Onpattro (patisiran sodium, lipid complex)
Amyloidosis Agents - Transthyretin (TTR) Suppression Intravenous Vial (Ml)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Patisiran, a small interfering RNA (siRNA) that targets transthyretin messenger RNA (mRNA), is a transthyretin (TTR) silencer.
Patisiran sodium is a double-stranded small interfering RNA (siRNA) that targets and causes degradation of transthyretin messenger RNA (mRNA); this RNA interference mechanism reduces production of transthyretin (the disease-causing protein) in patients with hereditary transthyretin-mediated amyloidosis. Transthyretin is a carrier for retinol binding protein, which is involved in the transport of vitamin A and thyroxine.
Patisiran is commercially available as a lipid complex consisting of the siRNA molecule encapsulated in lipid nanoparticles; the lipid-based delivery system is essential for the targeted delivery of the siRNA to the liver where transthyretin is principally produced. Following IV administration of patisiran sodium lipid complex, the lipid nanoparticles are opsonized by apolipoprotein E (apo E) and delivered to the liver through interaction with apoE receptors expressed on hepatocytes. Patisiran siRNA targets a genetically conserved sequence (i.e., the noncoding 3' untranslated region) of wild-type and mutant variants of transthyretin mRNA, suppressing gene expression (''knockdown'') and resulting in dose-dependent reductions in plasma concentrations of both forms of transthyretin protein.
The high level of transthyretin knockdown with patisiran is comparable to the reduction in mutant transthyretin achieved following liver transplantation. In patients with hereditary transthyretin-mediated amyloidosis, mean serum transthyretin concentrations were reduced by approximately 80% within 10-14 days after a single patisiran dose of 0.3 mg/kg, with a mean maximum reduction of 88% observed with repeated dosing (0.3 mg/kg once every 3 weeks over 18 months). Studies have shown that patisiran-induced reductions in serum transthyretin concentrations are sustained throughout the 3-week dosing interval.
While transthyretin also is produced locally in the retina and choroid plexus, the drug does not appear to reduce transthyretin synthesis in the eye and CNS.
Following IV administration, peak plasma concentrations and systemic exposure of patisiran increase in a linear and dose-proportional manner over the dose range of 0.01-0.5 mg/kg. More than 95% of patisiran in the circulation is associated with the lipid complex. Plasma protein binding of the drug is low (no more than 2.1% bound to serum albumin and human alpha1-acid glycoprotein).
Patisiran is principally distributed to the liver, with a small fraction distributed to other organs with a fenestrated epithelium (e.g., spleen). The drug does not distribute into the CNS or the eye. Steady-state concentrations of the drug are attained within 24 weeks at the recommended dosage.
Patisiran is metabolized to nucleotides of various lengths by nucleases. The mean terminal elimination half-life of the drug is 3.2 days. Clearance of patisiran occurs principally through metabolism; less than 1% of a patisiran dose is excreted unchanged in the urine.
USES: This medication is used to treat nerve problems due to a certain inherited condition (transthyretin-mediated amyloidosis). This condition causes a protein that your body normally makes (transthyretin-TTR), to change shape and build up in different parts of your body, which can affect the nerves, heart, and stomach/intestines. This medication works by decreasing the buildup of TTR in your body.
Generic name: patisiran sodium, lipid complex
Pronunciation: (PAT-i-SIR-an)
Drug class: Amyloidosis Agents - Transthyretin (TTR) Suppression
Therapeutic class: Endocrine
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Onpattro
Indications
The following indications are listed for Onpattro:
- Transthyretin Familial Amyloid Polyneuropathy
Also known as: Polyneuropathy Due To Attr, Polyneuropathy Due To Transthyretin Amyloidosis, Transthyretin Amyloid Polyneuropathy, Ttr Familial Amyloid Polyneuropathy.
Dosing
Dosage of patisiran sodium is expressed in terms of patisiran.
The recommended dosage of patisiran for the treatment of polyneuropathy in adults with hereditary transthyretin-mediated amyloidosis is based on actual body weight. Patients weighing <100 kg should receive a dosage of 0.3 mg/kg by IV infusion once every 3 weeks and patients weighing >=100 kg should receive a dosage of 30 mg by IV infusion once every 3 weeks.
If a dose of patisiran is missed, administer the missed dose as soon as possible within 3 days and administer the next dose at the regularly scheduled time (i.e., 3 weeks from the day of the missed dose). If the missed dose is not administered within 3 days, adjust the schedule of administration to maintain the recommended 3-week dosing interval.
No dosing information is available for this tab.
| Drug label | Dosing type | Instructions |
|---|---|---|
| Onpattro 10 Mg/5 Ml Vial | Maintenance | Infuse 0.3 mg/kg over approximately 80 minute(s) by intravenous routeevery 3 weeks not to exceed 30 mg. |
No dosing information is available for this tab.
Drug interactions
Formal drug interaction studies have not been conducted to date with patisiran sodium lipid complex. Patisiran is not a substrate for cytochrome P-450 (CYP) isoenzymes, and also is not an inhibitor or inducer of CYP isoenzymes or transporters.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*None.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
- No disease contraindications
Adverse reactions
Adverse effects reported in at least 5% of patients receiving patisiran for the treatment of polyneuropathy caused by hereditary transthyretin-mediated amyloidosis and at least 3% more frequently than placebo include upper respiratory tract infections, infusion-related reactions, dyspepsia, dyspnea, muscle spasms, arthralgia, erythema, bronchitis, and vertigo.
More Frequent
- Vitamin A deficiency
Less Frequent
- Atrioventricular block
Rare or Very Rare
- Extravasation injury
- Hypotension
- Syncope
More Frequent
- Acute abdominal pain
- Back pain
- Dyspnea
- Flushing
- Nausea
- Upper respiratory infection
Less Frequent
- Arthralgia
- Blurred vision
- Bronchitis
- Dry eye
- Dyspepsia
- Headache disorder
- Muscle spasm
- Vertigo
- Vitreous floater
Rare or Very Rare
- Pruritus of skin
- Skin inflammation
Precautions
No enhanced messaging available.
Safety and efficacy of patisiran have not been established in pediatric patients.
There are no available data on patisiran use in pregnant women to inform a drug-associated risk of adverse developmental effects.
Developmental toxicity has been observed in animal reproductive studies. Weekly administration of moderate to high doses of patisiran to pregnant rabbits during the period of organogenesis resulted in embryofetal mortality, reduced fetal body weights, and maternal toxicity. No adverse developmental effects or effects on fertility were noted when patisiran (or a rodent-specific, pharmacologically active surrogate) was administered weekly to female rats starting 2 weeks prior to mating and continuing throughout pregnancy and lactation.
A pregnancy registry has been established; encourage patients to enroll by calling 1-877-256-9526 or contacting alnylampregnancyprogram@iqvia.com.
It is not known whether patisiran is distributed into human milk. The drug was not detected in the milk of lactating rats; however, some lipid components of the formulation were present. The effects of patisiran on breast-fed infants or on milk production are not known. Consider the benefits of breast-feeding and the woman's clinical need for patisiran along with any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.
No dosage adjustment is necessary in geriatric patients >=65 years of age.
Among patients receiving patisiran in the principal efficacy study, 42% were >=65 years of age and 6% were >=75 years of age. Although no overall differences in safety or efficacy have been observed between geriatric patients and younger adults, the possibility of increased sensitivity to patisiran in some older individuals cannot be ruled out.
ICD codes
| Code | Type | Description |
|---|---|---|
| Transthyretin familial amyloid polyneuropathy | ||
| E85.1 | ICD10CM | Neuropathic heredofamilial amyloidosis |
| G63 | ICD10CM | Polyneuropathy in diseases classified elsewhere |
ICD code information from First Databank (FDB).
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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