Temozolomide


Generic Medicine Info
Indications and Dosage
Intravenous
Glioblastoma multiforme
Adult: In newly diagnosed patients: Concomitant phase: 75 mg/m2 via infusion over 90 minutes once daily for 42 days, with focal radiotherapy. Dosing interruption or discontinuation may be required during the concomitant phase based on toxicity (refer to product guideline). Maintenance phase (starting 4 weeks after completion of concomitant phase): Cycle 1: 150 mg/m2 once daily on Days 1-5 of a 28-day cycle. Cycles 2-6: May increase to 200 mg/m2 once daily on Days 1-5 of each 28-day cycle; if the dose was not escalated at the onset of Cycle 2, do not increase the dose in succeeding cycles. Dose reduction, interruption or discontinuation may be required during the maintenance phase according to individual safety or tolerability (refer to detailed product guideline).

Intravenous
Refractory anaplastic astrocytoma
Adult: In patients who have experienced disease progression on a drug regimen containing nitrosourea and procarbazine: 150 mg/m2 via infusion over 90 minutes once daily on Days 1-5 of a 28-day cycle; dose for succeeding cycles may be increased to 200 mg/m2 once daily on Days 1-5 of a 28-day cycle if there is no toxicity. Continue until disease progression or unacceptable toxicity. Dose modifications may be needed according to individual safety or tolerability (refer to detailed product guideline).

Oral
Anaplastic astrocytoma, Recurrent glioblastoma multiforme
Adult: Patients who are not previously treated with chemotherapy: 200 mg/m2 once daily for Days 1-5 of a 28-day cycle. Patients previously treated with chemotherapy: 150 mg/m2 once daily on Days 1-5 of a 28-day cycle; dose for succeeding cycles may be increased to 200 mg/m2 daily on Days 1-5 of a 28-day cycle if there is no toxicity. Continue until disease progression or unacceptable toxicity. Dose modifications may be needed according to individual safety or tolerability (refer to detailed product guideline).
Child: ≥3 years Same as adult dose. Dosage recommendations may vary among countries or individual products. Refer to specific product guidelines.

Oral
Metastatic malignant melanoma
Adult: 200 mg/m2 once daily on Days 1-5 of a 28-day cycle.

Oral
Glioblastoma multiforme
Adult: In newly diagnosed patients: Concomitant phase: 75 mg/m2 once daily for 42 days, with focal radiotherapy. Dosing interruption or discontinuation may be required during the concomitant phase based on toxicity. Maintenance phase (starting 4 weeks after completion of concomitant phase): Cycle 1: 150 mg/m2 once daily on Days 1-5 of a 28-day cycle. Cycles 2-6: May increase to 200 mg/m2 once daily on Days 1-5 of a 28-day cycle; if the dose was not escalated at the onset of Cycle 2, do not increase the dose in succeeding cycles. Dose reduction, interruption or discontinuation may be required during the maintenance phase according to individual safety or tolerability (refer to detailed product guideline).
Administration
Should be taken on an empty stomach. Take at least 1 hr before meals.
Reconstitution
IV: Bring the vial to room temperature prior to reconstitution. Add 41 mL of sterile water for inj to the vial labelled as containing 100 mg to a final concentration of 2.5 mg/mL. Swirl gently; do not shake. Transfer reconstituted solution from each vial into an empty 250 mL infusion bag.
Contraindications
Hypersensitivity to temozolomide or dacarbazine. Severe myelosuppression. Pregnancy and lactation.
Special Precautions
Patient with Pneumocystis jirovecii pneumonia. Severe hepatic and renal impairment. Children.
Adverse Reactions
Significant: Hypersensitivity (e.g. anaphylaxis), Pneumocystis jirovecii pneumonia, nausea, vomiting. Rarely, myelodysplastic syndrome and secondary malignancies (e.g. myeloid leukaemia).
Ear and labyrinth disorders: Deafness, earache, tinnitus, vertigo.
Endocrine disorders: Cushingoid.
Eye disorders: Blurred vision, diplopia, eye pain, hemianopia, vision disorder, visual field defect.
Gastrointestinal disorders: Constipation, diarrhoea, dyspepsia, dysphagia, abdominal pain, stomatitis, taste perversion, oral candidiasis.
General disorders and administration site conditions: Fatigue, asthenia, fever, influenza-like symptoms, malaise, pain, oedema; petechiae, haematoma, pain, irritation, pruritus, warmth, swelling, erythema at the inj site (IV).
Infections and infestations: Herpes zoster.
Investigations: Increased liver enzymes, increased or decreased weight.
Metabolism and nutrition disorders: Anorexia, hyperglycaemia.
Musculoskeletal and connective tissue disorders: Arthralgia, myalgia, back pain, myopathy, musculoskeletal pain.
Nervous system disorders: Headache, convulsion, tremors, dizziness, hemiparesis, hypoaesthesia, aphasia or dysphasia, ataxia, neuropathy, paraesthesia, reduced consciousness, speech disorder; impaired balance, cognition, concentration or memory.
Psychiatric disorders: Agitation, amnesia, anxiety, confusion, depression, insomnia, somnolence.
Renal and urinary disorders: Urinary incontinence, micturition frequency.
Respiratory, thoracic and mediastinal disorders: Dyspnoea, sinusitis, bronchitis, pharyngitis, cough, upper respiratory infection.
Skin and subcutaneous tissue disorders: Alopecia, dry skin, erythema, rash, pruritus.
Vascular disorders: Haemorrhage, DVT, embolism, hypertension.
Potentially Fatal: Myelosuppression (e.g. anaemia, leucopenia, pancytopenia), hepatotoxicity (e.g. hepatic failure). Rarely, reactivation of infections (e.g. hepatitis B virus), herpes simplex encephalitis.
IV/Parenteral/PO: D
Patient Counseling Information
This drug may cause fatigue and somnolence; if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor CBC with differential and platelets (prior to treatment initiation, weekly during the concomitant phase with radiation therapy, and on days 1 and 22 of each 28-day cycle; may require more frequent monitoring if myelosuppression occur); LFT (at baseline, halfway through the 1st cycle, before each subsequent cycle, and at approx 2-4 weeks after the last dose). Evaluate pregnancy status prior to use in females of reproductive potential. Monitor for lymphopenia and for signs/symptoms of Pneumocystis jirovecii pneumonia, hypersensitivity, and secondary malignancies.
Overdosage
Symptoms: Myelosuppression, pyrexia, multiorgan failure. Management: Supportive treatment. Monitor CBC.
Drug Interactions
Decreased clearance with valproic acid. Increased risk of myelosuppression with other myelosuppressive agents.
Food Interaction
Food reduces the rate and extent of absorption of temozolomide.
Action
Description: Temozolomide, a triazene, is a prodrug which is rapidly hydrolysed to 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide (MTIC). The cytotoxicity of MTIC is believed to be due to alkylation of DNA, mainly at the O6 and N7 positions of guanine, leading to DNA double strand breaks and apoptosis.
Pharmacokinetics:
Absorption: Rapidly and completely absorbed from the gastrointestinal tract. Bioavailability: Approx 100%. Reduced rate and extent of absorption with food. Time to peak plasma concentration: 0.5-1.5 hours.
Distribution: Crosses the blood-brain barrier and detected in the CSF. Volume of distribution: 0.4 L/kg. Plasma protein binding: Approx 10-20%.
Metabolism: Undergoes spontaneous hydrolysis to its active metabolite 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide (MTIC), which is further hydrolysed to 5-amino-imidazole-4-carboxamide (AIC) and methylhydrazine.
Excretion: Mainly via urine (approx 38%; 5-10% as unchanged drug and 12% as AIC); faeces (<1%). Elimination half-life: Approx 1.8 hours.
Chemical Structure

Chemical Structure Image
Temozolomide

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 5394, Temozolomide. https://pubchem.ncbi.nlm.nih.gov/compound/Temozolomide. Accessed Sept. 27, 2021.

Storage
Cap: Store at or below 25°C. Protect from light and moisture. Powder for inj: Store between 2-8°C.
MIMS Class
Cytotoxic Chemotherapy
ATC Classification
L01AX03 - temozolomide ; Belongs to the class of other alkylating agents. Used in the treatment of cancer.
References
Anon. Temozolomide. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 18/06/2021.

Anon. Temozolomide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 18/06/2021.

Buckingham R (ed). Temozolomide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 18/06/2021.

Douglas Pharmaceuticals Ltd. Temaccord Capsules data sheet 23 September 2019. Medsafe. http://www.medsafe.govt.nz. Accessed 18/06/2021.

Temodar Capsule; Temodar Injection, Powder, Lyophilized, for Solution (Merck Sharp & Dohme Corp.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 21/06/2021.

Temodar Capsules; Temodar for Injection (Merck Sharp & Dohme Corp.). U.S. FDA. https://www.fda.gov. Accessed 21/06/2021.

Temozolomide 250mg Capsules (Generics UK Limited t/a Mylan). MHRA. https://products.mhra.gov.uk. Accessed 18/06/2021.

Temozolomide Capsule (Amneal Pharmaceuticals LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 18/06/2021.

Disclaimer: This information is independently developed by MIMS based on Temozolomide from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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