Temozolomide Side Effects: What to Expect and When to Call Your Doctor

Temozolomide (Temodar) is an effective treatment for glioblastoma and other brain tumors, but like all chemotherapy agents, it can cause side effects. Understanding what to expect can help you manage symptoms better and recognize when something requires urgent medical attention. This guide covers both common and serious temozolomide side effects.

Common Temozolomide Side Effects (Occurring in ≥20% of Patients)

The following side effects appear in at least 20% of patients taking temozolomide, according to the FDA-approved prescribing information:

• Alopecia (hair loss): Hair loss is one of the most common and visible effects. It is usually temporary and hair typically regrows after treatment ends.
• Nausea and vomiting: Very common. Taking temozolomide on an empty stomach or at bedtime may help. Anti-nausea medications like ondansetron (Zofran) or prochlorperazine are often prescribed alongside temozolomide.
• Fatigue: Many patients experience significant tiredness, especially during concurrent chemoradiation. Rest, gentle activity, and good nutrition can help manage fatigue.
• Headache: Headaches can be a side effect of temozolomide, and also a symptom of the underlying brain tumor. Report new or worsening headaches to your oncologist.
• Constipation: Constipation is common and often manageable with dietary adjustments and stool softeners.
• Anorexia (loss of appetite): Many patients have reduced appetite during treatment. Small, frequent meals and nutritional supplements can help maintain weight.
• Convulsions (seizures): Seizures can occur due to the brain tumor itself or as a side effect of treatment. Most GBM patients are already on anti-seizure medications.

Serious Temozolomide Side Effects: Call Your Doctor Immediately

The following side effects are less common but can be life-threatening. Contact your oncologist or go to the emergency room immediately if you experience any of these:

• Signs of infection (from low white blood cell counts): Fever of 100.4°F (38°C) or higher, chills, cough, or unusual fatigue. Temozolomide lowers neutrophil counts, increasing infection risk. A fever is a medical emergency during chemotherapy.
• Unusual bleeding or bruising: Low platelet counts (thrombocytopenia) can occur. Report black or tarry stools, blood in urine, red spots on skin, or unusual bruising immediately.
• Pneumocystis pneumonia (PCP): PCP is a serious lung infection that can develop during temozolomide treatment, especially during the concurrent RT phase. Symptoms include fever, cough, and shortness of breath. PCP prophylaxis (typically Bactrim/TMP-SMX) should be prescribed during the 42-day concurrent phase.
• Liver problems (hepatotoxicity): Signs include belly pain, yellowing of the skin or eyes (jaundice), dark urine, or swelling. Your oncologist will monitor your liver enzymes during treatment.
• Severe allergic reaction: Temozolomide is contraindicated in people with a history of hypersensitivity to temozolomide or dacarbazine. Call 911 immediately for hives, difficulty breathing, or facial/throat swelling.

Long-Term Risk: Secondary Malignancies

Temozolomide-containing regimens have been associated with an increased incidence of secondary malignancies, including myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (AML). These are rare but serious long-term risks. Your oncologist will discuss these risks with you before starting treatment.

Managing Side Effects: Tips for Daily Life

• Take temozolomide at bedtime on an empty stomach to reduce nausea.
• Take anti-nausea medication as prescribed — before your dose, not just when you feel sick.
• Check your temperature daily and call your care team at 100.4°F or higher.
• Never open, crush, or chew capsules — the powder inside is a chemotherapy agent and hazardous to skin and mucous membranes.
• Keep all scheduled blood count appointments — CBC monitoring is essential to safe dosing.

When Should You Go to the ER?

Go to the emergency room or call 911 for:

• Fever of 100.4°F (38°C) or higher
• Signs of serious bleeding (blood in stool, urine, coughing blood)
• Severe shortness of breath or chest pain
• Signs of allergic reaction (hives, facial swelling, difficulty breathing)
• New or worsening neurological symptoms (sudden weakness, confusion, speech changes)

See also: Temozolomide Drug Interactions: What to Avoid and What to Tell Your Doctor.