PCSK9-targeted siRNA Pregnancy: As a precautionary measure, preferable to avoid during pregnancy (limited data). Breast-feeding: a decision to discontinue breast-feeding or therapy should weigh benefits, as a risk to the infant cannot be excluded.

Inclisiran

Brand names: Leqvio

Inclisiran is a small interfering RNA (siRNA) therapeutic given as a subcutaneous injection to lower LDL-cholesterol in primary hypercholesterolaemia or mixed dyslipidaemia, used alongside a statin or when statins are unsuitable.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 284 mg as a single subcutaneous injection

Route: Subcutaneous injection (into the abdomen; alternatively upper arm or thigh)

Frequency: Initially, again at 3 months, then every 6 months

Each 284 mg dose is given using a single pre-filled syringe (single use), administered by a healthcare professional. Missed dose: if missed by <3 months, give and continue original schedule; if missed by >3 months, restart schedule (initial dose, again at 3 months, then every 6 months). Transition from a monoclonal antibody PCSK9 inhibitor: can be given immediately after the last dose, ideally within 2 weeks. Elderly: no dose adjustment. Hepatic impairment: no adjustment for mild/moderate (Child-Pugh A/B); use with caution in severe (Child-Pugh C, no data). Paediatric population (<18 years): safety and efficacy not established, no data. Do not inject into areas of active skin disease or injury.

Dose adjustments

Renal

No dose adjustment for mild, moderate or severe renal impairment or end-stage renal disease; use with caution in severe renal impairment (limited experience). Haemodialysis should not be performed for at least 72 hours after dosing.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to inclisiran or to any of the excipients

Side effects

Injection site reaction (common)
Injection site pain
Injection site erythema
Injection site rash
Mild elevations of serum hepatic transaminases (ALT/AST, up to <=3x ULN; asymptomatic)

Interactions

Not a substrate, inhibitor or inducer of cytochrome P450 enzymes or common drug transporters; no clinically significant medicinal-product interactions expected
No clinically meaningful interaction expected with atorvastatin, rosuvastatin or other statins

Clinical monograph

How it works

It is a small interfering RNA that, through the RNA interference pathway, reduces hepatic synthesis of PCSK9, allowing more LDL receptors to remain available to clear LDL-cholesterol from the blood.

Prescribing in practice

It should be prescribed within the NICE technology appraisal eligibility criteria, generally as an adjunct to maximally tolerated statin therapy or where statins are contraindicated or not tolerated.
It is administered by subcutaneous injection, initially and again after the first dose, then on a maintenance schedule given a few times a year by a healthcare professional.
Injection-site reactions are the most commonly reported adverse effect.

Monitoring

Check the lipid profile to confirm an adequate LDL-cholesterol response, in keeping with the prescribing pathway.

Counselling the patient

Explain that this is a long-acting injection given only a few times a year by a healthcare professional.
Stress that it complements, and does not replace, statin therapy and a healthy diet.
Report any persistent reaction at the injection site.

Evidence & guidelines

The ORION clinical trial programme demonstrated sustained LDL-cholesterol lowering with inclisiran, and NICE recommends it within defined eligibility criteria for cardiovascular risk reduction.

Reference: NICE TA733; ORION trials; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways