Patisiran
Patisiran Uses, Dosage, Side Effects, Food Interaction and all others data.
Parisiran is a first in class short interfering RNA for the treatment of patients with polyneuropathy caused by hereditary transthyretin-mediated amyloidosis . 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.
Transthyretin normally plays a role in the transport of vitamin A in conjunction with retinol binding protein . 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 . This has the effect of decreasing circulating transthyretin protein and reducing the amyloid deposits associated with transthyretin-mediated amyloidosis.
| Trade Name | Patisiran |
| Availability | Prescription only |
| Generic | Patisiran |
| Patisiran Other Names | Patisiran |
| Related Drugs | tafamidis, Vyndamax, Onpattro, Vyndaqel, Amvuttra |
| Weight | 2mg/ml, |
| Type | Intravenous Solution, Intravenous |
| Protein binding | Less than 2.1% of patisiran is bound to serum albumin and α1-acid glycoprotein . |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Patisiran is a transthyretin-directed small interfering RNA used to treat polyneuropathy of hereditary transthyretin-mediated amyloidosis.
Patisirant is indicated for the treatment of hereditary transthyretin-mediated amyloidosis in adults .
It is administered with pre-medication to reduce complications . 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
Patisiran is also used to associated treatment for these conditions: Hereditary transthyretin-mediated amyloidosis
How Patisiran works
Patisirant is a double-stranded short interfering RNA (siRNA) targeting mRNA encoding both wild-type and mutant transthyretin . 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.
Toxicity
Patisiran produced no signs of embryo-fetal toxicity at dosages of up to 1.5 mg/kg in rats . 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 .
Patisirant is immunogenic with specific antibodies appearing in 3.6% of treated patients . 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 .
Patisiran Disease Interaction
Moderate: hepatic impairment, severe renal impairment, vitamin A deficiency
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 .
Elimination Route
Patisiran follows a linear dose-proportional absorption curve . 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.
Half Life
Patisiran has a terminal elimination half-life of 3.2 ± 1.8 days .
Clearance
The total body clearance of patisiran is 3.0 ± 2.5 mL/h/kg .
Elimination Route
Less than 1% is excreted through the urine. The bulk of the drug is broken down by nucleases . 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.
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