Version July 2025
Ravulizumab, a complement inhibitor, increases the risk of serious infections caused by Neisseria meningitidis. Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early.
Complete or update vaccination for meningococcal bacteria (for serogroups A, C, W, Y, and B) at least 2 weeks prior to the first dose of ravulizumab, unless the risks of delaying therapy with ravulizumab outweigh the risk of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against meningococcal bacteria in patients receiving a complement inhibitor.
Patients receiving ravulizumab are at increased risk for invasive disease caused by N. meningitidis, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious meningococcal infections and evaluate immediately if infection is suspected.
Because of the risk of serious meningococcal infections, ravulizumab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called ULTOMIRIS and SOLIRIS REMS.
Dosage guidance:
Safety: Vaccinate with meningococcal vaccine at least 2 weeks prior to treatment initiation; revaccinate according to current guidelines. If urgent ravulizumab initiation is necessary and patient is not up to date with meningococcal vaccines (based on Advisory Committee on Immunization Practices [ACIP] recommendations), administer vaccination as soon as possible and provide antibacterial drug prophylaxis. To reduce the risk for meningococcal disease, consider antimicrobial prophylaxis with oral antibiotics (penicillin, or macrolides if penicillin-allergic) for the duration of therapy (Ref).
Dosage form information: Multiple concentrations of solution in vials are available (10 mg/mL and 100 mg/mL) for intravenous administration; only a single concentration should be used to prepare a dose for infusion.
Clinical considerations: Following the first maintenance dose, the ravulizumab dosing schedule is allowed to occasionally vary within 7 days (IV infusion) of the scheduled infusion day, although the subsequent dose should be administered according to the original schedule.
Atypical hemolytic uremic syndrome (aHUS):
Infants, Children, and Adolescents: IV infusion: Administer the first maintenance dose 2 weeks after loading dose; for subsequent maintenance doses, the interval varies with weight; use precaution to ensure appropriate interval. Treatment should continue for a minimum of 6 months. Dose is based on weight at time of treatment for that dose. Following the first maintenance dose, the ravulizumab dosing schedule is allowed to occasionally vary within 7 days of the scheduled infusion day; subsequent doses should be administered according to the original schedule.
|
Weight (at time of treatment) |
Loading dose (fixed, mg/dose) |
Interval between loading dose and maintenance dose #1 |
Maintenance dose (fixed, mg/dose) |
Maintenance interval |
|---|---|---|---|---|
|
5 to <10 kg |
600 mg |
2 weeks |
300 mg |
Every 4 weeks |
|
10 to <20 kg |
600 mg |
600 mg | ||
|
20 to <30 kg |
900 mg |
2,100 mg |
Every 8 weeks | |
|
30 to <40 kg |
1,200 mg |
2,700 mg | ||
|
40 to <60 kg |
2,400 mg |
3,000 mg | ||
|
60 to <100 kg |
2,700 mg |
3,300 mg | ||
|
≥100 kg |
3,000 mg |
3,600 mg |
Paroxysmal nocturnal hemoglobinuria (PNH):
Infants, Children, and Adolescents: IV infusion: Administer the first maintenance dose 2 weeks after loading dose; for subsequent maintenance doses, the interval varies with weight; use precaution to ensure appropriate interval. Dose is based on weight at time of treatment for that dose. Following the first maintenance dose, the ravulizumab dosing schedule is allowed to occasionally vary within 7 days of the scheduled infusion day; subsequent doses should be administered according to the original schedule.
|
Weight (at time of treatment) |
Loading dose (fixed, mg/dose) |
Interval between loading dose and maintenance dose #1 |
Maintenance dose (fixed, mg/dose) |
Maintenance interval |
|---|---|---|---|---|
|
5 to <10 kg |
600 mg |
2 weeks |
300 mg |
Every 4 weeks |
|
10 to <20 kg |
600 mg |
600 mg | ||
|
20 to <30 kg |
900 mg |
2,100 mg |
Every 8 weeks | |
|
30 to <40 kg |
1,200 mg |
2,700 mg | ||
|
40 to <60 kg |
2,400 mg |
3,000 mg | ||
|
60 to <100 kg |
2,700 mg |
3,300 mg | ||
|
≥100 kg |
3,000 mg |
3,600 mg |
Conversion from eculizumab: Administer the ravulizumab loading dose at the time of the next scheduled eculizumab dose; administer subsequent ravulizumab maintenance doses according to weight-based schedule, beginning 2 weeks after the ravulizumab loading dose.
Supplemental dose following plasma exchange (PE), plasmapheresis (PP), or IV immune globulin (IVIG):
Note: Serum levels of ravulizumab are decreased by PE, PP, or IVIG; supplemental ravulizumab dosing is necessary; the supplemental dose varies with intervention used. Dosing in patients weighing <40 kg has not been determined; use caution. Dose should be administered within 4 hours following PE or PP intervention or following completion of an IVIG cycle.
Children and Adolescents weighing ≥40 kg: IV infusion:
|
Weight (kg) at time of treatment |
Most recent ravulizumab dose (mg) |
Supplemental ravulizumab dose (mg) following each PE or PP interventiona |
Supplemental ravulizumab dose (mg) following completion of an IVIG cyclea |
|---|---|---|---|
|
a Supplemental doses should be administered within 4 hours following PE, PP, or IVIG completion. | |||
|
40 to <60 kg |
2,400 mg |
1,200 mg |
600 mg |
|
3,000 mg |
1,500 mg | ||
|
60 to <100 kg |
2,700 mg |
1,500 mg |
600 mg |
|
3,300 mg |
1,800 mg | ||
|
≥100 kg |
3,000 mg |
1,500 mg |
600 mg |
|
3,600 mg |
1,800 mg | ||
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, renal impairment had no clinically important effect on ravulizumab pharmacokinetics.
There are no dosage adjustments provided in the manufacturer's labeling; however, hepatic impairment had no clinically important effect on ravulizumab pharmacokinetics.
(For additional information see "Ravulizumab: Drug information")
Dosage guidance:
Safety: Vaccinate patients against meningococcal infection (serogroups A, C, W, Y and B) according to current guidelines at least 2 weeks prior to treatment initiation; revaccinate according to current guidelines. If urgent ravulizumab initiation is necessary in a patient not up to date with meningococcal vaccines according to current guidelines, provide antibacterial prophylaxis and administer vaccines as soon as possible. Following the first maintenance dose, the ravulizumab dosing schedule is allowed to occasionally vary within 7 days of the scheduled infusion day, although the subsequent dose should be administered according to the original schedule.
Clinical considerations: To reduce the risk for meningococcal disease, consider antimicrobial prophylaxis with oral antibiotics (penicillin, or macrolides if penicillin-allergic) for the duration of ravulizumab therapy (Ref).
Atypical hemolytic uremic syndrome:
Note: A minimum treatment duration of 6 months is recommended. Dose is based on weight at time of treatment.
IV:
Weight 20 kg to <30 kg:
Loading dose: IV: 900 mg as a single dose.
Maintenance dose: IV: 2,100 mg once every 8 weeks starting 2 weeks after the loading dose.
Weight 30 kg to <40 kg:
Loading dose: IV: 1,200 mg as a single dose.
Maintenance dose: IV: 2,700 mg once every 8 weeks starting 2 weeks after the loading dose.
Weight 40 kg to <60 kg:
Loading dose: IV: 2,400 mg as a single dose.
Maintenance dose: IV: 3,000 mg once every 8 weeks starting 2 weeks after the loading dose.
Weight 60 kg to <100 kg:
Loading dose: IV: 2,700 mg as a single dose.
Maintenance dose: IV: 3,300 mg once every 8 weeks starting 2 weeks after the loading dose.
Weight ≥100 kg:
Loading dose: IV: 3,000 mg as a single dose.
Maintenance dose: IV: 3,600 mg once every 8 weeks starting 2 weeks after the loading dose.
Myasthenia gravis, generalized (alternative agent):
Note: Dose is based on weight at time of treatment. For use as chronic immunosuppressive therapy in patients with anti-acetylcholine receptor antibody-positive (AChR+) myasthenia gravis as monotherapy (eg, in patients who cannot tolerate glucocorticoids), as bridge therapy with slower acting immunosuppressive agents, or in combination with glucocorticoids in patients with glucocorticoid-resistant or glucocorticoid-dependent disease (Ref).
Weight 40 kg to <60 kg:
Loading dose: IV: 2,400 mg as a single dose.
Maintenance dose: IV: 3,000 mg once every 8 weeks starting 2 weeks after the loading dose.
Weight 60 kg to <100 kg:
Loading dose: IV: 2,700 mg as a single dose.
Maintenance dose: IV: 3,300 mg once every 8 weeks starting 2 weeks after the loading dose.
Weight ≥100 kg:
Loading dose: IV: 3,000 mg as a single dose.
Maintenance dose: IV: 3,600 mg once every 8 weeks starting 2 weeks after the loading dose.
Neuromyelitis optica spectrum disorder:
Note: Dose is based on weight at time of treatment. Use in patients with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder.
Weight 40 kg to <60 kg:
Loading dose: IV: 2,400 mg as a single dose.
Maintenance dose: IV: 3,000 mg once every 8 weeks starting 2 weeks after the loading dose.
Weight 60 kg to <100 kg:
Loading dose: IV: 2,700 mg as a single dose.
Maintenance dose: IV: 3,300 mg once every 8 weeks starting 2 weeks after the loading dose.
Weight ≥100 kg:
Loading dose: IV: 3,000 mg as a single dose.
Maintenance dose: IV: 3,600 mg once every 8 weeks starting 2 weeks after the loading dose.
Paroxysmal nocturnal hemoglobinuria: Dose is based on weight at time of treatment:
IV:
Weight 20 kg to <30 kg:
Loading dose: IV: 900 mg as a single dose.
Maintenance dose: IV: 2,100 mg once every 8 weeks starting 2 weeks after the loading dose.
Weight 30 kg to <40 kg:
Loading dose: IV: 1,200 mg as a single dose.
Maintenance dose: IV: 2,700 mg once every 8 weeks starting 2 weeks after the loading dose.
Weight 40 kg to <60 kg:
Loading dose: IV: 2,400 mg as a single dose.
Maintenance dose: IV: 3,000 mg once every 8 weeks starting 2 weeks after the loading dose.
Weight 60 kg to <100 kg:
Loading dose: IV: 2,700 mg as a single dose.
Maintenance dose: IV: 3,300 mg once every 8 weeks starting 2 weeks after the loading dose.
Weight ≥100 kg:
Loading dose: IV: 3,000 mg as a single dose.
Maintenance dose: IV: 3,600 mg once every 8 weeks starting 2 weeks after the loading dose.
Conversion from eculizumab to IV ravulizumab: When converting from eculizumab to IV ravulizumab, administer the ravulizumab loading dose at the time of the next scheduled eculizumab dose and then administer ravulizumab maintenance doses once every 4 or 8 weeks (depending on body weight) beginning 2 weeks after the ravulizumab loading dose.
Supplemental dose following plasma exchange, plasmapheresis, or IV immune globulin (IVIG):
|
Weight (kg)b |
Most recent ravulizumab dose (mg) |
Supplemental ravulizumab dose (mg) following each PE or PP intervention |
Supplemental ravulizumab dose (mg) following completion of an IVIG cycle |
|---|---|---|---|
|
a PE = plasma exchange; PP = plasmapheresis; IVIG = IV immune globulin. | |||
|
b Weight at time of treatment. | |||
|
40 to <60 kg |
2,400 mg |
1,200 mg |
600 mg |
|
3,000 mg |
1,500 mg | ||
|
60 to <100 kg |
2,700 mg |
1,500 mg |
600 mg |
|
3,300 mg |
1,800 mg | ||
|
≥100 kg |
3,000 mg |
1,500 mg |
600 mg |
|
3,600 mg |
1,800 mg | ||
|
Timing of ravulizumab supplemental dose |
Within 4 hours following each PE or PP intervention |
Within 4 hours following completion of an IVIG cycle | |
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, renal impairment had no clinically important effect on ravulizumab pharmacokinetics.
There are no dosage adjustments provided in the manufacturer's labeling; however, hepatic impairment had no clinically important effect on ravulizumab pharmacokinetics.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults with paroxysmal nocturnal hemoglobinuria (PNH) unless otherwise indicated for generalized myasthenia gravis (gMG).
>10%:
Gastrointestinal: Diarrhea (gMG, PNH: 9% to 15%)
Nervous system: Headache (32%)
Respiratory: Upper respiratory tract infection (gMG, PNH: 14% to 39%)
1% to 10%:
Gastrointestinal: Abdominal pain (gMG, PNH: 6%), nausea (9%)
Genitourinary: Urinary tract infection (gMG: 6%)
Hypersensitivity: Infusion-related reaction (1%; including hypersensitivity reaction)
Nervous system: Dizziness (gMG, PNH: 5% to 9%)
Neuromuscular & skeletal: Arthralgia (5%), back pain (gMG: 8%), limb pain (6%)
Miscellaneous: Fever (7%)
<1%:
Immunologic: Antibody development
Nervous system: Hyperthermia
Frequency not defined (any indication): Infection: Meningococcal infection (including meningitis, septicemia)
Postmarketing (any indication):
Hypersensitivity: Anaphylaxis
Infection: Serious infection (including disseminated gonococcal infection)
Initiation in patients with unresolved serious N. meningitidis infection.
Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to ravulizumab or any component of the formulation.
Concerns related to adverse effects:
• Infection: Serious infections with Neisseria species (other than N. meningitidis), including disseminated gonococcal infections, have been reported. Ravulizumab blocks terminal complement activation and therefore may increase the risk for susceptibility to bacterial infections, especially encapsulated bacteria, such as infections caused by N. meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and, to a lesser extent, Neisseria gonorrhoeae. Pediatric patients receiving ravulizumab may be at increased risk for serious S. pneumoniae and H. influenzae type b (Hib) infections; vaccinate for S. pneumoniae and Hib according to the Advisory Committee on Immunization Practices (ACIP) recommendations. Patients may be at increased risk for infection despite developing antibodies after vaccination.
• Infusion reactions: Administration of ravulizumab may result in infusion reactions, including anaphylaxis and hypersensitivity. In clinical trials, a small number of patients experienced infusion reactions (lower back pain, abdominal pain, muscle spasms, BP changes, rigors, limb discomfort, allergic reaction, bad taste, and drowsiness) during administration. Infusion reactions did not require ravulizumab discontinuation.
• Meningococcal infection: The use of ravulizumab increases susceptibility to serious life-threatening or fatal meningococcal infections (septicemia and/or meningitis) in some patients despite vaccination. ACIP vaccination recommendations differ from the administration schedule in the vaccine prescribing information. Meningococcal disease due to any serogroup, including nongroupable strains, may occur. If urgent ravulizumab therapy is indicated in an unvaccinated patient, administer meningococcal vaccine(s) as soon as possible and provide at least 2 weeks of antibacterial prophylaxis. Educate patients on signs/symptoms of meningitis and steps necessary to seek immediate medical care. Consider interruption of ravulizumab therapy in patients who are undergoing treatment for serious meningococcal infection.
Concurrent drug therapy issues:
• Anticoagulation: Treatment with ravulizumab should not alter anticoagulation management; the effect of anticoagulant therapy withdrawal is unknown.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Other warnings/precautions:
• Discontinuation in atypical hemolytic uremic syndrome: If thrombotic microangiopathy complications occur after discontinuation, consider restarting ravulizumab treatment or appropriate organ-specific supportive measures.
• Discontinuation in paroxysmal nocturnal hemoglobinuria: If hemolysis signs/symptoms (including elevated lactate dehydrogenase) occur after discontinuation, consider restarting ravulizumab treatment.
• Plasmapheresis/plasma exchange: Plasmapheresis and plasma exchange may reduce ravulizumab levels; supplemental ravulizumab doses are recommended.
• REMS program: Counsel patients about the risk of meningococcal infection/sepsis; provide REMS educational materials to patients, and ensure patients are vaccinated with meningococcal vaccines. Additional information is available at https://www.UltSolREMS.com or 1-888-765-4747.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous [preservative free]:
Ultomiris: Ravulizumab-cwvz 300 mg/3 mL (3 mL); Ravulizumab-cwvz 300 mg/30 mL (30 mL [DSC]); Ravulizumab-cwvz 1100 mg/11 mL (11 mL) [contains polysorbate 80]
No
Solution (Ultomiris Intravenous)
300 mg/3 mL (per mL): $2,612.83
1100MG/11ML (per mL): $2,612.83
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Ultomiris: 300 mg/30 mL (30 mL); Ravulizumab-cwvz 300 mg/3 mL (3 mL); Ravulizumab-cwvz 1100 mg/11 mL (11 mL) [contains polysorbate 80]
Parenteral:
IV infusion: Infuse through a 0.2 or 0.22 micron filter. If previous refrigeration, allow solution to adjust to room temperature at ambient air temperature (do not use a heat source) prior to infusion. Infusion rate for loading and maintenance dose is highly variable as it is based on concentration of ravulizumab used to prepare the infusion and patient weight; use extra caution. Flush entire line with NS after infusion of dose.
Note: Multiple final concentrations for infusion exist (5 mg/mL or 50 mg/mL) and each concentration has different infusion rates; use extra caution in verifying concentration of infusion solution.
Loading and maintenance doses:
|
Weightb |
Dose type |
Total dose/Total volume (5 mg/mL) |
Maximum infusion rate (mL/hour) |
Minimum infusion time (hours) |
|---|---|---|---|---|
|
a Solutions prepared from the 10 mg/mL (30 mL) vial and further diluted in NS. | ||||
|
b Weight at time of treatment. | ||||
|
5 to <10 kg |
Loading |
600 mg/120 mL |
32 mL/hour |
3.8 hours |
|
Maintenance |
300 mg/60 mL |
32 mL/hour |
1.9 hours | |
|
10 to <20 kg |
Loading |
600 mg/120 mL |
64 mL/hour |
1.9 hours |
|
Maintenance |
600 mg/120 mL |
64 mL/hour |
1.9 hours | |
|
20 to <30 kg |
Loading |
900 mg/180 mL |
120 mL/hour |
1.5 hours |
|
Maintenance |
2,100 mg/420 mL |
128 mL/hour |
3.3 hours | |
|
30 to <40 kg |
Loading |
1,200 mg/240 mL |
185 mL/hour |
1.3 hours |
|
Maintenance |
2,700 mg/540 mL |
193 mL/hour |
2.8 hours | |
|
40 to <60 kg |
Loading |
2,400 mg/480 mL |
253 mL/hour |
1.9 hours |
|
Maintenance |
3,000 mg/600 mL |
261 mL/hour |
2.3 hours | |
|
60 to <100 kg |
Loading |
2,700 mg/540 mL |
318 mL/hour |
1.7 hours |
|
Maintenance |
3,300 mg/660 mL |
330 mL/hour |
2 hours | |
|
≥100 kg |
Loading |
3,000 mg/600 mL |
334 mL/hour |
1.8 hours |
|
Maintenance |
3,600 mg/720 mL |
328 mL/hour |
2.2 hours | |
|
Weightb |
Dose type |
Total dose/Total volume (50 mg/mL) |
Maximum infusion rate (mL/hour) |
Minimum infusion time (hours) |
|---|---|---|---|---|
|
a Solutions prepared from the 100 mg/mL (3 mL or 11 mL) vial and further diluted in NS. | ||||
|
b Weight at time of treatment. | ||||
|
5 to <10 kg |
Loading |
600 mg/12 mL |
9 mL/hour |
1.4 hours |
|
Maintenance |
300 mg/6 mL |
8 mL/hour |
0.8 hours | |
|
10 to <20 kg |
Loading |
600 mg/12 mL |
15 mL/hour |
0.8 hours |
|
Maintenance |
600 mg/12 mL |
15 mL/hour |
0.8 hours | |
|
20 to <30 kg |
Loading |
900 mg/18 mL |
30 mL/hour |
0.6 hours |
|
Maintenance |
2,100 mg/42 mL |
33 mL/hour |
1.3 hours | |
|
30 to <40 kg |
Loading |
1,200 mg/24 mL |
48 mL/hour |
0.5 hours |
|
Maintenance |
2,700 mg/54 mL |
50 mL/hour |
1.1 hours | |
|
40 to <60 kg |
Loading |
2,400 mg/48 mL |
60 mL/hour |
0.8 hours |
|
Maintenance |
3,000 mg/60 mL |
67 mL/hour |
0.9 hours | |
|
60 to <100 kg |
Loading |
2,700 mg/54 mL |
90 mL/hour |
0.6 hours |
|
Maintenance |
3,300 mg/66 mL |
95 mL/hour |
0.7 hours | |
|
≥100 kg |
Loading |
3,000 mg/60 mL |
150 mL/hour |
0.4 hours |
|
Maintenance |
3,600 mg/72 mL |
144 mL/hour |
0.5 hours | |
Rate adjustment for infusion-related reactions or anaphylaxis: Slow or stop infusion at physician discretion; for cardiovascular instability or respiratory compromise, pause infusion and initiate appropriate supportive care measures.
Supplemental dose: Supplemental doses are only indicated following plasma exchange, plasmapheresis, or IV immune globulin (IVIG) therapy, and should be administered within 4 hours following PE, PP, or IVIG completion.
|
Weight (kg)b |
Supplemental dose (mg) |
Total volume to be administered (mL) |
Maximum infusion rate (mL/hour) |
Minimum infusion time (hours) |
|---|---|---|---|---|
|
a Solutions prepared from the 10 mg/mL (30 mL) vial and further diluted in NS. | ||||
|
b Weight at time of treatment. | ||||
|
40 to <60 kg |
600 mg |
120 mL |
240 mL/hour |
0.5 hours |
|
1,200 mg |
240 mL |
240 mL/hour |
1 hour | |
|
1,500 mg |
300 mL |
250 mL/hour |
1.2 hours | |
|
60 to <100 kg |
600 mg |
120 mL |
300 mL/hour |
0.4 hours |
|
1,500 mg |
300 mL |
300 mL/hour |
1 hour | |
|
1,800 mg |
360 mL |
327 mL/hour |
1.1 hours | |
|
≥100 kg |
600 mg |
120 mL |
300 mL/hour |
0.4 hours |
|
1,500 mg |
300 mL |
300 mL/hour |
1 hour | |
|
1,800 mg |
360 mL |
327 mL/hour |
1.1 hours | |
|
Weight (kg)b |
Supplemental dose (mg) |
Total volume to be administered (mL) |
Maximum infusion rate (mL/hour) |
Minimum infusion time (hours)
|
|---|---|---|---|---|
|
a Solutions prepared from the 100 mg/mL (3 mL or 11 mL) vial and further diluted in NS. | ||||
|
b Weight at time of treatment. | ||||
|
40 to <60 kg |
600 mg |
12 mL |
48 mL/hour |
0.25 hours |
|
1,200 mg |
24 mL |
57 mL/hour |
0.42 hours | |
|
1,500 mg |
30 mL |
60 mL/hour |
0.5 hours | |
|
60 to <100 kg |
600 mg |
12 mL |
60 mL/hour |
0.2 hours |
|
1,500 mg |
30 mL |
83 mL/hour |
0.36 hours | |
|
1,800 mg |
36 mL |
86 mL/hour |
0.42 hours | |
|
≥100 kg |
600 mg |
12 mL |
71 mL/hour |
0.17 hours |
|
1,500 mg |
30 mL |
120 mL/hour |
0.25 hours | |
|
1,800 mg |
36 mL |
129 mL/hour |
0.28 hours | |
Rate adjustment for infusion-related reactions or anaphylaxis: Slow or stop infusion at physician discretion; for cardiovascular instability or respiratory compromise, pause infusion and initiate appropriate supportive care measures.
IV: Infuse through a 0.2- or 0.22-micron filter. Allow solution to adjust to room temperature (do not use a heat source) prior to infusion. Flush line with NS after administration. Infusion rate for loading, maintenance, and supplemental doses is based on patient weight.
3 mL or 11 mL vial (100 mg/mL):
Loading dose:
|
Weight (kg)a |
Loading dose (mg) |
Total volume to be administered (mL) |
Minimum infusion time (hours) |
Maximum infusion rate (mL/hour) |
|---|---|---|---|---|
|
a Weight at time of treatment. | ||||
|
20 to <30 kg |
900 mg |
18 mL |
0.6 hours |
30 mL/hour |
|
30 to <40 kg |
1,200 mg |
24 mL |
0.5 hours |
48 mL/hour |
|
40 to <60 kg |
2,400 mg |
48 mL |
0.8 hours |
60 mL/hour |
|
60 to <100 kg |
2,700 mg |
54 mL |
0.6 hours |
90 mL/hour |
|
≥100 kg |
3,000 mg |
60 mL |
0.4 hours |
150 mL/hour |
Maintenance dose:
|
Weight (kg)a |
Maintenance dose (mg) |
Total volume to be administered (mL) |
Minimum infusion time (hours) |
Maximum infusion rate (mL/hour) |
|---|---|---|---|---|
|
a Weight at time of treatment. | ||||
|
20 to <30 kg |
2,100 mg |
42 mL |
1.3 hours |
33 mL/hour |
|
30 to <40 kg |
2,700 mg |
54 mL |
1.1 hours |
50 mL/hour |
|
40 to <60 kg |
3,000 mg |
60 mL |
0.9 hours |
67 mL/hour |
|
60 to <100 kg |
3,300 mg |
66 mL |
0.7 hours |
95 mL/hour |
|
≥100 kg |
3,600 mg |
72 mL |
0.5 hours |
144 mL/hour |
Supplemental dose:
|
Weight (kg)b |
Supplemental dose (mg) |
Total volume to be administered (mL) |
Minimum infusion time (hours) |
Maximum infusion rate (mL/hour) |
|---|---|---|---|---|
|
a Supplemental doses are only indicated following plasma exchange, plasmapheresis, or IV immune globulin (IVIG) therapy. | ||||
|
b Weight at time of treatment. | ||||
|
40 to <60 kg |
600 mg |
12 mL |
0.25 hours |
48 mL/hour |
|
1,200 mg |
24 mL |
0.42 hours |
57 mL/hour | |
|
1,500 mg |
30 mL |
0.5 hours |
60 mL/hour | |
|
60 to <100 kg |
600 mg |
12 mL |
0.2 hours |
60 mL/hour |
|
1,500 mg |
30 mL |
0.36 hours |
83 mL/hour | |
|
1,800 mg |
36 mL |
0.42 hours |
86 mL/hour | |
|
≥100 kg |
600 mg |
12 mL |
0.17 hours |
71 mL/hour |
|
1,500 mg |
30 mL |
0.25 hours |
120 mL/hour | |
|
1,800 mg |
36 mL |
0.28 hours |
129 mL/hour | |
30 mL vial (10 mg/mL):
Loading dose:
|
Weight (kg)a |
Loading dose (mg) |
Total volume to be administered (mL) |
Minimum infusion time (hours) |
Maximum infusion rate (mL/hour) |
|---|---|---|---|---|
|
a Weight at time of treatment. | ||||
|
20 to <30 kg |
900 mg |
180 mL |
1.5 hours |
120 mL/hour |
|
30 to <40 kg |
1,200 mg |
240 mL |
1.3 hours |
185 mL/hour |
|
40 to <60 kg |
2,400 mg |
480 mL |
1.9 hours |
253 mL/hour |
|
60 to <100 kg |
2,700 mg |
540 mL |
1.7 hours |
318 mL/hour |
|
≥100 kg |
3,000 mg |
600 mL |
1.8 hours |
334 mL/hour |
Maintenance dose:
|
Weight (kg)a |
Maintenance dose (mg) |
Total volume to be administered (mL) |
Minimum infusion time (hours) |
Maximum infusion rate (mL/hour) |
|---|---|---|---|---|
|
a Weight at time of treatment. | ||||
|
20 to <30 kg |
2,100 mg |
420 mL |
3.3 hours |
128 mL/hour |
|
30 to <40 kg |
2,700 mg |
540 mL |
2.8 hours |
193 mL/hour |
|
40 to <60 kg |
3,000 mg |
600 mL |
2.3 hours |
261 mL/hour |
|
60 to <100 kg |
3,300 mg |
660 mL |
2 hours |
330 mL/hour |
|
≥100 kg |
3,600 mg |
720 mL |
2.2 hours |
328 mL/hour |
Supplemental dose:
|
Weight (kg)b |
Supplemental dose (mg) |
Total volume to be administered (mL) |
Minimum infusion time (hours) |
Maximum infusion rate (mL/hour) |
|---|---|---|---|---|
|
a Supplemental doses are only indicated following plasma exchange, plasmapheresis, or IV immune globulin (IVIG) therapy. | ||||
|
b Weight at time of treatment. | ||||
|
40 to <60 kg |
600 mg |
120 mL |
0.5 hours |
240 mL/hour |
|
1,200 mg |
240 mL |
1 hour |
240 mL/hour | |
|
1,500 mg |
300 mL |
1.2 hours |
250 mL/hour | |
|
60 to <100 kg |
600 mg |
120 mL |
0.4 hours |
300 mL/hour |
|
1,500 mg |
300 mL |
1 hour |
300 mL/hour | |
|
1,800 mg |
360 mL |
1.1 hours |
327 mL/hour | |
|
≥100 kg |
600 mg |
120 mL |
0.4 hours |
300 mL/hour |
|
1,500 mg |
300 mL |
1 hour |
300 mL/hour | |
|
1,800 mg |
360 mL |
1.1 hours |
327 mL/hour | |
Store intact vials at 2°C to 8°C (36°F to 46°F); do not freeze. Do not shake. Store in original carton to protect from light. Solutions diluted for infusion should be administered immediately following preparation; if the diluted solution is not used immediately, may store refrigerated at 2°C to 8°C (36°F to 46°F) for a maximum of 24 hours (accounting for infusion time); do not freeze. Once removed from refrigeration, allow solution to adjust to room temperature (do not use a heat source) prior to infusion and administer within 4 hours (3 mL or 11 mL vials) or 6 hours (30 mL vial). Do not shake diluted solution. Protect diluted solution from light.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Ultomiris: https://ultomiris.com/pdf/ULTOMIRIS-med-guide.pdf
Treatment of atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (FDA approved in ages ≥1 month and adults); treatment of paroxysmal nocturnal hemoglobinuria (PNH) (FDA approved in ages ≥1 month and adults); treatment of generalized myasthenia gravis in patients who are anti-acetylcholine receptor (AChR) antibody positive (FDA approved in adults); treatment of neuromyelitis optica spectrum disorder in patients who are anti-aquaporin (AQP4) antibody positive (FDA approved in adults).
Limitations of use: Not indicated for the treatment of Shiga toxin Escherichia coli-related hemolytic uremic syndrome.
Ravulizumab may be confused with eculizumab, ramucirumab, ranibizumab, raxibacumab, reslizumab.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Antithymocyte Globulin (Equine): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Therapeutic Immunosuppressant Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
Crovalimab: Ravulizumab may increase adverse/toxic effects of Crovalimab. Specifically, the risk of type III hypersensitivity reactions is increased. Ravulizumab may decrease serum concentration of Crovalimab. Risk C: Monitor
Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Efgartigimod Alfa: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Immune Globulin: May decrease serum concentration of Ravulizumab. Management: Administer a supplemental dose of ravulizumab (600 mg) within 4 hours of completion of the immune globulin cycle. Risk D: Consider Therapy Modification
Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification
Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Nipocalimab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Pimecrolimus. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Rozanolixizumab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid
Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Ravulizumab is a humanized monoclonal antibody (IgG2). Placental transfer of human IgG is dependent upon the IgG subclass, maternal serum concentrations, birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).
Data related to maternal use of ravulizumab during pregnancy (Tomazos 2020) or immediately postpartum (Gäckler 2021) are limited.
Adverse pregnancy outcomes are associated with untreated paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). Adverse maternal outcomes associated with PNH may include worsening cytopenias, thrombotic events, infections, bleeding, fetal loss, and increased maternal mortality; increased fetal death and premature delivery is also reported. Patients with aHUS may have an increased risk of preeclampsia and preterm delivery; intrauterine growth restriction/low birth weight and fetal death may also occur.
Health care providers are encouraged to enroll patients exposed to ravulizumab during pregnancy by contacting the website (www.UltomirisPregnancyStudy.com) or by calling 833-793-0563.
Signs/symptoms of infusion reactions (during infusion and for 1 hour after administration); signs/symptoms of meningococcal (Neisseria meningitidis) infection; sign/symptoms of worsening infection for patients with active systemic infection.
After discontinuation:
Paroxysmal nocturnal hemoglobinuria:
Monitor closely for ≥16 weeks (after discontinuation) for signs/symptoms of hemolysis including elevated lactate dehydrogenase (LDH).
Atypical hemolytic uremic syndrome:
Monitor closely for ≥12 months (after discontinuation) for signs/symptoms of thrombotic microangiopathy (TMA) complications. TMA complications identified by clinical symptoms (changes in mental status, seizures, angina, dyspnea, thrombosis, or increasing blood pressure) PLUS ≥2 of the following laboratory values observed concurrently (and confirmed by a second measurement 28 days apart with no interruption):
• Thrombocytopenia (platelet count decreased ≥25% compared to baseline or peak count during ravulizumab treatment).
• SCr increased ≥25% compared to baseline or to nadir during ravulizumab treatment.
• Lactic dehydrogenase increased ≥25% compared to baseline or to nadir during ravulizumab treatment.
Ravulizumab is a humanized monoclonal antibody which is a terminal complement inhibitor that 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 terminal complement complex [C5b-9]) and preventing generation of the terminal complement complex C5b9. Ravulizumab inhibits terminal complement-mediated intravascular hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) and complement-mediated thrombotic microangiopathy in atypical hemolytic uremic syndrome. The C5 inhibition of complement-mediated hemolysis achieved by ravulizumab in patients with PNH is immediate, thorough, and sustained (Lee 2019). The mechanism in generalized myasthenia gravis has not been fully elucidated but is presumed to involve reduction of terminal complement complex C5b-9 at the neuromuscular junction. The mechanism in neuromyelitis optica spectrum disorder has not been fully elucidated but is presumed to involve inhibition of aquaporin-4 antibody induced terminal complement complex C5b-9 deposition.
Onset of action: Lactate dehydrogenase (LDH) reduction: Rapid and sustained, beginning as early as day 8 (Roth 2018). LDH normalization: By week 4 (in complement-inhibitor naive patients with paroxysmal nocturnal hemoglobinuria [PNH]).
Distribution: Vd: IV: 5.22 L (atypical hemolytic uremic syndrome [aHUS] patients); 5.3 L (PNH patients); 5.74 L (generalized myasthenia gravis patients [gMG]); 4.77 L (neuromyelitis optica spectrum disorder [NMOSD]).
Half-life elimination: Terminal: IV: 51.8 days (aHUS patients); 49.6 days (PNH patients); 56.6 days (gMG patients); 64.3 days (NMOSD patients).
Excretion: Clearance: IV: 0.05 to 0.08 L/day.
