Bempedoic acid + Ezetimibe is a prescription tablet that lowers LDL cholesterol, often called "bad" cholesterol. Each tablet contains two medicines: bempedoic acid 180 mg and ezetimibe 10 mg. Bempedoic acid cuts down the cholesterol your liver makes, while ezetimibe reduces how much cholesterol your small intestine absorbs. Bempedoic acid + Ezetimibe is used in adults with high cholesterol (hypercholesterolaemia), including an inherited form called heterozygous familial hypercholesterolaemia, alongside a healthy diet and exercise. The bempedoic acid part is also used to lower the risk of heart attack, stroke and related heart events in adults at higher risk who cannot take the recommended statin medicines.

Many people start cholesterol treatment with a statin. Bempedoic acid + Ezetimibe works in a different way, attacking cholesterol from two sides at once.

The first ingredient, bempedoic acid, blocks an enzyme in the liver called ATP citrate lyase (ACL). This enzyme is one of the early steps the liver uses to build cholesterol, and it sits earlier in the same chain of steps that statins act on. Bempedoic acid has to be switched on by another enzyme found mainly in the liver before it starts working.

The second ingredient, ezetimibe, works in the small intestine. It blocks a protein called NPC1L1 that helps move cholesterol from the gut into the body. Less cholesterol then reaches the liver.

When the liver makes less cholesterol and receives less from the gut, it responds by making more LDL receptors. These receptors act like docking stations that pull LDL cholesterol out of the blood, so blood levels fall.

Bempedoic acid + Ezetimibe is used in adults with primary high cholesterol or mixed dyslipidaemia (high levels of several blood fats). It can be taken along with a statin, or without one in people who cannot tolerate statins. In a three-month study of 382 patients, LDL cholesterol fell by 36% with the combination compared with 23% with ezetimibe alone.

Having both medicines in one tablet taken once a day, with or without food, keeps the routine simple.

Bempedoic acid + Ezetimibe needs a doctor's prescription and regular follow-up. Your doctor will usually check your cholesterol again within 8 to 12 weeks of starting. Bempedoic acid can raise uric acid in the blood and has been linked to tendon rupture, so tell your doctor if you have ever had gout or tendon problems. Also mention any liver disease, and let your doctor know if you are pregnant, planning a pregnancy or breastfeeding.

1. High LDL cholesterol (primary hypercholesterolaemia, including heterozygous familial hypercholesterolaemia, or mixed dyslipidaemia) - Bempedoic acid + Ezetimibe is used in adults, together with a healthy diet and exercise, to lower LDL ("bad") cholesterol. Heterozygous familial hypercholesterolaemia is an inherited form of high cholesterol that runs in families. Mixed dyslipidaemia means high levels of several blood fats at once.
2. Lowering the risk of heart attack, stroke and related heart events (from the bempedoic acid part) - Bempedoic acid is used to lower the risk of heart-related death, heart attack, stroke, or needing a procedure to reopen the heart's blood vessels, in adults at higher risk of these events who cannot take recommended statin therapy.

1. Two ways of lowering cholesterol in one tablet - Bempedoic acid reduces the cholesterol your liver makes, and ezetimibe reduces the cholesterol your gut absorbs. Together they lower LDL cholesterol through two separate routes.
2. Greater LDL reduction than ezetimibe alone - In a three-month study of 382 patients, the combination lowered LDL cholesterol by 36%, compared with 23% for ezetimibe on its own.
3. An option when statins are not suitable - In a study of 269 people who could not take statins or could take only a low statin dose, and who were all already taking ezetimibe, adding bempedoic acid lowered LDL cholesterol by 23% after three months, while it rose by about 5% in those given a dummy tablet (placebo) instead.
4. Lower risk of heart events from the bempedoic acid part - In a trial of about 14,000 people, 11.7% of those given bempedoic acid had a heart or blood vessel event such as a heart attack or stroke, compared with 13.3% of those given a placebo.
5. Works mainly in the liver - Bempedoic acid is switched on by an enzyme found mainly in the liver, so its cholesterol-blocking action is focused where most cholesterol is made.
6. Simple once-daily routine - One tablet a day, with or without food, can make it easier to stay on treatment long term.

Not everyone gets side effects. Many people take Bempedoic acid + Ezetimibe with few or no problems.

Common Side Effects (Usually Mild and may lessen with continued use)

• Cold-like symptoms such as a sore throat, runny nose or sneezing (upper respiratory tract infection)
• Muscle spasms
• Back pain
• Stomach pain or discomfort
• Pain in the arms or legs
• Joint pain
• Chest infection with cough (bronchitis)
• Sinus infection
• Urinary tract infection
• Diarrhoea or constipation
• Tiredness
• Flu
• Changes on blood tests, such as higher liver enzymes, higher uric acid or a lower red blood cell (haemoglobin) count

Serious Side Effects (Seek Urgent Medical Attention)

• Tendon rupture: A tendon is the tough cord that joins muscle to bone. Bempedoic acid can make a tendon tear or snap. In studies, this happened in 0.5% of people on bempedoic acid and in none of those on placebo, mostly in the shoulder (rotator cuff), the biceps in the upper arm, or the Achilles tendon at the back of the ankle. The risk is higher if you are over 60, take steroid medicines (corticosteroids) or fluoroquinolone antibiotics, have kidney failure, or have had tendon problems before. Stop moving the area, rest it, and call your doctor straight away if you feel a snap or pop, sudden pain, swelling or bruising near a joint, or cannot move or put weight on it.
• Hyperuricaemia and gout: Hyperuricaemia means too much uric acid in the blood. In studies, 26% of people on bempedoic acid who started with normal levels developed it, compared with 9.5% on placebo. It usually shows up within the first 4 weeks. High uric acid can lead to gout, a painful swelling of a joint, often the big toe. Gout occurred in 1.5% of people on bempedoic acid compared with 0.4% on placebo.
• Severe allergic reaction (anaphylaxis) and angioedema: Anaphylaxis is a sudden, whole-body allergic reaction. Angioedema is swelling under the skin, often of the face, lips, tongue or throat. Watch for hives, rash, trouble breathing or swallowing, a fast heartbeat or dizziness.
• Muscle damage (myopathy), including rhabdomyolysis: Rhabdomyolysis is a severe form of muscle damage in which muscle tissue breaks down. The risk is higher if Bempedoic acid + Ezetimibe is taken with higher doses of simvastatin or pravastatin. Report unexplained muscle pain, tenderness or weakness.
• Inflamed pancreas (pancreatitis): The pancreas is an organ behind the stomach that helps with digestion. Pancreatitis has been reported in people using these medicines. Watch for severe stomach pain, with or without nausea.
• Liver problems: Yellowing of the skin or eyes can be a sign of a liver problem.
• Gallstones: Nausea with pain in the upper stomach can be a sign of gallbladder trouble.
• Low red blood cells (anaemia): Signs include unusual tiredness, paleness, shortness of breath or a fast heartbeat.
• Unusual bleeding or bruising.

• Take Bempedoic acid + Ezetimibe exactly as your doctor has prescribed. The label describes one tablet by mouth once a day.
• Swallow the tablet whole with a glass of plain water. Do not cut, chew or crush it.
• You can take it with or without food. Pick whichever suits you and keep to the same habit each day.
• Take it at around the same time every day so it becomes part of your routine.
• If you also take a bile acid binder such as cholestyramine, colesevelam or colestipol, take Bempedoic acid + Ezetimibe at least 2 hours before or at least 4 hours after it. These powders and tablets can stop ezetimibe from being absorbed properly.
• Keep following the low-fat, low-cholesterol diet and exercise plan your doctor or dietitian has given you. Bempedoic acid + Ezetimibe works alongside these, not instead of them.
• Keep taking it even when you feel well. Bempedoic acid + Ezetimibe controls high cholesterol but does not make it go away for good. Do not stop without talking to your doctor.

Bempedoic acid + Ezetimibe lowers LDL cholesterol by reducing both how much cholesterol the liver makes and how much the intestine absorbs.

Bempedoic acid - slows cholesterol-making in the liver

• Bempedoic acid is a "prodrug", meaning it is inactive when swallowed and has to be switched on inside the body. An enzyme called ACSVL1, found mainly in the liver, does this job.
• Once active, it blocks ATP citrate lyase (ACL). An enzyme is a protein that speeds up a chemical step in the body, and ACL is one of the early steps the liver uses to build cholesterol.
• ACL works earlier in the same production line as HMG-CoA reductase, the enzyme that statins block. So bempedoic acid slows the same process at an earlier point.
• With less cholesterol being made inside liver cells, the liver makes more LDL receptors. These receptors grab LDL cholesterol from the blood and bring it into the liver, which lowers blood LDL levels.

Ezetimibe - blocks cholesterol absorption in the gut

• Ezetimibe sits on the inner lining of the small intestine (the brush border).
• There it blocks a transporter protein called Niemann-Pick C1-Like 1 (NPC1L1). A transporter is like a doorway that carries substances into cells. NPC1L1 helps move cholesterol and similar plant fats (phytosterols) from the gut into the body.
• With this doorway blocked, less cholesterol travels from the gut to the liver. The liver then pulls more LDL cholesterol out of the blood to make up for it.

Working together

Because each ingredient acts in a different place, their effects add up. Both lead to the same end result: more LDL receptors on the liver and more LDL cholesterol removed from the blood.

• Take Bempedoic acid + Ezetimibe at the same time each day, with or without food.
• Swallow the tablet whole with plain water. Do not cut, chew or crush it.
• If you use a bile acid binder such as cholestyramine, take Bempedoic acid + Ezetimibe at least 2 hours before or at least 4 hours after it.
• Tell every doctor who treats you that you take Bempedoic acid + Ezetimibe, especially before starting simvastatin, pravastatin, cyclosporine, fenofibrate, a steroid or a fluoroquinolone antibiotic.
• Rest and call your doctor at the first sign of tendon pain, swelling, or a snapping feeling.
• Report sudden, painful swelling of a joint, such as the big toe, which could be gout.
• Keep your follow-up appointments. Your doctor will usually recheck your cholesterol within 8 to 12 weeks and may check your uric acid too.
• Keep following your low-fat, low-cholesterol diet and exercise plan.

• Store at room temperature, between 20°C and 25°C (68°F to 77°F). Short periods between 15°C and 30°C (59°F to 86°F) are acceptable.
• Keep the tablets in their original package, protected from heat and moisture.
• If the bottle has a small moisture-absorbing packet (desiccant), leave it inside. Do not throw it away.
• Keep out of the reach and sight of children and pets.

• Meals: Bempedoic acid + Ezetimibe can be taken with or without food. A high-fat meal slows absorption slightly, but this change is not considered important for how well the medicine works.
• Diet: A low-fat, low-cholesterol diet supports the effect of Bempedoic acid + Ezetimibe. The medicine is meant to be used alongside diet changes, not in place of them.
• Bile acid binders: Cholesterol-binding powders or tablets (cholestyramine, colesevelam, colestipol), which are sometimes mixed with drinks, reduce how much ezetimibe you absorb. Keep a gap of at least 2 hours before or at least 4 hours after taking them.

• Simvastatin: Bempedoic acid + Ezetimibe raises simvastatin levels in the blood, which increases the risk of muscle damage (myopathy). Simvastatin doses above 20 mg a day should be avoided with Bempedoic acid + Ezetimibe.
• Pravastatin: Bempedoic acid + Ezetimibe raises pravastatin levels and the risk of muscle damage. Pravastatin doses above 40 mg a day should be avoided with Bempedoic acid + Ezetimibe.
• Cyclosporine (an immune-suppressing medicine): Taking both raises the levels of ezetimibe and cyclosporine, more so in people with severe kidney problems. Your doctor will monitor cyclosporine levels.
• Fenofibrate and other fibrates: Fenofibrate and ezetimibe may both increase cholesterol in bile, raising the chance of gallstones. Bempedoic acid with fibrates may also raise triglycerides and lower HDL ("good") cholesterol, so your doctor may check these levels about four weeks after starting.
• Bile acid binders (cholestyramine, colesevelam, colestipol): These reduce ezetimibe absorption and make Bempedoic acid + Ezetimibe less effective. Take Bempedoic acid + Ezetimibe at least 2 hours before or at least 4 hours after them.
• Corticosteroids (steroid medicines): These raise the risk of tendon rupture when used with bempedoic acid.
• Fluoroquinolone antibiotics: These also raise the risk of tendon rupture when used with bempedoic acid.

Always give your doctor and pharmacist a full list of the medicines, vitamins and herbal products you take.

• Gout or high uric acid: Bempedoic acid raises uric acid levels and can trigger gout. Your doctor may check uric acid and start treatment to lower it if needed.
• Tendon disorders or a past tendon rupture: If you have had tendon problems or a tendon rupture before, your doctor may consider a different cholesterol medicine instead of Bempedoic acid + Ezetimibe.
• Liver disease: Bempedoic acid + Ezetimibe is not recommended in moderate or severe liver disease and should not be used together with a statin in active liver disease or when liver enzymes are high for no clear reason.
• Kidney failure: Kidney failure increases the risk of tendon rupture with bempedoic acid. Kidney problems were also reported slightly more often with bempedoic acid than with placebo in a large heart study.
• Gallbladder disease: Gallstones were reported slightly more often with bempedoic acid than with placebo. Tell your doctor if you have had gallbladder problems.
• Allergy to either ingredient: Bempedoic acid + Ezetimibe must not be used by anyone who has had an allergic reaction to bempedoic acid, ezetimibe or any other ingredient in the tablet.
• Lactose intolerance: The tablet contains lactose monohydrate as an inactive ingredient. Mention it to your doctor if you have been told you cannot tolerate some sugars.

Bempedoic acid + Ezetimibe comes as a single-strength tablet containing bempedoic acid 180 mg and ezetimibe 10 mg. According to the product label, the recommended dose is one tablet by mouth once a day, which is also the maximum in 24 hours. It can be taken with or without food.

Your doctor decides whether Bempedoic acid + Ezetimibe is right for you and how it fits with any other cholesterol medicines you take. Always follow the dose your doctor prescribes. Do not take extra tablets, change your dose or stop taking it on your own.

There is no clinical experience with overdose of Bempedoic acid + Ezetimibe, so no typical pattern of overdose symptoms has been described.

If you or someone else has taken more than the prescribed dose, contact your doctor or a poison information centre straight away. If the person has collapsed, has a seizure, has trouble breathing, or cannot be woken, call emergency services or go to the nearest hospital. Take the medicine pack with you so doctors know exactly what was taken.

• Take the missed dose as soon as you remember.
• If it is almost time for your next dose, skip the missed dose and take the next one at your usual time.
• Never take two doses together to make up for a forgotten one.
• A daily alarm or a weekly pill box can help you remember.

Get medical help straight away if you notice any of the following:

• A snap or pop in a tendon, sudden pain, swelling or bruising near a joint, or trouble moving a joint or putting weight on it (possible tendon rupture)
• Sudden, severe pain, redness and swelling in a joint such as the big toe (possible gout)
• Hives, rash, swelling of the face, lips, tongue or throat, trouble breathing or swallowing, or a fast heartbeat (possible severe allergic reaction)
• Unexplained muscle pain, tenderness or weakness
• Yellowing of the skin or eyes
• Nausea with pain in the upper stomach
• Severe stomach pain, with or without nausea (possible inflamed pancreas)
• Unusual tiredness, paleness or shortness of breath (possible anaemia)
• Unusual bleeding or bruising
• Dizziness
• A positive pregnancy test while taking Bempedoic acid + Ezetimibe