PCSK9 Inhibitor (siRNA — Small Interfering RNA) Pregnancy: As a precautionary measure it is preferable to avoid the use of inclisiran during pregnancy (no or limited data in pregnant women). It is unknown whether inclisiran or its metabolites are excreted in human milk; a risk to newborns/infants cannot be excluded, so a decision must be made whether to discontinue breast-feeding or to discontinue therapy (UK SPC §4.6).

Inclisiran

Brand names: Leqvio

Inclisiran is a subcutaneously administered small interfering RNA therapy that lowers LDL cholesterol in primary hypercholesterolaemia and mixed dyslipidaemia, given infrequently after initial loading.

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; alternative injection sites include the upper arm or thigh

Frequency: Initially, again at 3 months, followed by every 6 months

Each 284 mg dose is administered using a single pre-filled syringe; each pre-filled syringe is for single use only. Inclisiran is intended for administration by a healthcare professional. Do not inject into areas of active skin disease or injury such as sunburn, skin rashes, inflammation or skin infections. Missed doses: if a planned dose is missed by less than 3 months, administer inclisiran and continue dosing according to the patient's original schedule; if missed by more than 3 months, start a new dosing schedule (administer initially, again at 3 months, then every 6 months). Transition from a monoclonal antibody PCSK9 inhibitor: inclisiran can be given immediately after the last dose of the monoclonal antibody, and should be given within 2 weeks of that last dose to maintain LDL-C lowering. Elderly: no dose adjustments necessary. Hepatic impairment: no dose adjustment for mild (Child-Pugh A) or moderate (Child-Pugh B); no data in severe (Child-Pugh C) — use with caution. Paediatric (UK SPC): safety and efficacy in children aged under 18 years have not yet been established; no data available. NOTE: US labelling extends the same 284 mg regimen to paediatric patients aged 12 years and older with HeFH or HoFH — verify against current UK licensing before applying to under-18s.

Dose adjustments

Renal

No dose adjustments are necessary for patients with mild, moderate or severe renal impairment or with end-stage renal disease; there is limited experience in severe renal impairment, so use with caution. Because inclisiran is eliminated renally, haemodialysis should not be performed for at least 72 hours after inclisiran dosing (UK SPC §4.2 and §4.4).

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substance or to any of the excipients
US labelling specifies prior serious hypersensitivity reaction to inclisiran or any excipient, including anaphylaxis and angioedema

Side effects

Adverse reactions at the injection site (common; 8.2% vs 1.8% placebo) — all mild or moderate, transient and resolving without sequelae
Injection site reaction (3.1%)
Injection site pain (2.2%)
Injection site erythema (1.6%) and injection site rash (0.7%)
Asymptomatic elevations of serum hepatic transaminases between >1x and <=3x ULN were more frequent than with placebo (ALT 19.7%, AST 17.2%) but did not exceed 3x ULN
US labelling also reports arthralgia and bronchitis among common adverse reactions (>=3%)

Interactions

Inclisiran is not a substrate for common drug transporters and is not anticipated to be a substrate for cytochrome P450; it is not an inhibitor or inducer of cytochrome P450 enzymes or common drug transporters, so clinically significant interactions with other medicinal products are not expected (UK SPC §4.5)
Based on the limited data available, clinically meaningful interactions with atorvastatin, rosuvastatin or other statins are not expected

Clinical monograph

How it works

It is a small interfering RNA that silences hepatic PCSK9 messenger RNA, reducing PCSK9 production so more LDL receptors remain available to clear LDL cholesterol.

Prescribing in practice

It is used as an adjunct to diet and maximally tolerated statin therapy, or with other lipid-lowering drugs when statins are unsuitable, with NICE restricting use by LDL threshold and cardiovascular risk.
Injection-site reactions are the most common adverse effect.
Administration is by a healthcare professional, after loading doses, then maintained at infrequent intervals.

Monitoring

A lipid profile confirms response; no specific routine laboratory drug monitoring is otherwise mandated.

Counselling the patient

This treatment is given as an injection only a few times a year after the first doses.
Continue your statin and healthy lifestyle measures unless advised otherwise.
Mild injection-site reactions such as redness may occur and usually settle.

Evidence & guidelines

The ORION trial programme demonstrated sustained LDL reduction with twice-yearly maintenance dosing, supporting NICE-approved use in eligible patients.

Reference: ORION-10 trial (Ray et al. NEJM 2020); ORION-9 trial; NICE TA733; MHRA SPC Leqvio 2020; NHS England commissioning guidance; 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