Loading…
Ultomiris is a brand name for Ravulizumab. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Paroxysmal nocturnal haemoglobinuria (PNH) Ultomiris is indicated in the 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…
Verbatim from this product's EMA label. Tap a section to expand.
Ravulizumab must be administered by a healthcare professional and under the supervision of a physician experienced in the management of patients with haematological, renal, neuromuscular, or neuroinflammatory disorders. Posology 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, as shown in Table 1. 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.
Table 1:
Ravulizumab weight-based dosing regimen for adult patients with body weight greater than or equal to 40 kg Body weight range (kg) Loading dose (mg) Maintenance dose (mg)* Dosing interval ≥ 40 to < 60 2,400 3,000 Every 8 weeks ≥ 60 to < 100 2,700 3,300 Every 8 weeks ≥ 100 3,000 3,600 Every 8 weeks * First maintenance dose is administered 2 weeks after loading dose Treatment initiation instructions in patients who are complement-inhibitor treatment-naïve or switching treatment from eculizumab are shown in Table 2.
Table 2:
Ravulizumab treatment initiation instructions Population Weight-based ravulizumab loading dose Time of first ravulizumab weight- based maintenance dose Not currently on ravulizumab or eculizumab treatment At treatment start 2 weeks after ravulizumab loading dose Currently treated with eculizumab At time of next scheduled eculizumab dose 2 weeks after ravulizumab loading dose Paediatric patients with PNH or aHUS Paediatric patients with body weight ≥ 40 kg These patients should be treated in accordance with the adult dosing recommendations (See Table 1).
4 Paediatric patients with body weight ≥ 10 kg to < 40 kg The weight-based doses and dosing intervals for paediatric patients ≥ 10 kg to < 40 kg are shown in Table 3. For patients switching from eculizumab to ravulizumab, the loading dose of ravulizumab should be administered 2 weeks after the last eculizumab infusion, and then maintenance doses should be administered per weight-based dosing regimen shown in Table 3, starting 2 weeks after loading dose administration.
7%). 2%) including disseminated gonococcal infection and gonococcal infection. 10 Tabulated list of adverse reactions Table 7 gives the adverse reactions observed from clinical trials and from post-marketing experience. Adverse reactions are listed by MedDRA System Organ Class (SOC) and frequency, using the following convention: very common (≥ 1/ 10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); and not known (cannot be estimated from available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Table 7:
Adverse Drug reactions from clinical trials and postmarketing experience MedDRA System Organ Class Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1,000 to < 1/100) Infections and infestations Urinary tract infectiona Upper respiratory tract infection, Nasopharyngitis Meningococcal infectionb, Disseminated Gonococcal infectionc Immune system disorders Hypersensitivitye Anaphylactic reactiond Nervous system disorders Dizziness, Headache Gastrointestinal disorders Diarrhoea, Nausea, Abdominal pain Vomiting, Dyspepsia Skin and subcutaneous tissue disorders Urticaria, Pruritus, Rash Musculoskeletal and connective tissue disorders Arthralgia, Back pain Myalgia, Muscle spasms General disorders and administration site conditions Pyrexia, Fatigue Influenza like illness, Chills, Asthenia Injury, poisoning and procedural complications Infusion-related reaction a Urinary tract infection is a group term that includes Preferred Terms: Urinary tract infection, Urinary tract infection bacterial, Urinary tract infection enterococcal, and Escherichia urinary tract infection.
bMeningococcal infection includes preferred terms of meningococcal infection, meningococcal sepsis, meningococcal meningitis and encephalitis meningococcal c Disseminated gonococcal infection includes preferred terms of disseminated gonococcal infection and gonococcal infection d Estimated from postmarketing experience e Hypersensitivity is a group term for Preferred Term drug hypersensitivity with related causality and Preferred Term hypersensitivity Description of selected adverse reactions Meningococcal infection/sepsis/encephalitis Vaccination reduces, but does not eliminate, the risk of meningococcal infections.
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).
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 all available serogroups including A, C, Y, W135 and B, are recommended in preventing the commonly pathogenic meningococcal serogroups.
Patients must be vaccinated and 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.
1. 4). 4).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
Know a brand we are missing in European Union? Suggest a brand →
Brand names are compiled from public regulatory records for active-ingredient mapping only. Drugvu is not affiliated with any manufacturer. This is not medical advice.
Table 3:
Ravulizumab weight-based dosing regimen for paediatric patients with PNH or aHUS below 40 kg Body weight range (kg) Loading dose (mg) Maintenance dose (mg)* Dosing interval ≥ 10 to < 20 600 600 Every 4 weeks ≥ 20 to < 30 900 2,100 Every 8 weeks ≥ 30 to < 40 1,200 2,700 Every 8 weeks * First maintenance dose is administered 2 weeks after loading dose Ravulizumab has not been studied in paediatric patients with PNH who weigh less than 30 kg.
The recommended posology for these patients 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.
4). In aHUS, ravulizumab treatment to resolve thrombotic microangiopathy (TMA) manifestations should be for a minimum duration of 6 months, beyond which length of treatment needs to be considered for each patient individually. 4). 4).
Ravulizumab has not been studied in gMG patients with an MGFA Class V. Supplemental dosing following treatment with plasma exchange (PE), plasmapheresis (PP), or intravenous immunoglobulin (IVIg) Plasma exchange (PE), plasmapheresis (PP) and intravenous immunoglobulin (IVIg) have been shown to reduce ravulizumab serum levels.
A supplemental dose of ravulizumab is required in the setting of PE, PP or IVIg (Table 4).
Table 4:
Supplemental dose of ravulizumab after PP, PE, or IVIg Body weight range (kg) Most recent ravulizumab dose (mg) Supplemental dose (mg) following each PE or PP intervention Supplemental dose (mg) following completion of an IVIg cycle ≥ 40 to < 60 2,400 1,200 600 3,000 1,500 ≥ 60 to < 100 2,700 1,500 600 3,300 1,800 ≥ 100 3,000 1,500 600 3,600 1,800 Timing of ravulizumab supplemental dose Within 4 hours following each PE or PP intervention Within 4 hours following completion of an IVIg cycle 5 Abbreviations: IVIg = intravenous immunoglobulin, kg = kilogram, PE = plasma exchange, PP = plasmapheresis Special populations Elderly No dose adjustment is required for patients with PNH, aHUS, gMG, or NMOSD aged 65 years and over.
There is no evidence indicating any special precautions are required for treating a geriatric population – although experience with ravulizumab in elderly patients with PNH, aHUS, or NMOSD in clinical studies is limited. 2). Hepatic impairment The safety and efficacy of ravulizumab have not been studied in patients with hepatic impairment; however pharmacokinetic data suggest that no dose adjustment is required in patients with hepatic impairment.
Paediatric population The safety and efficacy of ravulizumab in children with a body weight below 10 kg with PNH or aHUS have not been established. 8 but no recommendation on a posology can be made. The safety and efficacy of ravulizumab in children with gMG or NMOSD have not been established.
No data are available. Method of administration For […]
In clinical trials, < 1% of patients developed serious meningococcal infections while receiving treatment with ravulizumab; all were adult patients with PNH or NMOSD who had been vaccinated. 4 for information on prevention and treatment of suspected meningococcal infection.
In patients treated with ravulizumab, meningococcal infections have presented as 11 meningococcal sepsis and encephalitis meningococcal. Patients should be informed of the signs and symptoms of meningococcal infection and advised to seek medical care immediately.
Infusion-related reactions In clinical trials, infusion-related reactions were common (≥1%). These events, which were mild to moderate in severity and transient, included back pain, abdominal pain, muscle spasms, drop in blood pressure, elevation in blood pressure, rigors, limb discomfort, hypersensitivity (allergic reaction), dysgeusia (bad taste), and drowsiness.
These reactions did not require discontinuation of ravulizumab. 3%) cases of development of treatment- emergent anti-drug antibody have been reported with ravulizumab (1 adult patient with PNH and 1 adult patient with aHUS). These anti-drug antibodies were transient in nature with low titre and did not correlate with clinical response or adverse events.
Paediatric population Paroxysmal nocturnal haemoglobinuria (PNH) In paediatric PNH patients (N= 13, aged 9 to 17 years old) enrolled in the paediatric PNH Study (ALXN1210-PNH-304), the safety profile appeared similar to that observed in adult PNH patients.
1%). Atypical haemolytic uremic syndrome (aHUS) In paediatric patients with evidence of aHUS (N= 34, aged 10 months to less than 18 years) included in ALXN1210-aHUS-312 study, the safety profile of ravulizumab appeared similar to that observed in adult patients with evidence of aHUS.
The safety profiles in the different paediatric subsets of age appear similar. The safety data for patient below 2 years of age is limited to four patients. The most common adverse reactions (> 20%) reported in paediatric patients were pyrexia, vomiting, diarrhoea, headache, nasopharyngitis, upper respiratory tract infection and abdominal pain.
Generalised Myasthenia Gravis (gMG) Ravulizumab has not been studied in paediatric patients with gMG. Neuromyelitis Optica Spectrum Disorder (NMOSD) Ravulizumab has not been studied in paediatric patients with NMOSD. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system […]
Physicians should provide patients with a Patient guide and a Patient card. 7 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.
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. 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: 8 - 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 […]