Posology : מינונים

4.2    Posology and method of administration

Therapy should be initiated under the supervision of a physician knowledgeable in the management of amyloidosis.

Posology

The recommended dose of Onpattro is 300 micrograms per kg body weight administered via intravenous (IV) infusion once every 3 weeks.

Dosing is based on actual body weight. For patients weighing ≥ 100 kg, the maximum recommended dose is 30 mg.

Vitamin A supplementation at approximately 2 500 IU vitamin A per day is advised for patients treated with Onpattro (see section 4.4).

Required premedication
All patients should receive premedication prior to Onpattro administration to reduce the risk of infusion-related reactions (IRRs) (see section 4.4). Each of the following medicinal products should be given on the day of Onpattro infusion at least 60 minutes prior to the start of infusion:
•      Intravenous corticosteroid (dexamethasone 10 mg, or equivalent)
•      Oral paracetamol (500 mg)
•      Intravenous H1 blocker (diphenhydramine 50 mg, or equivalent)
•      Intravenous H2 blocker (famotidine 20 mg, or equivalent) 
For premedications not available or not tolerated intravenously, equivalents may be administered orally.

If clinically indicated, the corticosteroid may be tapered in decrements no greater than 2.5 mg to a minimum dose of 5 mg of dexamethasone (IV), or equivalent. The patient should receive at least 3 consecutive IV infusions of Onpattro without experiencing IRRs before each reduction in corticosteroid premedication.

Additional or higher doses of one or more of the premedications may be administered to reduce the risk of IRRs, if needed (see sections 4.4 and 4.8).

Missed dose
If a dose is missed, Onpattro should be administered as soon as possible.
•      If Onpattro is administered within 3 days of the missed dose, dosing should be continued according to the patient’s original schedule.
•      If Onpattro is administered more than 3 days after the missed dose, dosing should be continued every 3 weeks thereafter.

Special populations

Elderly patients
No dose adjustment is required in patients ≥ 65 years of age (see section 5.2).
Hepatic impairment
No dose adjustment is necessary in patients with mild hepatic impairment (bilirubin ≤ 1 x upper limit of normal [ULN] and aspartate aminotransferase [AST] > 1 x ULN, or bilirubin > 1.0 to 1.5 x ULN and any AST). Onpattro has not been studied in patients with moderate or severe hepatic impairment and should not be used in these patients unless the anticipated clinical benefit outweighs the potential risk (see section 5.2).


Renal impairment
No dose adjustment is necessary in patients with mild or moderate renal impairment (estimated glomerular filtration rate [eGFR] ≥ 30 to < 90 mL/min/1.73m2). Onpattro has not been studied in patients with severe renal impairment or end-stage renal disease and should not be used in these patients unless the anticipated clinical benefit outweighs the potential risk (see section 5.2).

Paediatric population
The safety and efficacy of Onpattro in children or adolescents < 18 years of age have not been established. No data are available.
Onpattro is not indicated for children and adolescents under 18 years old 
Method of administration

Onpattro is for intravenous use.
•    Onpattro must be diluted prior to intravenous infusion (see section 6.6).

•     A dedicated line with an infusion set containing a 1.2 micron polyethersulfone (PES) in-line infusion filter must be used. The infusion sets and lines must be free of di(2- ethylhexyl)phthalate (DEHP).
•     The diluted solution of Onpattro should be infused intravenously over approximately 80 minutes at an initial infusion rate of approximately 1 mL/min for the first 15 minutes, followed by an increase to approximately 3 mL/min for the remainder of the infusion. The duration of infusion may be extended in the event of an IRR (see section 4.4).
•     Onpattro must be administered through a free-flowing venous access line. The infusion site should be monitored for possible infiltration during administration. Suspected extravasation should be managed according to local standard practice for non-vesicants.
•     The patient should be observed during the infusion and, if clinically indicated, following the infusion (see section 4.4).
•     After completion of the infusion, the intravenous administration set should be flushed with sodium chloride 9 mg/mL (0.9%) solution to ensure that all medicinal product has been administered.

Infusion of Onpattro at home may be considered for patients who have tolerated at least 3 infusions well in the clinic. The decision for a patient to receive home infusions should be made after evaluation and recommendation by the treating physician. Home infusions should be performed by a healthcare professional.