rav-ue-LIZ-ue-mab

Therapeutic Classification: hemostatic agents

Pharmacologic Classification: complement.inhibitors, monoclonal antibodies

• Paroxysmal nocturnal hemoglobinuria (PNH).
• Atypical hemolytic uremic syndrome (aHUS).

• Ravulizumab is a monoclonal antibody that binds to complement protein, C5. This binding inhibits complement activation, a necessary step in the initiation of hemolysis due to PNH

• Decreased hemolysis associated with PNH.
• Decreased complement-mediated thrombotic microangiopathy in aHUS.

Absorption: IV administration results in complete bioavailability.

Distribution: Distributed to tissues.

Metabolism/Excretion: Unknown.

Half-life: 50 days.

(inhibition of serum free C5)

Contraindicated in:

• Unresolved Neisseria meninigitidis infection
• Patients not vaccinated against Neisseria meninigitidis (unless risk of delaying treatment outweighs risks of developing a meningococcal infection)
• Lactation: Lactation.

Use Cautiously in:

• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk
• Pedi: Children <1 mo (safety and effectiveness not established).

CNS: headache, dizziness.

GI: abdominal pain, diarrhea, nausea.

Resp: upper respiratory tract infection.

MS: arthralgia.

Misc: MENINGOCOCCAL INFECTIONS, fever, Haemophilus influenzae infection, infusion reactions, Neisseria gonorrhoeae infection, Streptococcus pneumoniae infection.

Drug-Drug:

• None reported.

Paroxysmal Nocturnal Hemoglobinuria

• IV (Adults 100 kg): Loading dose — 3,000 mg single dose (if switching from eculizumab, give loading dose 2 wk after last eculizumab dose); Maintenance dose (initiated 2 wk after loading dose) — 3,600 mg every 8 wk.
• IV (Adults 60–99 kg): Loading dose — 2,700 mg single dose (if switching from eculizumab, give loading dose 2 wk after last eculizumab dose); Maintenance dose (initiated 2 wk after loading dose) — 3,300 mg every 8 wk.
• IV (Adults 40–59 kg): Loading dose — 2,400 mg single dose (if switching from eculizumab, give loading dose 2 wk after last eculizumab dose); Maintenance dose (initiated 2 wk after loading dose) — 3,000 mg every 8 wk.

Atypical Hemolytic Uremic Syndrome

• IV (Adults and Children 1 mo and 100 kg): Loading dose — 3,000 mg single dose (if switching from eculizumab, give loading dose 2 wk after last eculizumab dose); Maintenance dose (initiated 2 wk after loading dose) — 3,600 mg every 8 wk. Treatment should continue for 6 mo.
• IV (Adults and Children 1 mo and 60–99 kg): Loading dose — 2,700 mg single dose (if switching from eculizumab, give loading dose 2 wk after last eculizumab dose); Maintenance dose (initiated 2 wk after loading dose) — 3,300 mg every 8 wk. Treatment should continue for 6 mo.
• IV (Adults and Children 1 mo and 40–59 kg): Loading dose — 2,400 mg single dose (if switching from eculizumab, give loading dose 2 wk after last eculizumab dose); Maintenance dose (initiated 2 wk after loading dose) — 3,000 mg every 8 wk. Treatment should continue for 6 mo.
• IV (Adults and Children 1 mo and 30–39 kg): Loading dose — 1,200 mg single dose (if switching from eculizumab, give loading dose 2 wk after last eculizumab dose); Maintenance dose (initiated 2 wk after loading dose) — 2,700 mg every 8 wk. Treatment should continue for 6 mo.
• IV (Adults and Children 1 mo and 20–29 kg): Loading dose — 900 mg single dose (if switching from eculizumab, give loading dose 2 wk after last eculizumab dose); Maintenance dose (initiated 2 wk after loading dose) — 2,100 mg every 8 wk. Treatment should continue for 6 mo.
• IV (Children 1 mo and 10–19 kg): Loading dose — 600 mg single dose (if switching from eculizumab, give loading dose 2 wk after last eculizumab dose); Maintenance dose (initiated 2 wk after loading dose) — 600 mg every 4 wk. Treatment should continue for 6 mo.
• IV (Children 1 mo and 5–9 kg): Loading dose — 600 mg single dose (if switching from eculizumab, give loading dose 2 wk after last eculizumab dose); Maintenance dose (initiated 2 wk after loading dose) — 300 mg every 4 wk. Treatment should continue for 6 mo.

• Solution for injection: 10 mg/mL;

• Monitor for signs or symptoms of infusion reaction (lower back pain, drop in blood pressure, infusion-related pain, elevation in blood pressure, limb discomfort) for at least 1 hr following completion of infusion. If signs of cardiovascular instability or respiratory compromise occur, interrupt infusion and institute supportive measures.
• Monitor for early signs and symptoms of meningococcal infections (headache with nausea or vomiting, headache and fever, headache with stiff neck or stiff back, fever, fever and a rash, confusion, muscle aches with flu-like symptoms, eyes sensitive to light) during therapy. Evaluate immediately if infection is suspected. Consider discontinuation of therapy during treatment of serious meningococcal infections.
• PNH: Upon discontinuation of therapy, monitor for signs and symptoms of hemolysis (elevated LDH, re-appearance of fatigue, hemoglobinuria, abdominal pain, shortness of breath, major adverse vascular event, dysphagia, erectile dysfunction) for at least 12 mo. If signs and symptoms of hemolysis occur after discontinuation, including elevated LDH, may require restarting ravulizumab.
• aHUS: Upon discontinuation, monitor for signs and symptoms of complement-mediated thrombotic microangiopathy (TMA) (changes in mental status, seizures, angina, dyspnea, thrombosis, increasing blood pressure) for at least 6 mo. In addition to clinical symptoms, at least 2 concurrent lab values (↓ in platelet count 25% of baseline or peak platelet count during ravulizumab therapy; ↑ in serum creatinine 25% of baseline or to nadir during ravulizumab therapy; ↑ in serum LDH 25% of baseline or of nadir during ravulizumab therapy. If TMA complications occur upon discontinuation, consider restarting ravulizumab.

• Monitor LDH and platelet counts to determine progress.

• Vaccinate patients for meningococcal disease according to current Advisory Committee on Immunization Practices (ACIP) guidelines at least 2 wk before starting ravulizumab to reduce risk of serious infection. May revaccinate patients considering duration of ravulizumab therapy. If ravulizumab is started immediately and vaccines are administered <2 wk before starting ravulizumab therapy, administer 2 wk of antibacterial prophylaxis.
• In children, may increase risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). Vaccinate for prevention of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) infections according to ACIP guidelines.
• Available only through Ultomiris REMS program. Prescribers must enroll in program.
• Intermittent Infusion: Solution is clear to translucent, slight whitish; do not use solutions that are cloudy, discolored, or contain particulate matter.
  Diluent: Withdraw volume required and dilute with 0.9% NaCl.Concentration: 5 mg/mL.Mix gently; do not shake. Protect from light; do not freeze. Infuse immediately; stable for 24 hr if refrigerated. Once removed from refrigerator, must be infused within 6 hr. Allow to warm to room temperature before infusing; do not heat in a microwave or with any heat source other than ambient air temperature.
• Rate: Infuse through a 0.2 or 0.22 micron filter. Rate is based on body weight. See manufacturer's instructions for rate of loading dose and maintenance doses.

• Explain purpose of ravulizumab to patient. Advise patient to read Medication Guide before starting and periodically during therapy in case of changes.
• Caution patients about risk of meningococcal infection/sepsis. Advise patient to notify health care professional immediately if symptoms of meningitis or other infections occur. Inform patient of need for vaccination before starting therapy. May increase risk of infections caused by Streptococcus pneumoniae, Haemophilus influenzae, and gonorrhea. Advise patient to consult health care professional if at risk for gonorrhea infection, about gonorrhea prevention, and regular testing.
• Inform patient of REMS program. Provide REMS educational materials and ensure patients are vaccinated with meningococcal vaccines. Enrollment in the Ultomiris REMS and additional information are available by telephone: 1-888-765-4747 or at www.ultomirisrems.com.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breast feeding and for at least 8 mo after last dose of ravulizumab.
• Instruct patient to carry Ultomiris Patient Safety Card that describes symptoms and patient to immediately seek medical evaluation if symptoms occur, with them at all times during and for at least 8 mo after therapy.

• Normalization of LDH levels in patients with PNH.
• Normalization of hematological parameters (platelet count and LDH) and 25% improvement in serum creatinine from baseline in patients with aHUS.

Ultomiris

NDC Code^*

• 25682- Alexion Pharmaceuticals Inc.
  • 25682-022- Ultomiris
    • 25682-022-01- 1 VIAL, GLASS in 1 CARTON (25682-022-01) > 30 mL in 1 VIAL, GLASS