Ravulizumab

Ravulizumab is a prescription medicine used for the treatment of paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome and generalized myasthenia gravis.

• Ravulizumab is available under the following different brand names: Ultomiris, ravulizumab-cwvz

Common side effects of Ravulizumab include:

• upper respiratory infection,
• headache,
• diarrhea,
• nausea,
• abdominal pain,
• fever,
• pain in extremities,
• joint pain, and
• dizziness

Serious side effects of Ravulizumab include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• lightheadedness,
• chest pain,
• muscle pain with flu-like symptoms,
• fever with a rash,
• fever with a headache,
• headache and stiffness in the neck or back,
• headache with nausea or vomiting,
• confusion,
• your eyes may be more sensitive to light,
• pain or burning while urinating,
• pain or swelling of the genital or rectal area,
• unusual vaginal bleeding,
• foul discharge from the penis or vagina,
• tiredness,
• confusion,
• stomach pain,
• trouble swallowing,
• trouble having an erection,
• blood in your urine,
• seizure, and
• loss of consciousness

Rare side effects of Ravulizumab include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out. 

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Injectable IV solution

• 10 mg/mL (30-mL single-dose vial)
• 100 mg/mL (3-mL, 11-mL single-dose vials)

Injectable SC solution

• 70 mg/mL (245 mg/3.5-mL single-dose prefilled cartridge); for use only with supplied single-use on-body injector

Paroxysmal Nocturnal Hemoglobinuria

Adult dosage

• Loading dose
  • 40 to less than 60 kg: 2400 mg IV
  • More than 60 to less than 100 kg: 2700 mg IV
  • More than 100 kg: 3000 mg IV
• Maintenance dose
  • IV
  • Initiate maintenance doses 2 weeks after loading the dose
  • If currently treated with on-body SC delivery system, may switch to IV 1 week after last SC dose
  • The dosing schedule allows for occasional variation within 7 days of the scheduled infusion day (except for the first maintenance dose), but administer subsequent doses according to the original schedule
  • 40 to less than 60 kg: 3000 mg IV every 8 weeks
  • More than 60 to less than 100 kg: 3300 mg IV every 8 weeks 
  • More than 100 kg: 3600 mg IV every 8 weeks
• SC
  • Initiate maintenance doses 2 weeks after the IV loading dose or 8 weeks after the last IV maintenance dose
  • More than 40 kg: 490 mg SC every week
  • 490-mg dose delivered using 2 on-body delivery systems; each system contains 1 prefilled 245-mg cartridge
  • SC dosing schedule allows occasional variation by ± 1 day of scheduled dose day, but administer subsequent doses according to the original schedule

Pediatric dosage

• Age below 1 month: Safety and efficacy not established
• Aged above 1 month
  • Loading dose
    • 5 to less than 10 kg: 600 mg IV
    • More than 10 to less than 20 kg: 600 mg IV
    • More than 20 to less than 30 kg: 900 mg IV
    • More than 30 to less than 40 kg: 1,200 mg IV
    • More than 40 to less than 60 kg: 2,400 mg IV
    • More than 60 to less than 100 kg: 2,700 mg IV
    • More than 100 kg: 3,000 mg IV
  • Maintenance dose
    • Initiate maintenance dose 2 weeks after loading dose
    • 5 to less than 10 kg: 300 mg IV every 4 weeks
    • More than 10 to less than 20 kg: 600 mg IV every 4 weeks
    • More than 20 to less than 30 kg: 2,100 mg IV every 8 weeks
    • More than 30 to less than 40 kg: 2,700 mg IV every 8 weeks
    • More than 40 to less than 60 kg: 3,000 mg IV every 8 weeks
    • More than 60 to less than 100 kg: 3,300 mg IV every 8 weeks
    • More than 100 kg: 3,600 mg IV every 8 weeks

Atypical Hemolytic Uremic Syndrome

Adult dosage

• Loading dose
  • 40 to less than 60 kg: 2400 mg IV
  • More than 60 to less than 100 kg: 2700 mg IV
  • More than 100 kg: 3000 mg IV
• Maintenance dose
  • IV
    • Initiate maintenance doses 2 weeks after loading the dose
    • If currently treated with on-body SC delivery system, may switch to IV 1 week after last SC dose
    • The dosing schedule allows for occasional variation within 7 days of the scheduled infusion day (except for the first maintenance dose), but administer subsequent doses according to the original schedule
    • 40 to less than 60 kg: 3000 mg IV every 8 weeks
    • More than 60 to less than 100 kg: 3300 mg IV every 8 weeks 
    • More than 100 kg: 3600 mg IV every 8 weeks
  • SC
    • Initiate maintenance doses 2 weeks after the IV loading dose or 8 weeks after the last IV maintenance dose
    • More than 40 kg: 490 mg SC every week
    • 490-mg dose delivered using 2 on-body delivery systems; each system contains 1 prefilled 245-mg cartridge
    • SC dosing schedule allows occasional variation by ± 1 day of scheduled dose day, but administer subsequent doses according to the original schedule

Pediatric dosage

• Age below 1 month: Safety and efficacy not established
• Aged above 1 month
  • Loading dose
    • 5 to less than 10 kg: 600 mg IV
    • More than 10 to less than 20 kg: 600 mg IV
    • More than 20 to less than 30 kg: 900 mg IV
    • More than 30 to less than 40 kg: 1,200 mg IV
    • More than 40 to less than 60 kg: 2,400 mg IV
    • More than 60 to less than 100 kg: 2,700 mg IV
    • More than 100 kg: 3,000 mg IV
  • Maintenance dose
    • Initiate maintenance dose 2 weeks after loading dose
    • 5 to less than 10 kg: 300 mg IV every 4 weeks
    • More than 10 to less than 20 kg: 600 mg IV every 4 weeks
    • More than 20 to less than 30 kg: 2,100 mg IV every 8 weeks
    • More than 30 to less than 40 kg: 2,700 mg IV every 8 weeks
    • More than 40 to less than 60 kg: 3,000 mg IV every 8 weeks
    • More than 60 to less than 100 kg: 3,300 mg IV every 8 weeks
    • More than 100 kg: 3,600 mg IV every 8 weeks

Generalized myasthenia gravis

Adult dosage

• Loading dose
  • 40 to less than 60 kg: 2400 mg IV
  • More than 60 to less than 100 kg: 2700 mg IV
  • More than 100 kg: 3000 mg IV
• Maintenance dosage
  • Initiate maintenance doses 2 weeks after loading the dose
  • If currently treated with on-body SC delivery system, may switch to IV 1 week after last SC dose
  • The dosing schedule allows for occasional variation within 7 days of the scheduled infusion day (except for the first maintenance dose), but administer subsequent doses according to the original schedule
  • 40 to less than 60 kg: 3000 mg IV every 8 weeks
  • More than 60 to less than 100 kg: 3300 mg IV every 8 weeks 
  • More than 100 kg: 3600 mg IV every 8 weeks

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Ravulizumab has no noted severe interactions with any other drugs.
• Ravulizumab has no noted serious interactions with any other drugs.
• Ravulizumab has no noted moderate interactions with any other drugs.
• Ravulizumab has no noted minor interactions with any other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug 

Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Unresolved Neisseria meningitidis infection
• Patients who are not currently vaccinated against Neisseria meningitidis, unless the risks of delaying treatment outweigh the risks of developing a meningococcal infection

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Ravulizumab?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Ravulizumab?”

Cautions

• Ravulizumab blocks terminal complement activation; therefore, an increased susceptibility to encapsulated bacterial infections is possible, especially infections caused by N meningitidis, but also Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent, Neisseria gonorrhoeae
• Monitor for hemolysis signs and symptoms after discontinuing ravulizumab, including elevated LDH with sudden decrease in PNH clone size or hemoglobin, or reappearance of symptoms (eg, fatigue, hemoglobinuria, abdominal pain, dyspnea, thrombosis, dysphagia, erectile dysfunction); monitor any patient who discontinues treatment for at least 16 weeks to detect hemolysis and other reactions
• Minimum treatment duration of aHUS is 6 months; treatment duration beyond the initial 6 months should be individualized; after discontinuing, monitor for clinical symptoms and laboratory signs of TMA complications for at least 12 months; if TMA complications occur, consider reinitiating or implementing appropriate organ-specific supportive measures
• Effect of discontinuing anticoagulants during ravulizumab therapy is not established; therefore, do not alter anticoagulant management
• Infusion reactions were reported; reactions included lower back pain, drop in blood pressure, elevation in blood pressure, limb discomfort, drug hypersensitivity (allergic reaction), dysgeusia (bad taste), and drowsiness, but did not require discontinuation; interrupt the infusion and institute appropriate supportive measures if signs of cardiovascular instability or respiratory compromise occur
• On-body SC injector uses acrylic adhesive; may result in allergic reaction for patients with known allergy to acrylic adhesive; consider premedication and supportive measures if signs of allergy emerge
• Serious meningococcal infections
  • Life-threatening meningococcal infections have occurred
  • Use increases patients’ susceptibility to serious meningococcal infections (septicemia and/or meningitis)
  • Vaccinate for meningococcal disease according to most current Advisory Committee on Immunization Practices (ACIP) recommendations for patients with complement deficiencies; revaccinate patients according to ACIP recommendations considering the duration of therapy
  • Immunize patients without a history of meningococcal vaccination at least 2 weeks before initiating
  • If urgent therapy is indicated in an unvaccinated patient, administer meningococcal vaccine(s) as soon as possible and provide patients with 2 weeks of antibacterial drug prophylaxis; must receive appropriate prophylactic antibiotics until 2 weeks after vaccination
  • Closely monitor for signs and symptoms of meningococcal infection and evaluate if the infection is suspected
  • Consider discontinuation in patients who are undergoing treatment for serious meningococcal infection
• Risk Evaluation and Mitigation Strategy (REMS)
  • Owing to the risk of meningococcal infections, the drug is only available only through a restricted REMS program
  • Prescribers must enroll in the program, counsel patients about the risk of meningococcal infection/sepsis, provide patients with the REMS educational materials, and ensure patients are vaccinated with meningococcal vaccines; patients must carry the Patient Safety Card with them at all times during and for 8 months following treatment with this drug
  • Enrollment in the ULTOMIRIS REMS and additional information are available by telephone: 1-888-765-4747 or at www.ultomirisrems.com
• Drug interaction overview
  • Concomitant use with plasma exchange (PE), plasmapheresis (PP), or intravenous immunoglobulin (IVIg) treatment can reduce serum ravulizumab concentrations and requires a supplemental dose of ravulizumab

Pregnancy and Lactation

No data are available for use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

• There are risks to the mother and fetus associated with untreated PNH or aHUS, including preeclampsia and preterm delivery, and adverse fetal/neonatal outcomes, including intrauterine growth restriction (IUGR), fetal death and low birth weight
• Clinical considerations
  • PNH in pregnancy is associated with adverse maternal outcomes, including worsening cytopenias, thrombotic events, infections, bleeding, miscarriages, and increased maternal mortality, and adverse fetal outcomes, including fetal death and premature delivery
• Lactation
  • There are no data on the presence of ravulizumab in human milk, the effects on the breastfed child, or the effects on milk production
  • Because many drugs are excreted in human milk and because of the potential for adverse reactions in a breastfed child, advise lactating women not to breastfeed while receiving ravulizumab and for 8 months after the last dose