Patisiran: Compatibility with Commonly Used Infusion Components

Patisiran: Compatibility with Commonly Used Infusion Components

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The full Prescribing Information for ONPATTRO® (patisiran) is provided here. Alnylam Pharmaceuticals does not recommend the use of its products in any manner that is inconsistent with the approved Prescribing Information. This resource may contain information that is not in the approved Prescribing Information.

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INDEX

Dosing and Preparation Information – Label Information – Abbreviations – References

Dosing and preparation information

Compatibility Study Results

A compatibility and stability study was performed to evaluate the patisiran admixture with commonly used IV administration devices. Different configurations of the IV administration devices were tested with parameters including concentration of the admixture, residence time in the infusion components, temperature, and light exposure. The materials of construct are summarized in Table 1.1

All configurations of the IV administration devices passed the stability and compatibility evaluation with patisiran admixture. The evaluation of chemical and physical stability of the patisiran drug product admixture was performed by selecting commonly available infusion bags and administration components. The experiments were configured to evaluate commonly available configurations of the infusion bag and administration components as could be reasonably anticipated in a clinical or commercial setting.1

In no case did the prepared admixture exceed the allowable range from the initial concentration of siRNA or lipid content. Additionally, in no case did drug substance purity, pH, particle size, or percent encapsulation of the siRNA exceed the allowable ranges.1

These data thereby confirmed that the admixture was chemically and physically stable within the variables studied, and no chemical incompatibility or instability was expected for the admixture if exposed to the materials of construction of commonly available infusion components. The components utilized for the assessment and their materials of construction are summarized in Table 1.1

Due to the hydrophobic nature of the lipid nanoparticles, and an increased propensity for leaching of the plasticizer DEHP from PVC contact surfaces that contain this plasticizer, only DEHP-free PVC or non-PVC DEHP-free infusion components were selected for the analysis. Additionally, instructions to avoid the use of components containing this plasticizer are included on the product label.1,2

Compatibility with Other Infusion Components

The evaluation did not extend to devices other than the components tested in the study. The decision to administer patisiran via devices other than those recommended in the US Prescribing Information should be determined on a case-by-case basis in accordance with established policies and guidelines set forth by the relevant administrative body or bodies for a given health care setting.

Table 1. Materials of Construction by Component.1

onpattro prescribing information – Relevant content

The DOSAGE AND ADMINISTRATION section provides the following information2:

Preparation Instructions

• 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).

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.

Abbreviations

DEHP = di-(2-ethylhexyl)-phthalate; IV = intravenous; PES = polyethersulfone; PVC = polyvinyl chloride; siRNA = small interfering ribonucleic acid; US = United States.

Updated 4 December 2024

References

1.  Alnylam Pharmaceuticals. Data on file. MED-ALL-TTR02-1900027.

2.  ONPATTRO (patisiran) Prescribing Information. Cambridge, MA: Alnylam Pharmaceuticals, Inc.