Important Safety Information

  • WARNING: SERIOUS MENINGOCOCCAL INFECTIONS

    See full prescribing information for complete boxed warning

    Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris and 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 a meningococcal vaccine at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risks of developing a meningococcal infection. (See Serious Meningococcal Infections for additional guidance on the management of the risk of 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.

Risk of Discontinuation and Deviation from Recommended Dosing Schedule

Highly elevated biological markers of cellular processes observed in patients with aHUS reinforce the chronic nature of aHUS and the need for sustained terminal complement inhibition1

  • 41 patients from Study 4 with aHUS and ≥18 years of age were evaluated prior to and during Soliris® treatment2

    • Marker levels of biological processes considered to be associated with aHUS were evaluated and compared to those from normal, healthy volunteers (NHV)

Biological markers are elevated in patients at baseline (BL) and reduced or normalized with ongoing Soliris treatment2
Disease process (Biomarker) Fold increase over NHV at BL Outcome of ongoing Soliris treatment
(% reduction)
Proximal complement activity (Plasma Ba) 5.53x Sustained reduction from BL but remains elevated 30%*
Endothelial activation (sVCAM-1) 1.99x 60%*
Terminal complement activity (U-sC5b-9) 305x Sustained reduction to complete or near normal levels 100%§
Endothelial cell damage (Thrombomodulin) 3.64x 77%||
Renal damage (U-cystatin-C) 23.85x 99%*

Study description: A panel of biomarkers was evaluated in patients enrolled in an open-label, single-arm, multicenter, multinational trial of adults with aHUS (N=41) and treated with Soliris.
* Maximum reduction achieved by Week 17 of Soliris treatment.
† Urinary markers were normalized to urinary creatinine.
‡ Near level of NHV.
§ Maximum reduction achieved by Week 4 of Soliris treatment.
|| Maximum reduction achieved by 1 year.

  • At baseline, markers of a broad array of cellular processes were elevated in patients with aHUS regardless of platelet levels, LDH, or whether PE/PI was administered2

  • Ongoing Soliris treatment:

    • Normalized highly elevated measures of terminal complement activity and renal damage2

    • Reduced measures of endothelial damage to near normal2

    • Reduced but did not normalize measures of proximal complement activity and endothelial activation2

  • Persistent proximal complement activity underscores the underlying genetic dysregulation of the alternative pathway in patients with aHUS2

‡ Near level of NHV.


Sustained Soliris® treatment inhibits terminal complement activity and the ongoing risk of complement-mediated TMA1,2,3,4,5,6

Soliris blocks damage from terminal complement activity and potential damage from proximal activity, which, although reduced, remains elevated1,2
Soliris blocks damage from terminal complement activity and potential damage from proximal activity, which, although reduced, remains elevated

Discontinuation of Soliris puts patients with aHUS at ongoing risk of uncontrolled terminal complement activation1,2
Discontinuation of Soliris puts patients with aHUS at ongoing risk of uncontrolled terminal complement activation
Patients who discontinue Soliris are at high risk for severe TMA complications and forgo the clinical improvements of ongoing Soliris treatment1,2,6

Patients who discontinue or deviate from the recommended dosing schedule of Soliris® are at immediate and ongoing risk of severe complications from TMA1,6

Of 18 adults and pediatric patients who discontinued Soliris, 28% (5/18) experienced severe complications from TMA after a missed dose1,6

  • Soliris was reinitiated in 4 of 5 patients experiencing severe complications from TMA1,6

  • Patients who continued treatment had complete inhibition of complement activity sustained through 2 years1,6

  • Monitor patients for signs and symptoms of TMA complications1

Clinical signs and symptoms of TMA after discontinuation may include:

  • Change in mental status

  • Thrombosis

  • Dyspnea

  • Angina

  • Seizures

Laboratory signs of TMA after discontinuation include (any 2, or repeated measures of 1):

  • Decreased platelets

  • Increased LDH

  • Increased serum creatinine

In patients with aHUS who discontinue Soliris, clinical and laboratory signs should be monitored for at least 12 weeks1
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 measures1

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Important Safety Information

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WARNING: SERIOUS MENINGOCOCCAL INFECTIONS

See full prescribing information for complete boxed warning

Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris and 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 a meningococcal vaccine at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risks of developing a meningococcal infection. (See Serious Meningococcal Infections for additional guidance on the management of the risk of 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.

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.