Patisiran

Action and Spectrum

Actions and Spectrum: 

Patisiran is a lipid-based nanoparticle designed to suppress the gene responsible for transthyretin expression and contributing to hereditary transthyretin amyloidosis. It uses RNA interference to degrade wild-type and mutant transthyretin mRNAr, reduces serum TTR protein levels and TTR protein deposition in tissues. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Infusion-related reaction (19%) 

Upper respiratory tract infections (29%) 

1-10% 

Erythema (7%) 

Blurred vision (3%) 

Dyspnea (8%) 

Bronchitis (7%) 

AV heart block (2.7%) 

Dyspepsia (8%) 

Vitreous floaters (2%) 

Vertigo (5%) 

Arthralgia (7%) 

Muscle spasms (8%) 

<1% 

Syncope 

Hypotension 

Extravasation 

Postmarketing Reports 

Pruritis 

Black Box Warning

Limited data is available 

Contraindication / Caution

Contraindication/Caution: 

Contraindications include known hypersensitivity, renal impairment, infusion reactions, reduced serum vitamin A levels, advised vitamin supplementation, ocular symptoms, hepatic impairment, drug interactions, pregnancy, and breastfeeding. 

Pregnancy / Lactation

Pregnancy consideration:  

No data is available regarding the administration of the drug during pregnancy. 

Breastfeeding warnings:  

No data is available regarding the excretion of drug in breast milk. 

Pregnancy categories: 

• Category A: well-controlled and satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    
• Category N: No data is available for the drug under this category. 

Pharmacology

Pharmacology: 

Pharmacodynamics: 

ONPATTRO showed a significant reduction in serum TTR within 10-14 days. Repeated dosing over 9 and 18 months resulted in 83% and 84% reductions, respectively. 

Pharmacokinetics: 

Absorption 

Peak concentrations of 7.15 mcg/mL. 

Distribution 

Volume of distribution shows 0.26 L/kg. 

Metabolism 

Metabolized by nucleases resulting in the formation of nucleotides. 

Elimination and Excretion 

The half-life of the drug is 3.2 days. 

Adminstartion

Administration: 

Solution should reach room temperature without shaking or vortexing and the dosage should be calculated based on weight. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: patisiran 

Pronounced: puh-TISS-uh-ran 

Why do we use patisiran? 

Patisiran treatS hereditary transthyretin-mediated amyloidosis (hATTR) a genetic disorder characterized by abnormal amyloid protein accumulation in organs. It targets the liver the site of TTR production to slow down or stop hATTR progression by improving symptoms and quality of life.