Atorvastatin is a prescription medicine used to treat high cholesterol. It is marketed as a calcium salt under the brand name Lipitor (atorvastatin calcium), produced by Pfizer. It is also available as a generic medicine.
Atorvastatin is one of the most popular medicines for treating high cholesterol. Tens of millions of people use it, said Ken Sternfeld, a New York-based pharmacist. Atorvastatin is a member of the drug class HMG-CoA inhibitor (statin). Statins are typically used to help patients with high cholesterol. Since there are many statins, “it’s important to test patients to find out which is the best one for them,” Sternfeld said. He recommends a simple swab test that can determine which drugs a patient can best metabolize.
Atorvastatin, and other statins, work by potentially decreasing the production of cholesterol in the body through blocking the cholesterol-producing enzyme in the liver. Consequently, the amount of cholesterol (a fat-like substance) that collects in the arteries may be reduced. “Statins are drugs you take for the rest of your life,” Sternfeld said. “Though the dosing could change and perhaps you take it once a day or every other day.”
“Cholesterol has a useful purpose in the body when it’s doing what it’s supposed to do,” says Dr. Stephen Neabore, a primary care doctor at the Barnard Medical Center in Washington, D.C. “It helps keep the cell membrane somewhat soft, which is necessary for movement. But our bodies make all the cholesterol that we need. The recommended daily allowance is 0.”
Excessive cholesterol in arteries may block blood flow to the heart, brain and other parts of the body, leading to heart attack, stroke, chest pain, and other problems. Significant improvement often depends on combining a medicine, such as atorvastatin, with lifestyle changes.
“We try to really promote a lifestyle that can make a big difference in cholesterol management,” said Neabore. “We try to get people to consume less cholesterol. It’s essentially only found in animal products. Animals need it to help keep their cells soft like we do. A plant-based diet has been shown in many studies to be the most effective for promoting overall health.”
Atorvastatin would likely still work if a patient did not change his or her lifestyle, but there would be much more improvement if they did, said Neabore.
- Side effects
- 6 Things You Should Know About Generic Lipitor
- Atorvastatin vs Simvastatin: Main Differences and Similarities
- Atorvastatin vs Simvastatin Side by Side Comparison
- CLINICAL PHARMACOLOGY
- Mechanism Of Action
- Specific Populations
- Clinical Studies
- Prevention Of Cardiovascular Disease
- Hyperlipidemia And Mixed Dyslipidemia
- Homozygous Familial Hypercholesterolemia
- Heterozygous Familial Hypercholesterolemia In Pediatric Patients
- CLINICAL PHARMACOLOGY
- Pravastatin vs Lipitor: Main Differences and Similarities
- Pravastatin vs Lipitor Side by Side Comparison
- NCI Drug Dictionary
- Simvastatin vs. Atorvastatin: What You Should Know
Atorvastatin calcium’s potency is dosage-related, meaning that the higher the dose, the more cholesterol is inhibited. Typical doses are 10, 20, 40, or 80 mg daily, and the usual starting dose is 10-20 mg daily. Doctors may increase dosages gradually. Dosage should not be increased more than once every two to four weeks.
To find the proper dosage and help determine if a statin is the right choice, Neabore looks at risk calculators created by the American Heart Association. “We look at things like blood pressure, diabetes, and other conditions to get an estimated risk for patients for heart attack or stroke,” he said. Statins can cause severe side effects. “But if a patient scores over a certain percentage on the risk calculator we believe that that the benefits of a drug like this are worth it.”
Atorvastatin calcium comes in an oral tablet that is usually taken once a day. It should be taken at the same time every day, and can be taken with or without food. The tablet should not be crushed or chewed. It is important that patients continue to take atorvastatin even if they feel well.
If a dose is missed, it should be taken as soon as remembered unless there are less than 12 hours until the next scheduled dose. In this case, the missed dose should be skipped. Patients should not take a double dose to make up for a missed one.
“One of the side effects of statins is that they can cause muscle cramping and weakness,” said Sternfeld. If experienced, a patient should see a doctor immediately. “Doctors and pharmacists have to work together to balance out the importance of keeping cholesterol low and cramping. It’s important to find the right balance because people take these drugs for the rest of their lives.”
The NIH lists the following additional side effects as less serious, though a doctor should be consulted if they persist or become severe:
- joint pain
- forgetfulness or memory loss
The NIH lists the following symptoms as serious. If a patient experiences any of them, a doctor should be consulted immediately:
- muscle pain, tenderness, or weakness
- lack of energy
- chest pain
- extreme tiredness
- unusual bleeding or bruising
- loss of appetite
- pain in the upper right part of the stomach
- flu-like symptoms
- dark colored urine
- yellowing of the skin or eyes
- difficulty breathing or swallowing
- swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
It is important for patients taking atorvastatin calcium to maintain a low-fat, low-cholesterol diet. If a diet or exercise plan is prescribed by a doctor or dietician, it should be followed.
Alcohol intake should be limited, as it may increase the risk of liver problems when combined with atorvastatin. The NIH recommends telling a doctor if you drink more than two alcoholic beverages per day, and warns that drinking alcohol can “increase the risk of serious side effects.” No more than one quart of grapefruit juice should be consumed per day while taking atorvastatin.
Women who are breast-feeding or pregnant should not take atorvastatin. The NIH warns that taking atorvastatin while pregnant may harm the fetus. If a woman is planning to become pregnant, she should tell her doctor before taking atorvastatin, and if she becomes pregnant while taking the medicine, she should stop taking it immediately.
It is very important that patients tell their doctors and pharmacists what prescription and non-prescription medicines they are taking before beginning an atorvastatin prescription, said Sternfeld. Antifungal medications, birth control pills, and other cholesterol-inhibiting medications should especially be noted. Patients should tell their healthcare providers if they have any history of liver, kidney, or thyroid disease; diabetes; or seizures. Adverse drug reactions involving atorvastatin can be serious and doctors and pharmacists have different areas of expertise when it comes to drug reactions and interactions. “Healthcare is about collaboration. No one has all the answers. People need to take ownership of their own health. The only way the health care industry can help them is if they collaborate, tell their health care providers, so they can collaborate,” he said.
6 Things You Should Know About Generic Lipitor
WEDNESDAY, Nov. 30, 2011 — Many of the millions of Americans who take Lipitor, the world’s biggest-selling drug in 2010, will have an important decision to make as its maker, Pfizer, loses patent protection on the popular pill: Should I switch to generic Lipitor (atorvastatin)? Here’s what you need to know before you make the choice.
- Generic Lipitor won’t be drastically cheaper yet. Planning ahead for the generic release, Pfizer offered significant price reductions on Lipitor to help it remain competitive, according to John Santa, MD, MPH, director of the Consumer Reports Health Ratings Center. On top of marketing spend to keep brand loyalty afloat, the Associated Press via ABC News reports that Pfizer’s incentives for patients, pharmacies, and insurance companies will keepLipitor at the same price as or cheaper than the generic pills for at least the next six months.
According to the AP article, Pfizer is offering insured patients a discount card to get Lipitor for $4 a month (the average copayment for a brand-name drug is $25; for generic, $10), promoting the offer heavily through ads, pharmacies, doctors offices, and a Web site, LipitorForYou.com.
Currently the generic version of Lipitor will be produced by just two companies, according to The New York Times, which notes that when a drug patent expires, the law allows only limited competition among generic brands in the first six months. But after May 31, other generic versions will become available, which the Times says will dramatically lower prices of generics as Lipitor’s co-payments increase.
- You may not even be able to get generic Lipitor. According to both the AP and the New York Times, Pfizer has negotiated deals, considered controversial, with insurance plans and prescription benefits managers that would essentially block pharmacists from dispensing the generic drug for the next six months. This would prevent many Americans from switching initially.
- Taking a generic is usually safe and effective. “Generics generally work fine,” says Everyday Health expert ArthurAgatston, MD, a preventive cardiologist and an associate professor of medicine at the University of Miami Miller School of Medicine. “Sometimes I might wait a little while to put my patients on something new, depending on their economic status or their own feelings about generics.”
Still, Agatston reassures his patients that he hasn’t seen issues with effectiveness with the first generation of generic statins, so he wouldn’t expect problems with this one. The FDA supports generic drugs as “important options that allow greater access to health care for all Americans,” which work the same way and have met the same “rigid standards” as the brand-name versions.
“Over many years Consumer Reports has emphasized to consumers that generic drugs have to meet the same manufacturing specifications, requirements as brand drugs do,” says Santa.
But consumers still worry that the generic will be less effective than the brand-name. “One area of possible concern with generic medications is the possibility that the generic atorvastatin options will be different in potency compared to Lipitor brand atorvastatin,” Randal J. Thomas, MD, MS, from the Mayo Clinic’s Cardiovascular Health Clinic in Rochester, Minn., wrote in an email to MedPage Today and ABC News. “This difference is likely to be minimal, but it will be important for patients who switch from brand-name Lipitor to generic atorvastatin to follow up with blood tests and a check-up with the healthcare provider to make sure that the atorvastatin dose is the right one for them.”
- If a generic statin is working, you’ll know quickly. Unlike certain other medications, it’s easy to gauge whether cholesterol-lowering drugs are doing their job. “The good thing about statins is you see the results pretty quickly,” says Agatston. “If it’s not the right drug for you, your cholesterol won’t go lower, or if it’s been lower it will increase.” With his patients, Agatston normally waits about three months after trying a new drug to retest cholesterol levels, but he says you can usually see a difference as soon as a month after switching.
- Make sure you’re taking the right statin for your needs. Consumer Reports recommendsLipitor or its generic only for people who need to lower their bad cholesterol levels (LDL) by 30 percent or more, which a number of Americans may not actually need, says Santa. “Evidence shows that 90 percent of people onLipitor have mild to moderate ‘bad’LDL cholesterol,” he says. “We think it’s a good time for the millions of patients who are onLipitor reassess,” and talk to their doctors about whichstatin may be right for them.
As alternatives, Consumer Reports recommends generic lovastatin (brand names Altoprev and Mevacor) or pravastatin (brand name Pravachol) for people looking to lower their cholesterol levels by less than 30 percent, and generic simvastatin (brand name Zocor) for people with heart disease, diabetes, or who have had a heart attack or acute coronary syndrome but don’t have LDL levels high enough to merit Lipitor.
- Caregivers need to stay informed and educate older adults. The majority of people taking statins are older Americans, who may need help understanding the changes surrounding the availability of genericLipitor. According to theCDC, half of men and one-third of women age 65-74 takestatins. Santa points out that switching drugs is confusing, especially for older patients who receive care from their adult children. The generic bottles, for example, will be labeled “atorvastatin calcium,” which may puzzle patients. “You can just hear someone saying, ‘But I’m not taking calcium pills,’” Santa says.
If you’re caring for parents or loved ones who take Lipitor, it’s a good idea to work with them and their doctor to help them decide the best plan for their health and finances, and then make sure they understand the changes.
Atorvastatin vs Simvastatin: Main Differences and Similarities
Atorvastatin and simvastatin are both grouped into a class of medications known as HMG-coA reductase inhibitors. They work in much the same way by inhibiting the enzyme, HMG-coA reductase, and ultimately, treating high cholesterol. Because of their chemical similarities, there are miniscule differences between the two medications. We will discuss their similarities and differences below.
Atorvastatin is also known by its brand name, Lipitor. It is prescribed to reduce total cholesterol, LDL-C, VLDL-C, Apo B, and triglycerides in certain patients with elevated levels. It is also used to reduce the risk of cardiovascular death and other events such as heart attack and stroke.
Atorvastatin comes in oral tablets with strengths of 10 mg, 20 mg, 40 mg, and 80 mg. The usual recommended starting dose is 10 or 20 mg once daily in the morning or evening. However, dosing is variable depending on how elevated cholesterol levels are.
Atorvastatin is primarily metabolized in the liver and kidneys. Lower doses may be needed if you have kidney or liver impairment. Other notable adverse side effects include muscle pain or elevated liver enzymes. These side effects should be monitored as they arise.
Simvastatin is the generic name for Zocor. It is also indicated to reduce total cholesterol LDL-C, VLDL-C, Apo B, and triglycerides for certain people with high blood levels. Like atorvastatin, it is also indicated to decrease the risk of heart attack and stroke in adults with increased cardiovascular risks.
Simvastatin is available as an oral tablet with strengths of 10 mg, 20 mg, 40 mg, and 80 mg. Unlike atorvastatin, simvastatin is recommended to be taken in the evening. The usual starting dose is either 10 or 20 mg which can be increased as needed.
Simvastatin is also metabolized in the liver and kidneys and should be dose adjusted in cases of liver or kidney impairment. While side effects may be similar to those experienced with atorvastatin, the risk of myalgia, or muscle pain, may be higher with simvastatin especially with higher doses.
Atorvastatin vs Simvastatin Side by Side Comparison
Atorvastatin and simvastatin are two similar medications that are chemically identical. Although there are little differences between the two, it’s important to be aware of them. These similarities and differences can be found in the table below.
|Common Side Effects|
|Is there a generic?|
|Is it covered by insurance?|
|Average Cash Price|
|SingleCare Discount Price|
|Can I use while planning pregnancy, pregnant, or breastfeeding?|
Atorvastatin and simvastatin are two effective medications that can treat high cholesterol and high triglycerides in individuals with elevated levels. They have also been shown to reduce cardiovascular events, such as heart attack and stroke, in those with increased risks. Both drugs belong to the same class of medications and have very little differences.
Simvastatin may have an increased risk of muscle pain when compared to atorvastatin. However, muscle pain is a possible adverse effect of both drugs, especially if higher doses are being taken. This is why it is important to start these medications at a lower starting dose to better monitor for these side effects.
Another key difference between the two medications is that simvastatin is recommended to be taken in the evening whereas atorvastatin can be taken in the morning or evening. Other than these slight differences, both medications have similar drug interactions and are contraindicated in pregnant patients.
It is important to discuss these medications with your doctor when deciding which option may work better for you. Some of these differences may be sufficient enough to choose one over the other. Regardless, your doctor should evaluate your cholesterol levels and overall condition before prescribing one of these statins.
Mechanism Of Action
LIPITOR is a selective, competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3methylglutaryl-coenzyme A to mevalonate, a precursor of sterols, including cholesterol. In animal models, LIPITOR lowers plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and by increasing the number of hepatic LDL receptors on the cell surface to enhance uptake and catabolism of LDL; LIPITOR also reduces LDL production and the number of LDL particles.
LIPITOR, as well as some of its metabolites, are pharmacologically active in humans. The liver is the primary site of action and the principal site of cholesterol synthesis and LDL clearance. Drug dosage, rather than systemic drug concentration, correlates better with LDL-C reduction. Individualization of drug dosage should be based on therapeutic response.
LIPITOR is rapidly absorbed after oral administration; maximum plasma concentrations occur within 1 to 2hours. Extent of absorption increases in proportion to LIPITOR dose. The absolute bioavailability of atorvastatin(parent drug) is approximately 14% and the systemic availability of HMG-CoA reductase inhibitory activity is approximately 30%. The low systemic availability is attributed to presystemic clearance in gastrointestinal mucosa and/or hepatic first-pass metabolism. Although food decreases the rate and extent of drug absorption by approximately 25% and 9%, respectively, as assessed by Cmax and AUC, LDL-C reduction is similar whether LIPITOR is given with or without food. Plasma LIPITOR concentrations are lower (approximately 30% for Cmax and AUC) following evening drug administration compared with morning. However, LDL-C reduction is the same regardless of the time of day of drug administration .
Mean volume of distribution of LIPITOR is approximately 381 liters. LIPITOR is ≥ 98% bound to plasma proteins. A blood/plasma ratio of approximately 0.25 indicates poor drug penetration into red blood cells. Based on observations in rats, LIPITOR is likely to be secreted in human milk .
LIPITOR is extensively metabolized to ortho-and parahydroxylated derivatives and various beta-oxidation products. In vitro inhibition of HMG-CoA reductase by ortho-and parahydroxylated metabolites is equivalent to that of LIPITOR. Approximately 70% of circulating inhibitory activity for HMG-CoA reductase is attributed to active metabolites. In vitro studies suggest the importance of LIPITOR metabolism by cytochrome P450 3A4, consistent with increased plasma concentrations of LIPITOR in humans following co-administration with erythromycin, a known inhibitor of this isozyme . In animals, the ortho-hydroxy metabolite undergoes further glucuronidation.
LIPITOR and its metabolites are eliminated primarily in bile following hepatic and/or extra-hepatic metabolism; however, the drug does not appear to undergo enterohepatic recirculation. Mean plasma elimination half-life of LIPITOR in humans is approximately 14hours, but the half-life of inhibitory activity for HMG-CoA reductase is 20 to 30hours due to the contribution of active metabolites. Less than2% of a dose of LIPITOR is recovered in urine following oral administration.
Geriatric: Plasma concentrations of LIPITOR are higher (approximately 40% for Cmax and 30% for AUC)in healthy elderly subjects(age ≥ 65years)than in young adults. Clinical data suggest a greater degree of LDL-lowering at any dose of drug in the elderly patient population compared to younger adults .
Pediatric: Apparent oral clearance of atorvastatin in pediatric subjects appeared similar to that of adults when scaled allometrically by body weight as the body weight was the only significant covariate in atorvastatin population PK model with data including pediatric HeFH patients (ages 10years to 17years of age, n=29) in an open-label, 8-week study.
Gender: Plasma concentrations of LIPITOR in women differ from those in men (approximately 20% higher for Cmax and 10% lower for AUC); however, there is no clinically significant difference in LDL-C reduction with LIPITOR between men and women.
Renal Impairment: Renal disease has no influence on the plasma concentrations or LDL-C reduction of LIPITOR; thus, dose adjustment in patients with renal dysfunction is not necessary .
Hemodialysis: While studies have not been conducted in patients with end-stage renal disease, hemodialysis is not expected to significantly enhance clearance of LIPITOR since the drug is extensively bound to plasma proteins.
Hepatic Impairment: In patients with chronic alcoholic liver disease, plasma concentrations of LIPITOR are markedly increased. Cmax and AUC are each 4-fold greater in patients with Childs-Pugh A disease. Cmax and AUC are approximately 16-fold and 11-fold increased, respectively, in patients with Childs-Pugh B disease .
TABLE 4: Effect of Co-administered Drugs on the Pharmacokinetics of Atorvastatin
|Co-administered drug and dosing regimen||Atorvastatin|
|Dose (mg)||Change in AUC&||Change in Cmax&|
|#Cyclosporine 5.2 mg/kg/day, stable dose||10 mg QD for 28 days||8.7 fold||10.7 fold|
|#Tipranavir 500 mg BID/ritonavir 200 mg BID, 7 days||10 mg, SD||9.4 fold||8.6 fold|
|#Telaprevir 750 mg q8h, 10 days||20 mg, SD||7.88 fold||10.6 fold|
|#‡Saquinavir 400 mg BID/ ritonavir 400mg BID, 15 days||40 mg QD for 4 days||3.9 fold||4.3 fold|
|Clarithromycin 500 mg BID, 9 days||80 mg QD for 8 days||4.4 fold||5.4 fold|
|#Darunavir 300 mg BID/ritonavir 100 mg BID, 9 days||10 mg QD for 4 days||3.4 fold||2.25 fold|
|#Itraconazole 200 mg QD, 4 days||40 mg SD||3.3 fold||20%|
|#Fosamprenavir 700 mg BID/ritonavir 100 mg BID, 14 days||10 mg QD for 4 days||2.53 fold||2.84 fold|
|#Fosamprenavir 1400 mg BID, 14 days||10 mg QD for 4 days||2.3 fold||4.04 fold|
|#Nelfinavir 1250 mg BID, 14 days||10 mg QD for 28 days||74%||2.2 fold|
|#Grapefruit Juice, 240 mL QD *||40 mg, SD||37%||16%|
|Diltiazem 240 mg QD, 28 days||40 mg, SD||51%||No change|
|Erythromycin 500 mg QID, 7 days||10 mg, SD||33%||38%|
|Amlodipine 10 mg, single dose||80 mg, SD||15%||↓ 12 %|
|Cimetidine 300 mg QID, 2 weeks||10 mg QD for 2 weeks||↓ Less than 1%||↓ 11%|
|Colestipol 10 mg BID, 28 weeks||40 mg QD for 28 weeks||Not determined||↓26%**|
|MaaloxTC® 30 mL QD, 17 days||10 mg QD for 15 days||↓33%||↓ 34%|
|Efavirenz 600 mg QD, 14 days||10 mg for 3 days||↓ 41%||↓1%|
|#Rifampin 600 mg QD, 7 days (coadministered) †||40 mg SD||30%||2.7 fold|
|#Rifampin 600 mg QD, 5 days (doses separated)†||40 mg SD||↓ 80%||↓ 40%|
|#Gemfibrozil 600mg BID, 7 days||40mg SD||35%||↓ Less than 1%|
|#Fenofibrate 160mg QD, 7 days||40mg SD||3%||2%|
|Boceprevir 800 mg TID, 7 days||40 mg SD||2.30 fold||2.66 fold|
|& Data given as x-fold change represent a simple ratio between co-administration and atorvastatin alone (i.e., 1-fold = no change).Data given as% change represent% difference relative to atorvastatin alone (i.e., 0% = no change).
# See Sections WARNINGS AND PRECAUTIONS and DOSAGE AND ADMINISTRATION for clinical significance.
* Greater increases in AUC (up to2.5fold)and/or Cmax(up to 71%)have been reported with excessive grapefruit consumption ( ≥ 750 mL -1.2 liters per day).
** Single sample taken 8-16h post dose.
† Due to the dual interaction mechanism of rifampin, simultaneous co-administration of atorvastatin with rifampin is recommended, as delayed administration of atorvastatin after administration of rifampin has been associated with a significant reduction in atorvastatin plasma concentrations.
‡ The dose of saquinavir plus ritonavir in this study is not the clinically used dose. The increase in atorvastatin exposure when used clinicallyis likely to be higher than what was observed in this study. Therefore, caution should be applied and the lowest dose necessary should be used.
TABLE 5: Effect of Atorvastatin on the Pharmacokinetics of Co-administered Drugs
|Atorvastatin||Co-administered drug and dosing regimen|
|Drug/Dose (mg)||Change in AUC||Change in Cmax|
|80 mg QD for 15 days||Antipyrine, 600 mg SD||3%||↓ 11%|
|80 mg QD for 14 days||# Digoxin 0.25 mg QD, 20 days||15%||20 %|
|40 mg QD for 22 days||Oral contraceptive QD, 2 months|
|ethinyl estradiol 35μg||19%||30%|
|10 mg, SD||Tipranavir 500 mg BID/ritonavir 200 mg BID, 7 days||No change||No change|
|10 mg QD for 4 days||Fosamprenavir 1400 mg BID, 14 days||↓ 27%||↓ 18%|
|10 mg QD for 4 days||Fosamprenavir 700 mg BID/ritonavir 100 mg BID, 14 days||No change||No change|
|# See DOSAGE AND ADMINISTRATION for clinical significance.|
Prevention Of Cardiovascular Disease
The effect of 10mg/day of LIPITOR on lipid levels was similar to that seen in previous clinical trials.
LIPITOR significantly reduced the rate of coronary events with a relative risk reduction of 36% .The risk reduction was consistent regardless of age, smoking status, obesity, or presence of renal dysfunction. The effect of LIPITOR was seen regardless of baseline LDL levels. Due to the small number of events, results for women were inconclusive.
Figure 1: Effect of LIPITOR 10 mg/day on Cumulative Incidence of Non-Fatal Myocardial Infarction or Coronary Heart Disease Death (in ASCOT-LLA)
LIPITOR also significantly decreased the relative risk for revascularization procedures by 42%(incidences of 1.4% for LIPITOR and 2.5% for placebo). Although the reduction of fatal and non-fatal strokes did not reach a pre-defined significance level (p=0.01), a favorable trend was observed with a 26% relative risk reduction (incidences of 1.7% for LIPITOR and 2.3% for placebo). There was no significant difference between the treatment groups for death due to cardiovascular causes (p=0.51) or non-cardiovascular causes (p=0.17).
In the Collaborative Atorvastatin Diabetes Study (CARDS), the effect of LIPITOR on cardiovascular disease (CVD)endpoints was assessed in 2838subjects (94%white, 68% male), ages 40-75with type 2 diabetes based on WHO criteria, without prior history of cardiovascular disease and with LDL ≤ 160 mg/dL and TG ≤ 600 mg/dL. In addition to diabetes, subjects had 1 or more of the following risk factors: current smoking(23%), hypertension (80%), retinopathy (30%), or microalbuminuria (9%) or macroalbuminuria (3%). No subjects on hemodialysis were enrolled in the study. In this multicenter, placebo-controlled, double-blind clinicaltrial, subjects were randomly allocated to either LIPITOR 10mg daily (1429) or placebo (1411) ina1:1ratio and were followed for a median duration of 3.9 years. The primary endpoint was the occurrence of any of the major cardiovascular events: myocardial infarction, acute CHD death, unstableangina, coronary revascularization, or stroke. The primary analysis was the time to first occurrence of the primary endpoint.
The effect of LIPITOR 10mg/day on lipid levels was similar to that seen in previous clinical trials.
LIPITOR significantly reduced the rate of major cardiovascular events (primary endpoint events) (83 events in the LIPITOR group vs. 127events in the placebo group) with a relative risk reduction of 37%, HR0.63,95%CI(0.48, 0.83)(p=0.001)(see Figure 2). An effect of LIPITOR was seen regardless of age, sex, or baseline lipid levels.
There were 61deaths in the LIPITOR group vs. 82 deaths in the placebo group (HR 0.73, p=0.059).
Figure 2: Effect of LIPITOR 10 mg/day on Time to Occurrence of Major Cardiovascular Event (myocardial infarction, acute CHD death, unstable angina, coronary revascularization, or stroke) in CARDS
In the Treating to New Targets Study (TNT), the effect of LIPITOR80 mg/day vs. LIPITOR10 mg/day on the reduction in cardiovascular events was assessed in 10,001 subjects (94% white, 81% male, 38% ≥ 65 years) with clinically evident coronary heart disease who had achieved a target LDL-C level < 130 mg/dL after completing an 8-week, open-label, run-in period with LIPITOR 10 mg/day. Subjects were randomly assigned to either 10 mg/day or 80 mg/day of LIPITOR and followed for a median duration of 4.9 years. The primary endpoint was the time-to-first occurrence of any of the following major cardiovascular events (MCVE):death due to CHD, non-fatal myocardial infarction, resuscitated cardiacarrest, and fatal and non-fatal stroke. The mean LDL-C, TC, TG, non-HDL, and HDL cholesterol levels at 12 weeks were 73,145,128,98,and 47mg/dL during treatment with 80 mg of LIPITOR and 99, 177, 152, 129, and 48mg/dL during treatment with 10mg of LIPITOR.
overallrisk reduction was consistent regardless of age( < 65, ≥ 65) or gender.
Figure 3:Effect of LIPITOR 80mg/day vs.10 mg/day on Time to Occurrence of Major Cardiovascular Events (TNT)
TABLE 6: Overview of Efficacy Results in TNT
Of the events that comprised the primary efficacy endpoint, treatment with LIPITOR 80 mg/day significantly reduced the rate of nonfatal, non-procedure related MI and fatal and non-fatal stroke, but not CHD death or resuscitated cardiac arrest (Table6). Of the predefined secondary endpoints, treatment with LIPITOR 80 mg/day significantly reduced the rate of coronary revascularization, angina, and hospitalization for heart failure, but not peripheral vascular disease. The reduction in the rate of CHF with hospitalization was only observed in the 8% of patients with a prior history of CHF.
There was no significant difference between the treatment groups for all-cause mortality (Table6). The proportions of subjects who experienced cardiovascular death, including the components of CHD death and fatal stroke, were numerically smaller in the LIPITOR 80 mg group than in the LIPITOR 10 mg treatment group. The proportions of subjects who experienced non-cardiovascular death were numerically larger in the LIPITOR80 mg group than in the LIPITOR 10 mg treatment group.
In the Incremental Decrease in Endpoints Through Aggressive Lipid Lowering Study (IDEAL), treatment with LIPITOR80mg/day was compared to treatment with simvastatin 20-40 mg/day in 8,888 subjects up to80 years of age with a history of CHD to assess whether reduction in CV risk could be achieved. Patients were mainly male (81%), white (99%) with an average age of 61.7years, and an average LDL-Cof121.5 mg/dL at randomization; 76% were on stat in therapy. In this prospective, randomized, open-label, blinded endpoint (PROBE)trial with no run-in period, subjects were followed for a median duration of 4.8 years. The mean LDL-C, TC, TG, HDL, and non-HDL cholesterol levels at Week 12 were 78,145, 115, 45, and 100mg/dL during treatment with 80 mg of LIPITOR and105,179, 142, 47, and 132mg/dL during treatment with 20-40 mg of simvastatin.
There were no significant differences between the treatment groups for all-cause mortality: 366 (8.2%) in the LIPITOR 80mg/day group vs. 374(8.4%)in the simvastatin 20-40 mg/day group. The proportions of subjects who experienced CV or non-CV death were similar for the LIPITOR 80 mg group and the simvastatin 20-40 mg group.
Hyperlipidemia And Mixed Dyslipidemia
LIPITOR reduces total-C, LDL-C, VLDL-C, apo B, and TG, and increases HDL-C in patients with hyperlipidemia (heterozygous familial and non familial)and mixed dyslipidemia(Fredrickson Types IIa and IIb). Therapeutic response is seen within 2 weeks, and maximum response is usually achieved within 4 weeks and maintained during chronic therapy.
LIPITOR is effective in a wide variety of patient populations with hyperlipidemia, with and without hypertriglyceridemia, in men and women, and in the elderly.
In two multicenter, placebo-controlled, dose-response studies in patients with hyperlipidemia, LIPITOR given as a single doseover 6weeks,significantly reduced total-C, LDL-C, apo B, and TG.(Pooled results are provided in Table7.)
TABLE 7: Dose Response in Patients With Primary Hyperlipidemia (Adjusted Mean % Change From Baseline)a
In three multicenter, double-blind studies in patients with hyperlipidemia, LIPITOR was compared to other statins. After randomization, patients were treated for 16 weeks with either LIPITOR10mgper day or afixed dose of the comparative agent (Table 8).
TABLE 8: Mean Percentage Change From Baseline at Endpoint (Double-Blind, Randomized, Active-Controlled Trials)
The impact on clinical outcomes of the differences in lipid-altering effects between treatments shown in Table8is not known. Table8 does not contain data comparing the effects of LIPITOR10 mg and higher doses of lovastatin, pravastatin, and simvastatin. The drugs compared in the studies summarized in the table are not necessarily interchangeable.
The response to LIPITOR in 64 patients with isolated hypertriglyceridemia(Fredrickson Type IV) treated across several clinical trials is shown in the table below(Table 9). For the LIPITOR-treated patients, median (min, max) baseline TG level was 565(267-1502).
TABLE 9: Combined Patients With Isolated Elevated TG: Median(min, max)Percentage Change From Baseline
The results of an open-label crossover study of 16 patients (genotypes: 14 apo E2/E2 and 2 apo E3/E2) with dysbetalipoproteinemia (Fredrickson Type III) are shown in the table below (Table 10).
TABLE 10: Open-Label Crossover Study of 16 Patients With Dysbetalipoproteinemia (Fredrickson Type III)
Homozygous Familial Hypercholesterolemia
In a study without a concurrent control group, 29 patients ages 6yearsto37 years with HoFH received maximum daily doses of 20 to 80mgof LIPITOR. The mean LDL-C reduction in this study was 18%. Twenty-five patients with a reduction in LDL-Chad a mean response of 20% (range of 7% to 53%,median of 24%); the remaining 4patientshad 7% to 24% increases in LDL-C. Five of the 29 patients had absent LDL-receptor function. Of these, 2 patients also had a portacaval shunt and had no significant reduction in LDL-C. The remaining 3receptor-negative patients had a mean LDL-C reduction of 22%.
Heterozygous Familial Hypercholesterolemia In Pediatric Patients
In a double-blind, placebo-controlled study followed by an open-label phase, 187boys and post-menarchal girls 10years to17 years of age (mean age 14.1 years) with heterozygous familial hypercholesterolemia (HeFH)or severe hypercholesterolemia, were randomized to LIPITOR(n=140) or placebo (n=47) for 26 weeks and then all received LIPITOR for26weeks. Inclusion in the study required 1) a baseline LDL-C level ≥ 190 mg/dL or 2) a baseline LDL-C level ≥ 160 mg/dL and positive family history of FH or documented premature cardiovascular disease in a first or second-degree relative. The mean baseline LDL-C value was 218.6 mg/dL (range: 138.5-385.0 mg/dL)in the LIPITOR group compared to230.0 mg/dL (range: 160.0-324.5 mg/dL)in the placebo group. The dosage of LIPITOR (once daily) was 10mgforthe first 4weeks and uptitrated to 20 mgifthe LDL-C level was > 130mg/dL. The number of LIPITOR-treated patients who required uptitration to20 mg after Week 4during the double-blind phase was78(55.7%).
LIPITOR significantly decreased plasma levels of total-C, LDL-C, triglycerides, and apolipoprotein B during the 26-week double-blind phase (see Table 11).
TABLE 11: Lipid-altering Effects of LIPITOR in Adolescent Boys and Girls with Heterozygous Familial Hypercholesterolemia or Severe Hypercholesterolemia(Mean Percentage Change From Baseline at Endpoint in Intention-to-Treat Population)
Atorvastatin was also studied in a three year open-label, uncontrolled trial that included 163patientswith HeFH who were 10years to 15 years old (82boys and81girls). Allpatients had a clinical diagnosis of HeFH confirmed by genetic analysis (if not already confirmed by family history). Approximately 98% were Caucasian, andlessthan1% were Black or Asian. Mean LDL-Cat baseline was 232mg/dL. The starting atorvastatin dosage was 10 mg once daily and doses were adjusted to achieve a target of < 130 mg/dL LDL-C. The reductions in LDL-C from baseline were generally consistent across age groups within the trial as well as with previous clinical studies in both adult and pediatric placebo-controlled trials.
The long-term efficacy of LIPITOR therapy in childhood to reduce morbidity and mortality in adulthood has not been established.
Pravastatin vs Lipitor: Main Differences and Similarities
Pravastatin and Lipitor (atorvastatin) are medications that treat high cholesterol. High levels of cholesterol in the body is known to contribute to heart disease, heart attacks, and stroke. Pravastatin and Lipitor are statin drugs that are part of a group of medications called HMG-coA reductase inhibitors. While they have similar uses, there are some differences between these medications.
Pravastatin is the generic name for Pravachol. It is approved to decrease levels of total cholesterol, LDL cholesterol, and triglycerides. By lowering cholesterol, pravastatin helps to decrease the risk of heart attacks and stroke. Pravastatin can also reduce the risk of overall death from cardiovascular causes.
Pravastatin is available as a 20 mg, 40 mg, and 80 mg oral tablet. It can be taken once daily with or without food. Although it can be taken at any time of day, it is often recommended to be taken during the evening. In those with renal impairment, the dose of pravastatin needs to be decreased to prevent the risk of adverse side effects.
Lipitor is the brand name for atorvastatin. It can treat high levels of total cholesterol, LDL cholesterol, and triglycerides. Like a few other statins, Lipitor can help decrease the risk of heart attacks, stroke, and overall death from cardiovascular causes.
Atorvastatin is supplied as a 10 mg, 20 mg, 40 mg, or 80 mg oral tablet. It can be taken once daily in the morning or the evening because of its long half-life. The absorption of atorvastatin may be affected when it is taken with food. However, unlike pravastatin, renal impairment does not affect the absorption of atorvastatin.
Pravastatin vs Lipitor Side by Side Comparison
Pravastatin and Lipitor are two medications that can treat similar conditions. Despite their similarities, they also have some important differences. Their different attributes can be found below.
|Common Side Effects|
|Is there a generic?|
|Is it covered by insurance?|
|Average Cash Price|
|SingleCare Discount Price|
|Can I use while planning pregnancy, pregnant, or breastfeeding?|
Pravastatin and Lipitor (atorvastatin) are statin medications that help lower high levels of cholesterol. They are both effective for preventing heart attacks, stroke, and overall death from cardiovascular events. Both medications can be used in adults and children although pravastatin is approved for those aged 8 years and older while Lipitor is approved for those aged 10 years and older.
Lipitor is available in doses that are considered high intensity while pravastatin is available in doses that are moderate intensity. Therefore, Lipitor may be more potent in some cases. However, pravastatin may exhibit less side effects compared to Lipitor.
Pravastatin is usually taken in the evening while Lipitor can be taken at any time of day. People with renal impairment also need to take lower doses of pravastatin. The use of Lipitor is not affected by renal impairment, although liver problems may affect absorption.
It is important to talk with your doctor regarding these medications. One statin may be preferred depending on your overall condition and lifestyle. Both medications should not be used while taking certain medications at the same time. This is due to the increased risk of adverse effects when taking certain drugs.
NCI Drug Dictionary
atorvastatin calcium The calcium salt of atorvastatin, a synthetic lipid-lowering agent. Atorvastatin competitively inhibits hepatic hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase, the enzyme which catalyzes the conversion of HMG-CoA to mevalonate, a key step in cholesterol synthesis. This agent increases the number of LDL receptors on hepatic cell surfaces, enhancing the uptake and catabolism of LDL and reducing LDL production and the number of LDL particles, and lowers plasma cholesterol and lipoprotein levels. Like other statins, atorvastatin may also display direct antineoplastic activity, possibly by inhibiting farnesylation and geranylgeranylation of proteins such as small GTP-binding proteins, which may result in the arrest of cells in the G1 phase of the cell cycle. This agent may also sensitize tumor cells to cyctostatic drugs, possibly through the mTOR-dependent inhibition of Akt phosphorylation. Check for active clinical trials using this agent. (NCI Thesaurus)
|Synonym:||atorvastatin calcium trihydrate|
|US brand name:||Lipitor|
Simvastatin vs. Atorvastatin: What You Should Know
Both simvastatin and atorvastatin can cause various adverse effects. Some side effects are more likely to occur with simvastatin, and others are more likely with atorvastatin.
All statins can cause muscle pain, but this effect is more likely with simvastatin use. Muscle pain may develop gradually. It can feel like a pulled muscle or fatigue from exercise. Call your doctor about any new pain you have when you start taking a statin, especially simvastatin. Muscle pain can be a sign of developing kidney problems or damage.
A side effect that can occur with either drug is fatigue. A study funded by the National Institutes of Health (NIH) compared fatigue in patients who took small doses of simvastatin and another medication called pravastatin. Women, especially, have a substantial risk of fatigue from statins, although more so from simvastatin.
Upset stomach and diarrhea
Both drugs can cause stomach upset and diarrhea. These side effects usually resolve over the course of a few weeks.
Liver and kidney disease
If you have kidney disease, atorvastatin could be a good choice for you because there is no need to adjust the dosage. On the other hand, simvastatin can affect your kidneys when given at the highest dosage (80 mg per day). It may slow your kidneys. Simvastatin also builds up in your system over time. This means that if you take it for an extended period of time, the amount of the drug in your system can really add up. Your doctor might have to adjust your dosage.
However, based on results from a 2014 study by the American Heart Association, there is likely no increased risk of kidney injury between high-dose simvastatin and high-dose atorvastatin. What’s more, dosages of simvastatin as high as 80 mg per day are no longer very common.
A few people who take statins develop liver disease. If you have darkened urine or pain in your side while taking either drug, call your doctor immediately.
A high dosage of atorvastatin (80 mg per day) is associated with a higher risk of hemorrhagic stroke if you’ve had an ischemic stroke or a transient ischemic attack (TIA, sometimes called a mini stroke), in the last six months.
High blood sugar and diabetes
Both simvastatin and atorvastatin can increase your blood sugar and your risk of developing diabetes. All statins may increase your hemoglobin A1C level, which is a measure of long-term blood sugar levels.
Learn more: Statins and diabetes risk “
For those of you paying big bucks for your cholesterol medication Lipitor: you have an early Christmas present. Finally, atorvastatin, a generic alternative to Lipitor, has been shipped! On November 30, 2011, the Food and Drug Administration (FDA) approved two generic versions of the cholesterol lowering drug Lipitor (atorvastatin), made by Ranbaxy Laboratories and Watson Pharmaceuticals. Atorvastatin is a cholesterol medication known as a statin, similar to the already available generic simvastatin and the brand name drug Crestor.
Atorvastatin is used along with a low-fat diet to reduce the “bad” cholesterol (the LDL cholesterol) and free fatty acids (triglycerides) in the blood. Atorvastatin lowers the risk for heart attack, stroke, and chest pain in patients with heart disease or risk factors for heart disease such as age, smoking, high blood pressure, or family history of early heart disease.
Is atorvastatin equivalent to Lipitor? Yes, and what is interesting is that Pfizer, the maker of Lipitor, has an exclusive supply and distribution agreement with Watson Pharmaceuticals. This means that Pfizer manufactures and supplies Watson with all dosage strengths of atorvastatin.
Ranbaxy Laboratories has gained approval to make generic atorvastatin tablets in 10 mg, 20 mg, 40 mg, and 80 mg strengths.
Generic atorvastatin began shipping November 30th, so discuss changing to the generic version with your doctor.
Lipitor and atorvastatin should be available at most pharmacies. Lipitor 10 mg typically ranges in cost from $115 to $200 for a 30-day supply, while atorvastatin 10 mg should be around $80. Lipitor is covered by some insurance plans; it is typically a Tier 2 or Tier 3 drug, meaning you’ll likely pay your middle to maximum copay, or full price. This may change with the introduction of atorvastatin. Generic atorvastatin will likely be covered by insurance as a Tier 1 drug, meaning you’ll pay your minimum copay.
Pfizer also offers a Lipitor co-pay card, which reduces payments by $50 per month, to as low as $4. More information can be found here.