Temozolomide

About Temozolomide

• Temozolomide received FDA approval on August 11, 1999.
• It is an alkylating agent, that treats serious brain cancers. It’s used as the first line for glioblastoma and the second line for astrocytoma. 
• For glioblastoma, it’s given with radiotherapy and then as maintenance. 
• For refractory anaplastic astrocytoma, it’s used after progression on a regimen containing nitrosourea and procarbazine.
• Temozolomide, spontaneously converts to its active form, methyl-triazeno-imidazole-carboxamide (MTIC). MTIC alters DNA by attaching methyl groups to specific positions, notably the O6 and N7 sites of guanine bases. 
• This modification disrupts DNA replication and transcription in rapidly dividing cancer cells, ultimately inducing cell death. It specifically targets cancer cell DNA, impairing their proliferation and survival abilities.

Strength: 

Temozolomide capsule is available in strengths of 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, and 250 mg,  as well as 100 mg powder for injection. 

Recommended Dosage:

Temozolomide is offered in capsule form for self-administration or as an intravenous injection administered by a healthcare professional. Adhere precisely to your doctor’s instructions when taking the medicine. Follow all guidelines provided on your prescription label and carefully review all medication guides or instruction sheets. The dosing regimen recommended by a healthcare provider is tailored to the specific type of brain cancer tumor. Injection is typically administered by your healthcare provider as an infusion directly into your vein, which usually takes around 90 minutes.

• For newly diagnosed glioblastoma, medicine is administered orally or intravenously once daily for 42 consecutive days during the concomitant phase with focal radiotherapy. This is followed by once-daily dosing on Days 1 to 5 of each 28-day cycle for 6 cycles during the maintenance phase. The recommended dosage during the concomitant phase is 75 mg/m2. 
• During the maintenance phase, the dosage for Cycle 1 is 150 mg/m2 per day, which may be increased to 200 mg/m2 per day for Cycles 2 to 6 if specific conditions are met. For refractory anaplastic astrocytoma, the initial dosage is 150 mg/m2 once daily on Days 1 to 5 of each 28-day cycle, with a possible increase to 200 mg/m2 per day based on certain criteria. Regular monitoring of blood counts is necessary, and dosage adjustments are made accordingly.

Important:

This medicine is a cytotoxic drug, so it’s crucial to follow appropriate handling and disposal procedures. For capsules, consistency in administration concerning food intake is recommended to mitigate nausea and vomiting. Swallow the capsules whole and avoid opening or chewing them. If capsules are accidentally damaged, take precautions to prevent inhalation or skin/mucous membrane contact.

When preparing the Temozolomide 100 mg powder for injection, bring the vial to room temperature before reconstitution with Sterile Water for Injection. Reconstitute the vial with 41 mL of Sterile Water for Injection to achieve a concentration of 2.5 mg/mL. After reconstitution, visually inspect the solution for particulate matter and discoloration. Discard if any abnormalities are observed. The reconstituted solution should be used within 14 hours, including infusion time. Do not infuse other medications simultaneously through the same intravenous line due to a lack of compatibility data.

Warnings & Precaution:

• This medicine is contraindicated in individuals with a known history of hypersensitivity reactions to Temozolomide or any of its components. Additionally, it is contraindicated in patients who have experienced hypersensitivity reactions to dacarbazine, as both drugs are metabolized to the same active metabolite, 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide. Adverse reactions to the medicine have included cases of anaphylaxis.
• Myelosuppression, characterized by a reduction in blood cell counts, requires careful monitoring of absolute neutrophil count (ANC) and platelet count before each treatment cycle, especially in geriatric patients and women who are at higher risk. 
• Additionally, myelodysplastic syndrome and secondary malignancies, such as myeloid leukemia, have been reported. 
• Close monitoring for the development of lymphopenia and pneumocystis pneumonia (PCP), particularly in patients receiving steroids, is essential. 
• Hepatotoxicity, including fatal cases, has been observed; thus, liver function tests should be performed at various intervals throughout treatment. 
• It’s important to recognize that the medicine can cause harm to a developing fetus; therefore, females of reproductive potential should be advised of the risks and encouraged to use effective contraception. 
• Male patients with pregnant partners or female partners of reproductive potential should also be advised to use condoms.

Common Temozolomide Side Effects:

•  Nausea and vomiting
• Constipation
• Loss of appetite 
• Fatigue
• Headache
• Hair loss
• Increased risk of infection 
• Skin rash
• Neurological problems (memory issues, dizziness, concentration difficulties)

Use in Specific Population

• Temozolomide poses a risk of fetal harm if administered to pregnant women, based on its mechanism of action and animal studies. There is insufficient data on the medicine’s presence in human milk, its effects on breastfed infants, or its impact on milk production. 
• Due to potentially serious adverse reactions, including myelosuppression, breastfeeding is not recommended during the treatment and for at least one week after the final dose. Before initiating the therapy, verify the pregnancy status of females of reproductive potential.
• Contraception is advised for females of reproductive age during the treatment and for at least six months after the final dose to avoid embryo-fetal harm. 
• Male patients with pregnant partners or female partners of reproductive potential should use condoms during treatment and for at least three months post-treatment due to potential embryofetal toxicity and genotoxic effects on sperm cells. 
• Additionally, males should refrain from donating semen during treatment and for at least three months after the final dose due to its potential to impair male fertility.
• The safety and efficacy have not been established in pediatric patients. No significant safety differences were observed aged 65 years and older compared to younger patients. 
• No dosage adjustment is needed for patients with creatinine clearance (CLcr) between 36 to 130 mL/min/m². However, the recommended dose has not been determined for patients with severe renal impairment (CLcr < 36 mL/min/m²) or for those with end-stage renal disease on dialysis.
• In terms of hepatic impairment, no dosage adjustment is necessary for patients with mild to moderate hepatic impairment (Child-Pugh class A and B). However, the recommended dose for patients with severe hepatic impairment has not been established.

Storage and Handling 

• Store the capsules within a temperature range of 25°C (77°F), with excursions allowed between 15°C and 30°C (59°F and 86°F). 
• Properly dispose of any medication that has expired or is no longer required.
• Store Temozolomide injection at 2°C to 8°C (36°F to 46°F). Keep the medicine away from pets and children.