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.

  • 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.

 

Indications and Usage

Paroxysmal Nocturnal Hemoglobinuria (PNH)

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

Atypical Hemolytic Uremic Syndrome (aHUS)

Soliris is indicated for the treatment of patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy.

Limitation of Use

Soliris is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).

Generalized Myasthenia Gravis (gMG)

Soliris is indicated for the treatment of adult patients with generalized Myasthenia Gravis (gMG) who are anti-acetylcholine receptor (AchR) antibody positive.

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

Other Infections

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 influenza type b (Hib). Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenza 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.

Treatment Discontinuation for aHUS

After discontinuing Soliris, monitor patients with aHUS for signs and symptoms of thrombotic microangiopathy (TMA) complications for at least 12 weeks. In aHUS clinical trials, 18 patients (5 in the prospective studies) discontinued Soliris treatment. TMA complications occurred following a missed dose in 5 patients, and Soliris was reinitiated in 4 of these 5 patients.

 

Clinical signs and symptoms of TMA include changes in mental status, seizures, angina, dyspnea, or thrombosis. In addition, the following changes in laboratory parameters may identify a TMA complication: occurrence of two, or repeated measurement of any one of the following: a decrease in platelet count by 25% or more compared to baseline or the peak platelet count during Soliris treatment; an increase in serum creatinine by 25% or more compared to baseline or nadir during Soliris treatment; or, an increase in serum LDH by 25% or more over baseline or nadir during Soliris treatment.

 

If TMA complications occur after Soliris discontinuation, consider reinstitution of Soliris treatment, plasma therapy [plasmapheresis, plasma exchange, or fresh frozen plasma infusion (PE/PI)], or appropriate organ-specific supportive measures.

 

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.

 

The most frequently reported adverse reactions in aHUS single arm prospective trials (≥20%) are: headache, diarrhea, hypertension, upper respiratory infection, abdominal pain, vomiting, nasopharyngitis, anemia, cough, peripheral edema, nausea, urinary tract infections, pyrexia.

 

The most frequently reported adverse reaction in the gMG placebo-controlled clinical trial (≥10%) is: musculoskeletal pain.

 

Please see full Prescribing Information and Medication Guide for Soliris, including Boxed WARNING regarding serious meningococcal infections.

Glossary

Acquired

An acquired disease is not congenital or inherited from a family member. It’s a disease you develop over time.1

Allergic reaction

An overreaction after a substance is introduced into the body.2

Anemia

A condition in which your body does not have enough hemoglobin (the part of your blood that carries oxygen). With anemia, you may have fewer whole red blood cells. This may cause you to feel weak and tired.1

Aplastic anemia (AA)

“Aplastic” means that bone marrow can’t produce new blood cells properly. As a result, patients with aplastic anemia have fewer red blood cells, white blood cells, and platelets.1 PNH is often found along with aplastic anemia.3

atypical Hemolytic Uremic Syndrome (aHUS)

A disease of the blood that causes low red blood cell and platelet counts, kidney failure, and damage to other vital organs.4

Blood clot

Blood clots form when parts of your body’s blood clump together. In a healthy body, this can stop bleeding when you’re cut or injured. But in certain conditions, these clumps can block blood flow in the veins and arteries, which can be dangerous.5 In PNH, a clot can happen at any time and can cause serious health problems.6

Bone marrow

The soft tissue inside your large bones. It works to create the cells in your blood: red blood cells, white blood cells, and platelets.5

Bone marrow failure disorder

A disorder that causes bone marrow to decrease or stop making blood cells. AA and myelodysplastic syndrome (MDS) are bone marrow failure disorders.7

Clone size

The percentage of blood cells in your body affected by PNH.8

Complement

Components in the blood that interact as part of the body’’s immune system to destroy disease-causing substances.5

Complete blood count (CBC)

A lab test that gives the amounts of different cells in your blood.1

Dialysis

A procedure performed to remove toxic waste from the blood of a patient with acute or chronic renal failure.5

Enzyme

A type of protein that helps reactions/processes happen in the body.1

Erectile dysfunction (ED)

A condition found in men that affects their ability to achieve an erection.1

FDA

Food and Drug Administration.

Genetic

Relating to genes, which are units in cells that are passed down through families.1

Hemoglobin (Hgb)

The reddish-brown material found inside red blood cells. It carries oxygen throughout your body.1

Hemoglobinuria

Hemoglobin in the urine. Because of the reddish-brown color of hemoglobin, it results in dark, sometimes “cola-colored” urine.7

Hemolysis

When red blood cells burst.1 Hemolysis is the main cause of the major health problems in PNH.6

Hypertension

Another term for high blood pressure.1

Immune system

A complex group of cells, proteins, and other molecules that work together to identify foreign organisms and substances, such as bacteria; the main role of the system is to protect the body against these foreign organisms.1

Inflammation

An immune system reaction from the body as a result of some type of injury. Signs of inflammation may be redness, swelling, pain, and/or heat.1

Infusion

A process during which fluid is introduced into the body through a vein.1

Lactate dehydrogenase (LDH)

An enzyme found in red blood cells, released during hemolysis. Testing for LDH can help show how much hemolysis is happening in your body.9

Meningococcal infection

An infection caused by a group of bacteria called Neisseria meninigitidis. The most common forms of meningococcal infections include meningitis (infection of the membranes that surround the brain and spinal cord) and meningococcemia (blood stream infections).10

Myelodysplastic syndromes (MDS)

A condition in which there’s a problem with the way bone marrow makes blood cells.11 Approximately 10% of PNH patients also have MDS.12

Natural inhibitors

The body’’s natural protective immune system that regulates the body’s immune response.1

Paroxysmal nocturnal hemoglobinuria (PNH)

A rare, acquired clonal hematopoietic stem cell disease characterized by complement-mediated hemolysis and thrombosis.6

Plasma

The pale yellow liquid part of whole blood, in which the red and white blood cells and various other elements are floating.5

Plasma exchange/plasma infusion (PE/PI)

A process of removing, treating, and returning, or infusing plasma to the body.5

Platelet

A small, irregular, disc-shaped element in the blood that assists in blood clotting.5

Progressive

A progressive disease is one that gets worse over time.5

Pulmonary hypertension

Rare lung disorder characterized by increased pressure in the pulmonary artery.5

Pyrexia

A medical term for fever.1

Red blood cells (RBCs)

A type of cell found in your blood that carries hemoglobin (the molecule that transports oxygen) and helps remove wastes from tissues throughout the body.5 Red blood cells affected by PNH are attacked and destroyed because they are missing a protective protein.6

Transfusion

A transfusion is the process of transferring whole blood or blood components from one person (donor) to another (recipient).5

Thrombotic microangiopathy (TMA)

Formation of clots in small blood vessels throughout the body; this is an underlying cause of the clinical signs and symptoms of aHUS.5

Vaccine

A preparation that is used to increase the body’s natural defense against a disease.5

White blood cells (WBCs)

A type of cell found in your blood that helps your immune system fight disease and infection.5

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.

  • 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.

 

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

Atypical Hemolytic Uremic Syndrome (aHUS)
Soliris is indicated for the treatment of patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy.

Limitation of Use
Soliris is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).

Generalized Myasthenia Gravis (gMG)
Soliris is indicated for the treatment of adult patients with generalized Myasthenia Gravis (gMG) who are anti-acetylcholine receptor (AchR) antibody positive.

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
Other Infections
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 influenza type b (Hib). Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenza 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.
Treatment Discontinuation for aHUS
After discontinuing Soliris, monitor patients with aHUS for signs and symptoms of thrombotic microangiopathy (TMA) complications for at least 12 weeks. In aHUS clinical trials, 18 patients (5 in the prospective studies) discontinued Soliris treatment. TMA complications occurred following a missed dose in 5 patients, and Soliris was reinitiated in 4 of these 5 patients.

Clinical signs and symptoms of TMA include changes in mental status, seizures, angina, dyspnea, or thrombosis. In addition, the following changes in laboratory parameters may identify a TMA complication: occurrence of two, or repeated measurement of any one of the following: a decrease in platelet count by 25% or more compared to baseline or the peak platelet count during Soliris treatment; an increase in serum creatinine by 25% or more compared to baseline or nadir during Soliris treatment; or, an increase in serum LDH by 25% or more over baseline or nadir during Soliris treatment.

If TMA complications occur after Soliris discontinuation, consider reinstitution of Soliris treatment, plasma therapy [plasmapheresis, plasma exchange, or fresh frozen plasma infusion (PE/PI)], or appropriate organ-specific supportive measures.

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.

The most frequently reported adverse reactions in aHUS single arm prospective trials (≥20%) are: headache, diarrhea, hypertension, upper respiratory infection, abdominal pain, vomiting, nasopharyngitis, anemia, cough, peripheral edema, nausea, urinary tract infections, pyrexia.

The most frequently reported adverse reaction in the gMG placebo-controlled clinical trial (≥10%) is: musculoskeletal pain.

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

  1. Merriam Webster Dictionary website. https://www.merriam-webster.com/. 2017. Accessed September 8, 2017.

  2. MedicineNet website. http://www.medicinenet.com/script/main/hp.asp. 2016. Accessed September 8, 2017.

  3. Young NS, et al. Blood. 2006;108(8):2509-2519.

  4. National Organization for Rare Disorders website. https://rarediseases.org/rare-diseases/atypical-hemolytic-uremic-syndrome/. 2016. Accessed September 8, 2017.

  5. Free Medical Dictionary website. http://medical-dictionary.thefreedictionary.com/. 2017. Accessed September 8, 2017.

  6. Sahin F, et al. Am J Blood Res. 2015;5(1):1-9.

  7. Medscape website. http://www.medscape.com/. 2016. Accessed September 8, 2017.

  8. Brodsky RA. Blood. 2014;124:2804-2811.

  9. Healthline website. http://www.healthline.com/health/lactate-dehydrogenase-test. 2017. Accessed September 8, 2017.

  10. Centers for Disease Control and Prevention website. https://www.cdc.gov/meningococcal/index.html.  2017. Accessed September 8, 2017.

  11. Mayo Clinic website. http://www.mayoclinic.org/diseases-conditions/myelodysplastic-syndromes/basics/definition/con-20027168. 2017. Accessed September 8, 2017.

  12. Morado M, et al. Cytometry B Clin Cytom. 2017;92(5):361-370.