siRNA therapy
Small Interfering RNA (siRNA) Therapy
This activity focuses on small interfering RNA (siRNA) therapy, exemplified by FDA-approved agents such as patisiran, givosiran, lumasiran, inclisiran, nedosiran, and vutrisiran. These therapies are pivotal in managing rare metabolic ailments, including hereditary transthyretin amyloidosis (hATTR), acute hepatic porphyria (AHP), primary hyperoxaluria type 1 (PH1), and lowering low-density lipoprotein cholesterol (LDL-C) in subjects with heterozygous familial hypercholesterolemia (HeFH) or clinic
v1 · Reviewed Nov 8, 2026 by Automated Clinical Reviewer (Strict Verbatim v1)
- In the event of clinical signs such as hypotension, syncope, and anaphylaxis, the infusion should be discontinued immediately, and appropriate symptomatic management should be initiated.
- Anaphylaxis has been reported in <1% of subjects during clinical trials with givosiran.
- In the event of critical infusion-related adverse responses, therapy should not be continued.
- If any ocular symptoms that suggest a vitamin A deficiency occur, it is recommended to consult an ophthalmologist.
- Before prompting treatment, the interprofessional team should determine the patient's laboratory values, such as renal and liver function (givosiran), lipid levels (inclisiran), and vitamin A levels (patisiran, vutisiran) at baseline and periodically.
- Liver function tests (LFTs) should be monitored at baseline and routinely after that in patients receiving treatment with givosiran, as an increase in alanine transaminase (ALT) was observed during clinical trials.
- Baseline and routine monitoring of estimated glomerular filtration rate (eGFR) and serum creatinine levels is recommended along with LFTs when receiving givosiran.
- Patients receiving givosiran should also have their homocysteine levels measured at baseline and routinely afterward.
- Patients receiving treatment with patisiran should also have their vitamin A levels monitored routinely as therapy decreases its levels.
- The healthcare team should administer the abovementioned premedications (corticosteroid, acetaminophen, H1 blocker, and H2 blocker) at least 60 minutes before the infusion to prevent an infusion-related reaction.
- Patisiran should be administered immediately if an earlier dose was missed.
- Givosiran should be administered immediately if a prior dosage was missed and continued monthly afterward.
- Lumasiran should be administered immediately if a prior dosage was missed and continued monthly thereafter.
- Inclisiran should be administered immediately if a prior dosage was missed.
Patisiran
intervenous infusion
- Adult
- 0.3 mg/kg once every 3 weeks (weight <100 kg)
- Renal
- Not specified in source
- Duration
- Not specified in source
Patisiran
intervenous infusion
- Adult
- 30 mg once every 3 weeks (weight ≥100 kg)
- Renal
- Not specified in source
- Duration
- Not specified in source
Givosiran
subcutaneous injection
- Adult
- 2.5 mg/kg once monthly
- Renal
- Not specified in source
- Duration
- Not specified in source
Givosiran
subcutaneous injection
- Adult
- 1.25 mg/kg every month
- Renal
- Not specified in source
- Duration
- Not specified in source
Lumasiran
subcutaneous injection
- Adult
- 6 mg/kg administered once a month for 3 doses (weight <10 kg)
- Renal
- Not specified in source
- Duration
- Not specified in source
Lumasiran
subcutaneous injection
- Adult
- 3 mg/kg administered once a month (weight <10 kg)
- Renal
- Not specified in source
- Duration
- Not specified in source
Lumasiran
subcutaneous injection
- Adult
- 6 mg/kg administered once a month for 3 doses (10 to 20 kg)
- Renal
- Not specified in source
- Duration
- Not specified in source
Lumasiran
subcutaneous injection
- Adult
- 6 mg/kg administered once every 3 months quarterly (10 to 20 kg)
- Renal
- Not specified in source
- Duration
- Not specified in source
Lumasiran
subcutaneous injection
- Adult
- 3 mg/kg administered once a month for 3 doses (≥20 kg)
- Renal
- Not specified in source
- Duration
- Not specified in source
Lumasiran
subcutaneous injection
- Adult
- 3 mg/kg administered once every 3 months (≥20 kg)
- Renal
- Not specified in source
- Duration
- Not specified in source
Inclisiran
subcutaneous injection
- Adult
- 284 mg (initial dose)
- Renal
- Not specified in source
- Duration
- Not specified in source
Inclisiran
subcutaneous injection
- Adult
- 284 mg (at 3 months)
- Renal
- Not specified in source
- Duration
- Not specified in source
Inclisiran
subcutaneous injection
- Adult
- 284 mg (every 6 months after that)
- Renal
- Not specified in source
- Duration
- Not specified in source
Nedosiran
subcutaneous injection
- Adult
- 160 mg once monthly (pre-filled syringe, 1 mL)
- Renal
- Not specified in source
- Duration
- Not specified in source
Nedosiran
subcutaneous injection
- Adult
- 128 mg once monthly (pre-filled syringe, 0.8 mL)
- Renal
- Not specified in source
- Duration
- Not specified in source
Nedosiran
subcutaneous injection
- Adult
- 3.3 mg/kg once monthly, not to exceed 128 mg (round to nearest 0.1 mL)
- Renal
- Not specified in source
- Duration
- Not specified in source
Vutrisiran
subcutaneous injection
- Adult
- 25 mg administered by subcutaneous injection once every 3 months.
- Renal
- Not specified in source
- Duration
- Not specified in source
- No labeled contraindications have been reported for patisiran, lumasiran, neodosiran, vutisiran and inclisiran.
- Hypersensitivity to givosiran is an absolute contraindication to therapy.
- Inclisiran therapy is recommended to be discontinued during pregnancy.
- Childbearing females considering treatment with siRNA-based therapies during pregnancy should be evaluated to determine the benefits and risks before starting therapy.
- Patisiran reportedly decreases vitamin A levels, which is essential for fetal development.
- Pregnant patients considering givosiran should be informed about unfavorable fetal developmental outcomes during organogenesis in animal models.
- Patients receiving therapy with patisiran should be monitored for infusion-related adverse responses such as hypersensitivity reactions and anaphylaxis.
- Treatment with patisiran should be delayed or interrupted, and appropriate management should be initiated as clinically required.
- Patients receiving treatment with patisiran should also have their vitamin A levels monitored routinely as therapy decreases its levels.
- Liver function tests (LFTs) should be monitored at baseline and routinely after that in patients receiving treatment with givosiran, as an increase in alanine transaminase (ALT) was observed during clinical trials.
- Baseline and routine monitoring of estimated glomerular filtration rate (eGFR) and serum creatinine levels is recommended along with LFTs when receiving givosiran.
- Patients receiving givosiran should also have their homocysteine levels measured at baseline and routinely afterward.
- The healthcare team should monitor for headaches, back pain, abdominal pain, shortness of breath, and nausea during infusion.
- reviewSmall Interfering RNA (siRNA) Therapy. StatPearls [Internet] — Inderbir S. Padda, Arun U. Mahtani, Preeti Patel, Mayur Parmar — StatPearls Publishing, 2024
Decision support only. Verify against local protocols and current labeling. Source: www.ncbi.nlm.nih.gov