Dear Healthcare Professional Letter on the important changes to frequency of serum liver test monitoring for hepatotoxicity in patients treated with Votrient (pazopanib)
06.12.2013
The company Glaxo Smith Kline d.o.o., in agreement with the Agency for Medicinal Products and Medical Devices (HALMED) has sent a letter to healthcare professionals on the new, important recommendations related to frequency of serum liver test monitoring for hepatotoxicity i patients treated with pazopanib.
Summary
- Serum liver tests should be monitored more frequently during the first nine weeks of therapy than originally recommended.
- Serum liver function tests should be carried out before starting treatment with pazopanib, and now at weeks three, five, seven and nine.
- Subsequent tests should be made at months three and four, and periodically thereafter as indicated.
- If elevated liver enzymes are found, they should be managed by increased monitoring of temporary or permanent interruption of treatment, as described in the section 4.4 of the current Summary of Product Characteristics (SmPC).
Further information on the safety concern
Pazopanib is a kinase inhibitor indicated for the treatment of patients with advanced renal cell carcinoma and for the treatment of patients with advanced soft tissue sarcoma who have received prior chemotherapy.
Abnormalities of liver function are commonly associated with pazopanib (³ 1/100 to < 1/10) and there have been uncommon (³ 1/1,000 to < 1/100) cases of hepatic failure, including fatalities. In order to manage this risk, pazopanib was originally licensed with a requirement for monitoring of liver function at least once every four weeks during the first months of treatment.
The periodic safety review of data from pazopanib clinical trials has since then identified elevated ALT (>3x the upper limit of normal (ULN) and concurrent AST (>3xULN) and bilirubin (>2xULN) elevations occurring primarily between weeks 3 and 9 of therapy. A comparison across trials with pazopanib indicates that 1% of patients treated with pazopanib had ALT > 3xULN at week 2. Approximately 5 % of patients had ALT > 3xULN at week 3. Most new cases of ALT > 3xULN occurred by week 9. More frequent monitoring between weeks 3 and 9 may lead to earlier detection of elevated serum liver tests and hepatotoxicity in patients taking pazopanib.
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 medicinal product Votrient. HALMED will continue monitoring the safe use of Votrient 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.
