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. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early (5.1).
- 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 risk of developing a meningococcal infection. (See Serious Meningococcal Infections for additional guidance on the management 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. Enrollment in the Soliris REMS program and additional information are available by telephone: 1-888-soliris (1-888-765-4747).
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.
The effectiveness of Soliris in aHUS is based on the effects on thrombotic microangiopathy (TMA) and renal function. Prospective clinical trials in additional patients are ongoing to confirm the benefit of Soliris in patients with aHUS.
Limitation of Use
Soliris is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).
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 & PRECAUTIONS
Soliris blocks terminal complement activation; therefore patients may have increased susceptibility to infections, especially with encapsulated bacteria. 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 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 studies, 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, 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.
Serum LDH levels increase during hemolysis and may assist in monitoring Soliris effects, including the response to discontinuation of therapy. In clinical studies, six patients achieved a reduction in serum LDH levels only after a decrease in the Soliris dosing interval from 14 to 12 days. All other patients achieved a reduction in serum LDH levels with the 14 day dosing interval [see Clinical Pharmacology and Clinical Studies ].
Early signs of thrombotic microangiopathy (TMA) include a decrease in platelet count, and increases in serum LDH and creatinine levels. Follow patients for signs of TMA by monitoring serial platelet counts, serum LDH, and creatinine during Soliris therapy and following discontinuation of Soliris.
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.
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 (≥15% combined per patient incidence) are: hypertension, upper respiratory tract infection, diarrhea, headache, anemia, vomiting, nausea, urinary tract infection, and leukopenia.
Please see full
Prescribing Information for Soliris® (eculizumab),
including boxed WARNING regarding serious meningococcal infection.