Temozolomide: risk of hepatic injury, including fatal hepatic failure—updated warnings and monitoring guidance
- Medicines and Healthcare products Regulatory Agency
- 15 January 2014
- Therapeutic area:
- Cancer and GI, hepatology and pancreatic disorders
Liver function should be tested before and during treatment with temozolomide.
Article date: January 2014
Temozolomide (brand leader Temodal) is an alkylating agent indicated for the treatment of newly diagnosed glioblastoma multiforme in adults in combination with radiotherapy, and for treatment of malignant glioma showing recurrence or progression after standard therapy in children and adults.
Hepatic adverse drug reactions (ADRs) are known to be associated with temozolomide: elevations of liver enzymes; hyperbilirubinaemia; cholestasis; and hepatitis are listed in the current product information. To date, we have received eight spontaneous adverse drug reaction reports from the UK of hepatic disorders associated with temozolomide. There has been a European review of available data for hepatic failure and similar events with temozolomide after reports of hepatic injury. These data include published case reports.1 2 3 4
Hepatic ADRs reported include hepatic injury and hepatic failure. The review identified a total of 38 cases of hepatic failure. Typically, liver injury began with increased liver enzymes after several weeks of treatment, and led to cholestasis. A fatal outcome of the hepatic failure was reported in 30 of these 38 cases. The reports reviewed include cases where improvement in liver function tests (LFTs) or symptoms of hepatic injury were observed after temozolomide was stopped. Frequency of hepatic failure is estimated to be very rare—occurring in fewer than one in every 10 000 patients treated.
On the basis of the evidence from the review, the product information for prescribers and patients will be updated to include information on the potential for serious hepatic reactions, including the possibility of fatal outcome. The product information will also include the updated recommendations for monitoring of liver function in patients receiving temozolomide—see below.
A letter containing the updated safety information and the new advice on monitoring liver function was sent to healthcare professionals in December 2013.
Advice for healthcare professionals:
- Baseline LFTs should be done before starting temozolomide treatment. If these tests are abnormal, physicians should consider the balance of benefits and risks when deciding whether to start treatment
- Patients on a 42-day treatment cycle should have LFTs repeated midway through this cycle. All patients should have LFTs checked after every treatment cycle
- If a patient develops significantly abnormal LFTs, the benefits of continuing treatment should be carefully considered versus the risk of potentially severe liver
- Note that liver toxicity may occur several weeks or more after initiation of treatment or after the last treatment with temozolomide
- Please report suspected adverse reactions with temozolomide on a Yellow Card (www.mhra.gov.uk/yellowcard)
Information from the European Medicines Agency.
Article citation: Drug Safety Update volume 7 issue 6, January 2014: A3.
Published: 15 January 2014