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Class: Other Miscellaneous Therapeutic Agents
- Small Interfering Ribonucleic Acids (siRNAs)
- Small Interfering RNAs (siRNAs)
Molecular Formula: C412H480N148Na40O290P40
Brands: Onpattro

Medically reviewed by Last updated on June 3, 2019.


Small interfering RNA (siRNA) that targets transthyretin mRNA.1

Uses for Patisiran

Hereditary Transthyretin-mediated Amyloidosis

Treatment of polyneuropathy in patients with hereditary transthyretin-mediated amyloidosis (designated an orphan drug by FDA for this use).1 2 3 4

Patisiran Dosage and Administration


  • Prepare and administer by a healthcare professional.1

  • Monitor patients during and, if clinically indicated, after infusion for signs and symptoms of infusion-related reactions.1

  • Premedicate with an IV corticosteroid (e.g., dexamethasone phosphate 10 mg or equivalent), oral acetaminophen (500 mg), IV H1-receptor antagonist (diphenhydramine hydrochloride 50 mg or equivalent), and IV H2-receptor antagonist (e.g., ranitidine 50 mg or equivalent) at least 60 minutes prior to start of infusion.1 May give additional or higher doses of premedications as necessary; if IV preparations unavailable or not tolerated, use equivalent oral doses.1

  • In patients who are tolerating the patisiran infusion, but are experiencing adverse effects related to corticosteroid premedication, reduce dosage of the corticosteroid by 2.5-mg increments to a minimum IV dexamethasone phosphate dose of 5 mg or equivalent.1


IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion using an ambulatory infusion pump.1

Do not mix or dilute with other IV drugs.1

Infuse only through a free-flowing dedicated IV line with an infusion set containing an inline polyethersulfone filter (pore size of 1.2 µm).1 The IV line and infusion set should be free of diethylhexylphthalate (DEHP).1

Flush IV line with 0.9% sodium chloride injection after infusion.1


Must filter and dilute commercially available patisiran sodium lipid complex injection concentrate prior to IV infusion.1

Determine number of vials needed based on patient's body weight and recommended dosage.1 Remove vial(s) from the refrigerator and allow to reach room temperature.1 Do not shake or vortex vials.1

The injection concentrate should be a white to off-white homogenous solution; do not use if discoloration or particulate matter is observed.1 A white to off-white coating that may be visible at inner surface of vial should not impact quality of the drug.1

Withdraw entire contents of vial(s) into a single syringe.1 Remove needle and replace with a 0.45-µm polyethersulfone syringe filter.1 Inject contents of syringe into a sterile container using filter needle.1 To prepare final diluted solution for infusion, transfer appropriate volume of filtered solution from the sterile container into a DEHP-free infusion bag and dilute with 0.9% sodium chloride injection to a total volume of 200 mL.1 Gently invert infusion bag to mix.1

Vials contain no preservatives; for single use only.1 Discard any unused portions.1

Administer immediately after dilution; if immediate use not possible, may store infusion bag at room temperature (≤30°C) for up to 16 hours (including infusion time).1 Do not freeze.1

Rate of Administration

Infuse over approximately 80 minutes at an initial rate of approximately 1 mL/minute for the first 15 minutes, followed by approximately 3 mL/minute for remainder of infusion.1

If infusion-related reaction occurs, consider slowing or interrupting infusion depending on severity.1 If infusion has been interrupted, may consider resuming infusion at a slower rate when symptoms resolve.1 (See Infusion-related Reactions under Cautions.)


Dosage of patisiran sodium expressed in terms of patisiran.1


Hereditary Transthyretin-mediated Amyloidosis

Dosage is based on actual body weight.1

Patients weighing ≥100 kg: 0.3 mg/kg by IV infusion once every 3 weeks.1

Patients weighing <100 kg: 30 mg by IV infusion once every 3 weeks.1

If a dose is missed, administer missed dose as soon as possible within 3 days and give next dose at regularly scheduled time (i.e., 3 weeks from the day of the missed dose).1 If missed dose is not administered within 3 days, adjust administration schedule to maintain the recommended 3-week dosing interval.1

Special Populations

Hepatic Impairment

No dosage adjustment necessary in patients with mild hepatic impairment (AST >ULN with normal bilirubin concentrations, or bilirubin concentrations >1–1.5 times the ULN).1

Not studied in patients with moderate or severe hepatic impairment or in patients who have received a prior liver transplant.1

Renal Impairment

No dosage adjustment necessary in patients with mild or moderate renal impairment (estimated GFR 30 to <90 mL/minute per 1.73 m2).1

Not studied in patients with severe renal impairment or end-stage renal disease.1

Geriatric Patients

No dosage adjustment necessary in geriatric patients ≥65 years of age.1

Cautions for Patisiran


  • Manufacturer states none.1


Infusion-related Reactions

Infusion-related reactions (e.g., flushing, back pain, nausea, abdominal pain, dyspnea, headache) reported.1 4 5 6

Premedicate patients at least 60 minutes prior to start of infusion.1 (See General under Dosage and Administration.)

Monitor patients during infusion for signs and symptoms of infusion-related reactions.1 If an infusion-related reaction occurs, consider slowing or interrupting infusion and provide appropriate medical treatment (e.g., corticosteroids) as clinically indicated.1 If infusion has been interrupted, consider resuming infusion at a slower rate when symptoms resolve.1 Discontinue infusion permanently if a serious or life-threatening reaction occurs.1

Reduced Vitamin A Concentrations

Treatment with patisiran may reduce serum vitamin A concentrations.1

Patients receiving patisiran should receive supplementation with the recommended daily allowance (RDA) of vitamin A.1 Manufacturer states that dosages exceeding the RDA should not be administered in an attempt to achieve normal serum vitamin A concentrations since serum concentrations are not reflective of total vitamin A in the body.1

Refer patients who develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness) to an ophthalmologist.1


Anti-patisiran antibodies detected (by measuring antibodies specific to a lipid component of the drug formulation).1 Antibodies do not appear to affect efficacy, safety, pharmacokinetics, or pharmacodynamics of patisiran; however, insufficient data to make definitive conclusions.1

Specific Populations


No data regarding use of patisiran in pregnant women.1

Developmental toxicity (e.g., embryofetal mortality, reduced fetal body weights) and maternal toxicity observed in animal studies.1


Not known whether distributed into human milk.1 Drug not detected in milk of lactating rats; however, some lipid components of the formulation were present.1 Effects of the drug on nursing infants or on milk production not known.1

Consider benefits of breast-feeding and importance of drug to the woman; also consider potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.1

Pediatric Use

Safety and efficacy not established in pediatric patients.1

Geriatric Use

No overall differences in safety or efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1

Hepatic Impairment

Not studied in patients with moderate or severe hepatic impairment.1 Mild hepatic impairment is not expected to affect patisiran exposure.1

Renal Impairment

Not studied in patients with severe renal impairment or end-stage renal disease.1 Mild or moderate renal impairment is not expected to affect patisiran exposure.1

Common Adverse Effects

Upper respiratory tract infections,1 infusion-related reactions,1 4 dyspepsia,1 dyspnea,1 muscle spasms,1 arthralgia,1 erythema,1 bronchitis,1 vertigo.1

Interactions for Patisiran

No formal drug interaction studies to date.1 Not a substrate, inhibitor, or inducer of CYP isoenzymes or transporters.1

Drugs Affecting Hepatic Microsomal Enzymes

In a population pharmacokinetic analysis, concomitant use of potent or moderate CYP3A inducers or inhibitors did not affect patisiran pharmacokinetics.1

Not expected to be affected by inhibitors or inducers of CYP isoenzymes.1

Patisiran Pharmacokinetics

Age, race, gender, and antibody development did not affect steady-state pharmacokinetics of patisiran.1



Steady state attained by 24 weeks at recommended dosage.1


Mean serum transthyretin concentrations reduced by approximately 80% within 10–14 days after single dose of 0.3 mg/kg.1 6


Reductions in serum transthyretin concentrations sustained throughout 3-week dosing interval.1

Plasma Concentrations

Following IV administration of a single dose, peak plasma concentrations and systemic exposure increase in a linear and dose-proportional manner over dose range of 0.01–0.5 mg/kg.1 5 6

Special Populations

Mild hepatic impairment (AST >ULN with normal bilirubin, or bilirubin >1–1.5 times ULN): No effect on systemic exposure.1

Mild or moderate renal impairment (estimated GFR ≥30 to <90 mL/minute per 1.73 m2): No effect on systemic exposure.1



Distributed principally to liver;1 5 small fraction distributed to other organs with fenestrated epithelium (e.g., spleen).5 Does not distribute into CNS or eye.5

Not known whether distributed into human milk.1

Plasma Protein Binding

Low (≤2.1% binding to serum albumin and human α1-acid glycoprotein).1



Metabolized by nucleases to nucleotides of various lengths.1

Elimination Route

Clearance principally through metabolism.1

<1% excreted unchanged in urine.1


3.2 days.1




Injection Concentrate

2–8°C.1 Do not freeze; discard vial if frozen.1

Administer immediately after dilution; alternatively, may store at room temperature (<30°C) for up to 16 hours (including infusion time).1 Do not freeze.1


For information on systemic interactions resulting from concomitant use, see Interactions.


Solution Compatibility1


Sodium chloride 0.9%

Drug Compatibility

Do not mix or dilute with other drugs.1


  • Double-stranded siRNA that targets and causes degradation of a genetically conserved sequence of both wild-type and mutant variants of transthyretin mRNA; reduces transthyretin (disease-causing protein) in patients with hereditary transthyretin-mediated amyloidosis through this RNA interference mechanism.1 3 4 5 7 8

  • Produces high level of transthyretin “knockdown” (suppression of gene expression) and reduces serum concentrations of transthyretin by approximately 80–88%.1 4 5 6 7 8

  • Commercially available as a lipid complex consisting of the siRNA molecule encapsulated in lipid nanoparticles; the lipid-based delivery system is essential for targeted delivery of the drug to liver where transthyretin is principally produced.3 6 7 8 9

Advice to Patients

  • Risk of infusion-related reactions.1 Advise patients to notify their clinician immediately if signs and/or symptoms of infusion-related reactions (e.g., flushing, dyspnea, chest pain, rash, increased heart rate, facial edema) occur.1

  • Importance of advising patients to take the RDA of vitamin A.1 Advise patients to notify their clinician if they experience ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness), and refer patients who develop such symptoms to an ophthalmologist.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., renal disease, hepatic disease).1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Patisiran Sodium Lipid Complex


Dosage Forms


Brand Names



For injection, concentrate, for IV infusion

2 mg/mL (of patisiran)



AHFS DI Essentials™. © Copyright 2021, Selected Revisions June 3, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.


1. Alnylam Pharmaceuticals, Inc. Onpattro (patisiran) lipid complex injection prescribing information. Cambridge, MA; 2018 Aug.

2. Food and Drug Administration. FDA Application: Search Orphan Drug Designations and Approvals. Silver Spring, MD. From FDA website. Accessed 2018 Oct 29.

3. Adams D, Suhr OB, Dyck PJ et al. Trial design and rationale for APOLLO, a Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy. BMC Neurol. 2017; 17:181.

4. Adams D, Gonzalez-Duarte A, O'Riordan WD et al. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018; 379:11-21.

5. Coelho T, Adams D, Silva A et al. Safety and efficacy of RNAi therapy for transthyretin amyloidosis. N Engl J Med. 2013; 369:819-29.

6. Suhr OB, Coelho T, Buades J et al. Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study. Orphanet J Rare Dis. 2015; 10:109.

7. Hawkins PN, Ando Y, Dispenzeri A et al. Evolving landscape in the management of transthyretin amyloidosis. Ann Med. 2015; 47:625-38.

8. Titze-de-Almeida R, David C, Titze-de-Almeida SS. The Race of 10 Synthetic RNAi-Based Drugs to the Pharmaceutical Market. Pharm Res. 2017; 34:1339-1363.

9. Kerschen P, Planté-Bordeneuve V. Current and Future Treatment Approaches in Transthyretin Familial Amyloid Polyneuropathy. Curr Treat Options Neurol. 2016; 18:53.

10. Kristen AV. [What gnaws at the heart and gets on the nerves]. Internist (Berl). 2018; 59:1208-1213.

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