Brand name: Ultomiris
Drug class: Complement Inhibitors
Chemical name: Immunoglobulin G2/G4, anti-(human complement C5) (human-Mus musculus ALXN1210 heavy chain), disulfide with human-Mus musculus ALXN1210 κ-chain, dimer
Molecular formula: C6430H9888N1696O2028S48
CAS number: 1803171-55-2
Warning: Serious Meningococcal Infections
See full prescribing information for complete boxed warning.
Life-threatening meningococcal infections/sepsis have occurred in patients treated with ravulizumab-cwvz and may become rapidly life-threatening or fatal if not recognized and treated early.
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 ravulizumab-cwvz, unless the risks of delaying ravulizumab-cwvz therapy outweigh the risks of developing a meningococcal infection. Vaccination reduces, but does not eliminate, the risk of meningococcal infection.
Monitor patients for early signs of meningococcal infections, and evaluate immediately if infection is suspected.
Ravulizumab-cwvz is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the ravulizumab-cwvz REMS, prescribers must enroll in the program.
Risk Evaluation and Mitigation Strategy (REMS):
FDA approved a REMS for ravulizumab-cwvz to ensure that the benefits outweigh the risk. The REMS may apply to one or more preparations of ravulizumab-cwvz and consists of the following: elements to assure safe use. See https://www.accessdata.fda.gov/scripts/cder/rems/.
Ravulizumab-cwvz is a complement inhibitor.
Uses for Ravulizumab-cwvz
Ravulizumab-cwvz has the following uses:
Ravulizumab-cwvz is a complement inhibitor indicated for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH).
Ravulizumab-cwvz Dosage and Administration
Ravulizumab-cwvz is available in the following dosage form(s) and strength(s):
Injection: 300 mg/30 mL (10 mg/mL) in a single-dose vial.
It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:
Dosage and Administration
Only administer as an intravenous infusion.
Recommended dosing regimen consists of a loading dose followed by maintenance dosing. Starting 2 weeks after the loading dose administration, begin maintenance doses at once every 8-week intervals.
Recommended doses are based on the patient's body weight as shown in the following table:
Body Weight Range (kg)
Loading Dose (mg)
Maintenance Dose (mg)
greater or equal to 40 to less than 60
greater than or equal to 60 to less than 100
greater than or equal to 100
See Full Prescribing Information for important preparation and administration instructions.
Cautions for Ravulizumab-cwvz
Ravulizumab-cwvz is contraindicated in patients with unresolved Neisseria Meningitidis infection.
Serious Meningococcal Infections
Risk and Prevention
Life-threatening meningococcal infections have occurred in patients treated with ravulizumab-cwvz. The use of ravulizumab-cwvz increases a patient's susceptibility to serious meningococcal infections (septicemia and/or meningitis). Meningococcal disease due to any serogroup may occur.
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 ravulizumab-cwvz therapy.
Immunize patients without a history of meningococcal vaccination at least 2 weeks prior to receiving the first dose of ravulizumab-cwvz. If urgent ravulizumab-cwvz 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.
In clinical studies, 59 patients with PNH were treated with ravulizumab-cwvz less than 2 weeks after meningococcal vaccination. All of these 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 ravulizumab-cwvz have not been established.
Vaccination reduces, but does not eliminate, the risk of meningococcal infections. In clinical studies, 3 out of 261 PNH patients developed serious meningococcal infections/sepsis while receiving treatment with ravulizumab-cwvz; all 3 had been vaccinated. These 3 patients recovered while continuing treatment with ravulizumab-cwvz.
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 steps to be taken to seek immediate medical care. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider discontinuation of ravulizumab-cwvz in patients who are undergoing treatment for serious meningococcal infection.
Due to the risk of meningococcal infections, ravulizumab-cwvz is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the ravulizumab-cwvz REMS, prescribers must enroll in the program.
Prescribers must counsel patients about the risk of meningococcal infection/sepsis, provide the patients with the REMS educational materials, and ensure patients are vaccinated with meningococcal vaccines.
Enrollment in the ravulizumab-cwvz REMS and additional information are available by telephone: 1-888-765-4747 or at www.ultomirisrems.com.
Ravulizumab-cwvz blocks terminal complement activation; therefore, patients may have increased susceptibility to encapsulated bacteria infections, especially infections caused by Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent, Neisseria gonorrhoeae. If ravulizumab-cwvz therapy is administered to patients with active systemic infections, monitor closely for signs and symptoms of worsening infection.
Monitoring Disease Manifestations after Ravulizumab-cwvz Discontinuation
After discontinuing treatment with ravulizumab-cwvz, closely monitor for signs and symptoms of hemolysis, identified by elevated LDH along with sudden decrease in PNH clone size or hemoglobin, or re-appearance of symptoms such as fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction. Monitor any patient who discontinues ravulizumab-cwvz for at least 16 weeks to detect hemolysis and other reactions. If signs and symptoms of hemolysis occur after discontinuation, including elevated LDH, consider restarting treatment with ravulizumab-cwvz.
Thromboembolic Event Management
The effect of withdrawal of anticoagulant therapy during ravulizumab-cwvz treatment has not been established. Therefore, treatment with ravulizumab-cwvz should not alter anticoagulant management.
Administration of ravulizumab-cwvz may result in infusion reactions. In clinical trials, 3 out of 222 patients with PNH treated with ravulizumab-cwvz experienced infusion reactions (lower back pain, drop in blood pressure and infusion-related pain) during ravulizumab-cwvz administration. These reactions did not require discontinuation of ravulizumab-cwvz. Interrupt ravulizumab-cwvz infusion and institute appropriate supportive measures if signs of cardiovascular instability or respiratory compromise occur.
Risk Summary: There are no available data on ravulizumab-cwvz 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 paroxysmal nocturnal hemoglobinuria (PNH) in pregnancy. Animal studies using a mouse analogue of the ravulizumab-cwvz molecule (murine anti-C5 antibody) showed increased rates of developmental abnormalities and an increased rate of dead and moribund offspring at doses 0.8-2.2 times the human dose.
The estimated background risk of major birth defects and miscarriage for the indicated population 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 defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
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.
Animal Data: Animal reproduction studies were conducted in mice using doses of a murine anti-C5 antibody that approximated 1-2.2 times (loading dose) and 0.8-1.8 times (maintenance dose) the recommended human ravulizumab-cwvz dose, based on a body weight comparison. When animal exposure to the antibody occurred in the time period from before mating until early gestation, no decrease in fertility or reproductive performance was observed. When maternal exposure to the antibody occurred during organogenesis, two cases of retinal dysplasia and one case of umbilical hernia were observed among 230 offspring born to mothers exposed to the higher antibody dose; however, the exposure did not increase fetal loss or neonatal death. When maternal exposure to the antibody occurred in the time period from implantation through weaning, a higher number of male offspring became moribund or died (1/25 controls, 2/25 low dose group, 5/25 high dose group). Surviving offspring had normal development and reproductive function. Human IgG are known to cross the human placental barrier, and thus ravulizumab-cwvz may potentially cause terminal complement inhibition in the fetal circulation.
Risk Summary: There are no data on the presence of ravulizumab-cwvz in human milk, the effect on the breastfed child, or the effect on milk production. Since many medicinal products and immunoglobulins are secreted into human milk, and because of the potential for serious adverse reactions in a nursing child, breastfeeding should be discontinued during treatment and for 8 months after the final dose.
The safety and efficacy of ravulizumab-cwvz in pediatric patients have not been established.
Clinical studies of ravulizumab-cwvz did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
Common Adverse Effects
The most frequent adverse drug reactions (>10%) were upper respiratory infection and headache.
It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:
Please see product labeling for drug interaction information.
Mechanism of Action
Ravulizumab-cwvz is a terminal complement inhibitor that specifically binds to the complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a (the proinflammatory anaphylatoxin) and C5b (the initiating subunit of the terminal complement complex [C5b-9]) and preventing the generation of the terminal complement complex C5b9. Ravulizumab-cwvz inhibits terminal complement-mediated intravascular hemolysis in patients with PNH.
Advice to Patients
Advise the patient to read FDA-approved patient labeling (Medication Guide).
Advise patients of the risk of meningococcal infection/sepsis. Inform patients that they are required to receive meningococcal vaccination at least 2 weeks prior to receiving the first dose of ravulizumab-cwvz, if they have not previously been vaccinated. They are required to be revaccinated according to current medical guidelines for meningococcal vaccines use while on ravulizumab-cwvz therapy. Inform patients that vaccination may not prevent meningococcal infection. Inform patients about the signs and symptoms of meningococcal infection/sepsis, and strongly advise patients to seek immediate medical attention if these signs or symptoms occur. These signs and symptoms are as follows: headache with nausea or vomiting; headache and a fever; headache with a stiff neck or stiff back; fever; fever and a rash; confusion; muscle aches with flu-like symptoms; eyes sensitive to light.
Inform patients that they will be given an ravulizumab-cwvz Patient Safety Card that they should carry with them at all times. This card describes symptoms which, if experienced, should prompt the patient to immediately seek medical evaluation.
Counsel patients of the increased risk of infections, particularly those due to encapsulated bacteria, especially Neisseria species. Advise patients of the need for vaccination against meningococcal infections according to current medical guidelines. Counsel patients about gonorrhea prevention and advise regular testing for patients at risk. Advise patients to report any new signs and symptoms of infection.
Inform patients with PNH that they may develop hemolysis due to PNH when ravulizumab-cwvz is discontinued and that they will be monitored by their healthcare professional for at least 16 weeks following ravulizumab-cwvz discontinuation.
Inform patients who discontinue ravulizumab-cwvz to keep the ravulizumab-cwvz Patient Safety Card with them for eight months after the last ravulizumab-cwvz dose, because the increased risk of meningococcal infection persists for several weeks following discontinuation of ravulizumab-cwvz.
Advise patients that administration of ravulizumab-cwvz may result in infusion reactions.
AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
For injection, concentrate, for IV infusion only
300 mg /30 mL
Alexion Pharmaceuticals Inc.
AHFS Drug Information. © Copyright 2023, Selected Revisions January 31, 2022. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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