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Patisiran: Drug information

Patisiran: Drug information
(For additional information see "Patisiran: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Onpattro
Brand Names: Canada
  • Onpattro
Pharmacologic Category
  • Anti-Transthyretin Small Interfering Ribonucleic Acid (siRNA) Agent
Dosing: Adult

Note: Safety: Concomitant vitamin A supplementation is advised at appropriate recommended daily allowances during therapy due to patisiran-associated decreases in serum vitamin A concentrations. Premedication: 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; see “Premedications” below.

Polyneuropathy of hereditary-transthyretin mediated amyloidosis

Polyneuropathy of hereditary-transthyretin mediated amyloidosis:

<100 kg (Actual body weight): IV: 0.3 mg/kg once every 3 weeks.

≥100 kg (Actual body weight): IV: 30 mg once every 3 weeks.

Missed dose:

Within 3 days of missed dose: Administer missed dose as soon as possible, then continue dosing according to original schedule.

More than 3 days after missed dose: Administer missed dose as soon as possible, then continue dosing every 3 weeks thereafter.

Premedication:

Premedicate at least 60 minutes prior to each patisiran administration with an IV corticosteroid (eg, dexamethasone 10 mg or equivalent), oral acetaminophen (500 mg), an IV H1 blocker (eg, diphenhydramine 50 mg or equivalent), and an IV H2 blocker (eg, famotidine 20 mg or equivalent) (Ref). An oral equivalent may be administered for premedications not tolerated or not available IV. Additional or higher doses of one or more premedications may be necessary. For patients tolerating patisiran infusions but with adverse effects due to corticosteroid premedication, may reduce IV dexamethasone (or equivalent doses of another corticosteroid) by 2.5 mg increments to a minimum dose of 5 mg.

Dosing: Kidney Impairment: Adult

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).

Dosing: Hepatic Impairment: Adult

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).

Dosing: Adjustment for Toxicity: Adult

Infusion-related reactions:

Mild to moderate: Consider slowing or interrupting the infusion and resuming at a slower infusion rate when symptoms have resolved; consider additional or higher doses of premedication during subsequent infusions to reduce infusion-related reactions risk.

Serious or life-threatening: Discontinue therapy and do not readminister.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

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

Contraindications

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.

Warnings/Precautions

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).

• Reduced vitamin A levels: A decrease in serum vitamin A has been reported with patisiran treatment. Supplement 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.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Onpattro: 10 mg/5 mL (5 mL)

Generic Equivalent Available: US

No

Pricing: US

Solution (Onpattro Intravenous)

10 mg/5 mL (per mL): $2,348.40

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Onpattro: 10 mg/5 mL (5 mL)

Administration: Adult

IV: Following dilution and filtering, administer via an ambulatory infusion pump through a dedicated free-flowing DEHP-free line. Use a DEHP-free infusion set containing a 1.2 micron polyethersulfone 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.

Use: Labeled Indications

Polyneuropathy of hereditary-transthyretin mediated amyloidosis: Treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

Metabolism/Transport Effects

None known.

Drug Interactions

There are no known significant interactions.

Pregnancy Considerations

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 [email protected]). Pregnant women may also register themselves.

Breastfeeding Considerations

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

Monitoring Parameters

Infusion-related reactions; ocular symptoms indicative of vitamin A deficiency (eg, night blindness)

Mechanism of Action

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.

Pharmacokinetics (Adult Data Unless Noted)

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

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AT) Austria: Onpattro;
  • (BE) Belgium: Onpattro;
  • (BG) Bulgaria: Onpattro;
  • (BR) Brazil: Onpattro;
  • (DE) Germany: Onpattro;
  • (ES) Spain: Onpattro;
  • (FR) France: Onpattro;
  • (GB) United Kingdom: Onpattro;
  • (IT) Italy: Onpattro;
  • (JP) Japan: Onpattro;
  • (NL) Netherlands: Onpattro;
  • (PR) Puerto Rico: Onpattro;
  • (PT) Portugal: Onpattro;
  • (RO) Romania: Onpattro;
  • (SE) Sweden: Onpattro;
  • (SI) Slovenia: Onpattro;
  • (SK) Slovakia: Onpattro
  1. Adams D, Gonzalez-Duarte A, O'Riordan WD, et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N Engl J Med. 2018;379(1):11-21. doi:10.1056/NEJMoa1716153 [PubMed 29972753]
  2. Onpattro (patisiran) [prescribing information]. Cambridge, MA: Alnylam Pharmaceuticals Inc; January 2023.
  3. Onpattro (patisiran) [prescribing information]. Cambridge, MA: Alnylam Pharmaceuticals Inc; July 2022.
  4. Onpattro (patisiran) [product monograph]. Oakville, Ontario, Canada: Innomar-Strategies; June 2023.
  5. Refer to manufacturer's labeling.
Topic 118739 Version 45.0

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