sion bag containing 0.9% Sodium ChlorideInjection, USP for a total volume of 200 mL. Use infusion bags that are di(2-ethylhexyl)phthalate-free (DEHPfree).
•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 afterpreparation. If not used immediately, store in the infusion bag at room temperature (up to 30°C [86°F]) for up to16 hours (including infusion time). Do not freeze.
2.4 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 approximately80 minutes, at an initial infusion rate of approximately 1 mL/min for the first 15 minutes, then increase toapproximately 3 mL/min for the remainder of the infusion. The duration of infusion may be extended in the eventof an IRR [see Warnings and Precautions (5.1)].
•Administer only through a free-flowing venous access line. Monitor the infusion site for possible infiltrationduring drug administration. Suspected extravasation should be managed according to local standard practice fornon-vesicants.
•Observe the patient during the infusion and, if clinically indicated, following the infusion [see Warnings andPrecautions (5.1)].
•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.
3 DOSAGE FORMS AND STRENGTHS
Lipid Complex Injection: 10 mg/5 mL (2 mg/mL) white to off-white, opalescent, homogeneous solution in a single-dose
vial.
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 Infusion-Related ReactionsInfusion-related reactions (IRRs) have been observed in patients treated with ONPATTRO. In clinical studies, all patientsreceived premedication with a corticosteroid, acetaminophen, and antihistamines (H1 and H2 blockers) to reduce the riskof IRRs. In a controlled clinical study, 19% of ONPATTRO-treated patients experienced IRRs, compared to 9% ofplacebo-treated patients. Among ONPATTRO-treated patients who experienced an IRR, 79% experienced the first IRR
within the first 2 infusions. The frequency of IRRs decreased over time. IRRs led to infusion interruption in 5% ofpatients. IRRs resulted in permanent discontinuation of ONPATTRO in less than 1% of patients in clinical studies. Acrossclinical studies, the most common symptoms (reported in greater than 2% of patients) of IRRs with ONPATTRO wereflushing, back pain, nausea, abdominal pain, dyspnea, and headache [see Adverse Reactions (6.1)].
One patient in theONPATTRO expanded access program had a severe adverse reaction of hypotension and syncope during an ONPATTROinfusion.
Patients should receive premedications on the day of ONPATTRO infusion, at least 60 minutes prior to the start ofinfusion [see Dosage and Administration (2.2)]. Monitor patients during the infusion for signs and symptoms of IRRs. Ifan IRR occurs, consider slowing or interrupting the ONPATTRO infusion and instituting medical management (e.g.,corticosteroids or other symptomatic treatment), as clinically indicated. If the infusion is int |
