Common high cholesterol medication


High-Cholesterol Lowering Medications

If lifestyle measures don’t lower your cholesterol enough, or you’ve had a heart attack, these treatments can help.

If you’ve been following your doctor’s advice to lower your cholesterol levels, but exercise and a healthy diet haven’t worked, they may prescribe a cholesterol-lowering drug.

But if you’ve had a heart attack, or if you have familial hypercholesterolemia (FH), cholesterol-lowering medication will likely be the first step in your treatment program.

Before prescribing a drug, your doctor will most likely set a goal for your cholesterol levels. This target number will factor in your age, overall health, risk factors (especially those for heart disease), medical history, and other considerations.

Depending on your situation, you may need one or more drugs to get your cholesterol levels to a healthier range.

Cholesterol-Lowering Medications

The most commonly prescribed types of cholesterol-lowering drugs include:

Statins These drugs work by blocking a substance your liver needs to make cholesterol, which in turn causes your liver to remove cholesterol from your blood.

Statins may also potentially reverse coronary artery disease by helping your body reabsorb cholesterol from built-up deposits along the walls of your arteries.

Commonly prescribed statins include:

Bile-Acid-Binding Resins Your body needs cholesterol to make bile acids, which aid in digestion.

As the name suggests, these drugs bind to bile acids, triggering your liver to use excess cholesterol to make more bile acids, which reduces the level of cholesterol in your blood.

Bile-acid-binding drugs are typically prescribed along with a statin. They include:

  • Colestid (colestipol)
  • Prevalite (cholestyramine)
  • WelChol (colesevelam)

Cholesterol Absorption Inhibitors This type of drug limits the amount of dietary cholesterol your small intestine absorbs, so that it can’t be released into your bloodstream.

The drug Zetia (ezetimibe), the only cholesterol absorption inhibitor on the market at the moment, can be used in combination with any of the statin drugs.

Combination Cholesterol Absorption Inhibitor and Statin This combination drug limits the absorption of dietary cholesterol by your small intestine and the production of cholesterol by your liver.

Two such combination drugs are:

  • Vytorin (ezetimibe and simvastatin)
  • Liptruzet (torvastatin and ezetimibe)

Triglyceride-Lowering Medications

If you have high triglycerides — another type of fat found in the blood that’s similar to cholesterol — in addition to high cholesterol, your doctor may also prescribe:

Fibrates These medications reduce your liver’s production of very-low-density lipoprotein (VLDL), which is made up mostly of triglycerides. They also increase the removal of triglycerides from your blood.

Two commonly prescribed fibrates are:

  • Lopid (gemfibrozil)
  • TriCor (fenofibrate)

Omega-3 Fatty Acid Supplements Omega-3 fatty acid supplements — the most common of which is fish oil — can help lower your triglycerides.

You can take these supplements in conjunction with a statin. and they are available over-the-counter or by prescription, under several brand names:

  • Epanova
  • Lovaza
  • Omtryg
  • Vascepa

If you opt to take over-the-counter fish oil or omega-3 supplements, be sure to let your doctor know. Even OTC varieties of fish oil may affect other medications you’re taking.

Niacin Also known as vitamin B3 (and sold under several brand names), niacin limits your liver’s ability to produce low-density lipoprotein (LDL) and VLDL cholesterol. It also reduces the production of triglycerides and raises HDL (“good”) cholesterol.

But niacin hasn’t been shown to provide any additional benefit over using statins alone, and it’s been linked to liver damage and increased risk of stroke.

Because of these risks, most doctors recommend niacin only for people who can’t take statins.

Side Effects of Cholesterol Medications

The most common side effects of these cholesterol-lowering medications include:

  • Muscle pain and weakness
  • Stomach pain
  • Constipation
  • Nausea
  • Diarrhea

To reduce side effects and increase the performance of cholesterol-lowering drugs, it’s important to take them exactly as your doctor prescribes.

Let your doctor know if you’re experiencing any problems since starting on a drug for cholesterol.

Your doctor may be able to change your dosage or suggest an alternative medication.

Always contact your doctor immediately if your symptoms are severe.

Because some cholesterol-lowering drugs affect your liver, you may need to have your liver function tested occasionally.

Injectable Biologic Medications for High Cholesterol

In addition to oral medicines, injectable drugs are now available that can help some people lower their high cholesterol levels.

Praluent (alirocumab) and Repatha (evolocumab) are FDA-approved treatments that are part of a class of drugs known as PCSK9 inhibitors.

Drugs in this class work by inhibiting an enzyme (PCSK9) that leads to increase in LDL cholesterol levels.

Praluent is used along with diet and statins to treat people with heterozygous familial hypercholesterolemia (an inherited form of high cholesterol).

Side effects of Praluent may include itching or soreness at the injection site; flu-like symptoms such as fever or chills; or cold symptoms, including a stuffy nose, sneezing, or a sore throat.

Repatha is approved for people with high cholesterol levels due to homozygous or heterozygous familial hypercholesterolemia.

Repatha side effects can include pain or bruising at the injection site, back pain, cold or flu symptoms, and dizziness.

Help to control your cholesterol levels

For some people, lifestyle changes, like a better diet and more exercise, may prevent or treat unhealthy cholesterol levels. For others with high cholesterol, medication may also be needed.

Work with your doctor to develop a treatment plan that’s right for you. If medication is required, be sure to take all medicines as prescribed by your doctor. The potential benefit to your health is well worth making these medications part of your normal routine.

Types of cholesterol-lowering drugs

Various medications are used to lower blood cholesterol levels.

Statins are recommended for most patients. Statins are the only cholesterol-lowering drug class that has been directly associated with a reduction in the risk of heart attack or stroke.

Guidelines recommend that people in any of these groups talk to their doctor about the risks and benefits of statin therapy:

  • Adults with a history of known cardiovascular disease, including stroke, caused by atherosclerosis
  • Those with LDL-C level of greater than 190mg/dL
  • Adults 40-75 years, with diabetes
  • Adults 40–75 years, with LDL-C level of 70-189 mg/dL and a 5%to 19.9% 10-year risk of developing cardiovascular disease from atherosclerosis, with risk enhancing factors
  • Adults 40–75 years, with LDL-C level of 70-189 mg/dL and a 20% or greater 10-year risk of developing cardiovascular disease from atherosclerosis

It is important to talk to your healthcare provider about your 10-year or lifetime risk. He or she will assess your risk factors to determine your level of risk and work with you to choose the best treatment approach.

Some people who do not fall into these categories may also benefit from statin therapy.

View an interactive slideshow to see how cholesterol drugs work.

Some of the major types of commonly prescribed cardiovascular medications are summarized in this section. We’ve included generic names as well as major trade names to help you identify what you may be taking. Please understand that the American Heart Association is not recommending or endorsing any specific products. If your prescription medication isn’t on this list, your doctor and pharmacist are your best sources of information. It’s important to discuss all the drugs you take with your doctor and to understand their desired effects and possible side effects. Never stop taking a medication or change your dosage (or frequency) without first consulting your doctor. Some cholesterol-lowering medications may interact with grapefruit, grapefruit juice, pomegranate and pomegranate juice. Please talk to your doctor about any potential risks.


This class of drugs, also known as HMG CoA reductase inhibitors, works in the liver to prevent cholesterol from forming. This reduces the amount of cholesterol circulating in the blood. Statins are most effective at lowering LDL (bad) cholesterol. They also help lower triglycerides (blood fats) and raise HDL (good) cholesterol.

Talk to your doctor about the possible side effects before starting statins. Most side effects are mild and go away as your body adjusts. Muscle problems and liver abnormalities are rare, but your doctor may order regular liver function tests. People who are pregnant or who have active or chronic liver disease should not take statins.

If statins don’t help you enough, or if you develop side effects, your doctor may recommend different medications.

Statins available in the U.S. include:

  • Atorvastatin (Lipitor®)
  • Fluvastatin (Lescol®)
  • Lovastatin (Mevacor®, Altoprev™)
  • Pravastatin (Pravachol®)
  • Rosuvastatin Calcium (Crestor®)
  • Simvastatin (Zocor®)

Statins are also found in the combination medications Advicor® (lovastatin + niacin), Caduet® (atorvastatin + amlodipine) and Vytorin™ (simvastatin + ezetimibe).

PCSK9 inhibitors

PCSK9 inhibitors bind to and inactivate a protein in liver in order to lower LDL (bad) cholesterol. They can be given in combination with a statin. Some names are alirocumab and evolocumab

Selective cholesterol absorption inhibitors

This relatively new class of cholesterol-lowering medications works by preventing cholesterol from being absorbed in the intestine. Selective cholesterol absorption inhibitors are most effective at lowering LDL cholesterol. They may also have modest effects on lowering triglycerides (blood fats) and raising HDL cholesterol.

The first medication of this class, ezetimibe (Zetia®), was approved in 2002 for treating high cholesterol and certain inherited lipid abnormalities.


This class of LDL-lowering drugs, also known as bile acid sequestrants or bile acid-binding drugs, works in the intestines by promoting increased disposal of cholesterol.

Your body uses cholesterol to make bile, an acid used in the digestive process. These medicines bind to bile, so they can’t be used during digestion. Your liver responds by making more bile. The more bile your liver makes, the more cholesterol it uses. That means less cholesterol is left to circulate through your bloodstream.

Resins available in the U.S. include:

  • Cholestyramine (Questran®, Questran® Light, Prevalite®, Locholest®, Locholest® Light)
  • Colestipol (Colestid®)
  • Colesevelam Hcl (WelChol®)

Lipid-lowering therapies

Fibrates (fibric acid derivatives):

Fibrates are best at lowering triglycerides and in some cases increasing HDL levels. These drugs aren’t very effective in lowering LDL cholesterol.

Fibrates now available in the U.S. include:

  • Gemfibrozil (Lopid®)
  • Fenofibrate (Antara®, Lofibra®, Tricor®, and Triglide™)
  • Clofibrate (Atromid-S)

Niacin (nicotinic acid):

This drug works in the liver by affecting the production of blood fats.

Niacin side effects may include flushing, itching and stomach upset. Your liver functions may be closely monitored because niacin can cause toxicity. Nonprescription immediate-release forms of niacin usually have the most side effects, especially at higher doses. Niacin is used cautiously in diabetic patients because it can raise blood sugar levels.

Niacin comes in prescription form and as a dietary supplement. Dietary supplement niacin must not be used as a substitute for prescription niacin because of potentially serious side effects. Dietary supplement niacin is not regulated by the Food and Drug Administration and may contain widely variable amounts of niacin – from none to much more than the label states. The amount of niacin may even vary from lot to lot of the same dietary supplement brand. Consult your doctor before starting any niacin therapy.

Omega-3 Fatty Acid Ethyl Esters

These medications are derived from fish oils that are chemically changed and purified. They’re used in tandem with dietary changes, to help people with very high triglyceride levels (over 500 mg/dL) lower their levels.

Omega-3 fatty acid ethyl esters may cause serious side effects. They may also interact negatively with other medications, herbal preparations and nutritional supplements. People with allergies or sensitivities to fish, shellfish or both may have a severe adverse reaction to these medications. The same precaution applies to those with sensitivities to certain drug components.

Omega-3 Fatty Acid Ethyl Esters available in the U.S. include:

  • Lovaza®
  • Vascepa™

Marine-Derived Omega-3 Polyunsaturated Fatty Acids (PUFA)

Marine derived omega-3 PUFAs, commonly referred to as omega-3 fish oils or omega-3 fatty acids, are used in large doses to lower high blood triglyceride levels. They help decrease triglyceride secretion and facilitate triglyceride clearance. The amount of marine-derived omega-3 PUFAs needed to significantly lower triglyceride (2 to 4 g) is hard to get from a daily diet alone, so supplementing with capsules may be needed.

Use these supplements only under a doctor’s direction and care, because large doses may cause serious side effects. These can include increased bleeding, hemorrhagic stroke and reduced blood sugar control in diabetics. Negative interactions with other medications, herbal preparations and nutritional supplements are also possible. People with allergies to fish, shellfish or both may have a severe adverse reaction to using these supplements.

10 truths about statins and high cholesterol

Do statins cause muscle pain and weakness?

Muscle aches occur in about 10 percent of people who take statins. It’s the most common side effect of statins, but another way to look at it is that nine out of 10 patients don’t experience it at all.
When patients do have muscle pain:

  • The symptom is often resolved by adjusting the medication dosage or switching to a different statin.
  • Occasionally, the statins have to be stopped altogether.
  • When the medication is switched or stopped, the symptoms go away and there is no damage to the muscle.

Actual muscle damage occurs in only 1 in 10,000 patients. In the rare event that muscle damage occurs, it is almost always reversible. To correct it while still protecting you from heart attack or stroke, we can adjust your medication or try a different statin. There also are many strategies to effectively manage muscle symptoms while continuing to take your medication.
If you experience muscle pain while taking a statin, don’t stop taking it without first talking with your doctor. For almost all patients, we’re able to find an effective medication that the body can tolerate. If you simply can’t tolerate statins, there are other cholesterol medications we can prescribe.

Can statins increase my risk for memory loss or dementia?

Memory and cognitive symptoms from statin use are very uncommon, and it is unclear if statins are really the culprit. When symptoms have been reported, they’re typically not severe and usually resolve when the statin dosage is adjusted or the medication is switched.

Affected patients have reported feeling unfocused or “fuzzy” in their thinking, but these experiences are rare. Concerns about long-term cognitive problems and memory loss due to use of statins have not been proven. On the contrary, most recent data actually point to potential prevention of dementia due to statin use.
These data are logical because one of the major causes of dementia is atherosclerosis, which is hardening of the arteries in the brain. There is strong evidence that statins protect against atherosclerosis. It’s one of the “invisible” benefits of taking a statin medication.
Also, keep in mind that increasingly high cholesterol (requiring treatment) and memory problems both are common symptoms of aging. Sometimes it’s difficult to disentangle these two, and that’s why statin use and memory problems may seem related at times.
If you’re concerned about statins and memory loss, don’t stop taking your medication without consulting your doctor. There may be other reasons for your memory symptoms, or alternate treatments for your high cholesterol can be considered.

Will statins increase my risk for diabetes or complicate my existing diabetes?

This risk is true to some extent, but it’s wildly exaggerated.

  • If your blood sugar was under control before you began taking statins, your sugars may rise slightly. But if you’re slim, trim, and not predisposed to diabetes because of obesity, statins won’t cause you to develop diabetes.
  • If you already had prediabetes or have borderline blood sugar levels, the statin may make your blood sugar rise enough to put you in the diabetes category. This happens to about one of every 255 patients taking statins. When it does happen, the patient is already on the path to getting diabetes – it just happens a little faster. In these patients, statin use simply accelerates by a few weeks to a few months a condition that was already inevitable over their lifetime.
  • Statins slightly increase the incidence of Type 2 diabetes in people who have two or more symptoms of metabolic syndrome, but the benefits of statins for these patients generally far exceed the risk of elevated blood sugar.

In fact, there are good data to show that people who have problems with their blood sugar or who have diabetes benefit most from statins. Even though their blood sugar may go up slightly, the added risk is significantly offset by the reduction in heart disease risk that a statin can provide.
If you’re already at risk for developing Type 2 diabetes, or if you have prediabetes, you may monitor your blood glucose more closely after starting a statin. But exercise and weight loss have been shown to lower the risk of developing diabetes in those with borderline blood glucose levels, regardless of statin use.

Can statins damage my liver?

Liver damage from taking statins is extremely uncommon. We used to test patients for liver damage throughout the course of statin treatment, but because of the rarity of that potential side effect, the Food and Drug Administration (FDA) determined that regular monitoring of liver function tests is unnecessary for patients taking statins. Now, we check a patient’s liver enzymes before we begin statin therapy to ensure the liver is healthy before treatment begins, and we don’t put anyone through unnecessary testing during treatment, unless symptoms arise.
Interestingly, there is a statin study examining people who already had abnormal liver function tests and fatty liver. Roughly half of the participants took a statin medication, and the other half took a placebo. The people who took statins actually had improvements in their liver function compared to the placebo group and had a lower risk of cardiovascular events. People who have blood sugar issues, have insulin resistance, and are obese or have other risks for heart disease often have fatty liver and abnormal liver function tests. The study suggests that these people may need statins the most.
On the rare chance that symptoms of liver damage arise, we’ll definitely want to perform tests right away. Symptoms of liver damage include weakness and fatigue, loss of appetite, upper abdominal pain, dark-colored urine, or yellowing of the eyes or skin. Again, it’s very rare, but if you experience any of these symptoms while taking a statin medication, contact your doctor right away.

Do statins cause cancer?

There is no evidence to suggest that taking statins increases cancer risk. Several studies suggest possible benefits for patients who take statins and are currently fighting cancer; research is ongoing as to whether statins actually may help prevent cancer.

Why do doctors focus on my LDL cholesterol?

Some cholesterol is necessary for normal cell and body function. But too much cholesterol can lead to atherosclerosis (hardening of the arteries), which results in heart disease, heart attack, and stroke.
There are two types of cholesterol: high-density lipoprotein (HDL, or good cholesterol) and low-density lipoprotein (LDL, or bad cholesterol). The amount of each that circulates in your blood is added together to form your total cholesterol number. Thus, focus on total cholesterol can be confusing as it may be elevated due to high HDL cholesterol.
When your LDL cholesterol is above 130 it is considered borderline, while above 160 is considered high. Ideally, we would all have an LDL under 100 (or even closer to 70), but not everyone needs medications above this level.
We focus on the bad cholesterol because it is one of the main culprits responsible for blocking and hardening the arteries. A blocked artery can lead to a heart attack or stroke. Statin therapy helps control the bad cholesterol of patients who are at high risk for heart disease, stroke, and other serious cardiovascular events. In general, the lower your LDL levels, the better off you will be.
There’s a lot of science around how HDL cholesterol affects your risk for heart disease. But it’s the function – how well it works – that may be more important than how high its level is.
For example, people in a small village in Italy have very low HDL numbers (10 to 30mg/dL), and they have a longer life expectancy and very little heart disease. That’s because their HDL is like a factory – it shuttles cholesterol from the arteries to the liver rapidly, and then disappears. Good cholesterol doesn’t last in their blood very long, but it is very efficient.

Society’s focus on raising HDL is likely misguided when compared to the actual evidence. Two recent studies of raising HDL with niacin showed no improvement in risk of heart attacks and strokes, and potentially some harms. There is a lot of work to be done to determine what we can and should do in targeting HDL.

Can ‘natural’ remedies lower high cholesterol without statins?

Exercise on its own doesn’t lower your LDL (bad cholesterol) much – often only a few points. Exercise helps minimize many heart disease risk factors, including obesity and Type 2 diabetes. Make a point to exercise five days a week for at least 30 minutes each day.
Diet is incredibly important in managing your cholesterol.

  • Certain foods, such as fried food and fast food, are high in saturated fat, which contributes to high cholesterol.
  • Not all fats are unhealthy – good fats, such as those found in fatty fish, nuts, and olive oil, have many health benefits.
  • Read food labels and limit your daily intake of saturated fat to 16 grams, and omit trans fats completely.
  • Eating more fiber can help reduce LDL significantly. For some patients, eating fiber along with maintaining an exercise program is enough to manage cholesterol. But for high-risk patients, it’s not enough to prevent the need for statins.

Every patient who comes to our preventive cardiology clinic for cholesterol management sees a nutritionist as part of the visit because we feel so strongly about the importance of diet. There are many patients for whom we’ve delayed prescribing statins, or suggested that they get off their medication if it isn’t appropriate for their level of risk.
Some patients think, “I’m on a statin – I don’t have to exercise, and I can eat whatever I want!” But that’s not the case. Lifestyle choices absolutely matter. For high-risk patients, it’s not a question of either improving the diet or getting on a medication, it’s both – lifestyle changes and taking a statin together are necessary to protect high-risk patients against heart attack and stroke.
If your cholesterol is borderline but not yet high, changing your diet and incorporating healthier food choices can help lower your cholesterol a decent amount. Eating more fiber and lowering your intake of saturated fat definitely can help. For people with relatively low risk, this may be enough to lower heart attack and stroke risk.

Are there alternatives to statins for lowering high cholesterol?

In patients whose cholesterol can’t be controlled by lifestyle changes or who simply can’t tolerate statins, we can offer alternative treatments.



Mechanism Of Action

Pravastatin is a reversible inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate, an early and rate limiting step in the biosynthetic pathway for cholesterol. In addition, pravastatin reduces VLDL and TG and increases HDL-C.



Absorption: PRAVACHOL is administered orally in the active form. In studies in man, peak plasma pravastatin concentrations occurred 1 to 1.5 hours upon oral administration. Based on urinary recovery of total radiolabeled drug, the average oral absorption of pravastatin is 34% and absolute bioavailability is 17%. While the presence of food in the gastrointestinal tract reduces systemic bioavailability, the lipid-lowering effects of the drug are similar whether taken with or 1 hour prior to meals.

Pravastatin plasma concentrations, including area under the concentration-time curve (AUC), Cmax , and steady-state minimum (Cmin ), are directly proportional to administered dose. Systemic bioavailability of pravastatin administered following a bedtime dose was decreased 60% compared to that following an AM dose. Despite this decrease in systemic bioavailability, the efficacy of pravastatin administered once daily in the evening, although not statistically significant, was marginally more effective than that after a morning dose.

The coefficient of variation (CV), based on between-subject variability, was 50% to 60% for AUC. The geometric means of pravastatin C max and AUC following a 20 mg dose in the fasted state were 26.5 ng/mL and 59.8 ng*hr/mL, respectively.

Steady-state AUCs, C max , and C min plasma concentrations showed no evidence of pravastatin accumulation following once or twice daily administration of PRAVACHOL tablets.

Distribution: Approximately 50% of the circulating drug is bound to plasma proteins.

Metabolism: The major biotransformation pathways for pravastatin are: (a) isomerization to 6-epi pravastatin and the 3α-hydroxyisomer of pravastatin (SQ 31,906) and (b) enzymatic ring hydroxylation to SQ 31,945. The 3α-hydroxyisomeric metabolite (SQ 31,906) has 1/10 to 1/40 the HMG-CoA reductase inhibitory activity of the parent compound. Pravastatin undergoes extensive first-pass extraction in the liver (extraction ratio 0.66).

Excretion: Approximately 20% of a radiolabeled oral dose is excreted in urine and 70% in the feces. After intravenous administration of radiolabeled pravastatin to normal volunteers, approximately 47% of total body clearance was via renal excretion and 53% by non-renal routes (i.e., biliary excretion and biotransformation).

Following single dose oral administration of 14C-pravastatin, the radioactive elimination t½ for pravastatin is 1.8 hours in humans.

Specific Populations

Renal Impairment: A single 20 mg oral dose of pravastatin was administered to 24 patients with varying degrees of renal impairment (as determined by creatinine clearance). No effect was observed on the pharmacokinetics of pravastatin or its 3α-hydroxy isomeric metabolite (SQ 31,906). Compared to healthy subjects with normal renal function, patients with severe renal impairment had 69% and 37% higher mean AUC and Cmax values, respectively, and a 0.61 hour shorter t ½ for the inactive enzymatic ring hydroxylation metabolite (SQ 31,945).

Hepatic Impairment: In a study comparing the kinetics of pravastatin in patients with biopsy confirmed cirrhosis (N=7) and normal subjects (N=7), the mean AUC varied 18-fold in cirrhotic patients and 5-fold in healthy subjects. Similarly, the peak pravastatin values varied 47-fold for cirrhotic patients compared to 6-fold for healthy subjects.

Geriatric: In a single oral dose study using pravastatin 20 mg, the mean AUC for pravastatin was approximately 27% greater and the mean cumulative urinary excretion (CUE) approximately 19% lower in elderly men (65-75 years old) compared with younger men (19-31 years old). In a similar study conducted in women, the mean AUC for pravastatin was approximately 46% higher and the mean CUE approximately 18% lower in elderly women (65-78 years old) compared with younger women (18-38 years old). In both studies, Cmax , Tmax , and t½ values were similar in older and younger subjects.

Drug-Drug Interactions

Table 3: Effect of Coadministered Drugs on the Pharmacokinetics of Pravastatin

Coadministered Drug and Dosing Regimen Pravastatin
Dose (mg) Change in AUC Change in C max
Cyclosporine 5 mg/kg single dose 40 mg single dose 282% 327%
Clarithromycin 500 mg BID for 9 days 40 mg OD for 8 days 110% 128%
Boceprevir 800 mg TID for 6 days 40 mg single dose 63% 49%
Darunavir 600 mg BID/Ritonavir 100 mg BID for 7 days 40 mg single dose 81% 63%
Colestipol 10 g single dose 20 mg single dose ↓47% ↓53%
Cholestyramine 4 g single dose
Administered simultaneously
Administered 1 hour prior to cholestyramine
Administered 4 hours after cholestyramine
20 mg single dose ↓40% ↓39%
12% 30%
↓12% ↓6.8%
Cholestyramine 24 g OD for 4 weeks 20 mg BID for 8 weeks 5 mg BID for 8 weeks 10 mg BID for 8 weeks ↓51% 4.9%
↓38% 23%
↓18% ↓33%
Fluconazole 200 mg IV for 6 days
200 mg PO for 6 days
20 mg PO+10 mg IV 20 mg PO+10 mg IV ↓34% ↓33%
↓16% ↓16%
Kaletra 400 mg/100 mg BID for 14 days 20 mg OD for 4 days 33% 26%
Verapamil IR 120 mg for 1 day and Verapamil ER 480 mg for 3 days 40 mg single dose 31% 42%
Cimetidine 300 mg QID for 3 days 20 mg single dose 30% 9.8%
Antacids 15 mL QID for 3 days 20 mg single dose ↓28% ↓24%
Digoxin 0.2 mg OD for 9 days 20 mg OD for 9 days 23% 26%
Probucol 500 mg single dose 20 mg single dose 14% 24%
Warfarin 5 mg OD for 6 days 20 mg BID for 6 days ↓13% 6.7%
Itraconazole 200 mg OD for 30 days 40 mg OD for 30 days 11% (compared to Day 1) 17% (compared to Day 1)
Gemfibrozil 600 mg single dose 20 mg single dose ↓7.0% ↓20%
Aspirin 324 mg single dose 20 mg single dose 4.7% 8.9%
Niacin 1 g single dose 20 mg single dose ↓3.6% ↓8.2%
Diltiazem 20 mg single dose 2.7% 30%
Grapefruit juice 40 mg single dose ↓1.8% 3.7%
BID = twice daily; OD = once daily; QID = four times daily

Table 4: Effect of Pravastatin on the Pharmacokinetics of Coadministered Drugs

Pravastatin Dosing Regimen Name and Dose Change in AUC Change in C max
20 mg BID for 6 days Warfarin 5 mg OD for 6 days Change in mean prothrombin time 17% 0.4 sec 15%
20 mg OD for 9 days Digoxin 0.2 mg OD for 9 days 4.6% 5.3%
20 mg BID for 4 weeks
10 mg BID for 4 weeks
5 mg BID for 4 weeks
Antipyrine 1.2 g single dose 3.0% ti.6% Less than 1% Not Reported
20 mg OD for 4 days Kaletra 400 mg/100 mg BID for 14 days No change No change
BID = twice daily; OD = once daily

Animal Toxicology And/Or Pharmacology

CNS Toxicity

CNS vascular lesions, characterized by perivascular hemorrhage and edema and mononuclear cell infiltration of perivascular spaces, were seen in dogs treated with pravastatin at a dose of 25 mg/kg/day. These effects in dogs were observed at approximately 59 times the HD of 80 mg/day, based on AUC. Similar CNS vascular lesions have been observed with several other drugs in this class.

A chemically similar drug in this class produced optic nerve degeneration (Wallerian degeneration of retinogeniculate fibers) in clinically normal dogs in a dose-dependent fashion starting at 60 mg/kg/day, a dose that produced mean plasma drug levels about 30 times higher than the mean drug level in humans taking the highest recommended dose (as measured by total enzyme inhibitory activity). This same drug also produced vestibulocochlear Wallerian-like degeneration and retinal ganglion cell chromatolysis in dogs treated for 14 weeks at 180 mg/kg/day, a dose which resulted in a mean plasma drug level similar to that seen with the 60 mg/kg/day dose.

When administered to juvenile rats (postnatal days 4 through 80 at 5-45 mg/kg/day), no drug related changes were observed at 5 mg/kg/day. At 15 and 45 mg/kg/day, altered body-weight gain was observed during the dosing and 52-day recovery periods as well as slight thinning of the corpus callosum at the end of the recovery period. This finding was not evident in rats examined at the completion of the dosing period and was not associated with any inflammatory or degenerative changes in the brain. The biological relevance of the corpus callosum finding is uncertain due to the absence of any other microscopic changes in the brain or peripheral nervous tissue and because it occurred at the end of the recovery period.

Neurobehavioral changes (enhanced acoustic startle responses and increased errors in water-maze learning) combined with evidence of generalized toxicity were noted at 45 mg/kg/day during the later part of the recovery period. Serum pravastatin levels at 15 mg/kg/day are approximately ≥ 1 times (AUC) the maximum pediatric dose of 40 mg. No thinning of the corpus callosum was observed in rats dosed with pravastatin ( ≥ 250 mg/kg/day) beginning PND 35 for 3 months suggesting increased sensitivity in younger rats. PND 35 in a rat is approximately equivalent to an 8-to 12-year-old human child. Juvenile male rats given 90 times (AUC) the 40 mg dose had decreased fertility (20%) with sperm abnormalities compared to controls.

Clinical Studies

Prevention Of Coronary Heart Disease

PRAVACHOL significantly reduced the rate of first coronary events (either CHD death or nonfatal MI) by 31% (248 events in the placebo group versus 174 events in the PRAVACHOL group , p=0.0001 ). The risk reduction with PRAVACHOL was similar and significant throughout the entire range of baseline LDL cholesterol levels. This reduction was also similar and significant across the age range studied with a 40% risk reduction for patients younger than 55 years and a 27% risk reduction for patients 55 years and older. The Pravastatin Primary Prevention Study included only men, and therefore it is not clear to what extent these data can be extrapolated to a similar population of female patients.

PRAVACHOL also significantly decreased the risk for undergoing myocardial revascularization procedures (coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty ) by 37% (80 vs 51 patients, p=0.009) and coronary angiography by 31% (128 vs 90, p=0.007). Cardiovascular deaths were decreased by 32% (73 vs 50, p=0.03) and there was no increase in death from non-cardiovascular causes.

Secondary Prevention Of Cardiovascular Events

In the LIPID4 study, the effect of PRAVACHOL, 40 mg daily, was assessed in 9014 patients (7498 men; 1516 women; 3514 elderly patients ; 782 diabetic patients) who had experienced either an MI (5754 patients) or had been hospitalized for unstable angina pectoris (3260 patients) in the preceding 3 to 36 months. Patients in this multicenter, double-blind, placebo-controlled study participated for an average of 5.6 years (median of 5.9 years) and at randomization had Total-C between 114 and 563 mg/dL (mean 219 mg/dL), LDL-C between 46 and 274 mg/dL (mean 150 mg/dL), TG between 35 and 2710 mg/dL (mean 160 mg/dL), and HDL-C between 1 and 103 mg/dL (mean 37 mg/dL). At baseline, 82% of patients were receiving aspirin and 76% were receiving antihypertensive medication. Treatment with PRAVACHOL significantly reduced the risk for total mortality by reducing coronary death (see Table 5). The risk reduction due to treatment with PRAVACHOL on CHD mortality was consistent regardless of age. PRAVACHOL significantly reduced the risk for total mortality (by reducing CHD death) and CHD events (CHD mortality or nonfatal MI) in patients who qualified with a history of either MI or hospitalization for unstable angina pectoris.

Table 5: LIPID -Primary and Secondary Endpoints

PRAVACHOL significantly reduced the rate of first recurrent coronary events (either CHD death or nonfatal MI), the risk of undergoing revascularization procedures (PTCA, CABG), and the risk for stroke or TIA (see Table 6).

Table 6: CARE -Primary and Secondary Endpoints

In the PLAC I6 study, the effect of pravastatin therapy on coronary atherosclerosis was assessed by coronary angiography in patients with coronary disease and moderate hypercholesterolemia (baseline LDL-C range: 130-190 mg/dL). In this double-blind, multicenter, controlled clinical trial, angiograms were evaluated at baseline and at 3 years in 264 patients. Although the difference between pravastatin and placebo for the primary endpoint (per-patient change in mean coronary artery diameter) and 1 of 2 secondary endpoints (change in percent lumen diameter stenosis) did not reach statistical significance, for the secondary endpoint of change in minimum lumen diameter, statistically significant slowing of disease was seen in the pravastatin treatment group (p=0.02).

In the REGRESS7 study, the effect of pravastatin on coronary atherosclerosis was assessed by coronary angiography in 885 patients with angina pectoris, angiographically documented coronary artery disease, and hypercholesterolemia (baseline total cholesterol range: 160-310 mg/dL). In this double-blind, multicenter, controlled clinical trial, angiograms were evaluated at baseline and at 2 years in 653 patients (323 treated with pravastatin). Progression of coronary atherosclerosis was significantly slowed in the pravastatin group as assessed by changes in mean segment diameter (p=0.037) and minimum obstruction diameter (p=0.001).

Analysis of pooled events from PLAC I, PLAC II,8 REGRESS, and KAPS9 studies (combined N=1891) showed that treatment with pravastatin was associated with a statistically significant reduction in the composite event rate of fatal and nonfatal MI (46 events or 6.4% for placebo versus 21 events or 2.4% for pravastatin, p=0.001). The predominant effect of pravastatin was to reduce the rate of nonfatal MI.

Primary Hypercholesterolemia (Fredrickson Types IIa and IIb)

PRAVACHOL is highly effective in reducing Total-C, LDL-C, and TG in patients with heterozygous familial, presumed familial combined, and non-familial (non-FH) forms of primary hypercholesterolemia, and mixed dyslipidemia. A therapeutic response is seen within 1 week, and the maximum response usually is achieved within 4 weeks. This response is maintained during extended periods of therapy. In addition, PRAVACHOL is effective in reducing the risk of acute coronary events in hypercholesterolemic patients with and without previous MI.

A single daily dose is as effective as the same total daily dose given twice a day. In multicenter, double-blind, placebo-controlled studies of patients with primary hypercholesterolemia, treatment with pravastatin in daily doses ranging from 10 to 40 mg consistently and significantly decreased Total-C, LDL-C, TG, and Total-C/HDL-C and LDL-C/HDL-C ratios (see Table 7).

In a pooled analysis of 2 multicenter, double-blind, placebo-controlled studies of patients with primary hypercholesterolemia, treatment with pravastatin at a daily dose of 80 mg (N=277) significantly decreased Total-C, LDL-C, and TG. The 25th and 75th percentile changes from baseline in LDL-C for pravastatin 80 mg were -43% and -30%. The efficacy results of the individual studies were consistent with the pooled data (see Table 7).

Treatment with PRAVACHOL modestly decreased VLDL-C and PRAVACHOL across all doses produced variable increases in HDL-C (see Table 7).

Table 7: Primary Hypercholesterolemia Studies: Dose Response of PRAVACHOL Once Daily Administration

In another clinical trial, patients treated with pravastatin in combination with cholestyramine (70% of patients were taking cholestyramine 20 or 24 g per day) had reductions equal to or greater than 50% in LDL-C. Furthermore, pravastatin attenuated cholestyramine-induced increases in TG levels (which are themselves of uncertain clinical significance).

Hypertriglyceridemia (Fredrickson Type IV)

Table 8: Patients with Fredrickson Type IV Hyperlipidemia Median (25th, 75th percentile) % Change from Baseline

Dysbetalipoproteinemia (Fredrickson Type III)

The response to pravastatin in two double-blind crossover studies of 46 patients with genotype E2/E2 and Fredrickson Type III dysbetalipoproteinemia is shown in Table 9.

Table 9: Patients with Fredrickson Type III Dysbetalipoproteinemia Median (min, max) % Change from Baseline

Pediatric Clinical Study

A double-blind, placebo-controlled study in 214 patients (100 boys and 114 girls) with heterozygous familial hypercholesterolemia (HeFH), aged 8 to 18 years was conducted for 2 years. The children (aged 8-13 years) were randomized to placebo (N=63) or 20 mg of pravastatin daily (N=65) and the adolescents (aged 14-18 years) were randomized to placebo (N=45) or 40 mg of pravastatin daily (N=41). Inclusion in the study required an LDL-C level > 95th percentile for age and sex and one parent with either a clinical or molecular diagnosis of familial hypercholesterolemia. The mean baseline LDL-C value was 239 mg/dL and 237 mg/dL in the pravastatin (range: 151-405 mg/dL) and placebo (range: 154-375 mg/dL) groups, respectively.

Pravastatin significantly decreased plasma levels of LDL-C, Total-C, and ApoB in both children and adolescents (see Table 10). The effect of pravastatin treatment in the 2 age groups was similar.

Table 10: Lipid-Lowering Effects of Pravastatin in Pediatric Patients with Heterozygous Familial Hypercholesterolemia: Least-Squares Mean % Change from Baseline at Month 24 (Last Observation Carried Forward: Intent-to-Treat)a

The safety and efficacy of pravastatin doses above 40 mg daily have not been studied in children. The long-term efficacy of pravastatin therapy in childhood to reduce morbidity and mortality in adulthood has not been established.

3. Shepherd J, Cobbe SM, Ford I, et al, for the West of Scotland Coronary Prevention Study Group (WOS). Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med. 1995;333:1301-1307.

4. The Long-term Intervention with Pravastatin in Ischemic Disease Group (LIPID). Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339:1349-1357.

5. Sacks FM, Pfeffer MA, Moye LA, et al, for the Cholesterol and Recurrent Events Trial Investigators (CARE). The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med. 1996;335:1001-1009.

6. Pitt B, Mancini GBJ, Ellis SG, et al, for the PLAC I Investigators. Pravastatin limitation of atherosclerosis in the coronary arteries (PLAC I): Reduction in atherosclerosis progression and clinical events. J Am Coll Cardiol. 1995;26:1133-1139.

7. Jukema JW, Bruschke AVG, van Boven AJ, et al, for the Regression Growth Evaluation Statin Study Group (REGRESS). Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic man with normal to moderately elevated serum cholesterol levels. Circ. 1995;91:2528-2540.

8. Crouse JR, Byington RP, Bond MG, et al. Pravastatin, lipids, and atherosclerosis in the carotid arteries: Design features of a clinical trial with carotid atherosclerosis outcome (PLAC II). Control Clin Trials. 1992;13:495-506.

9. Salonen R, Nyyssonen K, Porkkala E, et al. Kuopio Atherosclerosis Prevention Study (KAPS). A population-based primary preventive trial of the effect of LDL lowering on atherosclerotic progression in carotid and femoral arteries. Circ. 1995;92:1758-1764.

Cholesterol Medicines

What is cholesterol?

Your body needs some cholesterol to work properly. But if you have too much in your blood, it can stick to the walls of your arteries and narrow or even block them. This puts you at risk for coronary artery disease and other heart diseases.

Cholesterol travels through the blood on proteins called lipoproteins. One type, LDL, is sometimes called the “bad” cholesterol. A high LDL level leads to a buildup of cholesterol in your arteries. Another type, HDL, is sometimes called the “good” cholesterol. It carries cholesterol from other parts of your body back to your liver. Then your liver removes the cholesterol from your body.

What are the treatments for high cholesterol?

If you have high cholesterol, lifestyle changes can help you to lower your cholesterol level. But sometimes the lifestyle changes are not enough, and you need to take cholesterol medicines. You should still continue with the lifestyle changes even though you are taking medicines.

Who needs cholesterol medicines?

Your health care provider may prescribe medicine if:

  • You have already had a heart attack or stroke, or you have peripheral arterial disease
  • Your LDL (bad) cholesterol level is 190 mg/dL or higher
  • You are 40-75 years old, you have diabetes, and your LDL cholesterol level is 70 mg/dL or higher
  • You are 40-75 years old, you have a high risk of developing heart disease or stroke, and your LDL cholesterol level is 70 mg/dL or higher

What are the different types of medicines for cholesterol?

There are several types of cholesterol-lowering drugs available, including

  • Statins, which block the liver from making cholesterol
  • Bile acid sequestrants, which decrease the amount of fat absorbed from food
  • Cholesterol absorption inhibitors, which decrease the amount of cholesterol absorbed from food and lower triglycerides.
  • Nicotinic acid (niacin), which lowers LDL (bad) cholesterol and triglycerides and raises HDL (good) cholesterol. Even though you can buy niacin without a prescription, you should talk to your health care provider before taking it to lower your cholesterol. High doses of niacin can cause serious side effects.
  • PCSK9 inhibitors, which block a protein called PCSK9. This helps your liver remove and clear LDL cholesterol from your blood.
  • Fibrates, which lower triglycerides. They may also raise HDL (good) cholesterol. If you take them with statins, they may increase the risk of muscle problems.
  • Combination medicines, which include more than one type of cholesterol-lowering medicine

There are also a few other cholesterol medicines (lomitapide and mipomersen) that are only for people who have familial hypercholesterolemia (FH). FH is an inherited disorder that causes high LDL cholesterol.

How does my health care provider decide which cholesterol medicine I should take?

When deciding which medicine you should take and which dose you need, your health care provider will consider

  • Your cholesterol levels
  • Your risk for heart disease and stroke
  • Your age
  • Any other health problems you have
  • Possible side effects of the medicines. Higher doses are more likely to cause side effects, especially over time.

Medicines can help control your cholesterol, but they don’t cure it. You need to keep taking your medicines and get regular cholesterol checks to make sure that you cholesterol levels are in a healthy range.

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