Onpattro

ONPATTRO is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

• For patients weighing less than 100 kg, the recommended dosage is 0.3 mg/kg every 3 weeks by intravenous infusion. For patients weighing 100 kg or more, the recommended dosage is 30 mg (
  2.1 Dosing Information

  ONPATTRO should be administered by a healthcare professional.

  ONPATTRO is administered via intravenous (IV) infusion. Dosing is based on actual body weight.

  For patients weighing less than 100 kg, the recommended dosage is 0.3 mg/kg once every 3 weeks.

  For patients weighing 100 kg or more, the recommended dosage is 30 mg once every 3 weeks.

  Missed Dose

  If a dose is missed, administer ONPATTRO as soon as possible.

  • If ONPATTRO is administered within 3 days of the missed dose, continue dosing according to the patient's original schedule.
  • If ONPATTRO is administered more than 3 days after the missed dose, continue dosing every 3 weeks thereafter.
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• Premedicate with a corticosteroid, acetaminophen, and antihistamines (
  2.2 Required Premedication

  All patients should receive premedication prior to ONPATTRO administration to reduce the risk of infusion-related reactions (IRRs)

  [see Warnings and Precautions (5.1)]

  . 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 (5.1)]

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• Filter and dilute prior to administration (
  2.3 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 (2.1)].
  • 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.
  )
• Infuse over approximately 80 minutes (
  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 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 (5.1)].
  • 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 (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.
  )

Lipid Complex Injection: 10 mg/5 mL (2 mg/mL) white to off-white, opalescent, homogeneous solution in a single-dose vial.

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ONPATTRO during pregnancy. Physicians are encouraged to enroll pregnant patients, or pregnant women may register themselves in the program by calling 1-877-256-9526 or by contacting alnylampregnancyprogram@iqvia.com.

• Infusion-related reactions: Monitor for signs and symptoms during infusion. Slow or interrupt the infusion if clinically indicated. Discontinue the infusion if a serious or life-threatening infusion-related reaction occurs (
  5.1 Infusion-Related Reactions

  Infusion-related reactions (IRRs) have been observed in patients treated with ONPATTRO. In clinical studies, all patients received premedication with a corticosteroid, acetaminophen, and antihistamines (H1 and H2 blockers) to reduce the risk of IRRs. In a controlled clinical study, 19% of ONPATTRO-treated patients experienced IRRs, compared to 9% of placebo-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% of patients. IRRs resulted in permanent discontinuation of ONPATTRO in less than 1% of patients in clinical studies. Across clinical studies, the most common symptoms (reported in greater than 2% of patients) of IRRs with ONPATTRO were flushing, back pain, nausea, abdominal pain, dyspnea, and headache

  [see Adverse Reactions (6.1)]

  . Severe hypotension and syncope have been reported as symptoms of IRRs in the expanded access program and postmarketing setting.

  Patients should receive premedications on the day of ONPATTRO infusion, at least 60 minutes prior to the start of infusion

  [see Dosage and Administration (2.2)]

  . Monitor patients during the infusion for signs and symptoms of IRRs. If an 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 interrupted, consider resuming at a slower infusion rate only if symptoms have resolved. In the case of a serious or life-threatening IRR, the infusion should be discontinued and not resumed.

  Some patients who experience IRRs may benefit from a slower infusion rate or additional or higher doses of one or more of the premedications with subsequent infusions to reduce the risk of IRRs

  [see Dosage and Administration (2.2)]

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• Reduced serum vitamin A levels and recommended supplementation: Supplement with the recommended daily allowance of vitamin A. Refer to an ophthalmologist if ocular symptoms suggestive of vitamin A deficiency occur (
  5.2 Reduced Serum Vitamin A Levels and Recommended Supplementation

  ONPATTRO treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance of vitamin A is advised for patients taking ONPATTRO. Higher doses than the recommended daily allowance of vitamin A should not be given to try to achieve normal serum vitamin A levels during treatment with ONPATTRO, as serum vitamin A levels do not reflect the total vitamin A in the body.

  Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness).
  )