Does Lipitor (atorvastatin) cause side effects?
Lipitor (atorvastatin) is an HMG-CoA reductase inhibitor (a “statin”) that lowers the level of cholesterol in the blood and is used to treat elevated total cholesterol, LDL, and triglycerides, and to elevate HDL cholesterol.
The effectiveness of Lipitor in lowering cholesterol is dose-related, meaning that higher doses reduce cholesterol more.
All statins, including Lipitor, prevent the production of cholesterol in the liver by blocking HMG-CoA reductase, an enzyme that makes cholesterol. Statins reduce total cholesterol as well as LDL cholesterol in blood.
LDL cholesterol is believed to be the "bad" cholesterol that is primarily responsible for the development of coronary artery disease. Reducing LDL cholesterol levels retards progression and may even reverse coronary artery disease. Lipitor also raises the concentrations of HDL ("good") cholesterol that protects against coronary artery disease and reduces the concentration of triglycerides in the blood. (High blood concentrations of triglycerides also have been associated with coronary artery disease.)
Common side effects of Lipitor include
- common cold,
- joint pain,
- pain in extremities, and
- urinary tract infection (UTI).
Serious side effects of Lipitor include
- liver damage,
- serious breakdown of muscle cells (rhabdomyolysis) which can lead to kidney failure and even death, increases in HbA1c and fasting serum glucose levels as seen in
Drug interactions of Lipitor include erythromycin, ketoconazole, itraconazole, clarithromycin, telithromycin, cyclosporine, nefazodone, and HIV protease inhibitors such as indinavir and ritonavir because these drugs decrease elimination of Lipitor which could increase levels of Lipitor in the body and increase the risk of muscle toxicity from Lipitor.
Large quantities of grapefruit juice (more than 1.2 liters daily) also will increase blood levels of Lipitor and should not be taken.
The following drugs also may increase the risk of muscle toxicity when combined with Lipitor:
Cholestyramine decreases the absorption of Lipitor. Lipitor should be given at least two hours before and at least four hours after cholestyramine.
Rifampin increases breakdown of Lipitor. To reduce the likelihood of this interaction both drugs should be given at the same time. Lipitor should not be given after rifampin.
Lipitor should not be taken during pregnancy because the developing fetus requires cholesterol for development, and Lipitor reduces the production of cholesterol. Lipitor should only be administered to women of childbearing age if they are not likely to become pregnant.
What are the side effects of Lipitor (atorvastatin)?
Lipitor is generally well tolerated. Minor side effects include:
Other commonly reported side effects include:
Lipitor may cause liver and muscle damage. Serious liver damage caused by statins is rare. Liver tests should be performed at the beginning of treatment then as needed thereafter.
Inflammation of the muscles caused by statins can lead to serious breakdown of muscle cells called rhabdomyolysis. Rhabdomyolysis causes the release of muscle protein (myoglobin) into the blood, and myoglobin can cause kidney failure and even death.
When used alone, statins cause rhabdomyolysis in less than one percent of patients. To prevent the development of serious rhabdomyolysis, patients taking atorvastatin should contact their health-care professional immediately if they develop unexplained muscle pain, weakness, or muscle tenderness.
Statins have been associated with increases in HbA1c and fasting serum glucose levels as seen in diabetes.
Post-marketing reports for atorvastatin of adverse events include:
- Memory loss
- Memory impairment
Symptoms may start one day to years after starting treatment and resolve within a median of three weeks after stopping the statin.
Lipitor (atorvastatin) side effects list for healthcare professionals
The following serious adverse reactions are discussed in greater detail in other sections of the label:
- Rhabdomyolysis and myopathy
- Liver enzyme abnormalities
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
In the Lipitor placebo-controlled clinical trial database of 16,066patients (8755 Lipitor vs. 7311 placebo; age range 10-93 years, 39% women, 91% Caucasians, 3% Blacks, 2% Asians, 4% other) with a median treatment duration of 53 weeks, 9.7% of patients on Lipitor and 9.5% of the patients on placebo discontinued due to adverse reactions regardless of causality.
The five most common adverse reactions in patients treated with Lipitor that led to treatment discontinuation and occurred at a rate greater than placebo were:
- myalgia (0.7%),
- diarrhea (0.5%),
- nausea (0.4%),
- alanine aminotransferase increase (0.4%), and
- hepatic enzyme increase (0.4%).
The most commonly reported adverse reactions(incidence ≥ 2% and greater than placebo) regardless of causality, in patient streated with Lipitor in placebo controlled trials (n=8755) were:
- nasopharyngitis (8.3%),
- arthralgia (6.9%),
- diarrhea (6.8%),
- pain in extremity (6.0%), and
- urinary tract infection (5.7%).
Table 3 summarizes the frequency of clinicaladverse reactions, regardless of causality, reported in ≥ 2% and at a rate greater than placebo in patients treated with Lipitor (n=8755), from seventeen placebo-controlled trials.
Table 3: Clinical adverse reactions occurring in ≥ 2% in patients treated with any dose of Lipitor and at an incidence greater than placebo regardless of causality (% of patients).
|Adverse Reaction*||Any dose|
|Pain in extremity||6.0||8.5||3.7||9.3||3.1||5.9|
|Urinary tract infection||5.7||6.9||6.4||8.0||4.1||5.6|
|*Adverse Reaction ≥ 2% in any dose greater than placebo|
Other Adverse Reactions Reported in Placebo-controlled Studies Include:
- Body as a whole: malaise, pyrexia;
- Digestive system: abdominal discomfort, eructation, flatulence, hepatitis, cholestasis;
- Musculoskeletal system: musculoskeletal pain, muscle fatigue, neck pain, joint swelling;
- Metabolic and nutritional system: transaminases increase, liver function test abnormal, blood alkaline phosphatase increase, creatine phosphokinase increase, hyperglycemia;
- Nervous system: nightmare;
- Respiratory system: epistaxis;
- Skin and appendages: urticaria;
- Special senses: vision blurred, tinnitus;
- Urogenital system: white blood cells urine positive.
Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)
In ASCOT involving 10,305 participants (age range 40-80 years, 19% women; 94.6% Caucasians, 2.6% Africans, 1.5% South Asians, 1.3% mixed/other) treated with Lipitor 10 mg daily (n=5,168) or placebo (n=5,137), the safety and tolerability profile of the group treated with Lipitor was comparable to that of the group treated with placebo during a median of 3.3 years of follow-up.
Collaborative Atorvastatin Diabetes Study (CARDS)
In CARDS involving 2,838 subjects (age range 39-77 years, 32% women; 94.3% Caucasians, 2.4% South Asians, 2.3% Afro-Caribbean, 1.0% other) with type 2 diabetes treated with Lipitor 10 mg daily(n=1,428) or placebo (n=1,410), there was no difference in the overall frequency of adverse reactions or serious adverse reactions between the treatment groups during a median follow-up of 3.9 years. No cases of rhabdomyolysis were reported.
Treating to New Targets Study(TNT)
- In TNT involving 10,001 subjects (age range 29-78 years, 19% women; 94.1% Caucasians, 2.9% Blacks, 1.0%Asians, 2.0% other) with clinically evident CHD treated with Lipitor10mg daily (n=5006) orLipitor80 mg daily (n=4995), there were more serious adverse reactions and discontinuations due to adverse reactions in the high-dose atorvastatin group (92, 1.8%; 497, 9.9%,respectively) as compared to the low-dose group (69, 1.4%; 404, 8.1%, respectively) during a median follow-up of 4.9 years.
- Persistent transaminase elevations ( ≥ 3x ULN twice within 4-10days) occurred in 62 (1.3%) individuals with atorvastatin80mg andinnine(0.2%)individualswithatorvastatin10mg.ElevationsofCK( ≥ 10x ULN) were low overall, but were higher in the high-dose atorvastatin treatment group (13, 0.3%) compared to the low-dose atorvastatin group (6, 0.1%).
Incremental Decrease in Endpoints through Aggressive Lipid Lowering Study (IDEAL)
- In IDEAL involving 8,888 subjects (age range 26-80 years, 19% women; 99.3% Caucasians, 0.4% Asians, 0.3% Blacks, 0.04% other) treated with Lipitor80 mg/day (n=4439) or simvastatin 20-40 mg daily (n=4449), there was no difference in the overall frequency of adverse reactions or serious adverse reactions between the treatment groups during a median follow-up of 4.8 years.
Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL)
- In SPARCL involving 4731 subjects (age range 21-92 years, 40% women; 93.3% Caucasians, 3.0% Blacks, 0.6% Asians, 3.1% other) without clinically evident CHD but with a stroke or transient ischemic attack (TIA) within the previous 6 months treated with Lipitor 80 mg (n=2365) or placebo (n=2366) for a median follow-up of 4.9 years, there was a higher incidence of persistent hepatic transaminase elevations ( = 3xULN twice within 4-10days) in the atorvastatin group (0.9%) compared to placebo (0.1%).
- Elevations of CK ( > 10 x ULN) were rare, but were higher in the atorvastatin group (0.1%) compared to placebo (0.0%).
- Diabetes was reported as an adverse reaction in 144 subjects (6.1%) in the atorvastatin group and 89 subjects (3.8%) in the placebo group.
- In a post-hoc analysis, Lipitor 80 mg reduced the incidence of ischemic stroke(218/2365, 9.2% vs. 274/2366, 11.6%) and increased the incidence of hemorrhagic stroke (55/2365, 2.3% vs. 33/2366, 1.4%) compared to placebo.
- The incidence of fatal hemorrhagic stroke was similar between groups (17Lipitor vs. 18placebo).
- The incidence of non-fatal hemorrhagic strokes was significantly greater in the atorvastatin group (38 non-fatal hemorrhagic strokes) as compared to the placebo group (16 non-fatal hemorrhagic strokes).
- Subjects who entered the study with a hemorrhagic stroke appeared to be at increased risk for hemorrhagic stroke [7 (16%) Lipitor vs.2 (4%) placebo].
- There were no significant differences between the treatment groups for all-cause mortality: 216 (9.1%) in the Lipitor 80mg/day group vs. 211(8.9%)in the placebo group.
- The proportions of subjects who experienced cardiovascular death were numerically smaller in the Lipitor80 mg group (3.3%) than in the placebo group (4.1%). The proportions of subjects who experienced non-cardiovascular death were numerically larger in the Lipitor80 mg group (5.0%) than in the placebo group(4.0%).
Adverse Reactions From Clinical Studies Of Lipitor In Pediatric Patients
- In a 26-week controlled study in boys and postmenarchal girls with HeFH (ages 10years to17 years)(n=140, 31% female; 92% Caucasians, 1.6% Blacks, 1.6% Asians, 4.8% other), the safety and tolerability profile of Lipitor10 to 20mg daily, as an adjunct to diet to reduce total cholesterol, LDL-C, and apoB levels, was generally similar to that of placebo.
- The following adverse reactions have been identified during post-approval use of Lipitor.
- Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Adverse reactions associated with Lipitor therapy reported since market introduction, that are notlisted above, regardless of causality assessment, include the following:
- angioneurotic edema,
- bullous rashes (including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis),
- tendon rupture,
- fatal and non-fatal hepatic failure,
- peripheral neuropathy,
- pancreatitis and
- interstitial lung disease.
- There have been rare reports of immune-mediated necrotizing myopathy associated with stat in use.
- There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use.
- These cognitive issues have been reported for all statins.
- The reports aregenerally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).
What drugs interact with Lipitor (atorvastatin)?
- The risk of myopathy during treatment with statins is increased with concurrent administration of fibric acid derivatives, lipid-modifying doses of niacin, cyclosporine, or strong CYP 3A4 inhibitors (e.g., clarithromycin, HIV protease inhibitors, and itraconazole).
Strong Inhibitors Of CYP 3A4
- Lipitor is metabolized by cytochrome P450 3A4.Concomitant administration of Lipitor with strong inhibitors of CYP 3A4 can lead to increases in plasma concentrations of atorvastatin.
- The extent of interaction and potentiation of effects depend on the variability of effect on CYP 3A4.
- Atorvastatin AUC was significantly increased with concomitant administration of Lipitor 80 mg with clarithromycin (500mg twice daily)compared to that of Lipitor alone.
- Therefore, in patients taking clarithromycin, caution should be used when the Lipitor dose exceeds 20mg.
Combination Of Protease Inhibitors
- Atorvastatin AUC was significantly increased with concomitant administration of Lipitor with several combinations of HIV protease inhibitors, as well as with the hepatitis C protease inhibitor telaprevir, compared to that of Lipitor alone.
- Therefore, in patients taking the HIV protease inhibitor tipranavir plus ritonavir, or the hepatitis C protease inhibitor telaprevir, concomitant use of Lipitor should be avoided.
- In patients taking the HIV protease inhibitor lopinavir plus ritonavir, caution should be used when prescribing Lipitor and the lowest dose necessary should be used.
- In patients taking the HIV protease inhibitors saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, or fosamprenavir plus ritonavir, the dose of Lipitor should not exceed 20 mg and should be used with caution.
- In patients taking the HIV protease inhibitor nelfinavir or the hepatitis C protease inhibitor boceprevir, the dose of Lipitor should not exceed 40 mg and close clinical monitoring is recommended.
- Atorvastatin AUC was significantly increased with concomitant administration of Lipitor 40 mg and itraconazole200mg.
- Therefore, in patients taking itraconazole, caution should be used when the Lipitor dose exceeds 20 mg.
- Contains one or more components that inhibit CYP 3A4 and can increase plasma concentrations of atorvastatin, especially with excessive grapefruit juice consumption ( > 1.2 liters per day).
- Atorvastatin and atorvastatin-metabolites are substrates of the OATP1B1 transporter.
- Inhibitors of the OATP1B1 (e.g., cyclosporine) can increase the bioavailability of atorvastatin.
- Atorvastatin AUC was significantly increased with concomitant administration of Lipitor 10 mg and cyclosporine 5.2 mg/kg/day compared to that of Lipitor alone.
- The co-administration of Lipitor with cyclosporine should be avoided.
- Due to an increased risk of myopathy/rhabdomyolysis when HMG-CoA reductase inhibitors are co-administered with gemfibrozil, concomitant administration of Lipitor with gemfibrozil should be avoided.
- Because it is known that the risk of myopathy during treatment with HMG-CoA reductase inhibitors is increased with concurrent administration of other fibrates, Lipitor should be administered with caution when used concomitantly with other fibrates.
- The risk of skeletal muscle effects may be enhanced when Lipitor is used in combination with niacin; a reduction in Lipitor dosage should be considered in this setting.
Rifampin Or Other Inducers Of Cytochrome P450 3A4
- Concomitant administration of Lipitor with inducers of cytochrome P450 3A4 (e.g., efavirenz, rifampin) can lead to variable reductionsin plasma concentrations of atorvastatin.
- Due to the dual interaction mechanism of rifampin, simultaneous co-administration of Lipitor with rifampin is recommended, as delayed administration of Lipitor after administration of rifampin has been associated with a significant reduction in atorvastatin plasma concentrations.
- When multiple doses of Lipitor and digoxin were co-administered, steady state plasma digoxin concentrations increased.
- Patients takingdigoxin should be monitored appropriately.
- Co-administration of Lipitor and an oral contraceptive increased AUC values for norethindrone and ethinyl estradiol.
- These increases should be considered when selecting an oral contraceptive for a woman taking Lipitor.
- Lipitor had no clinically significant effect onprothrombin time when administered to patients receiving chronic warfarin treatment.
- Cases of myopathy, including rhabdomyolysis, have been reported withatorvastatin co-administered with colchicine, and caution should be exercised when prescribing atorvastatin with colchicine.
Lipitor (atorvastatin) is an HMG-CoA reductase inhibitor (a “statin”) that lowers the level of cholesterol in the blood and is used to treat elevated total cholesterol, LDL, and triglycerides, and to elevate HDL cholesterol. Common side effects of Lipitor include constipation, diarrhea, fatigue, gas, heartburn, headache, common cold, joint pain, pain in extremities, and urinary tract infection (UTI). Lipitor should not be taken during pregnancy because the developing fetus requires cholesterol for development, and Lipitor reduces the production of cholesterol. It is unknown if Lipitor is secreted in breast milk.
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HDL (high-density lipoprotein), or the "good" cholesterol, and LDL (low-density lipoprotein), or the "bad" cholesterol, are lipoproteins that carry cholesterol through the veins and arteries of the body. HDL and LDL combined, is your "total" blood cholesterol. The difference between the two are that high levels of the "good," or HDL cholesterol, may protect against narrowing of the blood vessels in the body, which protects you against heart attack, stroke, and other cardiovascular diseases. But high levels of LDL, or the "bad" cholesterol, may worsen the narrowing of the blood vessels in the body, which puts you at a greater risk of stroke, heart attack, and cardiovascular diseases, some of which are life threatening.Triglycerides are found in body fat and from the fats you eat.
Low Cholesterol Diet
Cholesterol is naturally produced by the body, and is a building block for cell membranes and hormones. Low-density lipoprotein (LDL) cholesterol is the "bad" cholesterol, and high-density lipoprotein (HDL) cholesterol is the "good" cholesterol. High levels of LDL and low levels of HDL cholesterol put a person at risk for heart attack, stroke, transient ischemic attack (TIA or mini stroke), and peripheral artery disease. High cholesterol can be lowered by eating foods that lower cholesterol, for example, eat more high soluble fiber foods (oatmeal, oat bran, vegetables, and certain fruits), use olive oil, eat foods fortified with plant sterols and stanols, soy, nuts, and omega-3 fatty acids. Foods that raise LDL or bad cholesterol include foods high in saturated and trans fats, fatty meats, limit egg yolks, limit milk products, limit crackers, muffins, and snacks, and avoid unhealthy fast foods that are high in fat and sugar High cholesterol treatment includes lifestyle changes (diet and exercise), and medications such as statins, bile acid resins, and fibric acid derivatives.
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Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.