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1 X 30 ml X 10 mg/ml
Soliris must be administered by a healthcare professional and under the supervision of a physician experienced in the management of patients with haematological, renal or neuromuscular disorders.
In Paroxysmal Nocturnal Haemoglobinuria (PNH):
The PNH dosing regimen for adult patients (≥18 years of age) consists of a 4-week initial phase followed by a maintenance phase:
• Initial phase: 600 mg of Soliris administered via a 25 – 45 minute intravenous infusion every week for the first 4 weeks.
• Maintenance phase: 900 mg of Soliris administered via a 25 – 45 minute intravenous infusion for the fifth week, followed by 900 mg of Soliris administered via a 25 – 45 minute intravenous infusion every 14 ± 2 days.
In atypical Haemolytic Uremic Syndrome (aHUS) and refractory generalized Myasthenia Gravis (gMG):
The aHUS and refractory gMG dosing regimen for adult patients (≥18 years of age) consists of a 4 week initial phase followed by a maintenance phase:
• Initial phase: 900 mg of Soliris administered via a 25 – 45 minute intravenous infusion every week for the first 4 weeks.
• Maintenance phase: 1,200 mg of Soliris administered via a 25 – 45 minute intravenous infusion for the fifth week, followed by 1,200 mg of Soliris administered via a 25 – 45 minute intravenous infusion every 14 ± 2 days.
Paediatric patients in PNH and aHUS:
Paediatric PNH patients, above 11 years old, and aHUS patients with body weight ≥ 40 kg are treated with the adult dosing recommendations, respectively.
In paediatric PNH patients, above 11 years old, and aHUS patients with body weight below 40 kg, the Soliris dosing regimen consists of:
Patient Body Weight 30 to <40 kg: Initial Phase: 600 mg weekly x 2, Maintenance Phase: 900 mg at week 3; then 900 mg every 2 weeks.
Patient Body Weight 20 to <30 kg: Initial Phase: 600 mg weekly x 2, Maintenance Phase: 600 mg at week 3; then 600 mg every 2 weeks.
Patient Body Weight 10 to <20 kg: Initial Phase: 600 mg weekly x 1, Maintenance Phase: 300 mg at week 3; then 300 mg every 2 weeks.
Patient Body Weight 5 to <10 kg: Initial Phase: 300 mg weekly x 1, Maintenance Phase: 300 mg at week 3; then 300 mg every 2 weeks.
Soliris has not been studied in patients with PNH who weigh less than 40 kg. The posology of Soliris for PNH patients less than 40 kg weight and who are above 11 years old is based on the posology used for patients with aHUS and who weigh less than 40 kg.
Soliris has not been studied in paediatric patients with refractory gMG.
For adult aHUS and refractory gMG patients and paediatric aHUS patients supplemental dosing of Soliris is required in the setting of concomitant PE/PI (plasmapheresis or plasma exchange, or fresh frozen plasma infusion): Please refer to table 2 at the attached doctor’s leaflet.
Treatment monitoring: aHUS patients should be monitored for signs and symptoms of thrombotic microangiopathy (TMA).
Soliris treatment is recommended to continue for the patient’s lifetime, unless the discontinuation of Soliris is clinically indicated.
Elderly: Soliris may be administered to patients aged 65 years and over. There is no evidence to suggest that any special precautions are needed when older people are treated – although experience with Soliris in this patient population is still limited.
Renal impairment: No dose adjustment is required for patients with renal impairment.
Hepatic impairment: The safety and efficacy of Soliris have not been studied in patients with hepatic impairment.
Method of administration: Do not administer as an intravenous push or bolus injection. Soliris should only be administered via intravenous infusion as described below.
For instructions on dilution of the medicinal product before administration, see section 6.6 at the attached doctor’s leaflet. The diluted solution of Soliris should be administered by intravenous infusion over 25 – 45 minutes in adults and 1-4 hours in paediatric patients via gravity feed, a syringe-type pump, or an infusion pump.
It is not necessary to protect the diluted solution of Soliris from light during administration to the patient.
Patients should be monitored for one hour following infusion. If an adverse event occurs during the administration of Soliris, the infusion may be slowed or stopped at the discretion of the physician. If the infusion is slowed, the total infusion time may not exceed two hours in adults and adolescents (aged 12 years to under 18 years) and four hours in children aged less than 12 years.
Refractory gMG: Available data suggest that clinical response is usually achieved by 12 weeks of Soliris treatment.
Discontinuation of the therapy should be considered in a patient who shows no evidence of therapeutic benefit by 12 weeks.
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Creation date March 2020
Soliris is indicated for the treatment of patients with:
– Paroxysmal nocturnal haemoglobinuria (PNH).
Evidence of clinical benefit is demonstrated in patients with haemolysis with clinical symptom(s) indicative of high disease activity, regardless of transfusion history. Eculizumab has not been studied in clinical trials in patients with PNH below 11 years of age.
– Atypical haemolytic uremic syndrome (aHUS).
Soliris is indicated in adults for the treatment of:
– Refractory generalized myasthenia gravis (gMG) in patients who are anti-acetylcholine receptor (AChR) antibody-positive.
Hypersensitivity to eculizumab, murine proteins or to any of the excipients.
Soliris therapy must not be initiated in patients:
– with unresolved Neisseria meningitidis infection.
– who are not currently vaccinated against Neisseria meningitidis unless they receive prophylactic treatment with appropriate antibiotics until 2 weeks after vaccination.
Soliris is not expected to affect the aplastic component of anaemia in patients with PNH.
Meningococcal Infection: Due to its mechanism of action, the use of Soliris increases the patient’s susceptibility to meningococcal infection (Neisseria meningitidis). Meningococcal disease due to any serogroup may occur. To reduce the risk of infection, all patients must be vaccinated at least 2 weeks prior to receiving Soliris unless the risk of delaying Soliris therapy outweighs the risks of developing a meningococcal infection. Patients who initiate Soliris 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, W 135 and B where available, are recommended in preventing the commonly pathogenic meningococcal serogroups. Patients must receive vaccination according to current national vaccination guidelines for vaccination use.
Other Systemic Infections: Due to its mechanism of action, Soliris therapy should be administered with caution to patients with active systemic infections. Patients may have increased susceptibility to infections, especially with Neisseria 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 to increase their awareness of potential serious infections and the signs and symptoms of them. Physicians should advise patients about gonorrhoea prevention.
Infusion Reactions: Administration of Soliris may result in infusion reactions or immunogenicity that could cause allergic or hypersensitivity reactions (including anaphylaxis), though immune system disorders within 48 hours of Soliris administration did not differ from placebo treatment in PNH, aHUS, refractory gMG, and other studies conducted with Soliris. In clinical trials, no PNH, aHUS, or refractory gMG patients experienced an infusion reaction which required discontinuation of Soliris. Soliris administration should be interrupted in all patients experiencing severe infusion reactions and appropriate medical therapy administered.
Immunogenicity: Infrequent antibody responses have been detected in Soliris-treated patients across all clinical studies.
In PNH placebo controlled studies low antibody responses have been reported with a frequency (3.4%) similar to that of placebo (4.8%).
In patients with aHUS treated with Soliris, antibodies to Soliris were detected in 3/100 (3%) by the ECL bridging format assay. 1/100 (1%) aHUS patients had low positive values for neutralizing antibodies.
In a refractory gMG placebo controlled study, none (0/62) of the Soliris treated patients showed antidrug antibody response during the 26 week active treatment.
There has been no observed correlation of antibody development to clinical response or adverse events.
Immunization: Prior to initiating Soliris therapy, it is recommended that PNH, aHUS, and refractory gMG patients initiate immunizations according to current immunization guidelines. Additionally, all patients must be vaccinated against meningococcal infections at least 2 weeks prior to receiving Soliris unless the risk of delaying Soliris therapy outweighs the risks of developing a meningococcal infection. Patients who initiate Soliris 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, W 135 and B where available are recommended in preventing the commonly pathogenic meningococcal serogroups. (see Meningococcal Infection).
Patients less than 18 years of age must be vaccinated against Haemophilus influenzae and pneumococcal infections, and strictly need to adhere to the national vaccination recommendations for each age group.
Anticoagulant therapy: Treatment with Soliris should not alter anticoagulant management.
Immunosuppressant and anticholinesterase therapies: Patients in refractory gMG clinical trials continued treatment with immunosuppressant and anticholinesterase therapies while on Soliris treatment. Withdrawal of immunosuppressant and anticholinesterase therapies during Soliris treatment for refractory gMG was not assessed in the placebo-controlled studies.
PNH Laboratory Monitoring: PNH patients should be monitored for signs and symptoms of intravascular haemolysis, including serum lactate dehydrogenase (LDH) levels. PNH patients receiving Soliris therapy should be similarly monitored for intravascular haemolysis by measuring LDH levels, and may require dose adjustment within the recommended 14±2 day dosing schedule during the maintenance phase (up to every 12 days). aHUS Laboratory Monitoring aHUS: patients receiving Soliris therapy should be monitored for thrombotic microangiopathy by measuring platelet counts, serum LDH and serum creatinine, and may require dose adjustment within the recommended 14±2 day dosing schedule during the maintenance phase (up to every 12 days). Treatment Discontinuation for PNH: If PNH patients discontinue treatment with Soliris they should be closely monitored for signs and symptoms of serious intravascular haemolysis. Serious haemolysis is identified by serum LDH levels greater than the pre-treatment level, along with any of the following: greater than 25% absolute decrease in PNH clone size (in the absence of dilution due to transfusion) in one week or less; a haemoglobin level of <5 g/dL or a decrease of >4 g/dL in one week or less; angina; change in mental status; a 50% increase in serum creatinine level; or thrombosis. Monitor any patient who discontinues Soliris for at least 8 weeks to detect serious haemolysis and other reactions. 7 If serious haemolysis occurs after Soliris discontinuation, consider the following procedures/treatments: blood transfusion (packed RBCs), or exchange transfusion if the PNH RBCs are >50% of the total RBCs by flow cytometry; anticoagulation; corticosteroids; or reinstitution of Soliris. In PNH clinical studies, 16 patients discontinued the Soliris treatment regimen. Serious haemolysis was not observed.
Treatment Discontinuation for aHUS: Thrombotic microangiopathy (TMA) complications have been observed as early as 4 weeks and up to 127 weeks following discontinuation of Soliris treatment in some patients. Discontinuation of treatment should only be considered if medically justified.
Treatment discontinuation for refractory gMG: Use of Soliris in refractory gMG treatment has been studied only in the setting of chronic administration. Patients that discontinue Soliris treatment should be carefully monitored for signs and symptoms of deterioration of disease.
Excipients: This medicinal product contains 5 mmol sodium per vial. It should be taken into consideration by patients on a controlled sodium diet.
See prescribing information for full details.
Supportive safety data were obtained from 29 completed and one ongoing clinical studies that included 1,407 patients exposed to eculizumab in ten disease populations, including PNH, aHUS, and refractory gMG.
The most common adverse reaction was headache, (occurred mostly in the initial phase), and the most serious adverse reaction was meningococcal sepsis.
See prescribing information for full details.
No interaction studies have been performed.
Chronic intravenous human immunoglobulin (IVIg) treatment may interfere with the endosomal neonatal Fc receptor (FcRn) recycling mechanism of monoclonal antibodies such as eculizumab and thereby decrease serum eculizumab concentrations. Drug interaction studies have not been conducted with eculizumab in patients treated with IVIg.
Pregnancy and Lactation
Pregnancy: There are no well-controlled studies in pregnant women treated with eculizumab. Data on a limited number of pregnancies exposed to eculizumab (less than 300 pregnancy outcomes) indicate there is no increased risk of foetal malformation or foetal-neonatal toxicity. However, due to the lack of well controlled studies, uncertainties remain. Therefore, an individual risk benefit analysis is recommended before starting and during treatment with eculizumab in pregnant women. Should such a treatment be considered necessary during pregnancy, a close maternal and foetal monitoring according to local guidelines is recommended.
Human IgG are known to cross the human placental barrier, and thus eculizumab may potentially cause terminal complement inhibition in the foetal circulation. Therefore, Soliris should be given to a pregnant woman only if clearly needed.
Lactation: No effects on the breastfed newborn / infant are anticipated as limited data available suggest that eculizumab is not excreted in human breast milk. However, due to the limitations of the available data, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for eculizumab and any potential adverse effects on the breastfed child from eculizumab or from the underlying maternal condition.
See prescribing information for full details.
No case of overdose has been reported.
Shelf life: After dilution, the medicinal product should be used immediately. However, chemical and physical stability has been demonstrated for 24 hours at 2°C – 8°C.
Storage: Store in a refrigerator (2°C – 8ºC). Do not freeze. Store in the original package in order to protect from light.
Soliris vials in the original package may be removed from refrigerated storage for only one single period of up to 3 days. At the end of this period the product can be put back in the refrigerator.