Ravulizumab
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From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: SERIOUS MENINGOCOCCAL INFECTIONS ULTOMIRIS, a complement inhibitor, increases the risk of serious infections caused by Neisseria meningitidis [see Warnings and Precautions (5.1) ] . 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 ULTOMIRIS, unless the risks of delaying therapy with ULTOMIRIS 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. See Warnings and Precautions (5.1) for additional guidance on the management of the risk of serious infections caused by meningococcal bacteria. Patients receiving ULTOMIRIS are at increased risk for invasive disease caused by Neisseria 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, ULTOMIRIS is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called ULTOMIRIS and SOLIRIS REMS [see Warnings and Precautions (5.2) ]. WARNING: SERIOUS MENINGOCOCCAL INFECTIONS See full prescribing information for complete boxed warning. ULTOMIRIS increases the risk of serious and life-threatening infections caused by Neisseria meningitidis . Complete or update meningococcal vaccination at least 2 weeks prior to the first dose of ULTOMIRIS, unless the risks of delaying ULTOMIRIS outweigh the risks of developing a serious infection.
Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients receiving a complement inhibitor. ( 5.1 ) Patients receiving ULTOMIRIS 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 meningococcal infections and evaluate immediately if infection is suspected. ( 5.1 ) ULTOMIRIS is available only through a restricted program called ULTOMIRIS and SOLIRIS REMS. ( 5.2 )
Complement Inhibitor
Dosing in kidney impairment
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Preparation and administration
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Important Dosage Information ULTOMIRIS is intended to be administered only as an intravenous infusion in adult or pediatric patients one month of age and older.
Recommended Dosage for Intravenous Administration in Adult and Pediatric Patients with PNH or aHUS, and in Adult Patients with gMG or NMOSD The recommended intravenous (IV) ULTOMIRIS loading and maintenance dosing in adult and pediatric patients, one month of age or older weighing 5 kg or greater, with PNH or aHUS, or in adult patients with gMG or NMOSD weighing 40 kg or greater, is based on the patient's body weight, as shown in Table 1, with maintenance doses administered every 4 or 8 weeks, starting 2 weeks after loading dose.
The IV dosing schedule is allowed to occasionally vary within 7 days of the scheduled infusion day (except for the first maintenance dose of ULTOMIRIS); but subsequent doses should be administered according to the original schedule. Following a missed IV ULTOMIRIS dose, the patient should contact their health care provider immediately. [See table below.] Refer to Table 2 for treatment initiation instructions in patients who are complement inhibitor treatment-naïve or switching treatment from eculizumab. [See table below.] Currently treated with eculizumab At time of next scheduled eculizumab dose 2 weeks after ULTOMIRIS loading dose
Preparation and Administration Preparation of ULTOMIRIS Vials for Intravenous Administration Each vial of ULTOMIRIS is intended for single-dose only. ULTOMIRIS vials are for intravenous administration by a healthcare provider and are intended for intravenous administration only. Dilute before use. Use aseptic technique to prepare ULTOMIRIS as follows: 1.
The number of vials to be diluted is determined based on the individual patient's weight and the prescribed dose [see Dosage and Administration ] . 2. Prior to dilution, visually inspect the solution in the vials; the solution should be free of any particulate matter or precipitation. Do not use if there is evidence of particulate matter or precipitation. 3.
Withdraw the calculated volume of ULTOMIRIS from the appropriate number of vials and dilute in an infusion bag using 0.9% Sodium Chloride Injection, USP to a final concentration of 50 mg/mL. The product should be mixed gently. Do not shake. Protect from light. Do not freeze. Refer to Table 4 (loading doses) , Table 5 (maintenance doses) , and Table 6 (supplemental doses) for IV preparation and minimum infusion duration. 4.
Administer the prepared solution immediately following preparation. 5. If the diluted ULTOMIRIS infusion solution is not used immediately, storage under refrigeration at 2°C - 8°C (36°F - 46°F) must not exceed 24 hours taking into account the expected infusion time. Once removed from refrigeration, administer the diluted ULTOMIRIS infusion solution within 4 hours.
Intravenous Administration of ULTOMIRIS (Healthcare Providers) Only administer as an intravenous infusion through a 0.2 or 0.22 micron filter. Dilute ULTOMIRIS to a final concentration of 50 mg/mL. Prior to administration, allow the admixture to adjust to room temperature (18°C - 25°C, 64°F - 77°F). Do not heat the admixture in a microwave or with any heat source other than ambient air temperature.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. After administration of ULTOMIRIS, flush the entire line with 0.9% Sodium Chloride Injection, USP. [See table below.] [See table below.] [See table below.] If an adverse reaction occurs during the administration of ULTOMIRIS, the infusion may be slowed or stopped at the discretion of the physician.
Monitor the patient for at least 1 hour following completion of the infusion for signs or symptoms of an infusion-related reaction.
| Indications | Body Weight Range (kg) | Loading Dose (mg)See Table 2 for ULTOMIRIS treatment initiation instruction and timing of loading dose and maintenance dose | Maintenance Dose (mg) and Dosing Interval | |
|---|---|---|---|---|
| PNH or aHUS | 5 to less than 10 | 600 | 300 | Every 4 weeks |
| 10 to less than 20 | 600 | 600 | ||
| 20 to less than 30 | 900 | 2,100 | Every 8 weeks | |
| 30 to less than 40 | 1,200 | 2,700 | ||
| PNH, aHUS, gMG, or NMOSD | 40 to less than 60 | 2,400 | 3,000 | Every 8 weeks |
| 60 to less than 100 | 2,700 | 3,300 | ||
| 100 or greater | 3,000 | 3,600 | ||
| Body Weight Range (kg) | Most Recent ULTOMIRIS Dose (mg) | Supplemental Dose (mg) following each PE or PP Intervention | Supplemental Dose (mg) following Completion of an IVIg Cycle |
|---|---|---|---|
| Abbreviations: IVIg = intravenous immunoglobulin; PE = plasma exchange; PP = plasmapheresis | |||
| 40 to less than 60 | 2,400 | 1,200 | 600 |
| 3,000 | 1,500 | ||
| 60 to less than 100 | 2,700 | 1,500 | 600 |
| 3,300 | 1,800 | ||
| 100 or greater | 3,000 | 1,500 | 600 |
| 3,600 | 1,800 | ||
| Timing of ULTOMIRIS Supplemental Dose | Within 4 hours following each PE or PP intervention | Within 4 hours following completion of an IVIg cycle | |
| Body Weight Range (kg)Body weight at time of treatment. | Loading Dose (mg) | ULTOMIRIS Volume (mL) | Volume of NaCl DiluentDilute ULTOMIRIS only using 0.9% Sodium Chloride Injection, USP. (mL) | Total Volume (mL) | Minimum Infusion Time (hr) | Maximum Infusion Rate (mL/hr) |
|---|---|---|---|---|---|---|
| 5 to less than 10For PNH and aHUS indications only. | 600 | 6 | 6 | 12 | 1.4 | 9 |
| 10 to less than 20 | 600 | 6 | 6 | 12 | 0.8 | 15 |
| 20 to less than 30 | 900 | 9 | 9 | 18 | 0.6 | 30 |
| 30 to less than 40 | 1,200 | 12 | 12 | 24 | 0.5 | 48 |
| 40 to less than 60 | 2,400 | 24 | 24 | 48 | 0.8 | 60 |
| 60 to less than 100 | 2,700 | 27 | 27 | 54 | 0.6 | 90 |
| 100 or greater | 3,000 | 30 | 30 | 60 | 0.4 | 150 |
Drug interactions
Check ravulizumab against a medication listLabel text (3 paragraphs)
Plasma Exchange, Plasmapheresis, or Intravenous Immunoglobulins: concomitant use requires supplemental dose of ULTOMIRIS. ( 7.1 ) Neonatal Fc Receptor Blockers (FcRn): Closely monitor for reduced effectiveness of ULTOMIRIS. ( 7.2 )
7.1 Plasma Exchange, Plasmapheresis, and Intravenous Immunoglobulins Concomitant use of ULTOMIRIS with plasma exchange (PE), plasmapheresis (PP), or intravenous immunoglobulin (IVIg) treatment can reduce serum ravulizumab concentrations and requires a supplemental dose of ULTOMIRIS [see Dosage and Administration (2.5) ].
7.2 Neonatal Fc Receptor Blockers Concomitant use of ULTOMIRIS with neonatal Fc receptor (FcRn) blockers (e.g., efgartigimod) may lower systemic exposures and reduce effectiveness of ULTOMIRIS. Closely monitor for reduced effectiveness of ULTOMIRIS.
Contraindications
4 CONTRAINDICATIONS ULTOMIRIS is contraindicated for initiation in patients with unresolved serious Neisseria meningitidis infection [see Warnings and Precautions (5.1) ] . ULTOMIRIS is contraindicated for initiation in patients with unresolved serious Neisseria meningitidis infection. ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ULTOMIRIS during pregnancy. Healthcare providers and patients may call 1-833-793-0563 or go to www.UltomirisPregnancyStudy.com to enroll in or to obtain information about the registry. Risk Summary There are no available data on ULTOMIRIS 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 and aHUS in pregnancy (see Clinical Considerations ) .
Animal studies using a mouse analogue of the ravulizumab-cwvz molecule (murine anti-mouse complement component 5 [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 (see Data ). The estimated background risk of major birth defects and miscarriage for the indicated populations 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 Disease-associated Maternal and/or Fetal/neonatal Risk 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. In pregnancy, aHUS is associated with adverse maternal outcomes, including preeclampsia and preterm delivery, and adverse fetal/neonatal outcomes, including intrauterine growth restriction (IUGR), fetal death and low birth weight.
Data 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 ULTOMIRIS 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, 2 cases of retinal dysplasia and 1 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…
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
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