Nustendi (Bempedoic Acid / Ezetimibe)
Fixed-dose cholesterol-lowering combination – ACL inhibitor plus cholesterol absorption inhibitor
Nustendi is a fixed-dose combination tablet containing bempedoic acid 180 mg and ezetimibe 10 mg. By combining two complementary mechanisms – reduced hepatic cholesterol synthesis (bempedoic acid) and reduced intestinal cholesterol absorption (ezetimibe) – Nustendi produces greater LDL-cholesterol lowering than either agent alone. It is prescribed for adults with primary hypercholesterolemia or mixed dyslipidemia, typically alongside a statin or when statins cannot be tolerated.
Quick Facts: Nustendi
Key Takeaways
- Nustendi combines bempedoic acid (180 mg) and ezetimibe (10 mg) in a single once-daily tablet for adults with elevated LDL cholesterol.
- The two drugs act through complementary pathways: bempedoic acid blocks hepatic cholesterol synthesis, while ezetimibe blocks intestinal absorption.
- LDL-C is reduced by approximately 36% versus placebo, and by about 28% when added to maximally tolerated statin therapy.
- Muscle side effects are uncommon because bempedoic acid is activated only in the liver, making it a useful option for statin-intolerant patients.
- Nustendi is contraindicated in pregnancy and breastfeeding; simvastatin doses must not exceed 40 mg per day when co-administered.
What Is Nustendi and What Is It Used For?
Nustendi is a fixed-dose combination tablet that brings together two lipid-lowering agents with complementary mechanisms. The first active ingredient, bempedoic acid, is a first-in-class inhibitor of ATP-citrate lyase (ACL). ACL sits upstream of HMG-CoA reductase – the enzyme targeted by statins – in the cholesterol biosynthesis pathway. Because bempedoic acid is a prodrug activated only in the liver by the enzyme ACSVL1, it does not accumulate in skeletal muscle and carries a markedly lower risk of muscle-related adverse effects than statins. The second active ingredient, ezetimibe, inhibits the Niemann-Pick C1-Like 1 (NPC1L1) transporter in the brush border of the small intestine, selectively reducing the absorption of dietary and biliary cholesterol.
The combination produces additive reductions in LDL-cholesterol that are greater than either agent achieves alone. By simultaneously decreasing hepatic synthesis and intestinal absorption, Nustendi triggers a strong upregulation of LDL receptors on the surface of hepatocytes, which accelerates the clearance of circulating LDL particles from the bloodstream. Clinical trials have demonstrated that the combination lowers LDL-C by around 36% versus placebo when used as monotherapy, and by approximately 28% when added to maximally tolerated statin therapy.
Nustendi is indicated in adults with primary hypercholesterolemia (both heterozygous familial and non-familial) or mixed dyslipidemia, as an adjunct to a cholesterol-lowering diet. It is typically prescribed in combination with a statin (or the highest tolerated statin dose) when LDL goals are not achieved, or as monotherapy when statins are contraindicated or not tolerated. It can also be added to other lipid-lowering therapies, including PCSK9 inhibitors and fibrates, when further LDL reduction is required.
Beyond LDL reduction, bempedoic acid has been shown to reduce cardiovascular events. The landmark CLEAR Outcomes trial, published in the New England Journal of Medicine in 2023, enrolled over 13,000 statin-intolerant patients and demonstrated a 13% reduction in major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularisation) compared with placebo. Ezetimibe, for its part, reduced cardiovascular events by about 6% in the IMPROVE-IT trial when added to simvastatin in post-acute coronary syndrome patients. The combination embodied in Nustendi therefore addresses an important clinical gap: patients who either cannot tolerate statins or cannot reach LDL targets despite maximal statin therapy.
Nustendi is marketed by Daiichi Sankyo Europe in Europe and by Esperion Therapeutics in the United States (where the same combination is sold as Nexlizet). It was first authorised by the European Medicines Agency (EMA) in 2020 and is approved in multiple regions including the EU/EEA, United Kingdom, and United States. Tablets are white to off-white, capsule-shaped, and film-coated, supplied in blister packs of various sizes.
What Should You Know Before Taking Nustendi?
Before starting Nustendi, your doctor will carefully review your medical history, current medications, and laboratory values. Because the product combines two active substances, contraindications and precautions apply to both bempedoic acid and ezetimibe. Understanding these is essential to ensure Nustendi is safe and appropriate for you.
Contraindications
Nustendi must not be used in the following situations. First, if you are pregnant or planning to become pregnant, Nustendi is strictly contraindicated. Cholesterol and cholesterol-derived molecules play a critical role in fetal development, and blocking their synthesis may cause harm to the developing baby. Similarly, Nustendi must not be used during breastfeeding, as it is unknown whether the active ingredients are excreted in human milk at levels that could affect the nursing infant.
Nustendi is also contraindicated in patients with a known hypersensitivity to bempedoic acid, ezetimibe, or any of the excipients in the tablet. If you have ever experienced a serious allergic reaction (rash, angioedema, anaphylaxis) to either active ingredient, you must not take Nustendi.
Another important contraindication is concurrent treatment with simvastatin at doses greater than 40 mg per day. Bempedoic acid inhibits hepatic OATP1B1/1B3 transporters, which significantly increases the plasma exposure of simvastatin and its active metabolite. This combination raises the risk of severe muscle damage (myopathy and rhabdomyolysis) to unacceptable levels. If you are currently on high-dose simvastatin, your doctor may either lower your simvastatin dose to ≤40 mg or switch you to a different statin before starting Nustendi.
When Nustendi is taken with a statin, it is contraindicated in patients with active liver disease or unexplained persistent elevations in serum transaminases. In such cases, any co-prescribed statin must be discontinued until the liver abnormalities are resolved.
Do not take Nustendi if you are pregnant, breastfeeding, have a known allergy to bempedoic acid or ezetimibe, or are taking more than 40 mg of simvastatin daily. Seek immediate medical advice if you experience unexplained muscle pain, dark urine, or yellowing of the skin or eyes while taking this medicine.
Warnings and Precautions
Several conditions warrant special consideration before and during treatment with Nustendi. If you have a history of gout or hyperuricemia, you should inform your doctor. Bempedoic acid raises serum uric acid levels (on average by around 0.8 mg/dL) by inhibiting the renal organic anion transporter OAT2, and can precipitate gout flares, particularly in patients with pre-existing hyperuricemia or prior gout attacks. Your doctor may monitor uric acid levels and consider prophylactic urate-lowering therapy if necessary.
In patients with severe renal impairment (estimated glomerular filtration rate below 30 mL/min/1.73 m²), Nustendi should be used with caution, as clinical experience is limited. Bempedoic acid can cause modest, reversible reductions in eGFR and increases in serum creatinine and blood urea nitrogen. Ezetimibe requires no dose adjustment in mild renal impairment but has limited data in severe renal disease. Regular renal function testing is recommended throughout treatment.
For patients with hepatic impairment, mild impairment (Child-Pugh class A) does not require dose adjustment. In moderate hepatic impairment (Child-Pugh class B), frequent monitoring is recommended. Nustendi is not recommended in severe hepatic impairment (Child-Pugh class C) due to limited data on the disposition of ezetimibe and increased exposure of its glucuronide metabolite. Liver enzyme testing (ALT, AST) before starting therapy and periodically during treatment is advised when Nustendi is given with a statin.
There is a theoretical risk of tendon rupture with bempedoic acid. In clinical trials, tendon rupture (including rotator cuff, biceps, and Achilles tendon) was reported in approximately 0.5% of patients treated with bempedoic acid versus 0.3% of patients given placebo. The risk may be higher in patients over 60 years of age, those taking oral corticosteroids or fluoroquinolone antibiotics, and those with renal failure or previous tendon disorders. Report any tendon pain, inflammation, or rupture to your doctor immediately and discontinue Nustendi if tendon rupture is suspected.
Patients who take Nustendi together with a statin should be aware of the small but real risk of muscle-related adverse events, including myalgia, myopathy, and, rarely, rhabdomyolysis. Report any unexplained muscle pain, tenderness, weakness, or brown urine to your doctor immediately, as these symptoms may require prompt investigation with creatine kinase (CK) measurement.
Your doctor may order liver function tests, renal function tests, and serum uric acid before starting Nustendi and periodically during treatment. These tests help ensure that the combination is being well tolerated and allow early detection of adverse effects.
Pregnancy and Breastfeeding
Nustendi must not be used during pregnancy. Women of childbearing potential should confirm they are not pregnant before starting Nustendi and should use effective contraception throughout treatment and for a period after discontinuation. If you become pregnant while taking Nustendi, stop the medication immediately and contact your doctor. Cholesterol is essential for the synthesis of bile acids, steroid hormones, vitamin D, and cell membranes, all of which are especially important during pregnancy.
Nustendi is also contraindicated while breastfeeding. It is unknown whether bempedoic acid or ezetimibe are excreted in human milk. In rat studies, ezetimibe was detected in milk, and a potential risk to the breastfed infant cannot be excluded. If you plan to breastfeed, discuss alternative lipid-lowering strategies with your doctor.
Children and Adolescents
Nustendi is not approved for use in children or adolescents under 18 years of age. Safety and efficacy have not been established in this population. Ezetimibe alone is approved in children aged 6 years and older for certain conditions (such as homozygous familial hypercholesterolemia and homozygous sitosterolemia), but the fixed-dose combination has not been studied in younger patients.
Elderly Patients
No dose adjustment is required in elderly patients. Both bempedoic acid and ezetimibe have been extensively studied in patients aged 65 years and older, with no overall differences in safety or efficacy compared with younger adults. However, older patients may be more susceptible to muscle-related and tendon-related adverse events, particularly when Nustendi is combined with a statin, so ongoing monitoring remains important.
Driving and Operating Machinery
Nustendi has no or negligible influence on the ability to drive or use machines. However, very rare cases of dizziness have been reported with ezetimibe, so caution is advised if you feel unwell when driving.
Important Information About Excipients
Nustendi tablets contain lactose monohydrate. If you have been told by your doctor that you have an intolerance to certain sugars (galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption), contact your doctor before taking this medicine. Nustendi also contains less than 1 mmol sodium (23 mg) per tablet, which is essentially "sodium-free".
How Does Nustendi Interact with Other Drugs?
Because Nustendi contains two active substances, drug interactions involve both bempedoic acid and ezetimibe. Bempedoic acid is a substrate of hepatic OATP1B1/1B3 transporters and an inhibitor of these transporters, meaning it can alter the plasma concentrations of co-administered drugs that rely on the same transport systems. Ezetimibe undergoes glucuronidation in the small intestine and liver and is subject to enterohepatic recirculation; its absorption and efficacy can be affected by drugs that alter bile acid handling or glucuronidation.
Major Interactions
| Drug / Class | Effect | Clinical Advice |
|---|---|---|
| Simvastatin (>40 mg/day) | Increased simvastatin exposure via OATP1B1/1B3 inhibition by bempedoic acid; raises risk of myopathy and rhabdomyolysis. | Do not exceed 40 mg simvastatin daily. Higher doses are contraindicated with Nustendi. |
| Pravastatin | Bempedoic acid increases pravastatin AUC approximately two-fold. | Use the lowest effective pravastatin dose. Monitor for muscle symptoms. |
| Other statins (atorvastatin, rosuvastatin, fluvastatin, pitavastatin) | Mild to moderate increase in statin exposure; small theoretical increase in muscle-related risk. | Can be used together with routine monitoring. Report unexplained muscle pain, tenderness, or weakness immediately. |
| Ciclosporin | Markedly increases plasma ezetimibe levels; ezetimibe may slightly increase ciclosporin trough concentrations. | Use with caution; monitor ciclosporin blood levels carefully. Avoid in patients with severe hepatic impairment. |
| Bile acid sequestrants (colestyramine, colestipol, colesevelam) | May reduce ezetimibe absorption if taken close together; approximately 55% reduction in ezetimibe AUC. | Administer Nustendi at least 2 hours before or 4 hours after a bile acid sequestrant. |
| Fibrates (fenofibrate, gemfibrozil) | Fibrates may increase cholesterol excretion into bile, potentially leading to cholelithiasis. Combination with ezetimibe is not recommended for some fibrates. | Fenofibrate can be used with caution. Gemfibrozil combinations should be avoided. Consult your doctor. |
| Warfarin and other coumarin anticoagulants | Ezetimibe may modestly increase INR in susceptible patients. | Monitor INR more frequently when starting, stopping, or changing the dose of Nustendi. |
| Bosentan | May reduce bempedoic acid plasma levels via induction of hepatic transporters. | Inform your doctor; dose adjustment or alternative lipid-lowering therapy may be considered. |
| Hepatitis C direct-acting antivirals (glecaprevir, voxilaprevir, asunaprevir) | May increase bempedoic acid levels through OATP1B1/1B3 inhibition. | Monitor for enhanced effects or side effects during co-administration. |
Additional Interaction Considerations
There is no clinically significant interaction between Nustendi and oral contraceptives. Bempedoic acid and ezetimibe have been co-administered with combined oral contraceptives in clinical studies without evidence of altered contraceptive efficacy. Similarly, no clinically relevant interactions have been observed with PCSK9 inhibitors (evolocumab, alirocumab), antacids, digoxin, or common antihypertensive agents such as angiotensin-converting enzyme (ACE) inhibitors and calcium-channel blockers.
Ezetimibe can be co-administered with food without any effect on absorption. However, the overall Nustendi tablet performance should be considered: take it at roughly the same time each day, with or without food, and avoid crushing or chewing the tablet. If you take grapefruit juice regularly, this is generally not a concern with Nustendi, as the active substances are not CYP3A4 substrates in a clinically meaningful way, but it may be relevant for any co-prescribed statin (e.g., simvastatin or atorvastatin), for which grapefruit juice intake should be limited.
Always ensure that every healthcare provider you consult – including dentists, specialists, and pharmacists – is aware that you are taking Nustendi. Keep an up-to-date list of all your medications, including over-the-counter drugs, vitamins, and herbal supplements such as St John's wort, which can induce hepatic enzymes and transporters and potentially affect Nustendi exposure.
If you use a bile acid sequestrant (colestyramine, colesevelam), take Nustendi at least 2 hours before or 4 hours after the sequestrant. This simple timing adjustment preserves the full effect of ezetimibe.
What Is the Correct Dosage of Nustendi?
Nustendi is supplied as a single strength – one tablet contains 180 mg of bempedoic acid and 10 mg of ezetimibe. The recommended dose is one tablet once daily. No dose titration is needed, and no dose adjustment is required on the basis of age, sex, body weight, or race. The tablet should be swallowed whole with a glass of water and can be taken with or without food, according to the patient's preference.
Nustendi should be used as part of a comprehensive cardiovascular risk-reduction strategy that also includes a heart-healthy diet (such as the Mediterranean-style diet), regular aerobic physical activity, weight management, and smoking cessation where applicable. If Nustendi is co-prescribed with a statin or other lipid-lowering agent, the individual components can be taken at the same or different times of day, based on patient convenience.
Adults
Standard Adult Dose
One tablet (180 mg / 10 mg) once daily, taken orally with or without food. No dose titration is required. Continue treatment as long as your doctor recommends, as stopping the medication will cause LDL-C levels to rise again.
The LDL-lowering effect of Nustendi becomes apparent within 1-2 weeks of starting therapy, with the maximum effect generally achieved by 4-12 weeks. A lipid panel is usually repeated 8-12 weeks after initiation to confirm response and guide any further therapeutic decisions.
Children and Adolescents
Pediatric Dose
Not recommended. Nustendi has not been studied in patients under 18 years of age and should not be used in this population. For pediatric dyslipidemia, specialists may consider ezetimibe monotherapy or other agents with age-appropriate evidence.
Elderly Patients
Dose in Patients Aged 65 and Older
No dose adjustment required. Clinical trials included a substantial proportion of patients ≥65 years; safety and efficacy were comparable to younger adults. However, older patients may be slightly more susceptible to muscle or tendon adverse events, especially when combined with a statin, so clinical monitoring should continue.
Renal Impairment
Patients with Kidney Disease
Mild to moderate impairment: No dose adjustment. Severe impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease: Use with caution, as clinical data are limited. Your doctor will monitor kidney function during therapy.
Hepatic Impairment
Patients with Liver Disease
Mild impairment (Child-Pugh A): No dose adjustment. Moderate impairment (Child-Pugh B): Use with caution and more frequent monitoring. Severe impairment (Child-Pugh C): Not recommended due to limited data.
Missed Dose
If you realise you have missed a dose later the same day, take the missed dose as soon as you remember and then take your next dose at the regular time the following day. If you realise that you missed the previous day's dose entirely, simply take your next scheduled dose at the usual time. Never take a double dose to make up for the one you missed. If you frequently miss doses, consider using a pillbox, phone reminder, or a regular daily routine (for example, taking the tablet with breakfast or brushing teeth) to help you remember.
Overdose
If you take more Nustendi than prescribed, contact your doctor, pharmacist, or nearest poison control centre immediately, or go to the nearest emergency department. In clinical studies, single doses of up to 240 mg of bempedoic acid and up to 50 mg of ezetimibe were generally well tolerated, but larger overdoses have not been systematically studied. Specific antidotes are not available; treatment is supportive. Due to high protein binding, haemodialysis is unlikely to be effective in removing bempedoic acid. Liver and kidney function, along with serum uric acid, may be monitored after significant overdose.
Cholesterol-lowering therapy is a long-term commitment. Do not stop Nustendi without consulting your doctor, even if your cholesterol numbers have improved – discontinuation almost always leads to a return of elevated LDL-C within weeks.
What Are the Side Effects of Nustendi?
Like all medicines, Nustendi can cause side effects, although not everyone who takes it will experience them. Because the tablet combines two active substances, the overall side-effect profile reflects events reported for bempedoic acid, ezetimibe, and any interactions between the two. Data from pivotal phase 3 trials and real-world pharmacovigilance show that most adverse events are mild to moderate and reversible on dose interruption or discontinuation.
The largest body of cardiovascular safety data for bempedoic acid comes from the CLEAR Outcomes trial, which followed over 13,000 patients for a median of 3.4 years. Ezetimibe has been used clinically since 2002 and has a well-characterised long-term safety record. The frequencies below are categorised according to the MedDRA convention used in EU Summary of Product Characteristics (SmPC) documents.
Very Common Side Effects
May affect more than 1 in 10 people
- None reported at this frequency for Nustendi as a fixed-dose combination at the approved dose.
Common Side Effects
May affect up to 1 in 10 people
- Hyperuricemia – elevated uric acid levels in the blood
- Gout – painful inflammatory arthritis, most often in the big toe
- Constipation – infrequent, hard, or difficult-to-pass stools
- Diarrhoea – loose or watery stools
- Abdominal pain or discomfort – upper or generalised abdominal pain, bloating, or flatulence
- Limb pain – pain in the shoulders, arms, or legs
- Muscle spasms – involuntary muscle contractions or cramps
- Anaemia – decreased red blood cells with possible fatigue or pallor
- Decreased eGFR – reduced estimated glomerular filtration rate
- Abnormal liver function tests – elevated ALT and/or AST
- Fatigue – unusual tiredness or lack of energy
Uncommon Side Effects
May affect up to 1 in 100 people
- Decreased haemoglobin – lower oxygen-carrying capacity of blood
- Elevated serum creatinine – marker of reduced kidney function
- Elevated blood urea nitrogen (BUN) – another kidney-function marker
- Weight loss – unintended decrease in body weight
- Nausea – uncomfortable feeling in the stomach with urge to vomit
- Dyspepsia – indigestion or heartburn
- Dizziness – light-headedness or feeling of unsteadiness
- Headache – mild to moderate head pain
- Hot flush – transient sensation of warmth
- Hypertension – small increases in blood pressure
- Cough – dry or productive cough
- Elevated creatine kinase (CK) – laboratory marker of muscle stress
- Joint pain or back pain – musculoskeletal discomfort
- Rash or pruritus – skin rash or itching
Rare Side Effects
May affect up to 1 in 1,000 people (or not known)
- Tendon rupture – tear of a tendon, particularly rotator cuff, biceps, or Achilles
- Rhabdomyolysis – severe muscle breakdown, especially when combined with a statin
- Myopathy – persistent muscle weakness with CK elevation
- Pancreatitis – inflammation of the pancreas causing severe upper abdominal pain
- Cholelithiasis or cholecystitis – gallstones or gallbladder inflammation
- Hepatitis or cholestatic liver injury – inflammatory or obstructive liver damage
- Thrombocytopenia – low platelet count
- Angioedema – deep-tissue swelling of face, lips, tongue, or throat
- Severe hypersensitivity reactions – urticaria, anaphylaxis, Stevens-Johnson-type reactions (very rare)
- Erythema multiforme – target-like skin lesions
- Depression – reported rarely with ezetimibe
When to Seek Medical Attention
You should contact your doctor or seek urgent medical advice if you experience any of the following during treatment with Nustendi:
- Unexplained muscle pain, tenderness, weakness, or brown/dark urine – may indicate myopathy or rhabdomyolysis, especially if you are also taking a statin.
- Tendon pain, swelling, or inflammation – may indicate tendinopathy or impending tendon rupture; discontinue Nustendi and avoid strenuous exercise until evaluated.
- Severe joint pain or swelling (especially the big toe) – may indicate a gout attack.
- Yellowing of the skin or eyes (jaundice), pale stools, or dark urine – may indicate liver problems.
- Severe abdominal pain, especially in the upper abdomen – may indicate pancreatitis or gallstones.
- Swelling of the face, lips, tongue, or throat; difficulty breathing; or widespread rash – may indicate a serious allergic reaction (angioedema or anaphylaxis). Seek emergency care.
- Persistent fatigue, shortness of breath, or pallor – may indicate anaemia.
Reporting suspected side effects is an important part of ongoing drug safety monitoring. If you experience any side effects not listed here, or if any listed side effects become severe, please report them through your national pharmacovigilance authority or via your healthcare provider. In the European Union, reports can be submitted through national reporting systems or directly to the EMA.
A small rise in liver enzymes or a modest decrease in eGFR shortly after starting Nustendi is common and usually reversible. Your doctor will interpret these trends in context; they rarely require stopping treatment.
How Should You Store Nustendi?
Proper storage of Nustendi is simple and does not require refrigeration or special protection from light. Keep the tablets in their original blister strip and outer carton until you are ready to take a dose. This packaging helps protect the tablets from moisture and accidental damage. Typical storage conditions are at temperatures below 30°C (86°F) in a dry place, away from direct sunlight and sources of heat such as radiators, windows, and bathrooms (where humidity tends to be high).
Always keep Nustendi out of the sight and reach of children. Accidental ingestion of cholesterol-lowering medicines by a child can cause harm and should be treated as a medical emergency. If a child swallows a tablet, contact your local poison control centre or emergency department immediately.
Check the expiry date printed on the blister strip (usually after "EXP") and on the outer carton. The expiry date refers to the last day of the stated month – for example, "EXP 06/2027" means the tablets should not be used after 30 June 2027. If the expiry date has passed, the tablets may lose potency or degrade, and should be safely disposed of.
Do not dispose of unused or expired Nustendi tablets via household waste or by flushing them down the toilet. Pharmaceutical residues in the environment contribute to water pollution. Instead, return unused medicines to your local pharmacy or community take-back programme, where they can be incinerated safely. Ask your pharmacist for advice about responsible disposal options available in your country.
What Does Nustendi Contain?
Each film-coated tablet of Nustendi contains two active pharmaceutical ingredients:
- Bempedoic acid 180 mg – the ACL (ATP-citrate lyase) inhibitor
- Ezetimibe 10 mg – the intestinal cholesterol absorption inhibitor
The inactive ingredients (excipients) that make up the tablet core and film coating typically include:
- Lactose monohydrate – a common pharmaceutical filler (patients with lactose intolerance should inform their doctor)
- Microcrystalline cellulose (E460) – a binding and bulking agent
- Croscarmellose sodium – a disintegrant that promotes tablet breakdown in the gut
- Hydroxypropyl cellulose (E463) – a binder
- Hypromellose (E464) – a film-forming agent
- Sodium lauryl sulfate – a wetting agent to aid dissolution
- Magnesium stearate (E470b) – a lubricant used in manufacturing
- Silica, colloidal anhydrous (E551) – an anti-caking agent
The film coating usually consists of hypromellose, titanium dioxide (E171), triacetin, and talc (E553b). These components give the tablet its smooth, uniform white to off-white appearance and help protect the active substances from moisture during storage.
Nustendi tablets are capsule-shaped and film-coated, typically embossed with an identification code on one or both sides to enable unambiguous identification. They are supplied in aluminium/aluminium blister packs in outer cartons containing various pack sizes (for example 10, 28, 30, 90, or 98 tablets). Not all pack sizes may be marketed in every country; your pharmacy will provide the size authorised locally.
If you have intolerance to any of the listed excipients, inform your doctor or pharmacist before starting Nustendi. While excipient-related reactions are rare, they can occur – particularly in patients with lactose intolerance or known sensitivity to specific dyes or coating agents.
Frequently Asked Questions About Nustendi
Nustendi is a fixed-dose combination tablet containing bempedoic acid 180 mg and ezetimibe 10 mg. It is used to lower LDL ("bad") cholesterol in adults with primary hypercholesterolemia (familial or non-familial) or mixed dyslipidemia. It is typically prescribed when a statin alone does not adequately control LDL cholesterol, or as an alternative for patients who cannot tolerate statins. Nustendi is usually combined with a heart-healthy diet and lifestyle measures, and may be used alongside or instead of a statin.
Clinically, there is no meaningful difference. Nustendi provides the same doses of bempedoic acid (180 mg) and ezetimibe (10 mg) as the two drugs taken separately, and bioequivalence studies have shown equivalent plasma exposures and LDL-lowering efficacy. The advantage of Nustendi is convenience: a single tablet once daily improves adherence compared with taking two separate products, which is particularly important for long-term cholesterol therapy where persistence often declines over time.
In phase 3 trials, Nustendi reduced LDL-cholesterol by approximately 36% compared with placebo after 12 weeks of treatment. When added to maximally tolerated statin therapy, it provided an additional LDL reduction of around 28%, which is greater than either bempedoic acid (around 17%) or ezetimibe (around 20%) alone on top of statins. Nustendi also modestly reduces non-HDL cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein (hsCRP), an independent cardiovascular risk marker.
Yes, Nustendi is commonly prescribed together with a statin to achieve greater LDL reduction. The only important restriction is with simvastatin: doses above 40 mg per day are contraindicated with Nustendi because bempedoic acid increases simvastatin blood levels and raises the risk of serious muscle damage. Atorvastatin, rosuvastatin, pravastatin, fluvastatin, and pitavastatin can all be co-administered at standard doses, with routine monitoring for muscle symptoms.
No. Nustendi is contraindicated during pregnancy and breastfeeding. Cholesterol is essential for fetal development and milk production, and inhibiting cholesterol synthesis may harm the developing baby or nursing infant. Women of childbearing potential should use effective contraception while on Nustendi and must stop the medication immediately if pregnancy is suspected or confirmed. Alternative strategies (such as diet, exercise, and bile acid sequestrants, which are not systemically absorbed) may be considered with your doctor.
Muscle-related side effects are uncommon with Nustendi. Bempedoic acid is a prodrug activated only in the liver and is not activated in skeletal muscle, which means it rarely causes the myalgia often attributed to statins. Ezetimibe does not directly affect muscle tissue. In the CLEAR Outcomes trial, muscle symptoms occurred at rates similar to placebo. However, when Nustendi is combined with a statin, the overall muscle-symptom risk may rise slightly, so any unexplained muscle pain, tenderness, weakness, or dark urine should be reported to your doctor promptly.
Bempedoic acid, one of the two active ingredients in Nustendi, can raise serum uric acid levels and precipitate gout flares in susceptible patients. This is a known common side effect (affecting up to 1 in 10 people). The risk is greater in patients with a prior history of gout or hyperuricemia. If you have experienced gout before, inform your doctor, who may monitor uric acid levels or prescribe urate-lowering therapy (such as allopurinol) alongside Nustendi. Adequate hydration and limiting alcohol and purine-rich foods may also help reduce the risk of flares.
No, Nustendi can be taken with or without food. Food does not significantly affect the absorption or efficacy of either bempedoic acid or ezetimibe. What matters most is consistency: take it at roughly the same time each day to maintain steady blood levels and make the routine easier to remember. Swallow the tablet whole with water – do not crush, chew, or split it.
References and Sources
This article is based on the following peer-reviewed sources and regulatory documents:
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- European Medicines Agency (EMA). Nustendi – Summary of Product Characteristics (SmPC). Last updated 2024. Available at: EMA – Nustendi EPAR
- U.S. Food and Drug Administration (FDA). NEXLIZET (bempedoic acid and ezetimibe) tablets – Prescribing Information. Approved February 2020, updated 2023.
- Ballantyne CM, Banach M, Mancini GBJ, et al. Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: A randomized, placebo-controlled study. Atherosclerosis. 2018;277:195-203. doi:10.1016/j.atherosclerosis.2018.06.002
- Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. 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.
- Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes (IMPROVE-IT). N Engl J Med. 2015;372(25):2387-2397. doi:10.1056/NEJMoa1410489
- Ray KK, Bays HE, Catapano AL, et al. Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol (CLEAR Harmony). 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
- British National Formulary (BNF). Bempedoic acid with ezetimibe. Royal Pharmaceutical Society. Updated 2025.
- World Health Organization (WHO). Cardiovascular diseases (CVDs) – Fact Sheet. 2023.
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About the Medical Editorial Team
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