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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, W135 and B where available, are recommended in preventing the commonly pathogenic meningococcal serotypes. Patients must receive vaccination according to current national vaccination guidelines for vaccination use.
Vaccination may further activate complement. As a result, patients with complement-mediated diseases, including PNH and aHUS, may experience increased signs and symptoms of their underlying disease, such as haemolysis (PNH) or TMA (aHUS). Therefore, patients should be closely monitored for disease symptoms after recommended vaccination.
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 have been reported in SOLIRIS treated patients. Sepsis is a common presentation of meningococcal infections in patients treated with SOLIRIS (see Adverse Reactions). All patients should be monitored for early signs of meningococcal infection, evaluated immediately if infection is suspected, and treated with antibiotics if necessary. Patients should be informed of these signs and symptoms and steps taken to seek medical care immediately. Physicians must discuss the benefits and risks of SOLIRIS therapy with patients and provide them with a patient information brochure and a patient safety card (see Package Leaflet for a description).
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 from the Patient Leaflet 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 and other studies conducted with SOLIRIS. In clinical trials, no PNH or aHUS 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.
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 and aHUS 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, W135 and B where available are recommended in preventing the commonly pathogenic meningococcal serogroups (see Meningococcal Infection as previously mentioned).
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 of each age group.
Vaccination may further activate complement. As a result, patients with complement-mediated diseases, including PNH and aHUS, may experience increased signs and symptoms of their underlying disease, such as haemolysis (PNH) or TMA (aHUS). Therefore, patients should be closely monitored for disease symptoms after recommended vaccination.
Anticoagulant therapy: Treatment with SOLIRIS should not alter anticoagulant management.
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 should be monitored for thrombotic microangiopathy by measuring platelet counts, serum LDH levels 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 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.
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.
In aHUS clinical studies, 61 patients (21 paediatric patients) discontinued SOLIRIS treatment with a median follow-up period of 24 weeks. Fifteen severe thrombotic microangiopathy (TMA) complications in 12 patients were observed following treatment discontinuation, and 2 severe TMA complications occurred in an additional 2 patients that received a reduced dosing regimen of SOLIRIS outside of the approved dosing regimen (see Dosage & Administration). Severe TMA complications occurred in patients regardless of whether they had an identified genetic mutation, high risk polymorphism or auto-antibody. Additional serious medical complications occurred in these patients including severe worsening of kidney function, disease-related hospitalization and progression to end stage renal disease requiring dialysis. Despite SOLIRIS re-initiation following discontinuation, progression to end stage renal disease occurred in one patient.
If aHUS patients discontinue treatment with SOLIRIS, they should be monitored closely for signs and symptoms of severe thrombotic microangiopathy complications. Monitoring may be insufficient to predict or prevent severe thrombotic microangiopathy complications in patients with aHUS after discontinuation of SOLIRIS.
Severe thrombotic microangiopathy complications post discontinuation can be identified by (i) any two, or repeated measurement of any one, of the following: a decrease in platelet count of 25% or more as compared to either baseline or to peak platelet count during SOLIRIS treatment; an increase in serum creatinine of 25% or more as compared to baseline or to nadir during SOLIRIS treatment; or, an increase in serum LDH of 25% or more as compared to baseline or to nadir during SOLIRIS treatment; or (ii) any one of the following: a change in mental status or seizures; angina or dyspnoea; or thrombosis.
If severe thrombotic microangiopathy complications occur after SOLIRIS discontinuation, consider reinstitution of SOLIRIS treatment, supportive care with PE/PI, or appropriate organ-specific supportive measures including renal support with dialysis, respiratory support with mechanical ventilation or anticoagulation.
Educational Materials: All physicians who intend to prescribe SOLIRIS must ensure they are familiar with the physician's guide to prescribing. Physicians must discuss the benefits and risks of SOLIRIS therapy with patients and provide them with a Patient/Parent Information Brochure and a Patient Safety Card.
Patients should be instructed that if they develop fever, headache accompanied with fever and/or stiff neck or sensitivity to light, they should immediately seek medical care as these signs may be indicative of meningococcal infection.
Excipients: This medicinal product contains 5 mmol sodium per vial. It should be taken into consideration by patients on a controlled sodium diet.
Effects on ability to drive and use machines: SOLIRIS has no or negligible influence on the ability to drive and use machines.
