Ultomiris 100 mg/ml

/ Alexion

Adult patients with PNH, aHUS, gMG or NMOSD
The recommended dosing regimen consists of a loading dose followed by maintenance
dosing, administered by intravenous infusion. The doses to be administered are based on the
patient’s body weight. For adult patients (≥ 18 years of age), maintenance doses should be administered at a once every 8-week interval, starting 2 weeks after loading dose administration.
Dosing schedule is allowed to occasionally vary by ± 7 days of the scheduled infusion day (except for the first maintenance dose of ravulizumab), but the subsequent dose should be administered according to the original schedule.
For patients switching from eculizumab to ravulizumab, the loading dose of ravulizumab should be administered 2 weeks after the last eculizumab maintenance infusion (or 1 week after the last eculizumab induction infusion), and then ravulizumab maintenance doses are administered once every 8 weeks, starting 2 weeks after loading dose administration.
Paediatric population
The doses to be administered are based on the patient’s body weight.
Paediatric patients with PNH and aHUS with body weight ≥ 40 kg are treated in accordance with the adult dosing recommendations.
Ravulizumab has not been studied in paediatric patients with PNH who weigh less than 30 kg.
The posology of ravulizumab for paediatric patients less than 30 kg is based on the posology used for paediatric patients with aHUS, on the basis of the pharmacokinetic/pharmacodynamic (PK/PD) data available in aHUS and PNH patients treated with ravulizumab.
For intravenous infusion only. This medicinal product must be administered through a 0.2 μm filter and should not be administered as an intravenous push or bolus injection.
Concentrate for solution for infusion is presented as 3 mL and 11 mL vials and must be diluted to a final concentration of 50 mg/mL. Following dilution, this medical product is to be administered by intravenous infusion using a syringe-type pump or an infusion pump over a minimal period of 0.17 to 1.3 hours (10 to 75 minutes) depending on body weight.

Paroxysmal nocturnal haemoglobinuria (PNH)
Treatment of adult and paediatric patients with a body weight of
10 kg or above with PNH:
* In patients with haemolysis with clinical symptom(s) indicative of high disease activity.
* In patients who are clinically stable after having been treated with eculizumab for at least the past 6 months.
Atypical haemolytic uremic syndrome (aHUS)
Treatment of patients with a body weight of 10 kg or above with aHUS who are complement inhibitor treatment-naïve or have received eculizumab for at least 3 months and have evidence of response to eculizumab.
Generalized myasthenia gravis (gMG)
Treatment of adult patients with gMG who are anti-acetylcholine receptor (AChR) antibody-positive.
Neuromyelitis optica spectrum disorder (NMOSD)
Treatment of adult patients with NMOSD who are anti-aquaporin 4 (AQP4) antibody-positive.

* Hypersensitivity to the active substance or to any of the excipients
* Patients who are not currently vaccinated against Neisseria meningitidis unless they
receive prophylactic treatment with appropriate antibiotics until 2 weeks after vaccination.

Serious meningococcal infection
Due to its mechanism of action, the use of ravulizumab increases the patient’s susceptibility to meningococcal infection/sepsis (Neisseria meningitidis).
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 all available serogroups including A, C, Y, W135 and B, are recommended in preventing the commonly pathogenic meningococcal serogroups.
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 guide 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 complementmediated 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.
Should advise patients about gonorrhoea prevention.
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)
* 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.
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
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.
See prescribing information for full details.

Very common: Urinary tract infection, Upper respiratory tract infection, Nasopharyngitis, Dizziness, Headache, Diarrhoea, Nausea, Abdominal pain, Arthralgia, Back pain, Pyrexia, Fatigue.
Common: Hypersensitivity, Vomiting, Dyspepsia, Urticaria, Pruritus, Rash, Myalgia, Muscle spasms, Influenza like illness, Chills, Asthenia, Infusion-related reaction.
See prescribing information for full details.

No interaction studies have been performed. Based on the potential inhibitory effect of ravulizumab on complement-dependent cytotoxicity of rituximab, ravulizumab may reduce the expected pharmacodynamic effects of rituximab.
Chronic intravenous human immunoglobulin (IVIg) treatment may interfere with the
endosomal neonatal Fc receptor (FcRn) recycling mechanism of monoclonal antibodies such as ravulizumab and thereby decrease serum ravulizumab concentrations.

Women of childbearing potential: Should use effective contraception methods during treatment and for 8 months after treatment.
Pregnancy: There are no clinical data from the use of ravulizumab in pregnant women. In pregnant women the use of ravulizumab may be considered following an assessment of the
risks and benefits.
Lactation: It is unknown whether ravulizumab is excreted into human milk.
A risk to infants cannot be excluded.
Since many medicinal products and immunoglobulins are secreted into human milk, and because of the potential for serious adverse reactions in nursing infants, breast-feeding should be discontinued during treatment with ravulizumab and for 8 months after treatment.

Patients who experience overdose should have immediate interruption of their infusion and be closely monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment be instituted.

Patient safety information card emphasizes important safety information that the patient should be aware of before and during treatment.
Please explain to the patient the need to review the card before starting treatment.
After dilution, the medicinal product should be used immediately. However, chemical and physical stability of the diluted product have been demonstrated for up to 24 hours at 2 °C-8°C and up to 4 hours at room temperature