Hypertriglyceridemia, including severe and life-threatening events, has been identified as an adverse reaction associated with ALECENSARO. Severe hypertriglyceridemia is considered a medical emergency, as it may lead to acute pancreatitis.

 

Audience

Healthcare professionals involved in the treatment of lung cancer, including medical oncologists, thoracic surgeons, surgical oncologists (Quebec), respirologists, oncology nurses, and oncology pharmacists.

 

Key messages

• Hypertriglyceridemia, including severe and life-threatening events, has been identified as an adverse reaction associated with ALECENSARO (alectinib).
• Severe hypertriglyceridemia is considered a medical emergency, as it may lead to acute pancreatitis.
• Healthcare professionals are advised that:
  • Patients should be counselled on the risks and benefits of ALECENSARO, including the risk of hypertriglyceridemia.
  • Blood triglyceride levels should be measured at baseline before initiating ALECENSARO and periodically during treatment.
  • Patients should be monitored for signs and symptoms of acute pancreatitis, especially those at increased risk.
  • If an acute episode of pancreatitis occurs, ALECENSARO should be temporarily withheld until full recovery before resuming treatment. ALECENSARO should also be temporarily withheld in patients who develop severe or life-threatening hypertriglyceridemia until triglyceride levels recover to moderate levels (see the Information to healthcare professionals section).
• The Canadian Product Monograph for ALECENSARO will be updated to include this safety information.

 

Background information

ALECENSARO is indicated:

• for the first-line treatment of patients with anaplastic lymphoma kinase (ALK)-positive, locally advanced (not amenable to curative therapy) or metastatic non-small cell lung cancer (NSCLC).
• as monotherapy for the treatment of patients with ALK-positive, locally advanced (not amenable to curative therapy) or metastatic NSCLC who have progressed on or are intolerant to crizotinib.
• for adjuvant treatment following tumour resection for patients with stage IB (tumours ≥ 4 cm) to IIIA* ALK-positive NSCLC.

       *According to the American Joint Committee on Cancer [7th edition].

Cumulative data from clinical studies and post-marketing sources identified hypertriglyceridemia as a risk associated with ALECENSARO.

Hypertriglyceridemia adverse events of any grade were reported in 4.3% of patients from pivotal clinical trials, and severe or life-threatening hypertriglyceridemia adverse events were reported in 1.5% of patients from these trials. The onset of severe or life-threatening hypertriglyceridemia adverse events ranged from 106 to 1001 days.

Triglycerides were not consistently monitored in clinical trials. In 3 clinical trials in which triglycerides were measured, laboratory data showed increases from baseline, where the majority of shifts from baseline were from normal to grade 1 (150 mg/dL to 300 mg/dL; 1.71 mmol/L to 3.42 mmol/L); however, grade ≥3 laboratory elevations were also reported in these trials. Overall, observed cases of hypertriglyceridemia were mostly mild to moderate in severity.

In the post-marketing setting, five medically confirmed severe to life-threatening cases of hypertriglyceridemia were reported internationally in patients treated with ALECENSARO. Three of these cases resulted in life-threatening pancreatitis, with all patients ultimately recovering following treatment. One of these cases demonstrated a positive rechallenge for life-threatening hypertriglyceridemia upon ALECENSARO resumption. The onset of these serious cases ranged from 6 weeks to 1 year after the start of ALECENSARO treatment.

 

Information for consumers

ALECENSARO (alectinib) is a prescription medicine used to treat non-small cell lung cancer in adults. 

ALECENSARO can cause high levels of triglycerides (a type of fat) in the blood. In some cases, very high triglyceride levels can be life‑threatening and may lead to acute pancreatitis (sudden inflammation of the pancreas), which is a medical emergency.

Healthcare professionals should test their patients’ blood triglyceride levels before and during treatment with ALECENSARO. Patients should be monitored for signs of pancreatitis.

Patients should stop taking ALECENSARO and seek immediate medical attention if they experience symptoms of pancreatitis, such as sudden, severe abdominal pain accompanied by nausea, vomiting, fast heart rate, fast breathing and/or fever.

Patients should talk to their healthcare professional if they have any questions or concerns about this information.

 

Information for health care professionals

Healthcare professionals are advised that:

• Patients should be counselled on the risks and benefits of ALECENSARO, including the risk of hypertriglyceridemia.
• Blood triglyceride levels should be measured at baseline before initiating ALECENSARO and periodically during treatment.
• Patients should be monitored for signs and symptoms of acute pancreatitis, particularly those at increased risk for pancreatitis.
• If an acute episode of pancreatitis occurs, ALECENSARO should be temporarily withheld until full recovery before resuming treatment. ALECENSARO should also be temporarily withheld in patients who develop severe hypertriglyceridemia (blood triglycerides >500 to 1000 mg/dL or >5.7 to 11.4 mmol/L) or life-threatening hypertriglyceridemia (blood triglycerides >1000 mg/dL or >11.4 mmol/L) until triglyceride levels recover to ≤500 mg/dL or ≤5.7 mmol/L. In these patients, risk factors for pancreatitis should be evaluated, and modifiable risk factors should be addressed before resuming treatment with ALECENSARO. ALECENSARO may be resumed at the same dose, with regular triglyceride monitoring.

 

Action taken by Health Canada

Health Canada, in collaboration with Hoffmann-La Roche Limited, will update the Canadian Product Monograph for ALECENSARO to include this new safety information.

Health Canada is communicating this important safety information to healthcare professionals and Canadians via the Recalls and Safety Alerts Database on the Healthy Canadians Web Site. This communication will be further distributed through the MedEffect™ e-Notice email notification system.

 

Report health or safety concerns

Managing marketed health product-related side effects depends on health care professionals and consumers reporting them. Any case of hypertriglyceridemia or other serious or unexpected side effects in patients receiving ALECENSARO should be reported to Hoffmann-La Roche Limited or Health Canada.
 

Hoffmann-La Roche Limited
Medical Information Department
7070 Mississauga Road
Mississauga, Ontario, L5N 5M8
Toll free: 1-888-762-4388
Fax: 905-542-5864
E-mail: mississauga.canada_medinfo@roche.com

To correct your mailing address or fax number, contact Hoffmann-La Roche Limited.

You can report any suspected adverse reactions associated with the use of health products to Health Canada by:

• Calling toll-free at 1-866-234-2345; or
• Visiting MedEffect Canada's Web page on Adverse Reaction Reporting for information on how to report online, by mail or by fax.

 

For other health product inquiries related to this communication, contact Health Canada at:

Marketed Health Products Directorate
E-mail: mhpd-dpsc@hc-sc.gc.ca
Telephone: 613-954-6522
Fax: 613-952-7738

 

Original signed by

 

Daniel P. Edgcumbe, MB BChir
Vice President, Medical & Regulatory Affairs
Hoffmann-La Roche Limited