PCSK9 Inhibitor (siRNA — Small Interfering RNA) Pregnancy: Avoid — insufficient data; potential impact on fetal cholesterol metabolism; effective contraception required

Inclisiran

Brand names: Leqvio

Adult dose

Dose: 284 mg SC at day 1, day 90, then every 6 months

Route: Subcutaneous injection (administered by healthcare professional)

Frequency: Every 6 months after initial loading doses

Max: 284 mg per dose

Primary hypercholesterolaemia or mixed dyslipidaemia — adjunct to diet and maximally tolerated statin; administered in clinic (not self-injection); dramatically reduces LDL-C (~50%) with only 2 injections per year

Paediatric dose

Dose: Not established N/A/kg

Route: N/A

Frequency: N/A

Max: N/A

Not licensed in paediatrics

Dose adjustments

Renal

No dose adjustment for mild-moderate renal impairment; limited data in severe

Hepatic

Mild: no adjustment; moderate-severe: limited data

Paediatric weight-based calculator

Patient weight (kg)

Not licensed in paediatrics

Clinical pearls

ORION-10 trial (Ray et al. NEJM 2020): inclisiran reduced LDL-C by 52% vs placebo at day 510 in patients with ASCVD on maximally tolerated statin — MHRA 2020 approved; NICE TA733
Novel siRNA mechanism: inclisiran targets PCSK9 mRNA in hepatocytes — prevents PCSK9 protein synthesis (not the protein itself like evolocumab/alirocumab); single hepatocyte uptake sustains effect for 6 months, explaining the ultra-long dosing interval
Adherence advantage: only 2 injections per year after the initial loading doses (day 1 and day 90) — compared to monthly/fortnightly injections for monoclonal PCSK9 inhibitors; administered in clinic ensuring adherence and eliminating self-injection barrier
LDL-C reduction consistency: inclisiran produces stable, sustained LDL-C reduction without the peaks and troughs seen with monoclonal PCSK9 inhibitors — flat pharmacodynamic profile because downstream mRNA suppression is maintained regardless of drug plasma levels
NHS England commissioning: inclisiran commissioned for secondary prevention in patients with ASCVD not achieving LDL-C targets on maximally tolerated statin ± ezetimibe; GP practices now administering via clinic injection appointments

Contraindications

Known hypersensitivity to inclisiran

Side effects

Injection site reactions (most common — erythema, pain, bruising at injection site)
Nasopharyngitis
Back pain
Arthralgia
UTI

Interactions

No clinically significant drug-drug interactions identified — siRNA mechanism is highly specific to PCSK9 mRNA

Monitoring

LDL-C (at 3 months after first dose to confirm response)
LFTs (baseline)
No routine monitoring required during maintenance — LDL-C at annual review

Reference: BNFc; BNF 90; ORION-10 trial (Ray et al. NEJM 2020); ORION-9 trial; NICE TA733; MHRA SPC Leqvio 2020; NHS England commissioning guidance. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways