ULTOMIRIS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ULTOMIRIS (ULTOMIRIS).
ULTOMIRIS (ravulizumab-cwvz) is a humanized monoclonal antibody that binds to complement protein C5, inhibiting its cleavage to C5a and C5b, thereby preventing terminal complement-mediated hemolysis and thrombotic microangiopathy.
| Metabolism | Degraded via general protein degradation pathways (catabolism) into small peptides and amino acids; no specific hepatic metabolism via CYP450 enzymes. |
| Excretion | Primarily eliminated via the reticuloendothelial system through target-mediated clearance; minimal renal excretion (<1% unchanged in urine). |
| Half-life | Terminal half-life approximately 32 days (range 27-40 days) at steady state, supporting every-8-week dosing. |
| Protein binding | Approximately 95% bound to plasma proteins, primarily to albumin and complement C5. |
| Volume of Distribution | Vd approximately 3.5 L (0.05 L/kg), indicating limited extravascular distribution, consistent with a large monoclonal antibody. |
| Bioavailability | Not applicable; administered exclusively as intravenous (IV) infusion. |
| Onset of Action | IV: Reduction in lactate dehydrogenase (LDH) seen within 1 week; maximal complement inhibition achieved within 1-2 hours after infusion. |
| Duration of Action | Duration of pharmacodynamic effect (complement blockade) persists for at least 8 weeks, matching the dosing interval for paroxysmal nocturnal hemoglobinuria (PNH). |
900 mg IV every week for 4 doses, then 1200 mg IV every 2 weeks starting at week 5; for atypical hemolytic uremic syndrome (aHUS) or generalized myasthenia gravis (gMG).
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment; not removed by dialysis. |
| Liver impairment | No formal studies in hepatic impairment; no specific dose adjustment recommendations. |
| Pediatric use | Body weight 5 to <10 kg: 300 mg IV weekly for 2 weeks, then 300 mg every 3 weeks; 10 to <20 kg: 600 mg IV weekly for 2 weeks, then 600 mg every 3 weeks; 20 to <30 kg: 900 mg IV weekly for 2 weeks, then 900 mg every 3 weeks; 30 to <40 kg: 1200 mg IV weekly for 2 weeks, then 1200 mg every 3 weeks; ≥40 kg: same as adult dosing. |
| Geriatric use | No specific dose adjustment for elderly; clinical studies included patients aged 65 and older, no overall differences in safety or efficacy observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ULTOMIRIS (ULTOMIRIS).
| Breastfeeding | There are no data on the presence of ravulizumab in human milk, effects on the breastfed infant, or effects on milk production. Ravulizumab is a large protein molecule; thus, the amount of drug excreted in breast milk is expected to be low. The M/P ratio is not known. Because of the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during treatment and for at least 8 months after the last dose. |
| Teratogenic Risk | ULTOMIRIS (ravulizumab) is a humanized monoclonal antibody that inhibits complement component C5. Based on animal studies, C5 inhibition may increase the risk of adverse fetal outcomes due to the role of complement in fetal development. There are no adequate human studies. In pregnant cynomolgus monkeys, no fetal harm was observed at exposures up to 7 times the human dose. However, because IgG antibodies cross the placenta, with increasing transfer as pregnancy progresses, especially in the third trimester, potential fetal exposure may occur. Therefore, ULTOMIRIS should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. |
■ FDA Black Box Warning
WARNING: SERIOUS MENINGOCOCCAL INFECTIONS. Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors. Vaccinate patients against Neisseria meningitidis at least 2 weeks prior to initiation; if urgent therapy is needed, vaccinate as soon as possible and provide antibacterial prophylaxis.
| Serious Effects |
["Unresolved serious Neisseria meningitidis infection","Patients not vaccinated against Neisseria meningitidis (unless vaccination delayed and antibiotics administered)"]
| Precautions | ["Increased susceptibility to serious infections, especially encapsulated bacteria (e.g., Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae)","Monitor for signs of infection during therapy","Risk of infusion-related reactions","Do not discontinue abruptly in PNH patients due to risk of hemolysis"] |
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| Fetal Monitoring | Monitor pregnant women for signs and symptoms of meningococcal infection due to increased risk with complement inhibition. Perform liver function tests periodically as elevations have been reported. Monitor for hypersensitivity reactions. Fetal monitoring should include standard prenatal care with attention to growth and development via ultrasound, as no specific fetal monitoring requirements are established. |
| Fertility Effects | No dedicated fertility studies have been conducted in humans. In animal studies, no adverse effects on male or female fertility were observed in cynomolgus monkeys at doses up to 5 times the human dose. The effect on human fertility is unknown. |