Temonix 100

Glioblastoma multiforme, Malignant gliomas, Metastatic melanoma

Should be taken on an empty stomach. Take on an empty stomach at least 1 hr before meals. 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.

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. Anaplastic Astrocytoma Indicated for the treatment of adults with refractory anaplastic astrocytoma (ie, patients with disease progression on a drug regimen containing nitrosourea and procarbazine) Initial: 150 mg/m² PO/IV qDay for 5 days; repeat at 28-day cycles Maintenance: May increase/maintain dose at 200 mg/m² PO/IV qDay for 5 days/28-day cycle if ANC >1500 mm³ and platelets >100,000 mm³ Infuse IV over 90 minutes Dosage modifications Measure ANC and platelet on days 22 & 29 (day 1 of next cycle); modify dose for following cycle if: ANC 1000-1500/mm³ or platelet 50,000-100,000/mm³: Postpone treatment until ANC >1500/mm³ and platelet >100,000/mm³; maintain initial dose ANC <1,000/mm³ or platelets <50,000/mm³: -Postpone therapy until ANC >1,500/mm³ and platelets >100,000/mm³ -Decrease dose by 50 mg/m²/day for subsequent cycles -Do NOT administer drug at dose <100 mg/m² for anaplastic astrocytoma Decrease maintenance dose Reduce from 200 mg/m²/day to 150 mg/m²/day and from 150 mg/m²/day to100 mg/m²/day if: -ANC< 10,000/mm³ -Platelets <50,000/mm² -CTC Grade 3 non-hematologic toxicity 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. Metastatic melanoma Adult: 200 mg/m2 daily for 5 days every 28 days.

Oral Recurrent or progressive malignant gliomas 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.

Hypersensitivity to dacarbazine. Severe myelosupression. Pregnancy.

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.

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. May impair ability to drive or operate machinery. 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. Lactation: Unknown if distributed into breastmilk, discontinue nursing due to potential risk.

>10% Alopecia (55-69%),Lymphopenia (55%),Nausea (53%),Vomiting (42%),Headache (41%),Fatigue (34%),Constipation (33%),Anorexia (9-27%),Convulsions (23%),Thrombocytopenia (19%),Rash (8-19%),Hemiparesis (18%),Diarrhea (16%),Neutropenia (14%),Fever (13%),Asthenia (13%),Dizziness (12%),Peripheral edema (11%),Viral infections (11%) 1-10% (selected) Amnesia (10%),Insomnia (10%),Abdominal pain (5-9%),Ataxia (8%),Back pain (8%),Paresis (8%),URI (8%),Urinary incontinence (8%),UTI (8%),Abnormal vision (5-8%),Pruritus (5-8%),Breast pain (6%),Depression (6%),Confusion (5%),Myalgia (5%),Weight gain (5%),Anemia (4%),Erythema (1%)

Valproic acid, other myelosuppressive agents.