Soliris

• Complete or update vaccination for meningococcal bacteria (for serogroups A, C, W, Y, and B) at least 2 weeks prior to the first dose of SOLIRIS, unless the risks of delaying therapy with SOLIRIS outweigh the risk of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against meningococcal bacteria in patients receiving a complement inhibitor. See

  5.1 Serious Meningococcal Infections

  SOLIRIS, a complement inhibitor, increases a patient's susceptibility to serious, life-threatening, or fatal infections caused by meningococcal bacteria (septicemia and/or meningitis) in any serogroup, including non-groupable strains. Life-threatening and fatal meningococcal infections have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors. The initiation of SOLIRIS treatment is contraindicated in patients with unresolved serious

  Neisseria meningitidis

  infection.

  Complete or update meningococcal vaccination (for serogroups A, C, W, Y and B) at least 2 weeks prior to administration of the first dose of SOLIRIS, according to current ACIP recommendations for patients receiving a complement inhibitor. Revaccinate patients in accordance with ACIP recommendations, considering the duration of therapy with SOLIRIS. Note that ACIP recommends an administration schedule in patients receiving complement inhibitors that differs from the administration schedule in the vaccine prescribing information. If urgent SOLIRIS therapy is indicated in a patient who is not up to date with meningococcal vaccines according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer meningococcal vaccines as soon as possible. Various durations and regimens of antibacterial drug prophylaxis have been considered, but the optimal durations and drug regimens for prophylaxis and their efficacy have not been studied in unvaccinated or vaccinated patients receiving complement inhibitors, including SOLIRIS. The benefits and risks of treatment with SOLIRIS, as well as the benefits and risks of antibacterial drug prophylaxis in unvaccinated or vaccinated patients, must be considered against the known risks for serious infections caused by

  Neisseria meningitidis

  .

  Vaccination does not eliminate the risk of serious meningococcal infections, despite development of antibodies following vaccination.

  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 instruct patients to seek immediate medical care if these signs and symptoms occur. Promptly treat known infections. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider interruption of SOLIRIS in patients who are undergoing treatment for serious meningococcal infection depending on the risks of interrupting treatment in the disease being treated.

  SOLIRIS is available only through a restricted program under a REMS

  [see Warnings and Precautions (5.2)]

  .

  for additional guidance on the management of the risk of serious infections caused by meningococcal bacteria.
• Patients receiving SOLIRIS are at increased risk for invasive disease caused by

  Neisseria meningitidis

  , even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious meningococcal infections and evaluate immediately if infection is suspected.

SOLIRIS is a complement inhibitor indicated for:

• the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. (
  1.1 Paroxysmal Nocturnal Hemoglobinuria (PNH)

  SOLIRIS is indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.
  )
• the treatment of patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy. (
  1.2 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).
  )
  
  
  Limitation of Use
  
  
  SOLIRIS is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).
• the treatment of generalized myasthenia gravis (gMG) in adult and pediatric patients six years of age and older who are anti-acetylcholine receptor (AChR) antibody positive. (
  1.3 Generalized Myasthenia Gravis (gMG)

  SOLIRIS is indicated for the treatment of generalized myasthenia gravis (gMG) in adult and pediatric patients six years of age and older who are anti-acetylcholine receptor (AChR) antibody positive.
  )
• the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive. (
  1.4 Neuromyelitis Optica Spectrum Disorder (NMOSD)

  SOLIRIS is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.
  )

For intravenous infusion only; recommended dosage for:

• PNH: (
  2.2 Recommended Dosage for Adults – PNH

  The recommended dosage of SOLIRIS for the treatment of PNH in patients 18 years of age and older is administered as an intravenous infusion

  [see Dosage and Administration (2.7)]

  as follows:

  • 600 mg weekly for the first 4 weeks, followed by
  • 900 mg for the fifth dose 1 week later, then
  • 900 mg every 2 weeks thereafter.

  Administer SOLIRIS at the recommended dosage regimen time points, or within two days of these time points

  [see Warnings and Precautions (5.4)]

  .
  )
• aHUS, gMG, and NMOSD in adults: (
  2.3 Recommended Dosage for Adults – aHUS, gMG, and NMOSD

  The recommended dosage of SOLIRIS for the treatment of aHUS, gMG, or NMOSD in patients 18 years of age and older is administered as an intravenous infusion

  [see Dosage and Administration (2.7)]

  as follows:

  • 900 mg weekly for the first 4 weeks, followed by
  • 1200 mg for the fifth dose 1 week later, then
  • 1200 mg every 2 weeks thereafter.
  )
• aHUS and gMG in pediatric patients: (
  2.4 Recommended Dosage for Pediatric Patients – aHUS and gMG

  The recommended dosage of SOLIRIS for the treatment of aHUS in pediatric patients less than 18 years of age or gMG in pediatric patients 6 years of age and older is administered as an intravenous infusion based upon body weight, according to the following schedule (Table 1):

  Table 1: Dosing Recommendations in Pediatric Patients Less Than 18 Years of Age with aHUS and Pediatric Patients 6 Years of Age and Older with gMG

  Patient Body Weight	Induction	Maintenance
  40 kg and over	900 mg weekly for the first 4 weeks	1200 mg at week 5; then 1200 mg every 2 weeks
  30 kg to less than 40 kg	600 mg for the first 2 weeks	900 mg at week 3; then 900 mg every 2 weeks
  20 kg to less than 30 kg	600 mg for the first 2 weeks	600 mg at week 3; then 600 mg every 2 weeks
  10 kg to less than 20 kg	600 mg single dose at Week 1	300 mg at week 2; then 300 mg every 2 weeks
  5 kg to less than 10 kg	300 mg single dose at Week 1	300 mg at week 2; then 300 mg every 3 weeks

  Administer SOLIRIS at the recommended dosage regimen time points, or within two days of these time points.
  )

Injection: 300 mg/30 mL (10 mg/mL) as a clear, colorless solution in a single-dose vial.

Limited data on outcomes of pregnancies that have occurred following SOLIRIS use in pregnant women have not identified a concern for specific adverse developmental outcomes (

Animal studies using a mouse analogue of the SOLIRIS molecule (murine anti-C5 antibody) showed increased rates of developmental abnormalities and an increased rate of dead and moribund offspring at doses 2-8 times the human dose (

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.