Ravulizumab-cwvz (Monograph)

Brand name: Ultomiris
Drug class: Complement Inhibitor Agents

Medically reviewed by Drugs.com on Feb 10, 2025. Written by ASHP.

Introduction

Terminal complement inhibitor; humanized monoclonal antibody.

Uses for Ravulizumab-cwvz

Paroxysmal Nocturnal Hemoglobinuria

Treatment of paroxysmal nocturnal hemoglobinuria (PNH) in adults and pediatric patients ≥1 month of age (designated an orphan drug by FDA for this use).

Options for PNH management include supportive care (e.g., iron supplementation, RBC transfusion, antibiotics for bacterial infection, anticoagulation, corticosteroids), allogeneic bone marrow transplantation, and/or terminal complement inhibitors (e.g., ravulizumab, eculizumab); choice of therapy depends on PNH classification and symptom severity.

Atypical Hemolytic Uremic Syndrome

Treatment of atypical hemolytic uremic syndrome (aHUS) in adults and pediatric patients ≥1 month of age to inhibit complement-mediated thrombotic microangiopathy (designated an orphan drug by FDA for this use).

Not indicated for treatment of patients with Shiga toxin E. coli-related hemolytic uremic syndrome.

Options for aHUS management include supportive care (e.g., packed RBCs for anemia, fluid and electrolytes, management of hypertension and renal impairment), plasma exchange or infusion, and complement inhibitors. Complement inhibitor therapy may provide an alternative option to plasma therapy.

Myasthenia Gravis

Treatment of generalized myasthenia gravis in adults who are anti-acetylcholine receptor (anti-AChR) antibody positive (designated an orphan drug by FDA for this use).

Conventional therapy includes immunosuppressive agents, plasma exchange, and, in some cases, thymectomy. Complement inhibitors (e.g., eculizumab, ravulizumab) may play a role in treatment of AChR-positive generalized myasthenia gravis by reducing deposition of complement and membrane attack complexes at the neuromuscular junction.

Neuromyelitis Optica Spectrum Disorder

Treatment of adults with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive. (designated an orphan drug by FDA for treatment of neuromyelitis optica).

Monoclonal antibody complement inhibitors (eculizumab, ravulizumab) are recommended as one of several first-line options for long-term immunotherapy in patients with AQP4-IgG-positive NMOSD. Other monoclonal antibodies that have demonstrated efficacy include inebilizumab, rituximab, and satralizumab; choice of therapy should be based on disease severity, comorbidities, patient age, family planning, adherence, patient and physician preferences, and drug-related factors (mechanism, onset of action, adverse effects, safety, route of administration, cost, availability).

Ravulizumab-cwvz Dosage and Administration

General

Pretreatment Screening

• Assess immunization status prior to initiating ravulizumab-cwvz therapy.

Patient Monitoring

• Closely monitor patients for early signs and symptoms of meningococcal infections during treatment with ravulizumab-cwvz, and evaluate immediately if infection is suspected.

• Monitor for infusion-related reactions during administration and for at least 1 hour following completion of infusion.

• Monitor for signs and symptoms of hemolysis and other reactions for at least 16 weeks in patients with PNH who discontinue ravulizumab-cwvz.

• Monitor for clinical symptoms and laboratory signs of thrombotic microangiopathy complications for at least 12 months in patients with aHUS who discontinue ravulizumab-cwvz.

Premedication and Prophylaxis

• Vaccinate or revaccinate patients against meningococcal infection (serogroups A, C, W, Y, and B) according to current Advisory Committee on Immunization Practices (ACIP) recommendations at least 2 weeks prior to initiating ravulizumab-cwvz. If ravulizumab-cwvz must be started urgently in a patient who is not up to date with meningococcal vaccines, provide antibacterial drug prophylaxis and administer these vaccines as soon as possible.

REMS

• Because of the risk of meningococcal infections, ravulizumab-cwvz can only be obtained through a restricted distribution program called the Ultomiris and Soliris REMS. The drug may be prescribed only by clinicians who are enrolled in the REMS program. In addition, clinicians must counsel patients regarding the risk of meningococcal infection/sepsis, provide educational materials, and ensure that patients are compliant with meningococcal vaccine and antibacterial drug prophylaxis requirements. Healthcare settings and pharmacies that dispense ravulizumab-cwvz must be certified in the REMS and must verify that prescribers are certified. Patients must carry the Patient Safety Card with them at all times during and for 8 months following treatment with the drug. .

• Additional information is available at 888-765-4747 or [Web].

Administration

IV Administration

Administer by IV infusion.

Available in single-dose vials containing ravulizumab-cwvz 100 mg/mL (3 and 11 mL vials) or ravulizumab-cwvz 10 mg/mL (30 mL vial). Must be diluted before IV administration.

Single-dose vials intended for IV administration by healthcare professional after dilution.

Do not use if particulate matter or precipitation observed.

Patients should contact a clinician immediately if a dose is missed. IV dosing schedule may occasionally vary within 7 days of the scheduled infusion day (except for the first maintenance dose of ravulizumab-cwvz), but subsequent doses should be administered according to the original schedule.

Dilution

Dilute ravulizumab-cwvz solution before IV infusion. Do not mix ravulizumab-cwvz 100 mg/mL (3 mL and 11 mL vials) and 10 mg/mL (30 mL vial) concentrations together.

Determine the number of vials to be diluted based on body weight and the prescribed dosage.

Withdraw the calculated volume from the appropriate number of vials and dilute to a final concentration of 50 mg/mL (for the 3 mL and 11 mL vial sizes) or 5 mg/mL (for the 30 mL vial size) in an infusion bag using 0.9% sodium chloride. Consult the full prescribing information for important instructions on the preparation of diluted solutions.

Mix the product gently; protect diluted solution from light and do not shake or freeze.

Administration

Prior to administration, allow admixture to adjust to room temperature (18–25ºC); do not heat in a microwave or with any heat source other than ambient air temperature.

Only administer as an IV infusion through a 0.2 or 0.22 micron filter.

After infusion, flush entire line with 0.9% sodium chloride injection.

Refer to full prescribing information for minimum infusion times and maximum infusion rates. If an adverse reaction occurs during IV administration, stop or slow the infusion.

Dosage

Pediatric Patients

PNH

IV

Dosage based on weight (see Table 1).

In patients not currently on ravulizumab-cwvz or eculizumab treatment, initiate IV ravulizumab-cwvz maintenance dosage 2 weeks after the loading dose.

In patients switching directly from eculizumab treatment to IV ravulizumab-cwvz, administer the IV ravulizumab-cwvz loading dose at the time of the next scheduled eculizumab dose, and initiate the ravulizumab-cwvz maintenance dosage 2 weeks after the loading dose.

aHUS

IV

Dosage based on weight (see Table 1).

In patients not currently on ravulizumab-cwvz or eculizumab treatment, initiate IV ravulizumab-cwvz maintenance dosage 2 weeks after the loading dose.

In patients switching directly from eculizumab treatment to IV ravulizumab-cwvz, administer the IV ravulizumab-cwvz loading dose at the time of the next scheduled eculizumab dose, and initiate the ravulizumab-cwvz maintenance dosage 2 weeks after the loading dose.

Adults

PNH

IV

Dosage based on weight (see Table 1).

In patients not currently on ravulizumab-cwvz or eculizumab treatment, initiate IV ravulizumab-cwvz maintenance dosage 2 weeks after the loading dose.

In patients switching directly from eculizumab treatment to IV ravulizumab-cwvz, administer the IV ravulizumab-cwvz loading dose at the time of the next scheduled eculizumab dose, and initiate the ravulizumab-cwvz maintenance dosage 2 weeks after the loading dose.

aHUS

IV

Dosage based on weight (see Table 1).

In patients not currently on ravulizumab-cwvz or eculizumab treatment, initiate IV ravulizumab-cwvz maintenance dosage 2 weeks after the loading dose.

In patients switching directly from eculizumab treatment to IV ravulizumab-cwvz, administer the IV ravulizumab-cwvz loading dose at the time of the next scheduled eculizumab dose, and initiate the ravulizumab-cwvz maintenance dosage 2 weeks after the loading dose.

Myasthenia Gravis

IV

For adults weighing ≥40 kg: dosage based on weight (see Table 2).

In patients not currently on ravulizumab-cwvz or eculizumab treatment, initiate IV ravulizumab-cwvz maintenance dosage 2 weeks after the loading dose.

In patients switching directly from eculizumab treatment to IV ravulizumab-cwvz, administer the IV ravulizumab-cwvz loading dose at the time of the next scheduled eculizumab dose, and initiate the ravulizumab-cwvz maintenance dosage 2 weeks after the loading dose.

NMOSD

For adults weighing ≥40 kg: Dosage based on weight (see Table 2).

In patients not currently on ravulizumab-cwvz or eculizumab treatment, initiate IV ravulizumab-cwvz maintenance dosage 2 weeks after the loading dose.

In patients switching directly from eculizumab treatment to IV ravulizumab-cwvz, administer the IV ravulizumab-cwvz loading dose at the time of the next scheduled eculizumab dose, and initiate the ravulizumab-cwvz maintenance dosage 2 weeks after the loading dose.

Dosage Modification with Concomitant Use with Plasma Exchange, Plasmapheresis, or Intravenous Immunoglobulin (IVIG)

Administer supplemental dose of IV ravulizumab-cwvz within 4 hours following each plasma exchange or plasmapheresis intervention or within 4 hours following completion of an IVIG cycle. Refer to Table 3 for supplemental dosages.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Cautions for Ravulizumab-cwvz

Contraindications

• Unresolved serious Neisseria meningitidis infection.

Warnings/Precautions

Warnings

Serious Meningococcal Infections

Serious, life-threatening, or fatal meningococcal infections (e.g., sepsis, meningitis) reported. Infections have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors. (See Boxed Warning.)

Complete or update meningococcal vaccination (for serogroups A, C, W, Y, and B) at least 2 weeks prior to first dose of ravulizumab according to ACIP recommendations for patients receiving a complement inhibitor. Revaccinate patients according to ACIP recommendations considering duration of ravulizumab-cwvz therapy. .

If urgent ravulizumab therapy indicated in a patient not up to date with meningococcal vaccines, provide antibacterial drug prophylaxis and administer these vaccines as soon as possible. Because optimal duration and drug regimen for prophylaxis has not been studied in unvaccinated or vaccinated patients, weigh benefits and risks of ravulizumab treatment and antibacterial drug prophylaxis against risks for serious infections caused by Neisseria meningitidis.

Vaccination does not eliminate risk of serious encapsulated bacterial infections.

Monitor closely for early signs and symptoms of meningococcal infection. Evaluate promptly if infection suspected.

Inform patients of signs and symptoms of infection; instruct patients to seek immediate medical care if these occur. Treat known infections promptly.

Consider interruption of therapy in patients undergoing treatment for serious meningococcal infection.

Due to risk of meningococcal infections, ravulizumab-cwvz is available only through a REMS program. (See REMS under Dosage and Administration.)

<C> Other Warnings and Precautions

Other Infections

Blocks terminal complement activation and may increase susceptibility to infections, especially those caused by encapsulated bacteria such as Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, and, to a lesser extent, Neisseria gonorrhoeae. Pediatric patients may be at increased risk for serious Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) infections.

Vaccinate patients for the prevention of Streptococcus pneumoniae and Hib infections in accordance with current ACIP guidelines. Patients receiving ravulizumab-cwvz are at increased risk of infections due to these organisms even if they develop antibodies following vaccination.

Monitoring Disease Manifestations After Treatment Discontinuation

Closely monitor patients with PNH for ≥16 weeks following ravulizumab discontinuation to detect hemolysis and other reactions. Signs and symptoms include elevated LDH along with sudden decrease in PNH clone size or hemoglobin, or reappearance of symptoms such as fatigue, hemoglobinuria, abdominal pain, dyspnea, major adverse vascular events (including thrombosis), dysphagia, or erectile dysfunction.

If signs and symptoms of hemolysis (including elevated LDH) occur after treatment discontinuation, consider restarting ravulizumab.

For treatment of aHUS, ravulizumab should be given for a minimum of 6 months; treatment duration beyond 6 months should be individualized.

Closely monitor patients with aHUS for ≥12 months following ravulizumab discontinuation for signs and symptoms of thrombotic microangiopathy complications. Thrombotic microangiopathy complications may be identified by clinical symptoms (e.g., changes in mental status, seizures, angina, dyspnea, thrombosis, or increasing BP) in addition to ≥2 of the following laboratory values observed concurrently (and confirmed by a second measurement 28 days later with no interruption): platelet count decreased ≥25% compared to baseline or to peak platelet count during treatment; serum creatinine increased ≥25% compared to baseline or to nadir during treatment; or LDH increased ≥25% compared to baseline or to nadir during treatment.

If thrombotic microangiopathy complications occur after discontinuation, consider restarting treatment with ravulizumab or using appropriate organ-specific supportive measures.

Thromboembolic Event Management

Ravulizumab should not alter anticoagulant management; effect of anticoagulant therapy withdrawal during ravulizumab therapy unknown.

Infusion-related Reactions

Systemic infusion-related reactions, including anaphylaxis and hypersensitivity reactions, reported.

Monitor for infusion-related reactions during administration and for at least 1 hour following completion of infusion.

If signs of cardiovascular instability or respiratory compromise occur, interrupt the IV infusion and manage supportively.

Immunogenicity

Potential for immunogenicity.

Treatment-emergent anti-ravulizumab antibodies detected in patients with PNH and aHUS receiving IV ravulizumab-cwvz. No apparent correlation of antibody development to altered pharmacokinetic profile, clinical response, or adverse events observed.

No treatment-emergent anti-ravulizumab antibodies detected in patients with generalized myasthenia gravis or NMOSD.

Specific Populations

Pregnancy

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

Untreated PNH and aHUS in pregnancy associated with adverse maternal and fetal outcomes.

Increased rates of developmental abnormalities and increased rate of dead and moribund offspring observed in animal reproduction studies.

Pregnancy exposure registry monitors pregnancy outcomes in women exposed to ravulizumab-cwvz; patients and clinicians can enroll or obtain more information at 833-793-0563 or [Web]

Lactation

Unknown whether ravulizumab distributes into human milk, or affects milk production or the breast-fed infant.

Advise women to not breast-feed during treatment with ravulizumab and for 8 months after the last dose.

Pediatric Use

Safety and efficacy established in pediatric patients ≥1 month of age with PNH. Safety and efficacy appear similar in pediatric and adult patients.

Safety and efficacy established in pediatric patients ≥1 month of age with aHUS. Safety and efficacy appear similar in pediatric and adult patients.

Safety and efficacy not established in pediatric patients with generalized myasthenia gravis in pediatric patients.

Geriatric Use

Ravulizumab-cwvz studies did not include sufficient numbers of geriatric patients (≥65 years of age) to determine whether they respond differently from younger patients.

No differences in responses between geriatric and younger patients identified in other reported clinical experience.

Hepatic Impairment

No clinically important differences in ravulizumab pharmacokinetics observed based on hepatic impairment.

Renal Impairment

No clinically important differences in ravulizumab pharmacokinetics observed based on any degree of renal impairment (including patients with proteinuria or receiving dialysis).

Common Adverse Effects

Patients with PNH: common adverse effects (≥10%) include upper respiratory tract infection and headache.

Patients with aHUS: common adverse effects (≥20%) include upper respiratory tract infection, diarrhea, nausea, vomiting, headache, hypertension, and pyrexia.

Patients with myasthenia gravis: common adverse effects (≥10%) include diarrhea and upper respiratory tract infection.

Patients with NMOSD: common adverse effects (≥10%) include COVID-19, headache, back pain, arthralgia, and urinary tract infection.

Drug Interactions

No drug-drug interaction studies performed with ravulizumab-cwvz.

Plasma Exchange or Plasmapheresis

May lower serum ravulizumab-cwvz concentrations Administer a supplemental dose of ravulizumab-cwvz when used concomitantly.

Specific Drugs

Ravulizumab-cwvz Pharmacokinetics

Absorption

Bioavailability

Following IV administration, ravulizumab pharmacokinetics increase proportionally over dose range of 200–5400 mg.

Distribution

Extent

Unknown whether distributes into human milk.

Elimination

Half-life

Mean of 49.6 days in adult and pediatric patients with PNH; 51.8 days in adult and pediatric patients with aHUS; 56.6 days in adult patients with generalized myasthenia gravis; 64.3 days in patients with NMOSD.

Special Populations

No clinically important differences in ravulizumab pharmacokinetics observed based on sex, age (10 months to 83 years), race, hepatic impairment, or degree of renal impairment (including patients with proteinuria or undergoing dialysis).

Body weight was a clinically important covariate on ravulizumab pharmacokinetics.

Stability

Storage

Parenteral

Injection concentrate

Unopened vials: Store under refrigeration at 2–8ºC; do not freeze or shake. Store in original carton to protect from light.

Diluted solution: If not used immediately after preparation, store under refrigeration (2–8ºC) for no longer than 24 hours, taking into account the expected infusion time. Protect from light. Once removed from refrigeration, administer diluted solution within 6 hours (for 30 mL vials) or within 4 hours (for 3 mL or 11 mL vials).

Actions

• Humanized monoclonal antibody and terminal complement inhibitor.

• Specifically binds to the complement protein C5 with high affinity, inhibiting its cleavage to C5a (the proinflammatory anaphylatoxin) and C5b (the initiating subunit of the membrane attack complex [C5b-9]); this prevents membrane attack complex formation.

• Inhibits terminal complement-mediated intravascular hemolysis in patients with PNH and complement-mediated thrombotic microangiopathy in patients with aHUS.

• Exact mechanism in patients with generalized myasthenia gravis not fully elucidated; presumed to involve reduction of terminal complement complex C5b-9 deposition at the neuromuscular junction.

• Exact mechanism in patients with NMOSD not known, but presumed to involve inhibition of aquaporin-4 antibody-induced terminal complement C5b-9 deposition.

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Medication Guide).

• Advise patients of the risk of serious meningococcal infection. Inform patients of the need to complete or update their meningococcal vaccinations at least 2 weeks prior to receiving the first dose of ravulizumab-cwvz or receive antibacterial drug prophylaxis if ravulizumab treatment must be initiated immediately and they have not been previously vaccinated. Inform patients that vaccination may not prevent meningococcal infection. Inform patients about the signs and symptoms of serious meningococcal infection (e.g., headache with nausea or vomiting, fever with high heart rate, headache with fever, headache with a stiff neck or stiff back, fever with or without rash, confusion, muscle aches with flu-like symptoms, eyes sensitive to light). Advise patients to seek immediate medical attention if these signs or symptoms occur.

• Inform patients that they will receive a Patient Safety Card about the risk of meningococcal infection. Instruct patients to carry their Patient Safety Card with them at all times during treatment with ravulizumab-cwvz and for 8 months following treatment discontinuation.

• Inform patients that ravulizumab-cwvz is available only through a restricted program called Ultomiris and Soliris REMS, and that this program requires patients to receive counseling (including written educational materials) about the risk of serious meningococcal infections, as well as comply with the most current recommendations for meningococcal vaccination.

• Advise patients of the increased risk of other infections, particularly those due to encapsulated bacteria such as Neisseria species. Inform 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 paroxysmal nocturnal hemoglobinuria that they may develop hemolysis when ravulizumab-cwvz is discontinued and that they will be monitored by their clinician for ≥16 weeks following treatment discontinuation.

• Inform patients with atypical hemolytic uremic syndrome that they may develop thrombotic microangiopathy when ravulizumab-cwvz is discontinued and that they will be monitored by their clinician for ≥12 months following treatment discontinuation.

• Advise patients that infusion-related reactions may occur with administration of ravulizumab-cwvz.

• Inform patients of the pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ravulizumab during pregnancy. Encourage participation and advise patients about how they may enroll in the registry.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Advise patients to inform their clinician if they are or plan to become pregnant or plan to breast-feed. Advise patients that breast-feeding is not recommended during treatment with ravulizumab-cwvz and for 8 months after the final dose.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

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.

Reload page with references included

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Frequently asked questions

• How does Ultomiris work for myasthenia gravis?

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