ONPATTRO Concentrate for solution for infusion Ref.[7631] Active ingredients: Patisiran

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 2500 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 (ranitidine 50 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 ULN and 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.

Method of administration

Onpattro is for intravenous use.

• Onpattro must be diluted prior to intravenous infusion (see instructions in 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.

In case of overdose, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and given symptomatic treatment, as appropriate.

Shelf life

Unopened vials: 3 years.

After dilution: Chemical and physical in-use stability has been demonstrated for 16 hours at room temperature (up to 30°C). From a microbiological point of view, it is recommended that the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and should not be longer than 16 hours at either 2°C to 8°C or room temperature (up to 30°C), including infusion time.

Store in a refrigerator (2°C to 8°C).

Do not freeze.

If refrigeration is not available, Onpattro can be stored at room temperature up to 25°C for up to 14 days.

For storage conditions after dilution of the medicinal product, see section 6.3.

5 mL concentrate in a Type I glass vial with a chlorobutyl stopper and an aluminium flip-off cap. Pack size of 1 vial.

This medicinal product is for single-use only.

Onpattro must be diluted with sodium chloride 9 mg/mL (0.9%) solution prior to intravenous infusion. The diluted solution for infusion should be prepared by a healthcare professional using aseptic technique as follows:

• Remove Onpattro from the refrigerator. Do not shake or vortex.
• Discard vial if it has been frozen.
• Inspect visually for particulate matter and discolouration. Do not use if discolouration or foreign particles are present. Onpattro is a white to off-white, opalescent, homogeneous solution. A white to off-white coating may be observed on the inner surface of the vial, typically at the liquid-headspace interface. Product quality is not impacted by presence of the white to off-white coating.
• Calculate the required volume of Onpattro based on the recommended weight-based dosage (see section 4.2).
• Withdraw the entire contents of one or more vials into a single sterile syringe.
• Filter Onpattro through a sterile 0.45 micron polyethersulfone (PES) syringe filter into a sterile container.
• Withdraw the required volume of filtered Onpattro from the sterile container using a sterile syringe.
• Dilute the required volume of filtered Onpattro into an infusion bag containing sodium chloride 9 mg/mL (0.9%) solution for a total volume of 200 mL. Use infusion bags that are free of di(2-ethylhexyl)phthalate (DEHP).
• Gently invert the bag to mix the solution. Do not shake. Do not mix or dilute with other medicinal products.
• Discard any unused portion of Onpattro. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.