Patisiran is a transthyretin-directed small interfering RNA used to treat polyneuropathy of hereditary transthyretin-mediated amyloidosis.

Brand Names
Generic Name
DrugBank Accession Number

Parisiran is a first in class short interfering RNA for the treatment of patients with polyneuropathy caused by hereditary transthyretin-mediated amyloidosis 4. It is marketed as Onpattro which is formulated as patisiran within a liposome envelope for better delivery to the liver, where transthyretin is produced. The approval for Onpattro was granted to Alnylam Pharmaceuticals, Inc. in August of 2018. Onpattro has been granted Fast Track, Priority Review and Breakthrough Therapy, and Orphan Drug designations.

Approved, Investigational
Biologic Classification
Gene Therapies
Other gene therapies
  • Patisiran
External IDs
  • ALN-18328
  • ALN-TTR02



Patisirant is indicated for the treatment of hereditary transthyretin-mediated amyloidosis in adults Label.

It is administered with pre-medication to reduce complications Label. These include an intravenous corticosteroid equivalent to 10 mg of dexamethasone, 500 mg of oral acetaminophen, an intravenous histamine H1 blocker equivalent to 50 mg of diphenhydramine, and an intravenous histamine H2 blocker equivalent to 50 mg of ranitidine

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Associated Conditions
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Transthyretin normally plays a role in the transport of vitamin A in conjunction with retinol binding protein 1. Mutant transthyretin of the ATTR genotype is capable of forming amyloid fibrils and creating protein deposits in a condition known as transthyretin-mediated amyloidosis.

Patisiran reduces the amount of wild-type and mutant transthyretin mRNA available for translation through RNA interference 2,3,Label. This has the effect of decreasing circulating transthyretin protein and reducing the amyloid deposits associated with transthyretin-mediated amyloidosis.

Mechanism of action

Patisirant is a double-stranded short interfering RNA (siRNA) targeting mRNA encoding both wild-type and mutant transthyretin 3,Label. Patisiran enters the cell an is processed by the Dicer enzyme. This processing involved cleaving overhanging nucleotides on the edges of the RNA. Once processed the siRNA can bind to the RNA-induced silencing complex (RISC). RISC separates the strands of the RNA sequence. One strand is released and one remains bound. The bound strand then acts as a targeting sequence for a complimentary mRNA sequence. In this case, the bound strand of patisiran binds to the complimentary transthyretin mRNA and aligns the RISC complex with it. The transthyretin mRNA is then cleaved and rendered non-functional. One targeting sequence may be used to destroy many copies of complimentary mRNA.

ATransthyretin mRNA

Patisiran follows a linear dose-proportional absorption curve Label. Over 95% of administered drug remains with the liposomal complex which distributes primarily to the liver. With chronic dosing at 0.3 mg/kg every 3 weeks, steady state is reached by 24 weeks. The accumulation factor of the AUC is 3.2 with chronic dosing.

Volume of distribution

The steady state volume of distribution of patisiran is 0.26 ± 0.20 L/kg observed with chronic dosing at 0.3 mg/kg every 3 weeks Label.

Protein binding

Less than 2.1% of patisiran is bound to serum albumin and α1-acid glycoprotein Label.


Patisiran is metabolized to individual nucleotides and oligonucleotides of varying lengths by nucleases similarly to endogenous RNA Label

Route of elimination

Less than 1% is excreted through the urine. The bulk of the drug is broken down by nucleases Label. No dosage adjustment is required in patients with mild hepatic impairment or mild to moderate renal impairment. No data exists for patients with severe to end-stage renal impairment or moderate to severe hepatic impairment.


Patisiran has a terminal elimination half-life of 3.2 ± 1.8 days Label.


The total body clearance of patisiran is 3.0 ± 2.5 mL/h/kg Label.

Adverse Effects
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Patisiran produced no signs of embryo-fetal toxicity at dosages of up to 1.5 mg/kg in rats Label. In rabbits given dosages of 0, 0.3, 1, and 2 mg/kg embryo-fetal and maternal toxicity were seen at mid and high dosages. No data exists in human subjects regarding risk during pregnancy.

Patisirant does not appear to be present in breast milk, however the lipid components of the liposomal dosage form are present Label.

Patisirant is immunogenic with specific antibodies appearing in 3.6% of treated patients Label. While there is no evidence of these antibodies reducing the efficacy of the drug, there is a risk of experiencing immunologic complications associated with the use of biologics.

Patisirant is known to reduce available vitamin A. Patients using the drug are at increased risk of vitamin A deficiency Label.

Not Available
Pharmacogenomic Effects/ADRs
Not Available


Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
No interactions found.


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Product Ingredients
IngredientUNIICASInChI Key
Patisiran sodiumWO0YM16LKG1386913-72-9Not applicable
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
OnpattroInjection, solution, concentrate2 mg/mlIntravenousAlnylam Netherlands B.V.2021-03-17Not applicableEU flag
OnpattroSolution2 mg / mLIntravenousAlnylam Netherlands B.V.2019-07-25Not applicableCanada flag
OnpattroInjection, lipid complex2 mg/1mLIntravenousAlnylam Pharmaceuticals, Inc.2018-08-13Not applicableUS flag


ATC Codes
N07XX12 — Patisiran
Drug Categories
Not classified
Affected organisms
  • Humans and other mammals

Chemical Identifiers

CAS number


General References
  1. Butler JS, Chan A, Costelha S, Fishman S, Willoughby JL, Borland TD, Milstein S, Foster DJ, Goncalves P, Chen Q, Qin J, Bettencourt BR, Sah DW, Alvarez R, Rajeev KG, Manoharan M, Fitzgerald K, Meyers RE, Nochur SV, Saraiva MJ, Zimmermann TS: Preclinical evaluation of RNAi as a treatment for transthyretin-mediated amyloidosis. Amyloid. 2016 Jun;23(2):109-18. doi: 10.3109/13506129.2016.1160882. Epub 2016 Mar 31. [Article]
  2. Adams D, Gonzalez-Duarte A, O'Riordan WD, Yang CC, Ueda M, Kristen AV, Tournev I, Schmidt HH, Coelho T, Berk JL, Lin KP, Vita G, Attarian S, Plante-Bordeneuve V, Mezei MM, Campistol JM, Buades J, Brannagan TH 3rd, Kim BJ, Oh J, Parman Y, Sekijima Y, Hawkins PN, Solomon SD, Polydefkis M, Dyck PJ, Gandhi PJ, Goyal S, Chen J, Strahs AL, Nochur SV, Sweetser MT, Garg PP, Vaishnaw AK, Gollob JA, Suhr OB: Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018 Jul 5;379(1):11-21. doi: 10.1056/NEJMoa1716153. [Article]
  3. Dana H, Chalbatani GM, Mahmoodzadeh H, Karimloo R, Rezaiean O, Moradzadeh A, Mehmandoost N, Moazzen F, Mazraeh A, Marmari V, Ebrahimi M, Rashno MM, Abadi SJ, Gharagouzlo E: Molecular Mechanisms and Biological Functions of siRNA. Int J Biomed Sci. 2017 Jun;13(2):48-57. [Article]
  4. FDA Announcement: Patisiran [Link]
  5. FDA Approved Drug Products: ONPATTRO (patisiran) injection [Link]
FDA label
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Clinical Trials

Clinical Trials
3Active Not RecruitingTreatmentAmyloidosis, Hereditary / Transthyretin Amyloidosis1
3Active Not RecruitingTreatmentTransthyretin Amyloidosis (ATTR) With Cardiomyopathy1
3CompletedTreatmentAmyloid Neuropathies / Amyloid Neuropathies, Familial / Amyloidosis, Hereditary / Amyloidosis, Hereditary, Transthyretin-Related / Familial Amyloid Polyneuropathy (FAP) / TTR-mediated Amyloidosis1
3CompletedTreatmentAmyloidosis, Familial / Transthyretin Amyloidosis1
2CompletedTreatmentTTR-mediated Amyloidosis2
1CompletedTreatmentTransthyretin Mediated Amyloidosis (ATTR)1
1CompletedTreatmentTTR-mediated Amyloidosis1
0Not Yet RecruitingTreatmentPolyneuropathies1
Not AvailableAvailableNot AvailableATTR Amyloidosis With Cardiomyopathy / Transthyretin-mediated Amyloidosis With Cardiomyopathy1


Not Available
Not Available
Dosage Forms
Injection, lipid complexIntravenous2 mg/1mL
Injection, solution, concentrateIntravenous2 mg/ml
Injection, solution, concentrateIntravenous; Parenteral2 MG/ML
SolutionIntravenous2 mg / mL
Not Available
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8802644No2014-08-122030-10-21US flag
US8778902No2014-07-152021-03-30US flag
US9234196No2016-01-122029-10-20US flag
US8822668No2014-09-022029-04-15US flag
US9364435No2016-06-142029-04-15US flag
US8158601No2012-04-172030-11-10US flag
US8741866No2014-06-032029-10-20US flag
US8168775No2012-05-012029-10-20US flag
US9193753No2015-11-242021-03-30US flag
US8334373No2012-12-182025-05-27US flag
US8058069No2011-11-152029-04-15US flag
US8492359No2013-07-232029-04-15US flag
US8642076No2014-02-042027-10-03US flag
US8362231No2013-01-292021-03-30US flag
US8895718No2014-11-252021-03-30US flag
US8552171No2013-10-082021-03-30US flag
US8372968No2013-02-122021-03-30US flag
US9943538No2018-04-172023-11-04US flag
US9943539No2018-04-172023-11-04US flag
US9567582No2017-02-142021-03-30US flag
US8895721No2014-11-252021-03-30US flag
US11079379No2021-08-032035-08-27US flag
US10240152No2019-03-262029-10-20US flag
US11141378No2021-10-122029-04-15US flag


Not Available
Experimental Properties
Not Available


Pharmacological action
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
Uniprot ID
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
Protein group
Pharmacological action
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...


Drug created at August 10, 2018 19:20 / Updated at February 05, 2023 22:13