Note: At least 60 minutes prior to administration of patisiran, premedicate with a corticosteroid, acetaminophen, an H1 blocker, and an H2 blocker to reduce the risk of infusion-related reactions (IRR).
Polyneuropathy: IV: Base dose on actual body weight.
<100 kg: 0.3 mg/kg once every 3 weeks
≥100 kg: 30 mg once every 3 weeks
Missed dose:
Within 3 days of missed dose: Administer dose, then continue dosing according to original schedule.
More than 3 days after missed dose: Administer dose, then continue dosing every 3 weeks thereafter.
eGFR ≥30 to <90 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR <30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Mild impairment (bilirubin ≤1 x ULN and AST >1 x ULN or bilirubin >1 to 1.5 x ULN): No dosage adjustment necessary.
Moderate or severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
Infusion-related reactions (IRR): Consider slowing or discontinuing the infusion and resume at a slower infusion rate when symptoms have resolved; consider additional or higher doses of premedication in these patients during subsequent infusions to reduce IRR risk. If a serious of life-threatening IRR occurs, discontinue and do not readminister.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Onpattro: 10 mg/5 mL (5 mL)
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Onpattro: 10 mg/5 mL (5 mL)
IV: Following dilution and filtering, administer via an ambulatory infusion pump through a dedicated free-flowing venous access line with a DEHP-free infusion set containing a 1.2 micron polyethersulfone (PES) in-line infusion filter. Infuse over ~80 minutes, with an initial infusion rate of 1 mL/minute for 15 minutes, then increase to ~3 mL/minute for the remainder of the infusion (may extend duration of infusion >80 minutes to manage or prevent infusion-related reactions. After infusion is complete, flush IV administration set with NS. Monitor infusion site for infiltration and manage suspected extravasation using local standard practice for nonvesicants.
Polyneuropathy: Treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Respiratory: Upper respiratory tract infection (29%)
Miscellaneous: Infusion related reaction (19%)
1% to 10%:
Cardiovascular: Atrioventricular block (3%; including complete atrioventricular block)
Dermatologic: Erythema of skin (7%)
Gastrointestinal: Dyspepsia (8%)
Nervous system: Vertigo (5%)
Neuromuscular & skeletal: Arthralgia (7%), muscle spasm (8%)
Ophthalmic: Blurred vision (3%), dry eye syndrome (5%), vitreous opacity (2%)
Respiratory: Bronchitis (7%), dyspnea (8%)
Frequency not defined:
Endocrine & metabolic: Vitamin A deficiency
Immunologic: Antibody development
There are no contraindications listed in the US manufacturer's labeling.
Canadian labeling: Severe hypersensitivity (eg, anaphylaxis) to patisiran or any component of the formulation.
Concerns related to adverse effects:
• Infusion-related reactions: Infusion-related reactions (IRR) have been reported, with a majority occurring within the first 2 infusions and the frequency decreasing with additional infusions. Common symptoms included abdominal, back or chest pain, dyspnea, facial edema, flushing, headache, nausea, rash, and tachycardia; severe hypotension and syncope have also been reported. Premedicate with a corticosteroid, acetaminophen, and antihistamines (H1 and H2 blockers). Monitor closely; if an IRR occurs, consider slowing or interrupting the infusion. If interrupted, wait until symptoms have resolved before resuming the infusion at a slower rate. With future infusions, consider a slower infusion rate or higher doses of premedications. If a serious IRR occurs, stop the infusion and do not resume.
• Reduced vitamin A levels: A decrease in serum vitamin A has been reported with patisiran treatment. Supplement at the recommended daily allowance (RDA) of vitamin A during treatment. Do not administer doses higher than the RDA; serum vitamin A levels do not reflect the total vitamin A in the body. If ocular symptoms such as night blindness develop, refer the patient to an ophthalmologist.
None known.
There are no known significant interactions.
Patisiran decreases serum concentrations of vitamin A, which is required for normal fetal development. The effects to the fetus of maternal vitamin A supplementation during patisiran therapy, or the effects to the fetus of reducing maternal serum transthyretin, are not known.
Data collection to monitor pregnancy and infant outcomes following exposure to patisiran is ongoing. Health care providers are encouraged to enroll females exposed to patisiran during pregnancy in the Pregnancy Registry (877-256-9526 or alnylampregnancyprogram@iqvia.com). Pregnant women may also register themselves.
It is not known if patisiran is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother
Infusion-related reactions; ocular symptoms indicative of vitamin A deficiency (eg, night blindness)
Patisiran is a double-stranded small interfering ribonucleic acid (siRNA) that causes degradation of mutant and wild-type transthyretin (TTR) mRNA through RNA interference, which results in a reduction of serum TTR protein and TTR protein deposits in tissues. Serum TTR is a carrier of retinol binding protein, which is involved in the transport of vitamin A in the blood.
Onset: 10 to 14 days (mean serum TTR reduced by ~80%)
Distribution: Vdss: 0.26 ± 0.2 L/kg
Protein binding: Plasma protein: ≤2.1% (albumin and human alpha1-acid glycoprotein)
Metabolism: By nucleases to nucleotides of various lengths
Half-life elimination: 3.2 ± 1.8 days
Excretion: Urine: <1% as unchanged drug
Solution (Onpattro Intravenous)
10 mg/5 mL (per mL): $2,348.40
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