Medicinal Products

Dear Healthcare Professional Letter on the severe hepatotoxicity associated with the use of temozolomide (Blastomat, Temodal and Temazol)


Alvogen, Merck Sharp & Dohme (MSD) and Pliva have in agreement with the Agency for Medicinal Products and Medical Devices (HALMED) sent a letter with new information to healthcare professionals concerning the safe use of temozolomide.


  • Cases of liver injury, including liver failure with lethal outcome have been reported in patients treated with temozolomide.
  • Hepatotoxicity may appear several weeks from the beginning of therapy or later, as well as after stopping the treatment with temozolomide.
  • Liver test function should be carried out:
    • before the beginning of treatment. In case of discrepancies from normal values, the decision on the beginning the treatment with temozolomide should be carefully considered based on the benefits/risks assessment for individual patient.
    • after every treatment cycle.
  • In patients on a 42-days treatment cycle, liver function tests should be repeated in the middle of this cycle.
  • In patients with significant discrepancies from normal liver functions , the benefits/risks ratio of the treatment continuation should be carefully considered.

Additional information

Temozolomide is indicated for treatment:

  • in adults with newly diagnosed multiform glioblastoma, simultaneously with radiotherapy (RT) and thereafter as monotherapy
  • children above three years, adolescents and adult patients with malignant glioma, such as multiform glioblastoma or anaplastic astrocytoma, reccurent or advancing after standard therapy.

Safety issue

A review was carried out recently of serious hepatotoxic cases, including those with a lethal outcome, reported after use of temzolomide worldwide. 44 cases of liver injuries were identified, including liver failure with lethal outcome in patients receiving temozolomide. Reported cases of liver failure with lethal outcome appeared approximately 42 to 77 days after beginning of the temozolomide treatment. Cases of hepatotoxicity without lethal outcome and with different times of appearance of 112 days have also been reported. The medicinal product information (Summary of Product Characteristics) for temozolomide already contains the hepatotoxicity, but not the fatal hepatocellular injury and liver failure and specific recommendations for liver function monitoring. As a result of this review, the information for temozolomide-containing medicinal products will be updated in the entire European Union according to the aforementioned summary of recommendations.

Here you may view the Dear Healthcare Professional Letter.

HALMED has not received any adverse reaction report to hepatotoxicity associated with the use of the temozolomide-containing medicinal products. HALMED will continue monitoring the safe use of temozolomide and will promptly inform the public about any new information.

We remind healthcare professionals that they should report any adverse reaction to HALMED, as well as quality defect. Patients who have developed any adverse reaction to medicinal product may report it directly to HALMED via form or on-line application, with recommendation regarding any adverse reaction they discover to consult with their doctor or pharmacist about the continuation of their therapy.