ravulizumab

REMS

Paroxysmal nocturnal hemoglobinuria.
Atypical hemolytic uremic syndrome.
Generalized myasthenia gravis in patients who are anti-acetylcholine receptor antibody-positive.
Neuromyelitis optica spectrum disorder in patients who are anti-aquaporin-4 antibody positive.

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).

GI: abdominal pain, diarrhea, nausea

Neuro: headache, dizziness

Resp: upper respiratory tract infection

MS: arthralgia

Misc: fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), INFECTIONS (INCLUDING HAEMOPHILUS INFLUENZAE, NEISSERIA GONORRHOEAE, AND STREPTOCOCCUS PNEUMONIAE)., Haemophilus influenzae, Neisseria gonorrhoeae, and Streptococcus pneumoniae)., MENINGOCOCCAL INFECTIONS, infusion reactions

Drug-drug:

None reported.

Solution for injection: 10 mg/mL; 100 mg/mL

Paroxysmal Nocturnal Hemoglobinuria or Atypical Hemolytic Uremic Syndrome

IV (Adults and Children ≥1 mo and ≥100 kg): Loading dose: 3000 mg single dose (if switching from eculizumab, give loading dose 2 wk after last eculizumab dose); Maintenance dose (initiated 2 wk after loading dose): 3600 mg every 8 wk. Treatment should continue for ≥6 mo for atypical hemolytic uremic syndrome.
IV (Adults and Children ≥1 mo and 60–<100 kg): Loading dose: 2700 mg single dose (if switching from eculizumab, give loading dose 2 wk after last eculizumab dose); Maintenance dose (initiated 2 wk after loading dose): 3300 mg every 8 wk. Treatment should continue for ≥6 mo for atypical hemolytic uremic syndrome.
IV (Adults and Children ≥1 mo and 40–<60 kg): Loading dose: 2400 mg single dose (if switching from eculizumab, give loading dose 2 wk after last eculizumab dose); Maintenance dose (initiated 2 wk after loading dose): 3000 mg every 8 wk. Treatment should continue for ≥6 mo for atypical hemolytic syndrome.
IV (Adults and Children ≥1 mo and 30–<40 kg): Loading dose: 1200 mg single dose (if switching from eculizumab, give loading dose 2 wk after last eculizumab dose); Maintenance dose (initiated 2 wk after loading dose): 2700 mg every 8 wk. Treatment should continue for ≥6 mo for atypical hemolytic uremic syndrome.
IV (Adults and Children ≥1 mo and 20–<30 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): 2100 mg every 8 wk. Treatment should continue for ≥6 mo for atypical hemolytic uremic syndrome.
IV (Adults and Children ≥1 mo and 10–<20 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 for atypical hemolytic uremic syndrome.
IV (Adults and Children ≥1 mo and 5–<10 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 for atypical hemolytic uremic syndrome.

Generalized Myasthenia Gravis or Neuromyelitis Optica Spectrum Disorder

IV (Adults ≥100 kg): Loading dose: 3000 mg single dose (if switching from eculizumab, give loading dose 2 wk after last eculizumab dose); Maintenance dose (initiated 2 wk after loading dose): 3600 mg every 8 wk.
IV (Adults 60–<100 kg): Loading dose: 2700 mg single dose (if switching from eculizumab, give loading dose 2 wk after last eculizumab dose); Maintenance dose (initiated 2 wk after loading dose): 3300 mg every 8 wk.
IV (Adults 40–<60 kg): Loading dose: 2400 mg single dose (if switching from eculizumab, give loading dose 2 wk after last eculizumab dose); Maintenance dose (initiated 2 wk after loading dose): 3000 mg every 8 wk.

Ultomiris

Binds to the complement protein C5 and inhibits its cleavage to C5a and C5b, preventing the production of the terminal complement complex, C5b-9, which is a necessary step in the initiation of hemolysis in paroxysmal noctural hemoglobinuria and development of thrombotic microangiopathy in atypical hemolytic uremic syndrome. Mechanism in generalized myasthenia gravis may be due to decreased deposition of C5b-9 complex at neuromuscular junction. Mechanism in neuromyelitis optica spectrum disorder may be due to inhibition of aquaporin-4 antibody-induced terminal complement C5b-9 deposition.

Therapeutic effects:

Decreased hemolysis associated with paroxysmal noctural hemoglobinuria.
Decreased complement-mediated thrombotic microangiopathy in atypical hemolytic uremic syndrome.
Reduction in muscle weakness and improvement in ability to perform activities of daily living in generalized myasthenia gravis.
Reduction in risk of relapse in neuromyelitis optica spectrum disorder.

Therapeutic Classification: hemostatic agents

Pharmacologic Classification: complement.inhibitors, monoclonal antibodies

Absorption: IV administration results in complete bioavailability.

Distribution: Distributed to tissues.

Metabolism/Excretion: Unknown.

Half-Life: 50 days.

(inhibition of serum free C5)

ROUTE	ONSET	PEAK	DURATION
IV	Rapid	End of infusion	8 wk

Explain the purpose and side effects of ravulizumab to patient. Do not stop receiving drug without consulting health care professional. If an appointment is missed, contact health care professional as soon as possible to reschedule. Advise patient to read Medication Guide before starting and periodically during therapy in case of changes.
Explain need for continued medical follow-up to assess effectiveness and possible side effects of medication. Periodic lab tests or exams may be needed.
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 ↑ risk of infections caused by Streptococcus pneumoniae, Haemophilus influenzae type b, and gonorrhea. Advise patient to consult health care professional if at risk for gonorrhea infection about gonorrhea prevention and regular testing.
REMS: Inform patient of REMS program. Provide REMS educational materials and ensure patients are vaccinated with meningococcal vaccines. Enrollment in the Ultomiris and Soliris REMS and additional information are available by telephone: 1-888-765-4747 or at UltSolREMS.com.
Instruct patient to carry Ultomiris Patient Safety Card that describes symptoms with them at all times and to immediately seek medical evaluation if symptoms occur during and for at least 8 mo after therapy.
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 breastfeeding during therapy and for≥8 mo after last dose of ravulizumab. Patients or health care providers may call 1-833-793-0563 or go to UltomirisPregnancyStudy.comto enroll in or to obtain information about the pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ravulizumab-cwvz.

rav-ue-LIZ-ue-mab

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

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