Ultomiris Special Precautions

Serious Meningococcal Infection: Due to its mechanism of action, the use of ULTOMIRIS increases the patient's susceptibility to meningococcal infection/sepsis (Neisseria meningitidis). Meningococcal disease due to any serogroup may occur. To reduce this risk of infection, all patients must be vaccinated against meningococcal infections at least two weeks prior to, or at the time of, initiating ULTOMIRIS. Patients who initiate ULTOMIRIS treatment less than 2 weeks after receiving a meningococcal vaccine must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Vaccines against serogroups A, C, Y, W135 and B, where available, are recommended in preventing the commonly pathogenic meningococcal serogroups. Patients must be vaccinated or revaccinated according to current national guidelines for vaccination use.
Vaccination may not be sufficient to prevent meningococcal infection. In clinical studies with ULTOMIRIS, 4 patients developed serious meningococcal infections/sepsis while receiving treatment with ULTOMIRIS. All were adult patients with PNH who had been vaccinated. These patients recovered while continuing treatment with ULTOMIRIS. Consideration should be given to official guidance on the appropriate use of antibacterial agents. Cases of serious or fatal meningococcal infections/sepsis have been reported in patients treated with ULTOMIRIS and other terminal complement inhibitors. All patients should be monitored for early signs of meningococcal infection and sepsis, evaluated immediately if infection is suspected, and treated with appropriate antibiotics. Patients should be informed of these signs and symptoms and steps should be taken to seek medical care immediately. Physicians should provide patients with a Patient/Parent Guide and a Patient card/Patient safety card.
Immunization: Vaccination may further activate complement. As a result, patients with complement-mediated diseases may experience increased signs and symptoms of their underlying disease, such as haemolysis (PNH), TMA (aHUS) or MG exacerbation (gMG). Therefore, patients should be closely monitored for disease symptoms after recommended vaccination.
Other Systemic Infections: ULTOMIRIS therapy should be administered with caution to patients with active systemic infections. ULTOMIRIS blocks terminal complement activation; therefore, patients may have increased susceptibility to infections, especially infections caused by Neisseria species and encapsulated bacteria. Serious infections with Neisseria species (other than Neisseria meningitidis), including disseminated gonococcal infections, have been reported in patients treated with ULTOMIRIS.
Patients should be provided with information from the Patient/Parent Guide to increase their awareness of potential serious infections and their signs and symptoms. Physicians should advise patients about gonorrhoea prevention. Patients below the age of 18 years old must be vaccinated against Haemophilus influenzae and pneumococcal infections and need to adhere strictly to the national vaccination recommendations for their age group.
Infusion Reactions: Intravenous (IV) administration of ULTOMIRIS may result in systemic infusion reactions (infusion-related reactions) that cause allergic or hypersensitivity reactions (including anaphylaxis).
In case of a systemic infusion reaction (infusion-related reaction), if signs of cardiovascular instability or respiratory compromise occur, administration of ULTOMIRIS should be interrupted and appropriate supportive measures should be instituted.
Immunogenicity: Treatment with any therapeutic protein may induce an immune response.
In ULTOMIRIS studies in PNH (N = 488), aHUS (N = 89), and gMG (N = 86), treatment-emergent anti-drug antibodies were reported in 2 patients (0.28%), one with PNH and one with aHUS. These anti-drug antibodies were transient in nature with low titer and did not correlate with clinical response or adverse events.
Treatment discontinuation: Treatment Discontinuation in PNH: Paroxysmal Nocturnal Hemoglobinuria (PNH) is a chronic disease, and treatment with ULTOMIRIS is recommended to continue for the patient's lifetime.
If patients with PNH discontinue treatment with ULTOMIRIS, they should be closely monitored 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. Any patient who discontinues ULTOMIRIS should be monitored 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 ULTOMIRIS.
Treatment Discontinuation in aHUS: ULTOMIRIS treatment to resolve aHUS should be a minimum duration of 6 months, beyond which length of treatment needs to be considered for each patient individually. Patients who are at higher risk for TMA recurrence, as determined by the treating healthcare provider (or clinically indicated), may require chronic therapy.
There are no specific data on ravulizumab discontinuation. In a long-term prospective observational study, discontinuation of complement C5 inhibitor treatment (SOLIRIS) resulted in a 13.5-fold higher rate of TMA recurrence and showed a trend toward reduced renal function compared to patients who continued treatment.
If patients must discontinue treatment with ravulizumab, they should be monitored closely for signs and symptoms of TMA on an on-going basis. However, monitoring may be insufficient to predict or prevent severe TMA complications.
TMA complications post-discontinuation can be identified if any of the following is observed: At least two of the following laboratory results observed concurrently: a decrease in platelet count of 25% or more as compared to either baseline or to peak platelet count during ravulizumab treatment; an increase in serum creatinine of 25% or more as compared to baseline or to nadir during ravulizumab treatment; or, an increase in serum LDH of 25% or more as compared to baseline or to nadir during ravulizumab treatment; (results should be confirmed by a second measurement 28 days apart).
Or any one of the following symptoms of TMA: a change in mental status or seizures or other extra renal TMA manifestations including cardiovascular abnormalities, pericarditis, gastrointestinal symptoms/diarrhoea; or thrombosis.
If TMA complications occur after ravulizumab discontinuation, consider reinitiation of ravulizumab treatment beginning with the loading dose and maintenance dose described in Dosage & Administration.
Treatment Discontinuation in gMG: Considering that gMG is a chronic disease, patients benefiting from ULTOMIRIS treatment who discontinue treatment should be monitored for symptoms of the underlying disease. If symptoms of gMG occur after discontinuation, consider restarting treatment with ULTOMIRIS.
Effect on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed.