Onpattro (Patisiran)

Onpattro (patisiran) is indicated for hereditary transthyretin‑mediated amyloidosis, a rare protein‑misfolding disorder affecting the nervous and cardiac systems.

• Hereditary transthyretin amyloidosis (polyneuropathy): slows disease progression and improves neurological function.
• Hereditary transthyretin amyloidosis (cardiomyopathy): stabilizes cardiac function and reduces deterioration.
• Familial amyloid polyneuropathy: alleviates sensory loss and motor impairment.

• Patisiran utilizes RNA interference to bind specifically to messenger RNA encoding transthyretin in hepatocytes. This binding triggers degradation of the target mRNA, markedly reducing hepatic synthesis of both mutant and wild‑type transthyretin protein, thereby decreasing circulating amyloidogenic precursor and limiting tissue deposition.

Common Side Effects

• Infusion‑related reactions: flushing, chills, or rash.
• Nausea and vomiting.
• Fatigue or weakness.
• Peripheral edema.
• Headache.
• Dizziness.

Serious or Rare Side Effects

• Anaphylaxis or severe hypersensitivity.
• Significant elevation of hepatic enzymes.
• Thrombocytopenia.
• Acute renal impairment.
• Cardiac arrhythmias.
• Severe infusion‑related cytokine release.

Before initiating therapy, evaluate baseline organ function and monitor throughout treatment.

• Renal function: assess serum creatinine and eGFR before each infusion.
• Hepatic function: monitor ALT, AST, and bilirubin levels regularly.
• Cardiovascular status: evaluate for heart failure signs prior to dosing.
• Pregnancy and lactation: avoid use unless benefits clearly outweigh potential risks.
• Infusion reactions: administer under qualified medical supervision with emergency equipment available.
• Store at 2-8°C: keep refrigerated, protect from light, do not freeze or shake.

Patisiran may interact with other agents that affect immune function or hepatic metabolism.

Major Interactions (Avoid)

• Concurrent siRNA therapies: risk of additive RNAi effects.
• Live vaccines: may compromise vaccine efficacy.
• Immunosuppressants: increased infection susceptibility.
• Other lipid nanoparticle formulations: potential overlapping toxicity.
• Strong CYP inducers: may alter metabolism of co‑administered drugs.

Moderate Interactions (Monitor Closely)

• Warfarin: monitor INR as hepatic changes can affect anticoagulation.
• Statins: watch for muscle toxicity.
• Antihypertensives: observe blood pressure for fluid‑shift related changes.
• Diuretics: adjust dosing if significant edema occurs.
• Antiplatelet agents: monitor for bleeding tendencies.