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Indication & Important Safety Information for Soliris® (eculizumab)

INDICATION

Paroxysmal Nocturnal Hemoglobinuria (PNH)
Soliris is indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS MENINGOCOCCAL INFECTIONS

Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris.
Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early.

  • Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies.
  • Immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection. (See Serious Meningococcal Infections for additional guidance on the management of the risk of meningococcal infection)
  • Vaccination reduces, but does not eliminate, the risk of meningococcal infections. Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected.

Soliris is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the Soliris REMS, prescribers must enroll in the program. Enrollment in the Soliris REMS program and additional information are available by telephone: 1-888-SOLIRIS (1-888-765-4747) or at www.solirisrems.com.

Contraindications

Soliris is contraindicated in:

  • Patients with unresolved serious Neisseria meningitidis infection
  • Patients who are not currently vaccinated against Neisseria meningitidis, unless the risks of delaying Soliris treatment outweigh the risks of developing a meningococcal infection

Warnings and Precautions

Serious Meningococcal Infections

Risk and Prevention

See Boxed WARNING for additional information on serious meningococcal infections.

Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris. The use of Soliris increases a patient’s susceptibility to serious meningococcal infections (septicemia and/or meningitis).

Vaccinate for meningococcal disease according to the most current ACIP recommendations for patients with complement deficiencies. Revaccinate patients in accordance with ACIP recommendations, considering the duration of Soliris therapy.

Immunize patients without a history of meningococcal vaccination at least 2 weeks prior to receiving the first dose of Soliris. If urgent Soliris therapy is indicated in an unvaccinated patient, administer meningococcal vaccine(s) as soon as possible and provide patients with two weeks of antibacterial drug prophylaxis.

The benefits and risks of antibiotic prophylaxis for prevention of meningococcal infections in patients receiving Soliris have not been established.
Vaccination reduces, but does not eliminate, the risk of meningococcal infections.

Closely monitor patients for early signs and symptoms of meningococcal infection and evaluate patients immediately if an infection is suspected. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Discontinue Soliris in patients who are undergoing treatment for serious meningococcal infections.

REMS
Because of the risk of meningococcal infections, Soliris is available only through a restricted program under a REMS. Under the Soliris REMS, prescribers must enroll in the program.

Prescribers must counsel patients about the risk of meningococcal infection, provide the patients with the REMS educational materials, and ensure patients are vaccinated with meningococcal vaccine(s).

Other Infections
Serious infections with Neisseria species (other than N. meningitidis), including disseminated gonococcal infections, have been reported.

Soliris blocks terminal complement activation; therefore patients may have increased susceptibility to infections, especially with encapsulated bacteria. Additionally, Aspergillus infections have occurred in immunocompromised and neutropenic patients. Children treated with Soliris may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) infections according to ACIP guidelines. Use caution when administering Soliris to patients with any systemic infection.

Monitoring Disease Manifestations After Soliris Discontinuation

Treatment Discontinuation for PNH
Monitor patients after discontinuing Soliris for at least 8 weeks to detect hemolysis.

Thrombosis Prevention and Management
The effect of withdrawal of anticoagulant therapy during Soliris treatment has not been established. Therefore, treatment with Soliris should not alter anticoagulant management.

Infusion Reactions
Administration of Soliris may result in infusion reactions, including anaphylaxis or other hypersensitivity reactions. In clinical trials, no patients experienced an infusion reaction which required discontinuation of Soliris. Interrupt Soliris infusion and institute appropriate supportive measures if signs of cardiovascular instability or respiratory compromise occur.

Adverse Reactions
The most frequently reported adverse reactions in the PNH randomized trial (≥10% overall and greater than placebo) are: headache, nasopharyngitis, back pain, and nausea.

Please see full Prescribing Information for Soliris, including boxed WARNING regarding serious meningococcal infections.

Full Clinical Assessment

A Full Clinical Assessment Helps Effectively Diagnose and Monitor PNH1

The Realities of Testing

The diverse and common symptomatology of PNH can delay diagnosis from 1 to more than 10 years2, and therefore it is critical to test high-risk patient groups in an effort to make an earlier diagnosis of PNH.1

A comprehensive clinical assessment is crucial to determine the risk for morbidities and premature mortality in your patient with PNH1

Monitor your high-risk patients for lab values and symptoms associated with PNH

Has your patient presented with any of the following conditions, signs, or symptoms? If so, any of these may raise the index of suspicion for PNH.


High-risk patient populations for PNH1,3

  • Coombs-negative hemolytic anemia, especially concurrent iron deficiency, or

  • Hemoglobinuria or hemosiderinuria, or

  • Aplastic anemia, or

  • RA-MDS, or

  • Unexplained thrombosis, or

  • Unexplained cytopenia, with any of the following

    • Any subtype with evidence of hemolysis

    • Refractory IDA

    • Nonresponsive to therapy

    • Thrombosis


Any evidence of elevated hemolysis1 (Normal ranges included in parentheses)

  • LDH ≥1.5 × ULN (105-333 IU/L)1,4,5, or

  • Low haptoglobin levelsa (<41-165 mg/dL)1,6, or

  • Elevated reticulocyte count (0.5-1.5%)1,7, or

  • Elevated indirect bilirubin (direct: 0-0.3 mg/dL)1,8


Any signs of renal dysfunction plus hemolysis9 (Normal ranges included in parentheses)

  • Proteinuria (<30 mg albumin/g creatinine)9,10, or

  • Low eGFR (90-120 mL/min/1.73 m2)9,11, or

  • Elevated serum creatinine (female: 0.4-1.1 mg/dL; male: 0.5-1.2 mg/dL)9,12


Evidence of comorbidities associated with PNH (Normal ranges included in parentheses)

  • Low platelet count (150,000-400,000/μL)13,14

  • Elevated D-dimers (<250 ng/mL)13,15

  • Elevated NT-proBNPb (normal ranges vary with both gender and age)16,17

  • Elevated pulmonary artery pressure (average <25 mmHg)16,18


Other signs or symptoms associated with PNH that could raise the index of suspicion3,19-21

  • Abdominal pain

  • Chest pain

  • Dyspnea

  • Fatigue

  • Impaired health-related quality of life

  • Anemia

  • Dysphagia

  • Increasing clone size


a Low haptoglobin is indicative of excess plasma-free hemoglobin released from hemolyzed RBCs.6
b N-terminal pro-brain natriuretic peptide, a marker of cardiac dysfunction.16

Please view the full clinical assessment document for a comprehensive list of details related to lab values or symptoms of patients at potential risk.

Important Safety Information

Indication & Important Safety Information for Soliris® (eculizumab)

INDICATION

Paroxysmal Nocturnal Hemoglobinuria (PNH)
Soliris is indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS MENINGOCOCCAL INFECTIONS

Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris.
Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early.

  • Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies.
  • Immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection. (See Serious Meningococcal Infections for additional guidance on the management of the risk of meningococcal infection)
  • Vaccination reduces, but does not eliminate, the risk of meningococcal infections. Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected.

Soliris is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the Soliris REMS, prescribers must enroll in the program. Enrollment in the Soliris REMS program and additional information are available by telephone: 1-888-SOLIRIS (1-888-765-4747) or at www.solirisrems.com.

Contraindications

Soliris is contraindicated in:

  • Patients with unresolved serious Neisseria meningitidis infection
  • Patients who are not currently vaccinated against Neisseria meningitidis, unless the risks of delaying Soliris treatment outweigh the risks of developing a meningococcal infection

Warnings and Precautions

Serious Meningococcal Infections

Risk and Prevention

See Boxed WARNING for additional information on serious meningococcal infections.

Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris. The use of Soliris increases a patient’s susceptibility to serious meningococcal infections (septicemia and/or meningitis).

Vaccinate for meningococcal disease according to the most current ACIP recommendations for patients with complement deficiencies. Revaccinate patients in accordance with ACIP recommendations, considering the duration of Soliris therapy.

Immunize patients without a history of meningococcal vaccination at least 2 weeks prior to receiving the first dose of Soliris. If urgent Soliris therapy is indicated in an unvaccinated patient, administer meningococcal vaccine(s) as soon as possible and provide patients with two weeks of antibacterial drug prophylaxis.

The benefits and risks of antibiotic prophylaxis for prevention of meningococcal infections in patients receiving Soliris have not been established.
Vaccination reduces, but does not eliminate, the risk of meningococcal infections.

Closely monitor patients for early signs and symptoms of meningococcal infection and evaluate patients immediately if an infection is suspected. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Discontinue Soliris in patients who are undergoing treatment for serious meningococcal infections.

REMS
Because of the risk of meningococcal infections, Soliris is available only through a restricted program under a REMS. Under the Soliris REMS, prescribers must enroll in the program.

Prescribers must counsel patients about the risk of meningococcal infection, provide the patients with the REMS educational materials, and ensure patients are vaccinated with meningococcal vaccine(s).

Other Infections
Serious infections with Neisseria species (other than N. meningitidis), including disseminated gonococcal infections, have been reported.

Soliris blocks terminal complement activation; therefore patients may have increased susceptibility to infections, especially with encapsulated bacteria. Additionally, Aspergillus infections have occurred in immunocompromised and neutropenic patients. Children treated with Soliris may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) infections according to ACIP guidelines. Use caution when administering Soliris to patients with any systemic infection.

Monitoring Disease Manifestations After Soliris Discontinuation

Treatment Discontinuation for PNH
Monitor patients after discontinuing Soliris for at least 8 weeks to detect hemolysis.

Thrombosis Prevention and Management
The effect of withdrawal of anticoagulant therapy during Soliris treatment has not been established. Therefore, treatment with Soliris should not alter anticoagulant management.

Infusion Reactions
Administration of Soliris may result in infusion reactions, including anaphylaxis or other hypersensitivity reactions. In clinical trials, no patients experienced an infusion reaction which required discontinuation of Soliris. Interrupt Soliris infusion and institute appropriate supportive measures if signs of cardiovascular instability or respiratory compromise occur.

Adverse Reactions
The most frequently reported adverse reactions in the PNH randomized trial (≥10% overall and greater than placebo) are: headache, nasopharyngitis, back pain, and nausea.

Please see full Prescribing Information for Soliris, including boxed WARNING regarding serious meningococcal infections.

  1. Parker C, et al. Blood. 2005;106:3699-3709.

  2. Dacie JV, Lewis SM Ser Haemat. 1972;3:3-23.

  3. Borowitz M, et al. Cytometry B Clin Cytom. 2010;78(4):211-230.

  4. Sahin F, et al. Am J Blood Res. 2016;6(2):19-27.

  5. Lactate dehydrogenase test. MedlinePlus website. https://medlineplus.gov/ency/article/003471.htm. 2017. Accessed October 5, 2017.

  6. Haptoglobin blood test. MedlinePlus website. https://medlineplus.gov/ency/article/003634.htm. 2016. Accessed October 5, 2017.

  7. Reticulocyte count. MedlinePlus website. https://medlineplus.gov/ency/article/003637.htm. 2016. Accessed October 5, 2017.

  8. Bilirubin blood test. MedlinePlus website. https://medlineplus.gov/ency/article/003479.htm. 2017. Accessed October 5, 2017

  9. Hillmen P, et al. Am J Hematol. 2010;85(8):553-559

  10. Proteinuria. Medscape website. http://emedicine.medscape.com/article/238158-overview. 2016. Accessed October 5, 2017.

  11. Harris K, Stribling B. Ther Clin Risk Manag. 2007;3(5):969–972.

  12. Creatinine. Medscape website. http://emedicine.medscape.com/article/2054342-overview. 2014. Accessed October 5, 2017.

  13. Hill A, et al. Blood. 2013;121:4985-4996.

  14. Platelet count. MedlinePlus website. https://medlineplus.gov/ency/article/003647.htm. 2017. Accessed October 5, 2017.

  15. Schwenk TL. Can d-dimer levels help to predict VTE recurrence? Medscape website. http://www.medscape.com/viewarticle/462314. 2003. Accessed October 5, 2017.

  16. Hill A, et al. Br J Haematol. 2012;158(3):409-414

  17. Test ID: PBNP. Mayo Clinic website. https://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/84291. 2017. Accessed October 5, 2017.

  18. Dweik R, et al. Pulmonary hypertension. Cleveland clinic website. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/pulmonary/pulmonary-hypertension/. 2011. Accessed October 5, 2017.

  19. Brodsky RA. In: Hoffman R, et al. eds. Hematology: Basic Principles and Practice. Saunders/Elsevier;2013:373-382.

  20. Rachidi S, et al. Eur J Intern Med. 2010;21(4):260-267

  21. Audebert HJ, et al. J Neurol. 2005;252:1379-1386.