Temozolomide


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Glioblastoma multiforme Concomitant phase: 75 mg/m2 once daily for 42 days w/ focal radiotherapy. Initiate monotherapy 4 wk after completing concomitant phase: 150 mg/m2 once daily for 5 days followed by a 23 day break (1 cycle). Cycle 2: 200 mg/m2 once daily for 5 days. If dose cannot be increased in cycle 2, do not increase dose in subsequent cycles. Dose used in cycle 2 is given for the rest of the cycles, toxicity allowing, up to 6 cycles. Recurrent or progressive malignant gliomas Chemotherapy naive: 200 mg/m2 once daily for 5 days, followed by a 23 day break (1 cycle). Chemotherapy-experienced: 150 mg/m2/day for 5 days followed by 23 day break (1 cycle), increased to 200 mg/m2/day for the 2nd cycle if there is no haematological toxicity. Metastatic melanoma 200 mg/m2/day for 5 days every 28 days.
Dosage Details
Oral
Recurrent or progressive malignant gliomas
Adult: Previously untreated with chemotherapy: 200 mg/m2 once daily for 5 days, followed by a 23 day break (1 cycle). Previously treated with chemotherapy: 150 mg/m2 daily for 5 days followed by 23 day break (1 cycle) increased to 200 mg/m2 daily for the 2nd cycle if there is no haematological toxicity.
Child: >3 yr: Previously untreated with chemotherapy: 200 mg/m2 once daily for 5 days, followed by a 23 day break (1 cycle). Previously treated with chemotherapy: 150 mg/m2 daily for 5 days followed by 23 day break (1 cycle) increased to 200 mg/m2 for the 2nd cycle if there is no haematological toxicity.

Oral
Metastatic melanoma
Adult: 200 mg/m2 daily for 5 days every 28 days.

Oral
Glioblastoma multiforme
Adult: 75 mg/m2 once daily for 42 days with focal radiotherapy (concomitant phase). Do not reduce dose during concomitant phrase but interrupt or discontinue therapy depending on toxicity. Continue if absolute neutrophil count (ANC)≥ 1.5x109/L, thrombocyte count ≥100x109/L and Common Toxicity Criteria (CTC) non-haematological toxicity ≤ Grade 1 (except for alopecia, nausea and vomiting). Initiate monotherapy 4 wk after completing concomitant phase: 150 mg/m2 once daily for 5 days followed by a 23 day break (1 cycle). In cycle 2, increase dose to 200 mg/m2 once daily for 5 days, if ANC ≥1.5x109/L, thrombocyte count ≥100x109/L and CTC non-haematological toxicity for cycle 1 is ≤ Grade 2 (except for alopecia, nausea and vomiting). If dose cannot be increased in cycle 2, do not increase dose in subsequent cycles. Dose used in cycle 2 is given for the rest of the cycles, toxicity allowing, up to 6 cycles.
Administration
Should be taken on an empty stomach. Take at least 1 hr before meals.
Contraindications
Hypersensitivity to dacarbazine. Severe myelosupression. Pregnancy.
Special Precautions
Severe hepatic and renal impairment. Elderly >70 yr, children. Women of child bearing potential should avoid becoming pregnant during therapy. Males should be advised not to father a child up to 6 mth after treatment and to consider cryoconservation of sperms due to possibility of irreversible infertility. Unknown if distributed into breastmilk, discontinue nursing due to potential risk. May impair ability to drive or operate machinery. Swallow capsules whole with a full glass of water on an empty stomach or at bedtime. Do not take a 2nd dose if capsules are vomited. Monitor CBC wkly during concomitant therapy and on day 22 of each 28 day treatment cycle, followed by wkly blood count until recovery. Hepatitis screening and prophylactic therapy with antiviral agents as clinically indicated to be considered. Prophylaxis for Pneumocystis jiroveci (or Pneumocystis carinii) pneumonia (PCP) needed for all patients receiving concomitant temozolomide and radiation therapy for the 42-day regimen; if patients experience lymphocytopenia during the concomitant phase of therapy, PCP prophylaxis should be continued until recovery from lymphocytopenia. Monitor closely for PCP development in all patients. Anti-emetic prophylaxis recommended.
Adverse Reactions
Nausea, vomiting, taste perversion, constipation, diarrhoea, abdominal pain, stomatitis, anorexia, headache, fatigue, convulsions, dizziness, memory impairment, impaired concentration, tremors, blurred vision, hearing impairment, speech disorder, rash, infection, oral candidiasis, dyspnoea, coughing, neutropenia, thrombocytopenia, leucopenia, anaemia, hyperglycemia, decreased wt, insomnia, anxiety, alopecia, muscle weakness, urinary incontinence, increased alanine aminotransferase. Rarely, myelodysplastic syndrome and secondary malignancies.
IV/Parenteral/PO: D
Drug Interactions
Reduced effectiveness of vaccines and generalised infection may occur in patients immunised with live vaccines. Decreased temozolomide clearance with valproic acid.
Potentially Fatal: Increased risk of myelosupression with other myelosuppressive agents. Increased risk of myelosuppression with colony stimulating factors (e.g. filgrastim, molgramostim and lenograstim) if given at the same time, colony stimulating factors to be used 24 hr before or until 24 hr after chemotherapy.
Action
Description: Temozolomide, a triazene, is an inactive prodrug. It is chemically hydrolysed to 3-methyl-(triazen-1-yl) imidazole-4-carboxamide (MTIC), the active metabolite of dacarbazine. The cytotoxicity of MTIC is believed to be due alkylation of DNA, mainly at the O6 and N7 positions of guanine.
Pharmacokinetics:
Absorption: Rapidly and completely absorbed from GI tract. Peak plasma concentration: 0.5-1.5 hr. Rate and extent of absorption decreased by food.
Distribution: Protein binding: 15%. Cross blood-brain barrier.
Metabolism: Undergoes rapid nonenzymatic conversion at physiologic pH to the reactive compound MTIC and to temozolomide acid metabolite. MTIC is further hydrolysed to 5-amino-imidazole-4-carboxamide (AIC) and methylhydrazine.
Excretion: Excreted mainly in urine as unchanged drug, AIC, temozolomide acid metabolite and unidentified polar metabolites. Plasma half life: 1.8 hr.
Storage
Store at 15-30°C.
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 © 2020 MIMS. All rights reserved. Powered by MIMS.com
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