Leqvio (Inclisiran)
siRNA-based PCSK9 inhibitor — lowers LDL cholesterol with twice-yearly injections
Leqvio (inclisiran) is a first-in-class small interfering RNA (siRNA) medication that lowers LDL cholesterol by silencing the gene responsible for PCSK9 protein production in the liver. Approved for adults with primary hypercholesterolaemia or mixed dyslipidaemia, Leqvio is administered as a subcutaneous injection just twice a year after initial dosing, offering a convenient alternative to daily oral therapies and more frequent injectable treatments. It is used alongside a cholesterol-lowering diet and typically in combination with statin therapy.
Quick Facts
Key Takeaways
- Leqvio uses RNA interference (RNAi) technology to silence PCSK9 production in the liver, resulting in sustained LDL cholesterol reductions of approximately 50% from baseline.
- After the initial injection and a second dose at 3 months, Leqvio is administered only twice a year (every 6 months), making it one of the most convenient injectable cholesterol-lowering therapies available.
- The most common side effect is mild injection site reactions (pain, redness, or rash), which are generally self-limiting and resolve without treatment.
- Leqvio is administered by a healthcare professional as a subcutaneous injection in the abdomen, upper arm, or thigh — it is not a self-injection medication.
- No dose adjustments are needed for elderly patients or those with mild-to-moderate liver or kidney impairment, though caution is advised in severe cases.
What Is Leqvio and What Is It Used For?
Quick Answer: Leqvio (inclisiran) is a prescription injectable medication that uses small interfering RNA (siRNA) technology to lower LDL cholesterol. It targets PCSK9 production in the liver, helping the body clear more LDL cholesterol from the bloodstream. It is given twice yearly after initial dosing.
Leqvio contains the active substance inclisiran, a synthetic double-stranded small interfering RNA (siRNA) conjugated to triantennary N-acetylgalactosamine (GalNAc). This GalNAc conjugation allows targeted delivery to hepatocytes (liver cells) via the asialoglycoprotein receptor, ensuring that the drug acts specifically where cholesterol metabolism is regulated. Once inside the hepatocyte, inclisiran engages the RNA interference pathway to catalytically degrade messenger RNA encoding PCSK9, thereby reducing PCSK9 protein synthesis.
PCSK9 (proprotein convertase subtilisin/kexin type 9) is a protein that plays a central role in cholesterol homeostasis. Under normal circumstances, LDL receptors on the surface of liver cells bind and internalise LDL particles from the bloodstream for clearance. PCSK9 binds to these LDL receptors and directs them to lysosomal degradation, reducing the number of receptors available to clear LDL. By inhibiting PCSK9 production, inclisiran allows more LDL receptors to be recycled back to the cell surface, resulting in enhanced clearance of LDL cholesterol from the circulation.
Clinical trials have demonstrated that inclisiran achieves time-averaged LDL cholesterol reductions of approximately 50% when added to maximally tolerated statin therapy. The ORION programme of clinical studies, including ORION-9, ORION-10, and ORION-11, enrolled thousands of patients with atherosclerotic cardiovascular disease (ASCVD) or ASCVD risk equivalents, as well as patients with heterozygous familial hypercholesterolaemia, and consistently showed robust and durable LDL-lowering efficacy over 18 months of follow-up.
Approved Indications
Leqvio is indicated for the treatment of adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet. It is used in the following clinical scenarios:
- In combination with a statin (with or without other lipid-lowering therapies) in patients who do not reach their LDL cholesterol target with the maximum tolerated dose of a statin.
- Alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant or for whom statin therapy is contraindicated.
Leqvio represents a significant advance in lipid management because its twice-yearly dosing after the initial phase provides a practical advantage for patients and clinicians, particularly those who struggle with adherence to daily oral medications or who require injections every two to four weeks with monoclonal antibody PCSK9 inhibitors such as evolocumab or alirocumab.
What Should You Know Before Receiving Leqvio?
Quick Answer: Do not receive Leqvio if you are allergic to inclisiran or any of its ingredients. Inform your doctor if you have severe liver disease, severe kidney disease, or if you are on dialysis. Leqvio should not be used during pregnancy.
Contraindications
Leqvio must not be administered to anyone who has a known hypersensitivity to inclisiran or any of the excipients in the formulation. The excipients include water for injections, sodium hydroxide (E524), and concentrated phosphoric acid (E338). Although rare, allergic reactions can occur with any injectable biological therapy, and patients with a history of severe allergic reactions to other injectable drugs should discuss this with their healthcare provider.
Warnings and Precautions
Before receiving Leqvio, tell your healthcare provider about all your medical conditions. Particular caution is advised in the following situations:
- Haemodialysis: The effect of haemodialysis on the pharmacokinetics of inclisiran has not been studied. Because inclisiran is eliminated through the kidneys, haemodialysis should not be performed until at least 72 hours after dosing to avoid premature drug removal from the bloodstream.
- Severe liver disease: There are no clinical data available for patients with severe hepatic impairment (Child-Pugh class C). Inclisiran acts within hepatocytes, and altered liver function could theoretically affect its efficacy and safety. Use with caution in this population.
- Severe kidney disease: While no dose adjustment is required for patients with mild, moderate, or severe renal impairment, clinical experience in patients with severe renal impairment is limited. Use with caution and monitor as appropriate.
- End-stage renal disease (ESRD): Patients with ESRD on dialysis should be managed carefully with timing considerations around haemodialysis sessions.
Pregnancy and Breastfeeding
Leqvio should not be used during pregnancy. Cholesterol and other products of cholesterol biosynthesis are essential for foetal development, and the potential risks of LDL reduction during pregnancy outweigh the benefits. Women of childbearing potential should use effective contraception during treatment.
It is not known whether inclisiran passes into human breast milk. Your doctor will help you decide whether to continue breastfeeding or to start treatment with Leqvio, taking into account the potential benefits of treatment for you and the health benefits and risks of breastfeeding for your child. If you are breastfeeding or planning to breastfeed, discuss this with your healthcare provider before receiving Leqvio.
Children and Adolescents
Leqvio should not be given to children and adolescents under 18 years of age. The safety and efficacy of inclisiran in the paediatric population have not been established, and no clinical data are available for this age group.
Driving and Using Machines
Leqvio is not expected to have any effect on the ability to drive or use machines. No studies on driving ability have been performed, but the pharmacological profile and known side effects of inclisiran do not suggest any impairment of these activities.
Leqvio contains less than 1 mmol (23 mg) sodium per dose, meaning it is essentially sodium-free. This is relevant for patients on a controlled sodium diet.
How Does Leqvio Interact with Other Drugs?
Quick Answer: No clinically significant drug interactions have been identified with Leqvio. It can be safely used alongside statins, ezetimibe, and other lipid-lowering therapies. If switching from a PCSK9 monoclonal antibody, Leqvio can be started immediately.
Inclisiran is metabolised by nucleases and is not a substrate, inhibitor, or inducer of cytochrome P450 enzymes or common drug transporters. This means it has a low potential for pharmacokinetic drug-drug interactions with most commonly prescribed medications. Clinical studies have not identified any significant interactions between inclisiran and other lipid-lowering agents, antihypertensives, anticoagulants, or antidiabetic medications.
However, as with all medications, it is important to inform your healthcare provider about all prescription medications, over-the-counter drugs, herbal supplements, and vitamins you are taking. While no clinically relevant interactions have been observed, comprehensive monitoring is always prudent when multiple therapies are used concurrently.
| Concomitant Drug | Interaction Type | Clinical Significance | Recommendation |
|---|---|---|---|
| Statins (e.g. atorvastatin, rosuvastatin) | Additive LDL-lowering | No pharmacokinetic interaction | Recommended combination; no dose adjustment needed |
| Ezetimibe | Additive LDL-lowering | No pharmacokinetic interaction | Can be used together safely |
| PCSK9 monoclonal antibodies (evolocumab, alirocumab) | Overlapping PCSK9 inhibition | Concurrent use not studied | Start Leqvio within 2 weeks of last antibody dose when switching |
| Fibrates (e.g. fenofibrate) | Complementary lipid-lowering | No interaction identified | No dose adjustment required |
| Warfarin / DOACs | None expected | No effect on coagulation parameters | No dose adjustment required |
Switching from PCSK9 Monoclonal Antibodies
If you are currently being treated with a PCSK9 monoclonal antibody (evolocumab or alirocumab) and your doctor decides to switch you to Leqvio, the transition can be made immediately after your last antibody dose. To maintain continuous LDL cholesterol reduction, Leqvio should ideally be administered within 2 weeks of the last monoclonal antibody dose. After the switch, Leqvio follows its standard dosing schedule: an initial dose, a second dose at 3 months, and then every 6 months thereafter.
What Is the Correct Dosage of Leqvio?
Quick Answer: The recommended dose is 284 mg given as a single subcutaneous injection. After the first dose, a second injection is given at 3 months, and then every 6 months thereafter. It is administered by a healthcare professional.
Leqvio is available as a single-strength formulation containing 284 mg of inclisiran (as inclisiran sodium) in 1.5 mL of solution. Each pre-filled syringe is for single use only and is equipped with an automatic needle guard to prevent needlestick injuries after injection. The medication is administered exclusively by a healthcare professional — it is not designed for self-injection at home.
Adults
Standard Adult Dosing Schedule
Initial dose: 284 mg subcutaneous injection
Second dose: 284 mg at 3 months after the initial dose
Maintenance: 284 mg every 6 months thereafter
Before starting Leqvio, patients should be on a cholesterol-lowering diet and, in most cases, already taking a statin at the maximum tolerated dose. The diet and statin therapy should be continued throughout treatment with Leqvio.
| Patient Group | Dose | Frequency | Notes |
|---|---|---|---|
| Adults (standard) | 284 mg SC | Day 1, Month 3, then every 6 months | No dose adjustment needed |
| Elderly (≥65 years) | 284 mg SC | Day 1, Month 3, then every 6 months | No dose adjustment necessary |
| Mild/moderate hepatic impairment | 284 mg SC | Day 1, Month 3, then every 6 months | No dose adjustment (Child-Pugh A/B) |
| Severe hepatic impairment | 284 mg SC | Day 1, Month 3, then every 6 months | Use with caution; no data available (Child-Pugh C) |
| Mild/moderate/severe renal impairment | 284 mg SC | Day 1, Month 3, then every 6 months | No dose adjustment; limited data in severe impairment |
| End-stage renal disease (dialysis) | 284 mg SC | Day 1, Month 3, then every 6 months | Avoid haemodialysis within 72 hours of dosing |
Children
The safety and efficacy of Leqvio in children and adolescents under 18 years of age have not been established. No clinical data are available, and therefore Leqvio is not recommended for use in the paediatric population.
Elderly
No dose adjustment is necessary for elderly patients. In the ORION clinical trial programme, a substantial proportion of participants were aged 65 years and older, and the safety and efficacy profile in this subgroup was consistent with the overall study population. Age-related changes in renal function do not appear to meaningfully affect inclisiran pharmacokinetics.
Administration
Leqvio is administered as a subcutaneous injection. The preferred injection site is the abdomen, with the upper arm or thigh as alternative sites. Injections should not be given into areas of active skin disease, injury, or inflammation, such as sunburn, rash, or skin infections. Each pre-filled syringe comes with an automatic needle guard that activates after the injection is completed, providing added safety during disposal.
Missed Dose
If a scheduled dose is missed by less than 3 months, it should be administered as soon as possible, and the original dosing schedule should be maintained.
If a scheduled dose is missed by more than 3 months, a new dosing schedule should be started — with the missed dose treated as a new initial dose, followed by a second dose at 3 months, and then every 6 months.
Overdose
Because Leqvio is administered by a healthcare professional, overdose is extremely unlikely. In clinical studies, single doses of up to 800 mg were administered without dose-limiting toxicity. There is no specific antidote for inclisiran. In the event of a suspected overdose, the patient should be monitored clinically, and supportive care should be provided as appropriate. Haemodialysis is unlikely to be useful given the rapid hepatic uptake of inclisiran following subcutaneous administration.
What Are the Side Effects of Leqvio?
Quick Answer: The most common side effects of Leqvio are injection site reactions, including pain, redness, and rash. These are generally mild, transient, and resolve without treatment. Serious side effects are rare.
Like all medicines, Leqvio can cause side effects, although not everybody gets them. The overall safety profile of inclisiran has been well characterised across the ORION clinical trial programme, which included over 3,600 patients treated with inclisiran. The majority of adverse events were mild to moderate in severity and did not lead to treatment discontinuation.
In the pivotal Phase III trials (ORION-9, ORION-10, and ORION-11), the overall incidence of adverse events was similar between the inclisiran and placebo groups, with the exception of injection site reactions, which were more common in the inclisiran group. Importantly, there were no significant differences in the rates of serious adverse events, liver enzyme elevations, creatine kinase elevations, or new-onset diabetes between the treatment groups.
Common
May affect up to 1 in 10 people
- Injection site reactions (pain, redness, or rash at the injection site)
Uncommon (Reported in Clinical Trials)
May affect up to 1 in 100 people
- Bronchitis (upper respiratory tract infections observed at similar rates in both treatment and placebo groups)
- Back pain
- Urinary tract infection
Rare / Not Yet Fully Characterised
May affect up to 1 in 1,000 people
- Hypersensitivity reactions (as with any injectable biological therapy)
- Severe injection site reactions requiring medical attention
Contact your healthcare provider immediately if you experience signs of a severe allergic reaction such as swelling of the face, lips, tongue, or throat; difficulty breathing; severe dizziness; or a widespread rash. Although extremely rare with Leqvio, anaphylactic-type reactions are possible with any injectable medication.
Injection Site Reactions in Detail
Injection site reactions were the most commonly reported adverse events in the ORION clinical trials, occurring in approximately 5% of patients receiving inclisiran compared with less than 1% in the placebo group. These reactions typically manifested as localised pain, erythema (redness), or rash at the injection site. The vast majority were mild in severity (Grade 1), resolved within a few days without specific treatment, and did not recur with subsequent injections. Fewer than 1% of injection site reactions were reported as severe, and none led to permanent treatment discontinuation in the Phase III trials.
Long-Term Safety
Data from the ORION long-term extension studies (ORION-3 and ORION-8), extending follow-up to up to 4 years, have been reassuring. The incidence of adverse events did not increase over time, and no new safety signals emerged with prolonged exposure. Liver transaminases, creatine kinase levels, platelet counts, and renal function parameters remained stable throughout extended treatment. Importantly, there was no evidence of an increased risk of hepatotoxicity, myopathy, or neurocognitive events.
Reporting Side Effects
Reporting suspected side effects after a medicine has been authorised is important, as it allows ongoing monitoring of the medicine's benefit-risk balance. Healthcare professionals and patients can report side effects to their national regulatory authority (e.g. the EMA in Europe, FDA in the United States, or MHRA in the United Kingdom).
How Should You Store Leqvio?
Quick Answer: Leqvio does not require special storage conditions. It should not be frozen. It must be kept out of the sight and reach of children and should not be used after the expiry date.
Leqvio does not require any special temperature storage conditions when stored in its original packaging. However, it must never be frozen, as freezing may damage the pre-filled syringe and alter the properties of the solution. The medication should be stored out of the sight and reach of children.
Before administration, the healthcare professional will inspect the solution visually. Leqvio should appear as a clear, colourless to pale yellow solution that is essentially free from visible particles. If the solution appears discoloured, cloudy, or contains visible particulate matter, it should not be used and must be discarded according to local regulations.
The pre-filled syringe is for single use only. Any unused product or waste material should be disposed of in accordance with local requirements for pharmaceutical waste. It should not be disposed of via wastewater or household waste in order to protect the environment.
Always check the expiry date printed on the label and carton before use. The expiry date refers to the last day of the stated month. Do not use Leqvio after this date.
What Does Leqvio Contain?
Quick Answer: Each pre-filled syringe contains 284 mg of inclisiran (as inclisiran sodium) in 1.5 mL of solution. The excipients are water for injections, sodium hydroxide, and concentrated phosphoric acid.
Active Ingredient
The active substance is inclisiran, present as inclisiran sodium. Each pre-filled syringe contains inclisiran sodium equivalent to 284 mg of inclisiran in 1.5 mL of solution. This equates to a concentration of approximately 189 mg of inclisiran per mL. Inclisiran is a chemically modified, double-stranded siRNA molecule conjugated to GalNAc for liver-targeted delivery.
Excipients (Inactive Ingredients)
- Water for injections — serves as the solvent
- Sodium hydroxide (E524) — used for pH adjustment
- Concentrated phosphoric acid (E338) — used for pH adjustment
The formulation is deliberately simple, containing no preservatives, buffers beyond those listed, or additional stabilisers. The solution is essentially sodium-free (less than 1 mmol sodium per dose).
Appearance and Packaging
Leqvio 284 mg solution for injection comes in a pre-filled syringe with an automatic needle guard. The solution is clear, colourless to pale yellow, and essentially free from particles. Each carton contains one single-use pre-filled syringe. The automatic needle guard helps prevent accidental needlestick injuries after the injection is completed, providing additional safety for healthcare professionals handling the device.
Manufacturer
Leqvio is manufactured by Novartis Pharmaceutical Manufacturing GmbH (Langkampfen, Austria) and Novartis Pharma GmbH (Nuremberg, Germany). The marketing authorisation is held by Novartis Europharm Limited (Dublin, Ireland). In the United States, Leqvio is marketed by Novartis Pharmaceuticals Corporation.
Frequently Asked Questions About Leqvio
Leqvio is used to lower LDL cholesterol ("bad" cholesterol) in adults with primary hypercholesterolaemia (including heterozygous familial and non-familial forms) or mixed dyslipidaemia. It is given as an add-on to a cholesterol-lowering diet, typically in combination with statin therapy. It is prescribed when maximum tolerated statin doses do not achieve target LDL levels, or when statins cannot be used.
After the initial injection, a second dose is given at 3 months. Thereafter, Leqvio is administered every 6 months. This twice-yearly maintenance schedule means you only need 2–3 injections per year, making it one of the most convenient injectable cholesterol treatments available. All injections are given by a healthcare professional.
Statins work by inhibiting the enzyme HMG-CoA reductase in the liver, which reduces cholesterol production. Leqvio works differently — it uses RNA interference to reduce PCSK9 protein production, which allows more LDL receptors to be available on liver cells to clear cholesterol from the blood. Leqvio is not a replacement for statins but is used alongside them for additional LDL lowering when statins alone are insufficient.
No, Leqvio is currently designed to be administered by a healthcare professional (doctor, nurse, or pharmacist) in a clinical setting. It is given as a subcutaneous injection in the abdomen, upper arm, or thigh. Because it only needs to be given twice a year after the initial loading phase, the need for clinic visits is minimal compared to other injectable therapies.
The most common side effects are injection site reactions, including mild pain, redness, or rash at the injection site. These occur in approximately 5% of patients and are typically mild and self-limiting, resolving within a few days. Serious side effects are rare. Long-term studies extending up to 4 years have shown no new safety concerns emerging over time.
In the ORION clinical trial programme, Leqvio demonstrated time-averaged LDL cholesterol reductions of approximately 50% when added to maximum tolerated statin therapy. These reductions were sustained and consistent over the 18-month study period and have been maintained in long-term extension studies. The LDL-lowering effect is comparable to that achieved with PCSK9 monoclonal antibodies (evolocumab and alirocumab).
References
- European Medicines Agency (EMA). Leqvio (inclisiran) — Summary of Product Characteristics. Last updated January 2026. Available at: ema.europa.eu/en/medicines/human/EPAR/leqvio
- Ray KK, Wright RS, Kallend D, et al. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med. 2020;382(16):1507-1519. doi:10.1056/NEJMoa1912387
- Raal FJ, Kallend D, Ray KK, et al. Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia. N Engl J Med. 2020;382(16):1520-1530. doi:10.1056/NEJMoa1913805
- Wright RS, Ray KK, Raal FJ, et al. Pooled Patient-Level Analysis of Inclisiran Trials in Patients With Familial Hypercholesterolemia or Atherosclerosis. J Am Coll Cardiol. 2021;77(9):1182-1193. doi:10.1016/j.jacc.2020.12.058
- Ray KK, Raal FJ, Kallend DG, et al. Inclisiran and cardiovascular events: a patient-level analysis of phase III trials. Eur Heart J. 2023;44(2):129-138. doi:10.1093/eurheartj/ehac594
- Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2020;41(1):111-188. doi:10.1093/eurheartj/ehz455
- National Institute for Health and Care Excellence (NICE). Technology Appraisal Guidance TA733: Inclisiran for treating primary hypercholesterolaemia or mixed dyslipidaemia. Published September 2021.
- U.S. Food and Drug Administration (FDA). Leqvio (inclisiran) prescribing information. Revised 2024.
- World Health Organization (WHO). Cardiovascular diseases (CVDs) — Fact Sheet. Updated June 2024.
- Khan SA, Naz A, Qamar Masood M, Shah R. Meta-Analysis of Inclisiran for the Treatment of Hypercholesterolemia. Am J Cardiol. 2020;134:69-73. doi:10.1016/j.amjcard.2020.08.018
Editorial Team
This article was written by the iMedic Medical Editorial Team, comprising licensed specialist physicians in clinical pharmacology, cardiology, and lipidology. All content is based on current international guidelines (ESC/EAS, NICE, EMA, FDA) and peer-reviewed clinical trial data.
Our editorial process follows the GRADE evidence framework. Every article undergoes multiple rounds of medical review to ensure accuracy, clinical relevance, and adherence to evidence-based medicine principles. We maintain strict editorial independence with no pharmaceutical industry funding or sponsorship.