SOLIRIS: Package Insert and Label Information

SOLIRIS- eculizumab injection, solution, concentrate
Alexion Pharmaceuticals Inc.

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 [ see Warnings and Precautions (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 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. [See Warnings and Precautions (5.1) for additional guidance on the management of the risk of meningococcal infection].
  • Vaccination reduces, but does not eliminate, the risk of meningococcal infections. 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 [ see Warnings and Precautions (5.1) ]. 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.

1 INDICATIONS AND USAGE

1.1 Paroxysmal Nocturnal Hemoglobinuria (PNH)

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

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).

1.3 Generalized Myasthenia Gravis (gMG)

Soliris is indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AchR) 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.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Vaccination and Prophylaxis

Vaccinate patients according to current ACIP guidelines to reduce the risk of serious infection [see Warnings and Precautions (5.1 and 5.2)].

Provide two weeks of antibacterial drug prophylaxis to patients if Soliris must be initiated immediately and vaccines are administered less than two weeks before starting Soliris therapy.

Healthcare professionals who prescribe Soliris must enroll in the Soliris REMS [see Warnings and Precautions (5.1) ].

2.2 Recommended Dosage Regimen – PNH

For patients 18 years of age and older, Soliris therapy consists of:

  • 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) ].

2.3 Recommended Dosage Regimen – aHUS

For patients 18 years of age and older, Soliris therapy consists of:

  • 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.

For patients less than 18 years of age, administer Soliris based upon body weight, according to the following schedule (Table 1):

Table 1: Dosing Recommendations in aHUS Patients Less Than 18 Years of Age
Patient Body Weight Induction Maintenance
40 kg and over 900 mg weekly × 4 doses 1200 mg at week 5;then 1200 mg every 2 weeks
30 kg to less than 40 kg 600 mg weekly × 2 doses 900 mg at week 3;then 900 mg every 2 weeks
20 kg to less than 30 kg 600 mg weekly × 2 doses 600 mg at week 3;then 600 mg every 2 weeks
10 kg to less than 20 kg 600 mg weekly × 1 dose 300 mg at week 2;then 300 mg every 2 weeks
5 kg to less than 10 kg 300 mg weekly × 1 dose 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.

2.4 Recommended Dosage Regimen – gMG and NMOSD

For adult patients with generalized myasthenia gravis or neuromyelitis optica spectrum disorder, Soliris therapy consists of:

  • 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.

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

2.5 Dose Adjustment in Case of Plasmapheresis, Plasma Exchange, or Fresh Frozen Plasma Infusion

For adult and pediatric patients with aHUS, and adult patients with gMG or NMOSD, supplemental dosing of Soliris is required in the setting of concomitant plasmapheresis or plasma exchange, or fresh frozen plasma infusion (PE/PI) (Table 2).

Table 2: Supplemental Dose of Soliris after PE/PI
Type of Plasma Intervention Most Recent Soliris Dose Supplemental Soliris Dose with Each Plasma Intervention Timing of Supplemental Soliris Dose
Plasmapheresis or plasma exchange 300 mg 300 mg per each plasmapheresis or plasma exchange session Within 60 minutes after each plasmapheresis or plasma exchange
≥600 mg 600 mg per each plasmapheresis or plasma exchange session
Fresh frozen plasma infusion ≥300 mg 300 mg per infusion of fresh frozen plasma 60 minutes prior to each infusion of fresh frozen plasma

2.6 Preparation

Dilute Soliris to a final admixture concentration of 5 mg/mL using the following steps:

  • Withdraw the required amount of Soliris from the vial into a sterile syringe.
  • Transfer the recommended dose to an infusion bag.
  • Dilute Soliris to a final concentration of 5 mg/mL by adding the appropriate amount (equal volume of diluent to drug volume) of 0.9% Sodium Chloride Injection, USP; 0.45% Sodium Chloride Injection, USP; 5% Dextrose in Water Injection, USP; or Ringer’s Injection, USP to the infusion bag.

The final admixed Soliris 5 mg/mL infusion volume is 60 mL for 300 mg doses, 120 mL for 600 mg doses, 180 mL for 900 mg doses or 240 mL for 1200 mg doses (Table 3).

Table 3: Preparation and Reconstitution of Soliris
Soliris Dose Diluent Volume Final Volume
300 mg 30 mL 60 mL
600 mg 60 mL 120 mL
900 mg 90 mL 180 mL
1200 mg 120 mL 240 mL

Gently invert the infusion bag containing the diluted Soliris solution to ensure thorough mixing of the product and diluent. Discard any unused portion left in a vial, as the product contains no preservatives.

Prior to administration, the admixture should be allowed to adjust to room temperature [18°-25° C, 64°-77° F]. The admixture must not be heated in a microwave or with any heat source other than ambient air temperature.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

2.7 Administration

Only administer as an intravenous infusion.

Do not administer as an intravenous push or bolus injection.

Administer the Soliris admixture by intravenous infusion over 35 minutes in adults and 1 to 4 hours in pediatric patients via gravity feed, a syringe-type pump, or an infusion pump. Admixed solutions of Soliris are stable for 24 h at 2°-8° C (36°-46° F) and at room temperature.

If an adverse reaction occurs during the administration of Soliris, the infusion may be slowed or stopped at the discretion of the physician. If the infusion is slowed, the total infusion time should not exceed two hours in adults. Monitor the patient for at least one hour following completion of the infusion for signs or symptoms of an infusion-related reaction.

3 DOSAGE FORMS AND STRENGTHS

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

4 CONTRAINDICATIONS

Soliris is contraindicated in:

  • Patients with unresolved serious Neisseria meningitidis infection [see Warnings and Precautions (5.1) ].
  • Patients who are not currently vaccinated against Neisseria meningitidis , unless the risks of delaying Soliris treatment outweigh the risks of developing a meningococcal infection [see Warnings and Precautions (5.1) ].

5 WARNINGS AND PRECAUTIONS

5.1 Serious Meningococcal Infections

Risk and Prevention

Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris. The use of Soliris increases a patient’s susceptibility to serious meningococcal infections (septicemia and/or meningitis). Soliris is associated with an approximate 2,000-fold increased risk of meningococcal disease in comparison to the general U.S. population annual rate (0.14 per 100,000 population in 2015).

Vaccinate for meningococcal disease according to the most current Advisory Committee on Immunization Practices (ACIP) recommendations for patients with complement deficiencies. Revaccinate patients in accordance with ACIP recommendations, considering the duration of Soliris therapy.

Immunize patients without a history of meningococcal vaccination at least 2 weeks prior to receiving the first dose of Soliris. If urgent Soliris therapy is indicated in an unvaccinated patient, administer meningococcal vaccine(s) as soon as possible and provide patients with two weeks of antibacterial drug prophylaxis.

In prospective clinical studies, 75/100 patients with aHUS were treated with Soliris less than 2 weeks after meningococcal vaccination and 64 of these 75 patients received antibiotics for prophylaxis of meningococcal infection until at least 2 weeks after meningococcal vaccination. The benefits and risks of antibiotic prophylaxis for prevention of meningococcal infections in patients receiving Soliris have not been established.

Vaccination reduces, but does not eliminate, the risk of meningococcal infections. In clinical studies, 2 out of 196 PNH patients developed serious meningococcal infections while receiving treatment with Soliris; both had been vaccinated [see Adverse Reactions (6.1) ]. In clinical studies among non-PNH patients, meningococcal meningitis occurred in one unvaccinated patient. In addition, 3 out of 130 previously vaccinated patients with aHUS developed meningococcal infections while receiving treatment with Soliris [see Adverse Reactions (6.1) ].

Closely monitor patients for early signs and symptoms of meningococcal infection and evaluate patients immediately if an infection is suspected. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Discontinue Soliris in patients who are undergoing treatment for serious meningococcal infections.

REMS

Because of the risk of meningococcal infections, 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.

Prescribers must counsel patients about the risk of meningococcal infection, provide the patients with the REMS educational materials, and ensure patients are vaccinated with meningococcal vaccine(s).

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.

5.2 Other Infections

Serious infections with Neisseria species (other than N. meningitidis), including disseminated gonococcal infections, have been reported.

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 influenzae type b (Hib). Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) infections according to ACIP guidelines. Use caution when administering Soliris to patients with any systemic infection [see Warnings and Precautions (5.1) ].

5.3 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.

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