation of DNA double-strand breaks, which are highly damaging to the DNA structure.
• As a result, the affected cells undergo apoptosis, a process of programmed cell death (Villano 2009).
• One important characteristic of temozolomide is that it is not specific to any particular phase of the cell cycle.
• This means that it can act on cells regardless of their phase in the cell cycle (Marchesi 2007).

Absorption:

• When taken orally, temozolomide is rapidly and completely absorbed into the bloodstream.

Distribution:

• Temozolomide has a volume of distribution of 0.4 L/kg.
• It is able to penetrate the blood-brain barrier, and the levels of the drug in the cerebrospinal fluid (CSF) are approximately 35% to 39% of the levels in the plasma (Yung 1999).

Protein Binding:

• Temozolomide is approximately 15% bound to proteins in the bloodstream.

Metabolism:

• Temozolomide is a prodrug that undergoes hydrolysis to its active form, MTIC.
• MTIC is eventually eliminated as carbon monoxide (CO) and 5-aminoimidazole-4-carboxamide (AIC), a naturally occurring substance found in urine.
• The metabolism of temozolomide and MTIC is primarily nonenzymatic, and the contribution of CYP isoenzymes to the metabolism is minimal.

Bioavailability:

• The bioavailability of oral temozolomide is 100%.
• This means that when compared on a milligram-per-milligram basis, intravenous (IV) temozolomide infused over 90 minutes is equivalent to an oral dose.

Half-life elimination:

• The average elimination half-life of the parent drug (temozolomide) is 1.7 hours in children and 1.8 hours in adults.
• This refers to the time it takes for half of the drug to be eliminated from the body.

Time to peak:

• When taken on an empty stomach, temozolomide reaches its peak concentration in the bloodstream after approximately 1 hour.
• If taken with a high-fat meal, the time to peak concentration is around 2.25 hours.

Excretion:

• Approximately 38% of temozolomide is excreted in the urine, with only about 6% of the drug being present in its original form.
• Less than 1% of the drug is excreted in the feces.

Clearance:

• The clearance of temozolomide is approximately 5.5 L/hour/m².
• Women have a slightly lower clearance than men, adjusted for body surface area.
• Pediatric patients between the ages of 3 and 17 years have a similar temozolomide clearance as adults.

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:

Temoergin