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Lipid-Lowering Agents Pregnancy: Contraindicated — animal reproductive toxicity; effective contraception required during treatment; discontinue at least 17 months before planned pregnancy

Inclisiran

Brand names: Leqvio

Adult dose

Dose: 284 mg SC on day 1, at 3 months, then every 6 months
Route: SC
Frequency: Every 6 months after initial loading doses
Max: 284 mg per dose
Administer only by a healthcare professional. Give as single injection into abdomen, upper arm, or thigh. Maintenance dosing is every 6 months — unique advantage for adherence.

Paediatric dose

Dose: Seek specialist opinion N/A/kg
Route: SC
Frequency: N/A
Max: N/A
Not established in paediatrics; seek specialist paediatric lipidology opinion

Dose adjustments

Renal

No dose adjustment required (including dialysis-dependent patients — studied in ORION-13)

Hepatic

No dose adjustment in mild-moderate impairment; use with caution in severe hepatic impairment — limited data

Paediatric weight-based calculator

Not established in paediatrics; seek specialist paediatric lipidology opinion

Clinical pearls

  • Mechanism: FIRST RNA-based therapy for cardiovascular disease — inclisiran is a synthetic siRNA (small interfering RNA) conjugated to N-acetylgalactosamine (GalNAc) for hepatocyte-specific delivery; silences PCSK9 mRNA in liver; PCSK9 production reduced → more LDL receptors → lower LDL-C
  • Unique dosing advantage: given only twice yearly after loading — dramatically improves adherence vs daily statins or bimonthly PCSK9 monoclonal antibodies; administered by HCP in clinic setting (reduces self-injection burden)
  • ORION-9/10/11 trials: LDL-C reductions of 50–52% sustained over 18 months; non-inferiority to evolocumab and alirocumab for LDL reduction; MACE outcomes data from ORION-4 (ongoing)
  • MHRA 2021: licensed as adjunct to diet and maximally tolerated statin therapy for adults with primary hypercholesterolaemia or mixed dyslipidaemia; NICE TA733 (2022) recommended on same criteria as PCSK9 monoclonal antibodies
  • Duration of action: siRNA mediates gene silencing lasting approximately 6 months — allows biannual dosing; this is pharmacologically distinct from monthly antibody administration
  • NHS implementation: NHS England included inclisiran in the Medicines Optimisation Commissioning Framework — GP-administered via health check or annual review

Contraindications

  • Known hypersensitivity to inclisiran or excipients
  • Pregnancy (animal reproductive toxicity)

Side effects

  • Injection site reactions (most common — redness, pain, bruising, injection site arthralgia)
  • Bronchitis
  • Nasopharyngitis
  • Generally very well tolerated

Interactions

  • No clinically significant drug interactions — inclisiran is a siRNA molecule with no CYP450 effects

Monitoring

  • Fasting lipid profile at 3 months (after 1st maintenance dose) to assess response
  • Liver function tests at baseline (no ongoing monitoring required)
  • Injection site reactions

Reference: BNFc; BNF 90; ORION-10 NEJM 2020;382(16):1507-1519; NICE TA733; MHRA 2021; ESC/EAS Lipid Guidelines 2019. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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