Posology : מינונים

4.2   Posology and method of administration
Soliris 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 neuro- inflammatory disorders.

Posology

In Paroxysmal Nocturnal Haemoglobinuria (PNH) in adults:
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 (35 minutes ± 10 minutes) intravenous infusion every week for the first 4 weeks.
• Maintenance phase: 900 mg of Soliris administered via a 25 – 45 minute (35 minutes ± 10 minutes) intravenous infusion for the fifth week, followed by 900 mg of Soliris administered via a 25 – 45 minute (35 minutes ± 10 minutes) intravenous infusion every 14 ± 2 days (see section 5.1).

Atypical Haemolytic Uremic Syndrome (aHUS), refractory generalized Myasthenia Gravis (gMG) and Neuromyelitis Optica Spectrum Disorder (NMOSD) in adults:
The aHUS, refractory gMG and NMOSD 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 (35 minutes ± 10 minutes) intravenous infusion every week for the first 4 weeks.
•      Maintenance phase: 1,200 mg of Soliris administered via a 25 – 45 minute (35 minutes ± 10 minutes) intravenous infusion for the fifth week, followed by 1,200 mg of Soliris administered via a 25 – 45 minute (35 minutes ± 10 minutes) intravenous infusion every 14 ± 2 days (see section 5.1).

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.

Paediatric patients in PNH, aHUS or refractory gMG:
Paediatric PNH patients, above 11 years old, aHUS or refractory gMG patients with body weight ≥ 40 kg are treated with the adult dosing recommendations.

In paediatric PNH patients, above 11 years old, aHUS and refractory gMG patients with body weight below 40 kg, the Soliris dosing regimen consists of:
For paediatric patient with aHUS
Patient Body          Initial Phase                    Maintenance Phase Weight
30 to <40 kg       600 mg weekly for       900 mg at week 3; then 900 mg every 2 weeks the first 2 weeks
20 to <30 kg       600 mg weekly for       600 mg at week 3; then 600 mg every 2 weeks the first 2 weeks
10 to <20 kg       600 mg single dose      300 mg at week 2; then 300 mg every 2 weeks at week 1
5 to <10 kg        300 mg single dose      300 mg at week 2; then 300 mg every 3 weeks at week 1


For paediatric patient with refractory gMG, above 6 years old
Patient Body         Initial Phase                  Maintenance Phase Weight
30 to <40 kg      600 mg weekly for      900 mg at week 3; then 900 mg every 2 weeks the first 2 weeks
20 to <30 kg      600 mg weekly for      600 mg at week 3; then 600 mg every 2 weeks the first 2 weeks

For paediatric patient with PNH, above 11 years old
Patient Body           Initial Phase                 Maintenance Phase Weight
30 to <40 kg         600 mg weekly for       900 mg at week 3; then 900 mg every 2 weeks the first 2 weeks

Soliris has not been studied in patients with PNH or refractory gMG who weigh less than 40 kg. The posology of Soliris to be used in paediatric patients with PNH patients weighing less than 40 kg and who are above 11 years old or refractory gMG is identical to the weight-based dose recommendation provided for paediatric patients with aHUS. Based on the pharmacokinetic (PK)/pharmacodynamic (PD) data available in patients with aHUS and PNH treated with Soliris, this body-weight based dose regimen for paediatric patients is expected to result in an efficacy and safety profile similar to that in adults. For patients with refractory gMG weighing less than 40 kg this body-weight based dose regimen is also expected to result in an efficacy and safety profile similar to that in adults.

Soliris has not been studied in paediatric patients with NMOSD.

Supplemental dosing of Soliris is required in the setting of concomitant plasmapheresis (PP) or plasma exchange (PE), or fresh frozen plasma infusion (PI) as described below: 
Type of Plasma               Most Recent           Supplemental Soliris        Timing of Intervention                 Soliris Dose          Dose With Each              Supplemental Soliris PP/PE/PI Intervention       Dose
Plasmapheresis or            300 mg                300 mg per each plasma exchange                                    plasmapheresis or plasma exchange             Within 60 minutes after session                     each plasmapheresis or
≥600 mg               600 mg per each             plasma exchange plasmapheresis or plasma exchange session
Fresh frozen plasma          ≥300 mg               300 mg per infusion of 60 minutes prior to each infusion                                           fresh frozen plasma infusion of fresh frozen plasma
Abbreviations: PP/PE/PI = plasmapheresis/plasma exchange/plasma infusion 
Supplemental dose of Soliris is required in the setting of concomitant intravenous immunoglobulin (IVIg) treatment as described below (see also Section 4.5):

Most Recent Soliris                                           Timing of Supplemental Supplemental Soliris Dose
Dose                                                          Soliris Dose 

≥ 900 mg                  600 mg per IVIg cycle               As soon as possible after ≤ 600 mg                  300 mg per IVIg cycle               IVIg cycle Abbreviation: IVIg = intravenous immunoglobulin


Treatment monitoring aHUS patients should be monitored for signs and symptoms of thrombotic microangiopathy (TMA) (see section 4.4 aHUS laboratory monitoring).
Soliris treatment is recommended to continue for the patient’s lifetime, unless the discontinuation of Soliris is clinically indicated (see section 4.4).

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 (see section 5.1).

Hepatic impairment
The safety and efficacy of Soliris have not been studied in patients with hepatic impairment.
Paediatric population
The safety and efficacy of Soliris in children with refractory gMG aged less than 6 years old have not been established.
The safety and efficacy of Soliris in children with NMOSD aged less than 18 years old have not been established.

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. The diluted solution of Soliris should be administered by intravenous infusion over 25 – 45 minutes (35 minutes ± 10 minutes) in adults and 1-4 hours in paediatric patients under 18 years of age 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 four hours in paediatric patients under 18 years of age.