Special Warning : אזהרת שימוש

4.4      Special warnings and precautions for use

Traceability
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Serious meningococcal infection

Due to its mechanism of action, the use of ravulizumab increases the patient's susceptibility to meningococcal infection/sepsis (Neisseria meningitidis). Meningococcal disease due to any serogroup may occur (see section 4.8). To reduce this risk of infection, all patients must be vaccinated against meningococcal infections at least two weeks prior to initiating ravulizumab unless the risk of delaying ravulizumab therapy outweighs the risk of developing a meningococcal infection. Patients who initiate ravulizumab 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. If the patient is being switched from eculizumab treatment, physicians should verify that meningococcal vaccination is current according to national guidelines for vaccination use.

Vaccination may not be sufficient to prevent meningococcal infection. 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 ravulizumab and in patients treated with 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 information brochure and a Patient card.

Immunisation

Prior to initiating ravulizumab therapy, it is recommended that patients initiate immunisations according to current immunisation guidelines.

Vaccination may further activate complement. As a result, patients with complement- mediated diseases, may experience increased signs and symptoms of their underlying disease.
Therefore, patients should be closely monitored for disease symptoms after recommended vaccination.

Patients below the age of 18 years old must be vaccinated against Haemophilus influenzae and pneumococcal infections, and strictly need to adhere to the national vaccination recommendations for each age group.

Other systemic infections

Ravulizumab therapy should be administered with caution to patients with active systemic infections. Ravulizumab blocks terminal complement activation; therefore, patients may have increased susceptibility to infections caused by Neisseria species and encapsulated bacteria.
Serious infections with Neisseria species (other than Neisseria meningitidis), including disseminated gonococcal infections, have been reported.
Patients should be provided with information from the Package Information Leaflet to increase their awareness of potential serious infections and their signs and symptoms.
Physicians should advise patients about gonorrhoea prevention.

Infusion-related reactions

Administration of ravulizumab may result in systemic infusion-related reactions and allergic or hypersensitivity reactions, including anaphylaxis (see section 4.8).
In case of systemic infusion-related reaction, if signs of cardiovascular instability or respiratory compromise occur, administration of ravulizumab should be interrupted and appropriate supportive measures should be instituted.

Treatment discontinuation for PNH

If patients with PNH discontinue treatment with ravulizumab, they should be closely monitored for signs and symptoms of serious intravascular haemolysis, identified by elevated LDH (lactate dehydrogenase) levels along with sudden decrease in PNH clone size or haemoglobin, or re-appearance of symptoms such as fatigue, haemoglobinuria, abdominal pain, shortness of breath (dyspnoea), major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction. Any patient who discontinues ravulizumab should be monitored for at least 16 weeks to detect haemolysis and other reactions. If signs and symptoms of haemolysis occur after discontinuation, including elevated LDH, consider restarting treatment with ravulizumab.

Treatment discontinuation for aHUS

There are no specific data on ravulizumab discontinuation. In a long-term prospective observational study, discontinuation of complement C5 inhibitor treatment (eculizumab) 

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 2 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)
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, reinitiation of ravulizumab treatment should be considered, beginning with the loading dose and maintenance dose (see section 4.2).

Treatment discontinuation for gMG

Considering that gMG is a chronic disease, patients benefiting from ravulizumab treatment who discontinue treatment should be monitored for symptoms of the underlying disease. If symptoms of gMG occur after discontinuation, consider restarting treatment with ravulizumab.

Treatment discontinuation for NMOSD

Considering that NMOSD is a chronic disease, patients benefiting from ravulizumab treatment who discontinue treatment should be monitored for symptoms of NMOSD relapse.
If symptoms of NMOSD relapse occur after discontinuation, consider restarting treatment with ravulizumab.

Switch from eculizumab to ravulizumab

In gMG patients who are not responding to eculizumab approved dosing regimen, treatment with ravulizumab is not recommended.

Sodium content

Ultomiris 300 mg/3 mL and 1,100 mg/11 mL concentrates for solution for infusion 
Once diluted with sodium chloride 9 mg/mL (0.9%) solution for injection, this medicinal product contains 0.18 g sodium per 72 mL at the maximal dose, equivalent to 9.1% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Ultomiris 300 mg/30 mL concentrate for solution for infusion

Once diluted with sodium chloride 9 mg/mL (0.9 %) solution for injection, this medicinal product contains 2.65 g sodium per 720 mL at the maximal dose, equivalent to 133 % of the WHO recommended maximum daily intake of 2 g sodium for an adult.




Effects on Driving

4.7    Effects on ability to drive and use machines

Ultomiris has no or negligible influence on the ability to drive and use machines.