Safety advisory - change to indications and addition of warnings
Consumers and health professionals are advised that the TGA has completed a review of idelalisib (marketed in Australia as Zydelig) and the medicine should no longer be used in combination with rituximab in specific situations outlined in further detail below.
Idelalisib belongs to a group of medicines called antineoplastic agents. It is approved to treat some rare kinds of blood cancer by affecting the growth of cancerous lymphocytes (a type of white blood cell).
The TGA's review was undertaken following advice from the sponsor, Gilead Sciences, of a potential increased risk of serious adverse events, including death, in patients receiving the medicine in combination with other cancer medicines to treat chronic lymphocytic leukaemia (CLL) and relapsed indolent non-Hodgkin's lymphoma (iNHL). These patients received the medicine as part of phase 3 clinical trials, which were ceased.
The TGA's review found that these results, which related to currently unapproved uses for the idelalisib, were also relevant to some of the previously approved uses for the medicine. As a result, there have been changes to the indications for idelalisib and additional information relating to serious infections, including a boxed warning, has been added to its Product Information (PI).
Information for consumers
If you or someone you provide care for takes idelalisib (Zydelig), talk to your health professional to make sure this medicine is still appropriate for you.
Your health professional will also be able to help if you have any other questions or concerns about this issue.
Information for health professionals
Gilead Sciences has written to health professionals providing further information about this issue, including details of the changes to idelalisib's PI.
The phase 3 clinical trials, through which patients received idelalisib in combination with other cancer medicines to treat CLL and relapsed iNHL, were discontinued early, as more participating patients who received idelalisib died than patients who received a placebo (7.4% vs 3.5%). The deaths often occurred within 180 days of starting treatment and were often due to infection (such as sepsis and pneumonia).
The subsequent TGA review concluded that idelalisib should no longer be indicated in combination with rituximab as first-line treatment in CLL/small lymphocytic lymphoma (SLL) patients in the presence of 17p deletion or TP53 mutation.
Additional clarifications to the indications include:
- Extension of the indication in CLL/SLL to include use in combination with ofatumumab in adult CLL/SLL patients upon relapse in patients for whom chemoimmunotherapy is not considered suitable.
- Revision of the indication in follicular lymphoma (FL) to specify that the disease must be refractory to both rituximab and an alkylating agent.
The revised indications are:
- Zydelig in combination with rituximab is indicated for the treatment of adult patients with CLL/SLL upon relapse in patients for whom chemo-immunotherapy is not considered suitable.
- Zydelig in combination with ofatumumab is indicated for the treatment of adult patients with CLL/SLL upon relapse in patients for whom chemo-immunotherapy is not considered suitable.
- Zydelig is indicated as monotherapy for the treatment of patients with FL which is refractory to at least two prior systemic therapies. The disease must be refractory to both rituximab and an alkylating agent.
Risk minimisation measures to prevent infection in all indications have been updated in the PI. A boxed warning has been added to the PI to alert prescribers of the risk of serious infections with specific reference to Pneumocystis jirovecii pneumonia (PJP) and cytomegalovirus (CMV) infection and also pneumonitis. Further guidance regarding PJP and CMV infection are provided as follows:
- All patients should receive prophylaxis for PJP during treatment with Zydelig. This should be continued for up to 2 to 6 months after discontinuation of Zydelig. The duration of post treatment prophylaxis should be based on clinical judgment, taking into account the patient's risk factors such as concomitant corticosteroid treatment and prolonged neutropenia.
- At least monthly clinical and laboratory monitoring for CMV infection is recommended in patients who are CMV-seropositive at the start of treatment with Zydelig or have other evidence of a history of CMV infection or disease. Patients with CMV viraemia without attributable symptoms or signs should be monitored for evidence of high or rising viral load. For asymptomatic patients with evidence of high or rising viral load, consideration should be given to interruption of Zydelig and commencement of antiviral therapy to prevent invasive disease. For patients with evidence of CMV viraemia and attributable symptoms or signs, initiate antiviral therapy; and strong consideration should be given to interrupting Zydelig until CMV disease has resolved. Zydelig may be restarted if the infection has resolved and if the benefits of resuming Zydelig are judged to outweigh the risks. Consideration should be given to administering pre-emptive CMV therapy.
The following previously issued guidance is unchanged:
- Patients should be informed about the risk of potential serious and/or fatal infections during treatment with Zydelig.
- Zydelig should not be initiated in patients with any evidence of ongoing systemic bacterial, fungal or viral infection.
- Patients should be monitored for respiratory signs and symptoms throughout treatment with Zydelig and be advised to promptly report new respiratory symptoms.
- Absolute neutrophil counts (ANC) should be monitored in all patients at least every two (2) weeks for the first six (6) months of treatment with Zydelig, and at least weekly in patients while ANC is less than 1.0X109/L (see table in PI).
If you have any questions or concerns about this issue, contact Gilead Sciences on 03 9272 4400.
Consumers and health professionals are encouraged to report problems with medicines or vaccines. Your report will contribute to the TGA's monitoring of these products.
The TGA cannot give advice about an individual's medical condition. You are strongly encouraged to talk with a health professional if you are concerned about a possible adverse event associated with a medical device.