Dosing and uses of Temodar (temozolomide)
Adult dosage forms and strengths
capsule
- 5mg
- 20mg
- 100mg
- 140mg
- 180mg
- 250mg
powder for injection
- 100mg/vial
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
Glioblastoma Multiforme
Indicated for the treatment of adults with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as maintenance treatment
Initial: 75 mg/m² PO/IV qDay for 42 days concomitant with focal radiotherapy
Infuse IV over 90 minutes
Continue treatment
- Continue for up to 49 days if the criteria listed below are met
- ANC ≥1,500/mm³, Platelet >100,000/mm³; CTC Grade 1 or lower
Dosage modifications (initial treatment and radiotherapy)
- Interrupt if
- - ANC ≥500/mm³ but <1,500/mm³; CTC ≤Grade 1
- - Platelets: ≥10,000/mm³ but ≤100,000/mm³
- - CTC Grade 2 nonhematologic toxicity
- Discontinue if
- - ANC <500/mm³
- - Platelets <10,000/mm³
- - CTC Grade 3 or 4 nonhematologic toxicity
Maintenance
- Cycle 1 (Start 4 weeks AFTER temozolomide + radiotherapy): 150 mg/m² PO/IV qDay for 5 days, then 23-treatment free days
- Cycle 2-6: may increase to 200 mg/m²/day if ANC >1500/mm³, platelets >100,000/mm³; CTC Grade <2
Newly Diagnosed High Grade Glioma (Orphan)
Indicated for treatment of newly diagnosed high grade glioma
Orphan indication sponsor
- Schering-Plough Research Institute; 2000 Galloping Hill Road; Kenilworth, NJ 07033
Advanced Metastatic Melanoma (Orphan)
Indicated for treatment of advanced metastatic melanoma
Orphan indication sponsor
- Schering-Plough Research Institute; 2000 Galloping Hill Road; Kenilworth, NJ 07033
Other Indications & Uses
Off-label: metastatic melanoma, other brain tumors (eg, oligodendroglioma)
Pediatric dosage forms and strengths
Glioblastoma Multiforme (Orphan)
Orphan designation for treatment of glioblastoma multiforme in pediatric patients
Sponsor
- AmpliPharm Pharmaceuticals, LLC; 970 Peachtree Industrial Boulevard, Suite 100; Suwanee, Georgia 30024
Temodar (temozolomide) adverse (side) effects
>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%)
Postmarketing Reports
Alveolitis
Interstitial pneumonitis
Pulmonary fibrosis
Hepatotoxicity including elevations of liver enzymes, hyperbillirubinemia, cholestasis, and hepatitis
Diabetes insipidus
Reactivation of infections including cytomegalovirus and hepatitis B
Warnings
Contraindications
Hypersensitivity to temozolomide, dacarbazine
Cautions
Myelosuppression reported, including prolonged pancytopenia; may result in aplastic anemia, which in some cases has resulted in a fatal outcome
Severe hepatic/renal impairment, elderly
Risk of myelodysplastic syndrome and secondary malignancies
Prophylaxis for P. jiroveci pneumonia (pneumocystis pneumonia) required for all patients treated with temozolomide and radiation
Obtain CBC prior to treatment on Day 1 and on Day 22 (21 days after the first dose) of each cycle; perform weekly if ANC declines
Fatal and severe hepatotoxicity reported; perform LFTs at baseline, midway through the first cycle, prior to each subsequent cycle, and ~2-4 weeks after the last dose
Causes fetal harm when administered to a pregnant women
All patients, particularly those receiving steroids, should be observed closely for the development of lymphopenia and PCp
As bioequivalence has been established only when given over 90 minutes, infusion over a shorter or longer period of time may result in suboptimal dosing; the possibility of an increase in infusion-related adverse reactions cannot be ruled out
Pregnancy and lactation
Pregnancy category: d
Lactation: Not known if excreted in breast milk, do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Temodar (temozolomide)
Mechanism of action
Imidazotetrazine derivative prodrug; active metabolite MTIC methylates guanine-rich areas of DNA that initiate transcription, which lead to DNA double strand breaks and apoptosis
Absorption
Rapidly and completely absorbed after oral administration
Peak Plasma Time: 1 hr (empty stomach); 2.25 hr (high-fat meal)
Bioequivalence: 100%; IV infusion (when administered over 90 min) is bioequivalent to same dose of oral capsule
Mean peak plasma concentration and AUC decreased by 32% and 9%, respectively when administered after a high-fat breakfast
Distribution
Protein Bound: 15%
Vd: 0.4 L/kg
Metabolism
Metabolite: Hydrolyzed at physiologic pH to 3-methyl-(triazen-1-yl) imidazole-4-carboxamide (MTIC); MTIC further hydrolyzed to to 5-amino-imidazole-4-carboxamide (AIC), which is known to be an intermediate in purine and nucleic acid biosynthesis, and to methylhydrazine, which is believed to be the active alkylating species
Elimination
Half-life: 1.8 hr
Clearance: 5.5 L/hr/m²
Excretion: primarily urine (~38%)
Administration
IV Preparation
Bring the vial to room temp
Reconstitute 100-mg vial with 41 mL SWI to obtain 2.5 mg/mL soln; gently swirl to dissolve (do not shake)
After reconstitution, store at room temp and use within 14 hr, including infusion time
Using aseptic technique, withdraw up to 40 mL per vial to get required dose and transfer into empty 250 mL PVC infusion bag
IV Administration
Infuse IV using pump over 90 min
Flush lines before and after infusion
Do not infuse other medications simultaneously thru same infusion line
Oral Administration
Take capsule consistently either with or without food; preferably take on empty stomach HS to avoid N/V
May consider antiemetics before/after
