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 solirisrems.com.

Whom do I test for PNH?

PNH: A progressive and life-threatening disease that causes thrombosis, end-organ damage, and impaired quality of life1,2,3

The life-threatening and destructive consequences of chronic hemolysis (as measured by LDH) warrant early identification in high-risk patient populations

Chronic complement-mediated hemolysis is the underlying cause of progressive morbidities in PNH;4 therefore, reducing chronic hemolysis is the primary goal of PNH treatment.1,5 Early identification of PNH in high-risk patient populations is optimal for long-term disease management.6,7

Early diagnosis is essential for improved patient management and prognosis1,2,3,6,7

  • Consistently evaluate high-risk patient populations for PNH5,7

The International Clinical Cytometry Society (ICCS) recommends testing for PNH in the following patient populations7

Evidence of Hemolysis

  • Intravascular hemolysis evidenced by hemoglobinuria or elevated plasma hemoglobin

  • Evidence of unexplained hemolysis with accompanying:

    • Iron deficiency, or

    • Abdominal pain, or esophageal spasm, or

    • Thrombosis, or

    • Granulocytopenia and/or thrombocytopenia

  • Non-schistocytic, non-infectious Coombs-negative hemolytic anemia


Thrombosis with unusual features

  • Unusual sites

    • Hepatic vein (Budd Chiari syndrome)

    • Other intra-abdominal veins (portal, splenic, splanchnic)

    • Cerebral sinuses

    • Dermal veins

  • With signs of accompanying hemolytic anemia

  • With unexplained cytopenia


Evidence of bone marrow failure

  • Suspected or proven aplastic or hypoplastic anemia

  • Refractory cytopenia with unilineage dysplasia

  • Other cytopenias of unknown etiology after adequate workup

  • Identification of PNH cells has important prognostic and therapeutic implications5,8

  • ICCS guidelines and the International PNH Interest Group (IPIG) recommend continued monitoring of patients at high risk for PNH5,7

Hemolysis

Chronic complement-mediated hemolysis is the underlying cause of progressive morbidities in PNH4

  • Even in the absence of symptoms, hemolysis is ongoing and destructive9,10

  • The consequences of hemolysis can be unpredictable, sudden, and potentially painful2

  • Hemolysis-induced nitric oxide depletion results in thrombosis, abdominal pain, pulmonary hypertension, dysphagia, and erectile dysfunction1

Hemolysis and clinical symptoms are associated with increased risk of TE11
LDH ≥1.5 x ULN
7.0

P=0.013

Abdominal pain
2.8

P=0.006

LDH ≥1.5 x ULN + abdominal pain
17.8

P=0.006

Chest pain
2.7

P=0.022

LDH ≥1.5 x ULN + chest pain
19.0

P<0.001

Dyspnea
2.9

P=0.003

LDH ≥1.5 x ULN + dyspnea
10.3

P=0.002

Hemoglobinuria
1.3

P=0.493

LDH ≥1.5 x ULN + hemoglobinuria
10.3

P=0.025

0 5 10 15 20 25
Odds ratio of TE
Study description: Multivariate, retrospective analysis of the medical charts of 301 PNH patients in a national registry. Data presented as odds ratios between PNH patients with and without listed symptoms.
  • The combination of LDH ≥1.5 x ULN with any of these clinical symptoms is associated with a greater increased risk of thromboembolism (TE) than elevated hemolysis or clinical symptoms alone11

ICCS guidelines recommend that any patient with unexplained hemoglobinuria should be tested for PNH7

  • Hemoglobinuria is a sign of intravascular hemolysis5

According to ICCS Guidelines, routine PNH screening may be appropriate for all patients with Coombs-negative hemolytic anemia, particularly when

  • Characteristic cellular abnormalities including, spherocytes, sickled cells, or schistocytes are not present7

  • Patients present with concomitant iron deficiency, as chronic intravascular hemolysis in PNH leads to urinary iron loss7

Thrombosis with unusual features

Thrombosis is the leading cause of death in PNH12,13

Thromboembolism (TE) in PNH is complex and multifactorial and may occur at any site, including intra-abdominal and cerebral veins14

Venous thromboembolism (VTE) is 62x more likely in patients with PNH vs the general population15,16

Relative risk of VTE in PNH vs inherited hypercoagulable states *15,16,17
Relative risk of VTE compared
to general population
70x
64
10
10
10
1
5
60x
50x
40x
30x
20x
10x
0
PNH AT deficiency PS deficiency PC deficiency PT mutation Factor V Leiden
Proportion of general
population (%)
0.0015 0.02 0.03 0.20 2.00 4.80
Expected patients
with VTE per year
280 1020 630 4200 6600 14,400
*Based on US population.

ICCS and IPIG recommend testing for PNH in patients with unusual presentation of thrombosis and additional risk factors5,7

  • TE involving unusual sites: Budd-Chiari syndrome, other intra-abdominal sites, cerebral or dermal veins

  • Patients with unexplained thrombosis with evidence of intravascular hemolysis

  • Patients with unexplained thrombosis with coexisting cytopenias

Evidence of bone marrow failure

PNH consensus guidelines recommend testing for PNH in all patients with aplastic anemia (AA) at diagnosis and routinely5,7

The number of PNH cells in patients with AA may increase rapidly and unpredictably over time5,7

  • In a study of 27 patients with AA, 48% experienced an increase in PNH clone size18

    • 81% received immunosuppressive therapy (IST)18

  • In another study, of 83 patients with AA with a detectable PNH clone and treated with IST alone, 30% showed an increase in clone size19

    • 8% showed evidence of hemolysis and thrombosis19

Select myelodysplastic syndrome (MDS) subgroups are more likely to present with a PNH granulocyte clone20

  • 17% of patients with refractory anemia-MDS (RA-MDS) have PNH granulocyte clones, as identified by high-sensitivity flow cytometry*20

  • Patients with MDS found to have a PNH clone are more likely to present with the following characteristics:21

    • Hypocellular marrow

    • Normal cytogenetics

    • Human leukocyte antigen (HLA)-DR15 positivity

    • High likelihood of response to IST

    • Moderate to severe thrombocytopenia

IPIG recommends that patients with RA-MDS be tested for PNH at diagnosis and annually5

PNH Consensus guidelines recommend testing patients with cytopenias and hemolysis or thrombosis, or patients with cytopenias that remain unexplained after a thorough workup7

  • 91% of patients with PNH have concomitant cytopenias22

  • Terminal complement C5 activity leads to platelet activation and consumption, with subsequent thrombocytopenia and an increased risk of TE in patients with PNH23

* Detects PNH cells down to a 0.01% clone size.

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Important Safety Information

CLOSE

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 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).

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

As with all protein products, 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.

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