Patisiran

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/1.73m 2 ) [see Clinical Pharmacology ] . ONPATTRO has not been studied in patients with severe renal impairment or end-stage renal disease.

Hepatic Impairment No dose adjustment is necessary in patients with mild hepatic impairment (bilirubin ≤1 × ULN and AST >1 × ULN, or bilirubin >1.0 to 1.5 × ULN) [see Clinical Pharmacology ] . ONPATTRO has not been studied in patients with moderate or severe hepatic impairment.

Required Premedication All patients should receive premedication prior to ONPATTRO administration to reduce the risk of infusion-related reactions (IRRs) [see Warnings and Precautions ] . Each of the following premedications should be given on the day of ONPATTRO infusion at least 60 minutes prior to the start of infusion: Intravenous corticosteroid (e.g., dexamethasone 10 mg, or equivalent) Oral acetaminophen (500 mg) Intravenous H1 blocker (e.g., diphenhydramine 50 mg, or equivalent) Intravenous H2 blocker (e.g., famotidine 20 mg, or equivalent) For premedications not available or not tolerated intravenously, equivalents may be administered orally.

For patients who are tolerating their ONPATTRO infusions but experiencing adverse reactions related to the corticosteroid premedication, the corticosteroid may be reduced by 2.5 mg increments to a minimum dose of 5 mg of dexamethasone (intravenous), or equivalent. Some patients may require additional or higher doses of one or more of the premedications to reduce the risk of IRRs [see Warnings and Precautions ] .

Preparation Instructions ONPATTRO must be filtered and diluted 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 and allow to warm to room temperature. Do not shake or vortex. Inspect visually for particulate matter and discoloration.

Do not use if discoloration 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 dose of ONPATTRO based on the recommended weight-based dosage [see Dosage and Administration ]. 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 0.9% Sodium Chloride Injection, USP for a total volume of 200 mL. Use infusion bags that are di(2-ethylhexyl)phthalate-free (DEHP-free). Gently invert the bag to mix the solution. Do not shake. Do not mix or dilute with other drugs. Discard any unused portion of ONPATTRO.

ONPATTRO does not contain preservatives. The diluted solution should be administered immediately after preparation. If not used immediately, store in the infusion bag at room temperature (up to 30°C [86°F]) for up to 16 hours (including infusion time). Do not freeze.

Infusion Instructions Use a dedicated line with an infusion set containing a 1.2 micron polyethersulfone (PES) in-line infusion filter. Use infusion sets and lines that are DEHP-free. Infuse the diluted solution of ONPATTRO intravenously, via an ambulatory infusion pump, over approximately 80 minutes, at an initial infusion rate of approximately 1 mL/min for the first 15 minutes, then 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 Warnings and Precautions ]. Administer only through a free-flowing venous access line. Monitor the infusion site for possible infiltration during drug administration. Suspected extravasation should be managed according to local standard practice for non-vesicants.

Observe the patient during the infusion and, if clinically indicated, following the infusion [see Warnings and Precautions ]. After completion of the infusion, flush the intravenous administration set with 0.9% Sodium Chloride Injection, USP to ensure that all ONPATTRO has been administered.