Temozolomide

Temozolomide (TEMODAL®)

🔴 Red Flags – Key Things to Remember

• Severe myelosuppression is dose-limiting → monitor FBC closely (neutropenia, thrombocytopenia, pancytopenia)
• PCP (Pneumocystis jirovecii) prophylaxis is mandatory during concurrent radiotherapy (42-day regimen)
• Do NOT use in pregnancy or breastfeeding → teratogenic and genotoxic
• Risk of secondary malignancies (MDS, AML) with prolonged exposure
• Capsules must be swallowed whole – cytotoxic powder (do not open/crush)
• Increased toxicity with other myelosuppressive agents
• Higher haematologic toxicity in elderly patients (>70 years)

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🔹 1. Basic Information

Generic name: Temozolomide
Brand name: TEMODAL®
Drug class: Alkylating agent (imidazotetrazene)
Formulation: Oral capsules
Strengths: 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, 250 mg

Mechanism of Action:
Temozolomide undergoes rapid conversion to the active metabolite MTIC, which methylates DNA at the O6 and N7 positions of guanine, leading to DNA damage, failed repair, and tumour cell death.
It crosses the blood–brain barrier, making it effective in CNS malignancies.

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🔹 2. FULL INDICATIONS (As per PI)

TEMODAL is indicated for the treatment of:

A. Newly Diagnosed Glioblastoma Multiforme (GBM) – Adults

• Following debulking surgery
• Concomitant use with radiotherapy, followed by
• Adjuvant temozolomide monotherapy

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B. Recurrent Malignant Glioma

Including:
• Glioblastoma multiforme
• Anaplastic astrocytoma

Used in patients with recurrent or progressive disease

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C. Advanced Metastatic Malignant Melanoma

• Adults with advanced metastatic melanoma

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🔹 3. Dosing & Administration

Newly Diagnosed GBM

Concomitant Phase (with Radiotherapy):
• 75 mg/m² once daily
• Given daily for 42 days (up to 49 days)
• With focal radiotherapy (60 Gy in 30 fractions)

Adjuvant Phase:
• Cycle 1: 150 mg/m² once daily for 5 days every 28 days
• Cycles 2–6: Escalate to 200 mg/m² if tolerated
• Maximum: 6 cycles

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Recurrent Glioma or Metastatic Melanoma

• Chemotherapy-naïve: 200 mg/m² once daily × 5 days every 28 days
• Previously treated: Start 150 mg/m² → escalate if tolerated

Continue until disease progression or unacceptable toxicity
(Maximum treatment duration: 2 years)

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Administration Rules

• Take fasting (≥1 hour before food)
• Swallow capsules whole with water
• Do NOT repeat dose if vomiting occurs

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🔹 4. Dose Modifications

Haematologic Toxicity

• ANC <1.0 ×10⁹/L or platelets <50 ×10⁹/L → reduce dose
• Persistent Grade 4 toxicity → discontinue permanently

Non-haematologic Toxicity

• Grade 3 → hold and reduce dose
• Grade 4 → discontinue

Lowest recommended dose: 100 mg/m²

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🔹 5. Co-medications

• PCP prophylaxis required during concurrent radiotherapy
• Antiemetics recommended (prophylactic use standard)
• Caution with other myelosuppressive agents

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🔹 6. Contraindications

• Hypersensitivity to temozolomide or dacarbazine (DTIC)
• Pregnancy and breastfeeding
• Severe myelosuppression

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🔹 7. Monitoring Requirements

• FBC:
– Weekly during concurrent phase
– Day 22 of each adjuvant cycle
• Liver function tests: Periodic
• Clinical monitoring for infection, especially PCP
• Neurological status and performance status

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🔹 8. Side Effects

Very Common (>10%)

• Nausea, vomiting
• Fatigue
• Constipation
• Anorexia
• Thrombocytopenia, neutropenia
• Alopecia

Common (1–10%)

• Anaemia, leukopenia
• Headache, dizziness, somnolence
• Rash, pruritus
• Diarrhoea, abdominal pain

Serious / Rare

• Pancytopenia, aplastic anaemia
• Opportunistic infections (PCP, herpes encephalitis)
• Interstitial pneumonitis
• Stevens–Johnson syndrome / TEN
• Secondary malignancies (MDS, AML)

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🔹 9. Drug Interactions

• No clinically significant interaction with food or ranitidine
• Valproic acid → ↓ temozolomide clearance
• Increased toxicity with other cytotoxics or radiotherapy

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🔹 10. Use in Special Populations

• Pregnancy: Contraindicated
• Breastfeeding: Contraindicated
• Elderly (>70 years): Higher risk of cytopenias
• Renal impairment: No dose adjustment generally required
• Hepatic impairment: Use with caution
• Paediatrics:
– Glioma: ≥3 years
– Melanoma: Not indicated

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🔹 11. Duration of Use / When to Stop

Continue until:
• Disease progression, OR
• Unacceptable toxicity, OR
• Completion of planned therapy

Permanently discontinue if:
• Recurrent Grade 4 myelosuppression
• Severe opportunistic infection
• Secondary haematologic malignancy
• Inability to tolerate minimum dose

 

https://www.sahpra.org.za/wp-content/uploads/2020/02/Temodal_PI_MSD_MCC-format-26-October-2012.pdf