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SOLIRIS (eculizumab) - Increased Risk of Hemolysis or Low Hemoglobin with Serogroup B Meningococcal Vaccination

Starting date:
October 25, 2016
Posting date:
October 25, 2016
Type of communication:
Dear Healthcare Professional Letter
Subcategory:
Biologic/vaccine
Source of recall:
Health Canada
Issue:
Important Safety Information
Audience:
Healthcare Professionals, General Public
Identification number:
RA-60752

Audience

Healthcare professionals (nephrologists, hematologists, hematologist-oncologists, pediatricians, hospital pharmacists, nurses)

Key messages

  • An increased risk of hemolysis or low hemoglobin has been observed when patients already being treated with SOLIRIS (eculizumab) were vaccinated against serogroup B meningococcal infection with Bexsero.
  • To minimize the risk of hemolysis when patients who are being treated with SOLIRIS are vaccinated, it is recommended that these patients be vaccinated only after their disease has been controlled and within one week following SOLIRIS infusion, when the SOLIRIS concentration in the blood is considered to be relatively high.
  • It is recommended that :
    • Unless the risks of delaying SOLIRIS therapy outweigh the risks of developing a meningococcal infection, all patients must be vaccinated with a meningococcal vaccine (against serotypes A, C, Y, W135, and B) prior to, or at the time of, initiating SOLIRIS.
    • Patients who have initiated treatment with SOLIRIS less than 2 weeks after receiving a meningococcal vaccine be treated with appropriate prophylactic antibiotics for a period of 2 weeks post vaccination.
  • The Canadian Product Monograph has been updated to include this new safety information.

   

Issue

During a safety review of Bexsero, a vaccine used to protect against Neisseria meningitides serogroup B, Health Canada found more reports of serious adverse reactions with Bexsero in patients with complement mediated diseases (such as paroxysmal nocturnal hemoglobinuria [PNH] and atypical haemolytic uremic syndrome [atypical HUS]) who were being treated with SOLIRIS (a complement inhibitor), than in other patients vaccinated with Bexsero.  Bexsero was marketed in Canada in 2014, which is 5 years after SOLIRIS (marketed since 2009).  A further review of the reports with Bexsero in patients already being treated with SOLIRIS concluded that there was an increased risk of low hemoglobin, including anemia, or hemolysis. The risk was highest in patients receiving Bexsero vaccine when their predicted systemic SOLIRIS concentrations were relatively low.

Products affected

SOLIRIS® (eculizumab), parenteral solution (10 mg / mL), 30 mL single use vial.

Background information

SOLIRIS is a complement inhibitor indicated for the treatment of patients with PNH to reduce hemolysis, and for the treatment of patients with atypical HUS to reduce complement-mediated thrombotic microangiopathy (TMA). 

SOLIRIS blocks terminal complement activation; therefore patients may have increased susceptibility to infections, particularly meningococcal disease caused by Neisseria meningitidis.  Consequently, all patients must be vaccinated against meningococcal infections prior to, or at the time of, initiating SOLIRIS, unless the risks of delaying SOLIRIS therapy outweigh the risks of developing a meningococcal infection.

Vaccination, particularly with a vaccine against serogroup B meningococcal infection, in patients already being treated with SOLIRIS, may further activate complement. As a result, patients with complement-mediated diseases, including PNH and atypical HUS, may experience increased symptoms of their underlying disease, such as hemolysis (PNH) or thrombotic microangiopathy (TMA) complications (atypical HUS). To minimize this risk, it is recommended to vaccinate patients who are already being treated with SOLIRIS only when the underlying complement-mediated disease is clinically controlled and within one week of SOLIRIS infusion, when systemic SOLIRIS concentrations are considered to be relatively high.

Who is affected

Information for consumers

SOLIRIS is used to treat patients with PNH to reduce hemolysis (destruction of red blood cells) or to treat patients with chronic atypical HUS, a very rare disease that affects the blood system, kidney and sometimes other body organs.

SOLIRIS works by decreasing the destruction of patients’ red blood cells and platelets, but it also lowers the ability of their immune system to fight infections, particularly meningococcal disease caused by Neisseria meningitidis. Patients must be vaccinated with a meningococcal vaccine prior to, or at the time of, initiating SOLIRIS, unless otherwise recommended by their healthcare professional. Meningococcal vaccine prevents meningococcal infection, (an inflammation of the membranes that cover the brain and spinal cord). Patients may also be revaccinated according to current medical guidelines for vaccine use.

Patients who receive SOLIRIS must be monitored for early signs of meningococcal infections, evaluated immediately if infection is suspected, and treated with antibiotics, if necessary. Patients, who receive SOLIRIS will be provided a card to carry with them, listing specific trigger symptoms of infection. This card is named: “Patient Safety Card”. Patients should carry this card with them at all times during treatment and for 3 months after their last dose of SOLIRIS.  Patients need to show their Patient Safety Card to any healthcare professional they see during this time.

Patients should immediately inform their doctor if they notice any symptoms listed on their “Patient Safety Card”, such as: headache with nausea or vomiting; headache and a fever; headache with a stiff neck or stiff back; fever; fever and a rash; confusion; muscle aches with flu-like symptoms; or eyes sensitive to light.

Patients and caregivers should contact their healthcare professional for more information about vaccination before starting treatment with SOLIRIS or if they are already being treated with SOLIRIS.

Information for healthcare professionals

It is recommended that careful consideration be given to the timing of meningococcal vaccination relative to the administration of SOLIRIS in patients who initiate therapy and also for those receiving maintenance therapy.

  • For patients stabilized on SOLIRIS and receiving maintenance therapy, and for whom additional vaccination is warranted, vaccination is only recommended when the underlying complement-mediated disease is clinically controlled with SOLIRIS, and within one week following SOLIRIS infusion, when systemic SOLIRIS concentrations are considered to be relatively high.
  • All patients taking SOLIRIS must be vaccinated with a meningococcal vaccine prior to, or at the time of, initiating SOLIRIS.
  • Patients who start on SOLIRIS treatment less than 2 weeks after receiving a meningococcal vaccine must receive treatment with appropriate prophylactic antibiotics for 2 weeks after they are vaccinated.

Healthcare professionals are reminded to provide their patients with information from the recently updated Patient Information Brochure to increase their awareness of potential serious infections and their signs and symptoms. All patients must be monitored for early signs of meningococcal infections, evaluated immediately if infection is suspected, and treated with antibiotics, if necessary.

Action taken by Health Canada

Health Canada in collaboration with Alexion has updated the SOLIRIS Canadian Product Monograph. In order to help Canadians to make informed decisions about their medication choices, Health Canada has also shared this important safety information by publishing a summary of the safety review on its Web site.

Health Canada is communicating this important safety information to healthcare professionals and to the public through its Healthy Canadians Web site.

Report health or safety concerns

Managing marketed health product-related side effects depends on healthcare professionals and consumers reporting them. Any cases of hemolysis, low hemoglobin, serious or fatal meningococcal infection or other serious or unexpected side effects in patients receiving SOLIRIS and vaccines directed against Neisseria meningitidis serogroup B should be reported to Alexion or Health Canada.

Alexion Pharma Canada
3100 Rutherford Road, Suite 300
Vaughan, Ontario, L4K 0G6
Toll-Free: 1-888-SOLIRIS (1-888-765-4747) [OneSourceTM]

To correct your mailing address or fax number, contact Alexion.

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: 613-964-6522
Fax: 613-952-7738

Original signed by

Roger Kaprielian, PhD
Associate Medical Director – aHUS
Alexion Pharma Canada
roger.kaprielian@alexion.com

Rafael Sierra, PhD
Associate Medical Director - PNH
Alexion Pharma Canada
rafael.sierra@alexion.com

References

  1. Soliris (eculizumab) [Product Monograph]. Zurich (CH): Alexion Pharma GmbH;  2016.