Nilemdo (Bempedoic Acid)
Cholesterol-lowering medication – ACL inhibitor for adults with hypercholesterolemia
Nilemdo contains bempedoic acid, a first-in-class ACL (ATP-citrate lyase) inhibitor that lowers LDL cholesterol by reducing cholesterol production in the liver. It is prescribed for adults with primary hypercholesterolemia or mixed dyslipidemia when statins alone are insufficient, or when statins cannot be used. The CLEAR Outcomes trial demonstrated that bempedoic acid significantly reduces the risk of major cardiovascular events.
Quick Facts: Nilemdo
Key Takeaways
- Nilemdo (bempedoic acid) lowers LDL cholesterol by inhibiting ATP-citrate lyase, an enzyme upstream of the statin target in the cholesterol biosynthesis pathway.
- It is only activated in the liver (not in muscle), which gives it a lower risk of muscle-related side effects compared to statins.
- The recommended dose is one 180 mg tablet once daily, taken with or without food.
- It can be used alone or added to statin therapy, but simvastatin should not exceed 40 mg daily when combined with Nilemdo.
- The CLEAR Outcomes trial showed a 13% reduction in major adverse cardiovascular events in statin-intolerant patients.
What Is Nilemdo and What Is It Used For?
Nilemdo belongs to a novel class of lipid-lowering agents known as ATP-citrate lyase (ACL) inhibitors. The active substance, bempedoic acid, is a prodrug that remains inactive until it reaches the liver, where it is converted to its active form by the enzyme very long-chain acyl-CoA synthetase 1 (ACSVL1). Once activated, bempedoic acid inhibits ACL, an enzyme that sits upstream of HMG-CoA reductase – the same pathway targeted by statins – in the cholesterol biosynthesis cascade.
By blocking ACL, Nilemdo reduces the production of cholesterol within hepatocytes (liver cells). This triggers an upregulation of LDL receptors on the surface of liver cells, which in turn increases the clearance of LDL cholesterol from the bloodstream. The net effect is a meaningful reduction in circulating LDL-C levels. Importantly, because the activating enzyme ACSVL1 is not expressed in skeletal muscle, bempedoic acid does not accumulate in muscle tissue, which accounts for its favorable muscle safety profile compared to traditional statins.
Nilemdo is approved for use in two main clinical scenarios. First, it is indicated for adults with primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidemia, as an add-on to a cholesterol-lowering diet. In this context, it may be prescribed alongside a statin when maximum tolerated statin therapy fails to achieve LDL-C goals, or it may be given alone or with other lipid-lowering agents when statins are contraindicated or not tolerated. Second, Nilemdo is indicated for the reduction of cardiovascular risk in adults with established atherosclerotic cardiovascular disease (ASCVD) or high cardiovascular risk, particularly those who are statin-intolerant.
The landmark CLEAR Outcomes trial, published in the New England Journal of Medicine in 2023, enrolled over 13,000 statin-intolerant patients and demonstrated that bempedoic acid reduced the composite endpoint of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization) by 13% compared to placebo. This trial provided the first direct cardiovascular outcomes evidence for a non-statin LDL-lowering therapy in statin-intolerant populations and was a pivotal milestone for the role of Nilemdo in clinical practice.
Nilemdo is manufactured by Daiichi Sankyo Europe GmbH and was first authorized in the European Union by the European Medicines Agency (EMA) in 2020. It is also approved by the U.S. Food and Drug Administration (FDA) and regulatory bodies in several other countries. It is available as a white to off-white, oval, film-coated tablet embossed with "180" on one side and "ESP" on the other, supplied in blister packs of various sizes.
What Should You Know Before Taking Nilemdo?
Contraindications
There are several important situations in which Nilemdo must not be used. You should not take this medication if you have a known allergy (hypersensitivity) to bempedoic acid or any of the other ingredients in the tablet, including lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, hydroxypropyl cellulose, magnesium stearate, colloidal anhydrous silica, or the film-coating components.
Nilemdo is strictly contraindicated during pregnancy and breastfeeding. Cholesterol and other products of the cholesterol biosynthesis pathway are essential for fetal development, and inhibiting cholesterol synthesis may cause harm to the unborn child. If you discover that you are pregnant while taking Nilemdo, stop the medication immediately and contact your doctor.
You must not take Nilemdo if you are currently receiving simvastatin at a dose higher than 40 mg per day. The combination of bempedoic acid with high-dose simvastatin increases the blood levels of simvastatin and its active metabolite, significantly raising the risk of serious muscle damage (myopathy and rhabdomyolysis).
Do not take Nilemdo if you are pregnant, breastfeeding, allergic to bempedoic acid, or taking more than 40 mg simvastatin daily. Doing so may result in serious harm.
Warnings and Precautions
Before starting Nilemdo, your doctor should be informed of your complete medical history. Certain conditions require special monitoring or dose adjustments. Speak to your doctor or pharmacist before taking Nilemdo if you have ever had gout or elevated uric acid levels. Bempedoic acid can increase serum uric acid concentrations, which may trigger gout flares or worsen pre-existing gout. In clinical trials, hyperuricemia was observed more frequently in patients receiving bempedoic acid compared to placebo.
Patients with severe renal impairment (estimated glomerular filtration rate below 30 mL/min/1.73 m²) should use Nilemdo with caution. The drug can cause a decrease in eGFR and elevations in serum creatinine and blood urea nitrogen. Your doctor may perform regular kidney function tests during treatment. Similarly, if you have significant liver disease, your liver function should be evaluated before starting therapy, as Nilemdo is primarily activated and metabolized in the liver.
If you are taking a statin alongside Nilemdo, be alert for any unexplained muscle pain, tenderness, or weakness. While bempedoic acid itself has a low risk of causing muscle symptoms, the combination with statins may increase the overall risk. Report any such symptoms to your doctor immediately, as they may indicate a rare but serious condition called rhabdomyolysis.
Your doctor may order blood tests before you begin treatment and periodically during therapy to monitor liver function, kidney function, uric acid levels, and blood counts. These tests help ensure that the medication is being well tolerated and allow early detection of any adverse effects.
Pregnancy and Breastfeeding
Nilemdo must not be used during pregnancy. Before starting treatment, women of childbearing potential should confirm they are not pregnant and should use effective contraception as recommended by their doctor. If you are using oral contraceptives (birth control pills) and experience vomiting or diarrhea lasting more than 2 days, you must use an alternative method of contraception (such as a condom or diaphragm) for 7 days after symptoms resolve, as the effectiveness of oral contraceptives may be reduced.
If you decide you wish to become pregnant after starting Nilemdo, inform your doctor so that your treatment can be changed to a pregnancy-compatible alternative. Should you become pregnant while taking this medication, stop it immediately and seek medical advice.
Nilemdo must not be taken while breastfeeding. It is not known whether bempedoic acid or its metabolites are excreted in human breast milk, and a risk to the nursing infant cannot be excluded.
Children and Adolescents
Nilemdo is not approved for use in children and adolescents under 18 years of age. The safety and efficacy of bempedoic acid have not been studied in this age group, and it should not be given to pediatric patients.
Driving and Operating Machinery
Nilemdo has no or negligible influence on the ability to drive or use machines. You may continue driving and operating machinery as normal while taking this medication.
Important Information About Excipients
Nilemdo tablets contain lactose monohydrate. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine. The tablets also contain sodium starch glycolate, but less than 1 mmol sodium (23 mg) per tablet, meaning they are essentially sodium-free.
How Does Nilemdo Interact with Other Drugs?
Drug interactions are an important consideration when using Nilemdo. Bempedoic acid and its active metabolite can affect the blood levels of certain co-administered drugs, and some drugs can alter the levels of bempedoic acid in your body. It is essential to provide your doctor with a complete list of all medications you are taking, including prescription drugs, over-the-counter medicines, vitamins, and herbal supplements.
Major Interactions
| Drug / Class | Effect | Clinical Advice |
|---|---|---|
| Simvastatin (>40 mg/day) | Increased simvastatin levels; risk of myopathy/rhabdomyolysis | Do not exceed 40 mg simvastatin daily. Contraindicated combination at higher doses. |
| Other statins (atorvastatin, rosuvastatin, pravastatin, fluvastatin, pitavastatin) | May increase statin exposure; theoretical increase in muscle-related risk | Can be used together. Report any unexplained muscle pain, tenderness, or weakness immediately. |
| Bosentan | May reduce bempedoic acid levels via OATP1B1/1B3 transporter interaction | Inform your doctor. Dose adjustment or monitoring may be needed. |
| Fimasartan | Potential pharmacokinetic interaction via hepatic transporters | Inform your doctor. Clinical significance is being evaluated. |
| Hepatitis C antivirals (asunaprevir, glecaprevir, grazoprevir, voxilaprevir) | May increase bempedoic acid levels via OATP1B1/1B3 inhibition | Inform your doctor. Monitoring recommended when co-administered. |
Additional Interaction Considerations
Beyond the specific drugs listed above, patients should be aware that bempedoic acid is a substrate of hepatic organic anion transporting polypeptides (OATP1B1 and OATP1B3). Drugs that inhibit or induce these transporters may alter the pharmacokinetics of bempedoic acid. Conversely, bempedoic acid itself can increase the systemic exposure of drugs that are substrates of OATP1B1/1B3, which is the primary mechanism behind its interaction with statins.
There are no clinically significant interactions reported between Nilemdo and commonly used medications such as ezetimibe, PCSK9 inhibitors (evolocumab, alirocumab), warfarin, or standard antihypertensive agents. However, you should always consult your doctor before starting, stopping, or changing the dose of any medication while on Nilemdo therapy.
Keep an up-to-date list of all your medications and share it with every healthcare provider you visit. This helps prevent harmful drug interactions and ensures optimal treatment outcomes.
What Is the Correct Dosage of Nilemdo?
Nilemdo dosing is straightforward. The recommended dose for all adult patients is 180 mg (one tablet) taken once daily. The tablet should be swallowed whole with a glass of water and can be taken with food or between meals, according to your preference. There is no need for dose titration or adjustment based on age, sex, or mild to moderate hepatic or renal impairment.
Adults
Standard Adult Dose
180 mg once daily, taken orally with or without food. No dose adjustment is required for elderly patients or those with mild to moderate renal or hepatic impairment.
Nilemdo should be taken as part of a comprehensive cholesterol management plan that includes a heart-healthy diet, regular physical activity, and weight management. If you are also taking a statin or other lipid-lowering therapy, Nilemdo can be taken at the same time or at different times of day. There is no requirement to take it at a specific time, although consistency (taking it at approximately the same time each day) is encouraged to help maintain steady blood levels.
Children and Adolescents
Pediatric Dose
Not recommended. Nilemdo has not been studied in patients under 18 years of age. It should not be used in this population.
Elderly Patients
No dose adjustment is necessary in elderly patients. Clinical trials of Nilemdo included a substantial proportion of patients aged 65 years and older, and no overall differences in safety or efficacy were observed between older and younger adults. Standard monitoring for side effects should be continued.
Missed Dose
If you realize you have missed a dose later in the same day, take the missed dose and then take the next dose at your usual time the following day. If you realize you missed the previous day's dose entirely, simply take your next scheduled dose at the regular time. Do not take a double dose to make up for the one you missed. If you have any concerns, consult your pharmacist or doctor.
Overdose
If you take more Nilemdo than prescribed, contact your doctor or pharmacist immediately, or go to the nearest emergency department. While no specific antidote for bempedoic acid overdose is available, supportive measures can be provided. In clinical studies, single doses of up to 240 mg were administered without severe adverse events, but the effects of higher overdoses have not been systematically studied. Due to the high protein binding of bempedoic acid, hemodialysis is unlikely to be effective in removing the drug from the body.
Do not stop taking Nilemdo without consulting your doctor, as stopping may cause your cholesterol levels to rise again. Consistent daily use is essential for maintaining the cholesterol-lowering effect.
What Are the Side Effects of Nilemdo?
Like all medicines, Nilemdo can cause side effects, although not everyone experiences them. The side effects observed in clinical trials are categorized below by how frequently they occur. Understanding these potential effects can help you and your doctor monitor your health during treatment and take prompt action if needed.
In the large-scale CLEAR Outcomes trial and other pivotal studies, bempedoic acid demonstrated a generally favorable safety profile. The most notable findings related to increases in uric acid and slight changes in renal and hepatic markers, most of which were mild and did not require treatment discontinuation. Importantly, rates of serious muscle-related adverse events (myopathy, rhabdomyolysis) were very low and comparable to placebo when bempedoic acid was used without a statin.
Common Side Effects
May affect up to 1 in 10 people
- Anemia – decreased number of red blood cells, which may cause tiredness or pallor
- Hyperuricemia – elevated uric acid levels in the blood
- Gout – painful joint inflammation, particularly in the big toe, caused by uric acid crystal deposition
- Limb pain – pain in the shoulders, arms, or legs
- Abnormal liver function tests – elevated liver enzymes (ALT, AST) detected in blood tests
- Decreased eGFR – reduced glomerular filtration rate indicating changes in kidney function
Uncommon Side Effects
May affect up to 1 in 100 people
- Decreased hemoglobin – lower levels of the oxygen-carrying protein in red blood cells
- Elevated creatinine – increased levels of a kidney waste product in the blood
- Elevated blood urea nitrogen (BUN) – another marker of kidney function
- Weight loss – unintended decrease in body weight
When to Seek Medical Attention
You should contact your doctor promptly if you experience any of the following during treatment with Nilemdo:
- Unexplained muscle pain, tenderness, or weakness – especially if you are also taking a statin, as this may indicate myopathy
- Severe joint pain or swelling suggestive of a gout attack
- Signs of anemia such as unusual tiredness, shortness of breath, or pale skin
- Yellowing of the skin or eyes (jaundice), which may indicate liver problems
- Dark-colored urine, reduced urine output, or swelling in the legs and ankles, which may signal kidney issues
- Signs of a serious allergic reaction: rash, itching, swelling of the face, lips, tongue, or throat, or difficulty breathing
Reporting suspected side effects is important for ongoing drug safety monitoring. If you experience any side effects not listed here, or if any of the listed side effects become severe, please report them to your national pharmacovigilance authority or through your healthcare provider. In the EU, reports can be submitted through national reporting systems or via the EMA website.
How Should You Store Nilemdo?
Proper storage of medication is essential to maintain its effectiveness and safety throughout its shelf life. Nilemdo does not require any special storage conditions – it can be kept at normal room temperature. There is no need to refrigerate the tablets or protect them from light.
Keep Nilemdo out of the sight and reach of children at all times. Store the tablets in the original blister packaging to protect them from moisture and physical damage until you are ready to take a dose. Check the expiry date printed on the blister pack (after "EXP") and on the outer carton. The expiry date refers to the last day of the stated month. Do not take the tablets if the expiry date has passed.
Do not dispose of unused or expired Nilemdo tablets by flushing them down the toilet or throwing them in household waste. Ask your pharmacist about local medication take-back programs or other environmentally responsible disposal methods. Proper disposal helps protect the environment and prevents accidental ingestion by others.
What Does Nilemdo Contain?
Each film-coated tablet of Nilemdo contains 180 mg of bempedoic acid as the active pharmaceutical ingredient. The inactive ingredients (excipients) that make up the tablet core include:
- Lactose monohydrate – a commonly used filler in pharmaceutical tablets (patients with known lactose intolerance should inform their doctor)
- Microcrystalline cellulose (E460) – a binding agent that helps the tablet maintain its shape
- Sodium starch glycolate (type A) – a disintegrant that helps the tablet break down in the digestive tract for proper absorption
- Hydroxypropyl cellulose (E463) – a binder
- Magnesium stearate (E470b) – a lubricant used in the manufacturing process
- Colloidal anhydrous silica (E551) – an anti-caking agent
The film coating consists of partially hydrolysed polyvinyl alcohol (E1203), talc (E553b), titanium dioxide (E171), and macrogol/PEG (E1521). These coating materials give the tablet its smooth, white to off-white appearance and help protect the core ingredients.
Nilemdo tablets are oval in shape, measuring approximately 13.97 mm × 6.60 mm × 4.80 mm. They are embossed with "180" on one side and "ESP" on the other side, which helps identify the medication. The tablets are supplied in plastic/aluminum blister packs in cartons containing 10, 14, 28, 30, 84, 90, 98, or 100 tablets, as well as unit-dose blisters of 10 × 1, 50 × 1, or 100 × 1 tablets. Not all pack sizes may be marketed in every country.
Frequently Asked Questions About Nilemdo
Nilemdo (bempedoic acid) is used to lower LDL cholesterol in adults with primary hypercholesterolemia or mixed dyslipidemia. It is prescribed when statins alone do not lower LDL enough, or when statins cannot be used or tolerated due to side effects. It can also reduce the risk of cardiovascular events such as heart attacks and strokes in patients with established cardiovascular disease or those at high cardiovascular risk.
Nilemdo works by inhibiting ATP-citrate lyase (ACL), an enzyme that acts upstream of HMG-CoA reductase (the target of statins) in the cholesterol biosynthesis pathway. The key advantage is that bempedoic acid is a prodrug activated only in the liver by the enzyme ACSVL1, which is not present in skeletal muscle. This means it is less likely to cause the muscle aches and pains (myalgia) that lead many patients to discontinue statin therapy.
Yes, Nilemdo can be taken alongside most statins to achieve additional LDL cholesterol reduction. However, there is one critical restriction: if you take simvastatin, your dose must not exceed 40 mg per day, because Nilemdo increases simvastatin blood levels and raises the risk of muscle damage. For other statins such as atorvastatin, rosuvastatin, or pravastatin, no specific dose limit applies, but you should always monitor for unexplained muscle symptoms and report them to your doctor.
In clinical trials, Nilemdo reduced LDL cholesterol by approximately 15–25% when used as monotherapy, and by about 18% when added to maximum tolerated statin therapy. It also reduces non-HDL cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein (hsCRP). The reduction in hsCRP is notable, as elevated hsCRP is an independent marker of cardiovascular risk.
No, Nilemdo must not be taken during pregnancy or while breastfeeding. Cholesterol and its byproducts are essential for fetal development, and blocking cholesterol synthesis could potentially harm the developing baby. Women of childbearing age should use effective contraception while taking Nilemdo and stop the medication immediately if pregnancy is suspected or confirmed.
Nilemdo has a significantly lower risk of causing muscle-related side effects compared to statins. This is because the prodrug bempedoic acid is activated only in the liver, not in skeletal muscle. In the CLEAR Outcomes trial, muscle-related adverse events were similar between bempedoic acid and placebo groups. However, when Nilemdo is combined with a statin, the overall risk of muscle symptoms may be slightly increased, so monitoring is still recommended.
References and Sources
This article is based on the following peer-reviewed sources and regulatory documents:
- Nissen SE, Lincoff AM, Brennan D, et al. Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients. N Engl J Med. 2023;388(15):1353-1364. doi:10.1056/NEJMoa2215024
- European Medicines Agency (EMA). Nilemdo – Summary of Product Characteristics (SmPC). Last updated 2024. Available at: EMA – Nilemdo EPAR
- U.S. Food and Drug Administration (FDA). NEXLETOL (bempedoic acid) tablets – Prescribing Information. Approved February 2020, updated 2023.
- 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 TA694: Bempedoic acid with ezetimibe for treating primary hypercholesterolaemia or mixed dyslipidaemia. 2021.
- Ray KK, Bays HE, Catapano AL, et al. Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol. N Engl J Med. 2019;380(11):1022-1032. doi:10.1056/NEJMoa1803917
- Goldberg AC, Leiter LA, Stroes ESG, et al. Effect of Bempedoic Acid vs Placebo Added to Maximally Tolerated Statins on Low-Density Lipoprotein Cholesterol in Patients at High Cardiovascular Risk: The CLEAR Wisdom Randomized Clinical Trial. JAMA. 2019;322(18):1780-1788. doi:10.1001/jama.2019.16585
- World Health Organization (WHO). Cardiovascular diseases (CVDs) – Fact Sheet. 2023.
About the Medical Editorial Team
This article was written and reviewed by the iMedic Medical Editorial Team, comprising board-certified specialists in cardiology, internal medicine, and clinical pharmacology. Our editorial process follows the GRADE evidence framework and adheres to international guidelines from the EMA, FDA, ESC/EAS, and NICE.
Licensed physicians with expertise in cardiovascular pharmacology and lipid disorders. All content is based on peer-reviewed research and current clinical guidelines.
Independent review by the iMedic Medical Review Board ensures accuracy, completeness, and clinical relevance. Content is updated regularly to reflect the latest evidence.
Conflict of Interest: The iMedic Medical Editorial Team has no financial relationships with pharmaceutical companies. This content is independently produced with no commercial funding or sponsorship.
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