Furthering Alexion’s commitment to adults living with PNH

Please see full Prescribing Information, including Boxed WARNING regarding serious and life-threatening meningococcal infections/sepsis.

Learn more at ULTOMIRIS.com

INDICATION & IMPORTANT SAFETY INFORMATION for ULTOMIRIS® (ravulizumab-cwvz), INCLUDING BOXED WARNING

INDICATION

Paroxysmal Nocturnal Hemoglobinuria (PNH)

ULTOMIRIS is indicated for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH).

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS MENINGOCOCCAL INFECTIONS

Life-threatening meningococcal infections/sepsis have occurred in patients treated with ULTOMIRIS. 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 ULTOMIRIS, unless the risks of delaying ULTOMIRIS therapy outweigh the risk of developing a meningococcal infection. See Warnings and Precautions 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.

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

CONTRAINDICATIONS

ULTOMIRIS is contraindicated in:

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

WARNINGS AND PRECAUTIONS
Serious Meningococcal Infections
Risk and Prevention
Life-threatening meningococcal infections have occurred in patients treated with ULTOMIRIS. The use of ULTOMIRIS increases a patient’s susceptibility to serious meningococcal infections (septicemia and/or meningitis). Meningococcal disease due to any serogroup may occur.

Vaccinate for meningococcal disease according to the most current Advisory Committee on Immunization Practices (ACIP) recommendations for patients with complement deficiencies. Revaccinate patients in accordance with ACIP recommendations considering the duration of ULTOMIRIS therapy.

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

In clinical studies, 59 patients with PNH were treated with ULTOMIRIS less than 2 weeks after meningococcal vaccination. All of these patients received antibiotics for prophylaxis of meningococcal infection until at least 2 weeks after meningococcal vaccination. The benefits and risks of antibiotic prophylaxis for prevention of meningococcal infections in patients receiving ULTOMIRIS have not been established.

Vaccination reduces, but does not eliminate, the risk of meningococcal infections. In PNH clinical studies, 3 out of 261 PNH patients developed serious meningococcal infections/sepsis while receiving treatment with ULTOMIRIS; all 3 had been vaccinated. These 3 patients recovered while continuing treatment with ULTOMIRIS.

Closely monitor patients for early signs and symptoms of meningococcal infection and evaluate patients immediately if infection is suspected. Inform patients of these signs and symptoms and steps to be taken to seek immediate medical care. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider discontinuation of ULTOMIRIS in patients who are undergoing treatment for serious meningococcal infection.

REMS
Due to the risk of meningococcal infections, ULTOMIRIS is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the ULTOMIRIS REMS, prescribers must enroll in the program.

Prescribers must counsel patients about the risk of meningococcal infection/sepsis, provide the patients with the REMS educational materials, and ensure patients are vaccinated with meningococcal vaccines.

Enrollment in the ULTOMIRIS REMS and additional information are available by telephone: 1-888-765-4747 or at www.ultomirisrems.com.

Other Infections
ULTOMIRIS blocks terminal complement activation; therefore patients may have increased susceptibility to encapsulated bacteria infections, especially infections caused by Neisseria meningitis but also Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent, Neisseria gonorrhoeae. If ULTOMIRIS therapy is administered to patients with active systemic infections, monitor closely for signs and symptoms of worsening infection.

Monitoring Disease Manifestations after ULTOMIRIS Discontinuation
Treatment Discontinuation for PNH
After discontinuing treatment with ULTOMIRIS, closely monitor for signs and symptoms of hemolysis, identified by elevated LDH along with sudden decrease in PNH clone size or hemoglobin, or re-appearance of symptoms such as fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction. Monitor any patient who discontinues ULTOMIRIS for at least 16 weeks to detect hemolysis and other reactions. If signs and symptoms of hemolysis occur after discontinuation, including elevated LDH, consider restarting treatment with ULTOMIRIS.

Thromboembolic Event Management
The effect of withdrawal of anticoagulant therapy during ULTOMIRIS treatment has not been established. Therefore, treatment with ULTOMIRIS should not alter anticoagulant management.

Infusion Reactions
Administration of ULTOMIRIS may result in infusion reactions. In clinical trials, 5 out of 296 patients treated with ULTOMIRIS experienced infusion reactions (lower back pain, drop in blood pressure, infusion-related pain, elevation in blood pressure and limbs discomfort) during ULTOMIRIS administration. These reactions did not require discontinuation of ULTOMIRIS. Interrupt ULTOMIRIS infusion and institute appropriate supportive measures if signs of cardiovascular instability or respiratory compromise occur.

ADVERSE REACTIONS
Adverse reactions reported in 5% or more of patients treated with ULTOMIRIS vs. Eculizumab was Upper respiratory tract infection (39% vs 39%), Headache (32% vs. 26%), Diarrhea (9% vs. 5%), Nausea (9% vs. 9%), Pyrexia (7% vs 8%), Pain in extremity (6% vs. 5%), Abdominal pain (6% vs. 7%), Dizziness (5% vs. 6%), Arthralgia (5% vs. 5%).

Serious adverse reactions were reported in 15 (6.8%) patients receiving ULTOMIRIS. The serious adverse reactions in patients treated with ULTOMIRIS included hyperthermia and pyrexia. No serious adverse reaction was reported in more than 1 patient treated with ULTOMIRIS.

One fatal case of sepsis was identified in a patient treated with ULTOMIRIS.

Please see the accompanying full Prescribing Information for ULTOMIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections/sepsis.

This information for
Healthcare Professionals Only

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. Soliris® (eculizumab) [Prescribing Information]. Boston, MA: Alexion Pharmaceuticals, Inc. 2018.

2. Kelly R, et al. Ther Clin Risk Manag. 2009;5:911-921.

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. Soliris® (eculizumab) [Prescribing Information]. Boston, MA: Alexion Pharmaceuticals, Inc. 2018.

2. Kelly R, et al. Ther Clin Risk Manag. 2009;5:911-921.