Medical Editor: John P. Cunha, DO, FACOEP
What Is Lipitor?
What Are Side Effects of Lipitor?
Side effects of Lipitor include:
Contact your doctor if you experience serious side effects of Lipitor including:
- muscle wasting and muscle breakdown (rhabdomyolysis),
- confusion or memory problems,
- dark urine,
- increased thirst or hunger,
- loss of appetite, or
- yellowing of the skin or eyes (jaundice).
Dosage for Lipitor
The recommended dose of Lipitor is 10-80 mg daily.
What Drugs, Substances, or Supplements Interact with Lipitor?
Erythromycin (E-Mycin), ketoconazole (Nizoral), itraconazole (Sporanox), cyclosporine (Sandimmune), indinavir (Crixivan) and ritonavir (Norvir) decrease elimination of Lipitor. Lipitor increases the effect of warfarin (Coumadin) and cholestyramine (Questran) decreases the absorption of Lipitor.
Lipitor During Pregnancy and Breastfeeding
Lipitor should not be taken during pregnancy because the developing fetus requires cholesterol for development, and Lipitor reduces the production of cholesterol. Lipitor passes into breast milk and could harm a nursing baby. Breastfeeding while taking Lipitor is not recommended.
Our Lipitor Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
In rare cases, atorvastatin can cause a condition that results in the breakdown of skeletal muscle tissue, leading to kidney failure. Call your doctor right away if you have unexplained muscle pain, tenderness, or weakness especially if you also have fever, unusual tiredness, and dark colored urine.
Also call your doctor at once if you have:
- muscle weakness in your hips, shoulders, neck, and back;
- trouble lifting your arms, trouble climbing or standing;
- liver problems--upper stomach pain, weakness, tired feeling, loss of appetite, dark urine, jaundice (yellowing of the skin or eyes); or
- kidney problems--little or no urinating, swelling in your feet or ankles, feeling tired or short of breath.
Common side effects may include:
- joint pain;
- stuffy nose, sore throat;
- diarrhea; or
- pain in your arms or legs.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Read the entire detailed patient monograph for Lipitor (Atorvastatin Calcium)
The following serious adverse reactions are discussed in greater detail in other sections of the label:
- Myopathy and Rhabdomyolysis [see WARNINGS AND PRECAUTIONS]
- Liver enzyme abnormalities [see WARNINGS AND PRECAUTIONS]
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 practice.
In the LIPITOR placebo-controlled clinical trial database of 16,066 patients (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 patients treated 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 2 summarizes the frequency of clinical adverse 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 2: 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 [see Clinical Studies] 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 [see Clinical Studies] 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 [see Clinical Studies] 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 LIPITOR 10 mg daily (n=5006) or LIPITOR 80 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 (≥3 x ULN twice within 4-10 days) occurred in 62 (1.3%) individuals with atorvastatin 80 mg and in nine (0.2%) individuals with atorvastatin 10 mg. Elevations of CK (≥ 10 x 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 [see Clinical Studies ] 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 LIPITOR 80 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 (≥ 3 x ULN twice within 4-10 days) 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 [see WARNINGS AND PRECAUTIONS].
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 (17 LIPITOR vs. 18 placebo). 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 80 mg/day group vs. 211 (8.9%) in the placebo group. The proportions of subjects who experienced cardiovascular death were numerically smaller in the LIPITOR 80 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 LIPITOR 80 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 10 years to 17 years) (n=140, 31% female; 92% Caucasians, 1.6% Blacks, 1.6% Asians, 4.8% other), the safety and tolerability profile of LIPITOR 10 to 20 mg daily, as an adjunct to diet to reduce total cholesterol, LDL-C, and apo B levels, was generally similar to that of placebo [see Use In Special Populations and Clinical Studies].
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 not listed above, regardless of causality assessment, include the following: anaphylaxis, angioneurotic edema, bullous rashes (including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis), rhabdomyolysis, myositis, fatigue, tendon rupture, fatal and non-fatal hepatic failure, dizziness, depression, peripheral neuropathy, pancreatitis and interstitial lung disease.
There have been rare reports of immune-mediated necrotizing myopathy associated with statin use [see WARNINGS AND PRECAUTIONS].
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 are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).
Drug Interactions That May Increase The Risk Of Myopathy And Rhabdomyolysis With LIPITOR
LIPITOR is a substrate of CYP3A4 and transporters (e.g., OATP1B1/1B3, P-gp, or BCRP). LIPITOR plasma levels can be significantly increased with concomitant administration of inhibitors of CYP3A4 and transporters. Table 3 includes a list of drugs that may increase exposure to Lipitor and may increase the risk of myopathy and rhabdomyolysis when used concomitantly and instructions for preventing or managing them [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].
Table 3: Drug Interactions that may Increase the Risk of Myopathy and Rhabdomyolysis with LIPITOR
|Cyclosporine or Gemfibrozil|
|Clinical Impact:||Atorvastatin plasma levels were significantly increased with concomitant administration of LIPITOR and cyclosporine, an inhibitor of CYP3A4 and OATP1B1 [see CLINICAL PHARMACOLOGY]. Gemfibrozil may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of cyclosporine or gemfibrozil with LIPITOR.|
|Intervention:||Concomitant use of cyclosporine or gemfibrozil with LIPITOR is not recommended.|
|Clinical Impact:||Atorvastatin plasma levels were significantly increased with concomitant administration of LIPITOR with many anti-viral medications, which are inhibitors of C YP3A4 and/or transporters (e.g., BCRP, OATP1B1/1B3, P-gp, MRP2, and/or OAT2) [see CLINICAL PHARMACOLOGY]. Cases of myopathy and rhabdomyolysis have been reported with concomitant use of ledipasvir plus sofosbuvir with LIPITOR.|
|Intervention:||1. Concomitant use of tipranavir plus ritonavir or glecaprevir plus pibrentasvir with LIPITOR is not recommended.
2. In patients taking lopinavir plus ritonavir, or simeprevir, consider the risk/benefit of concomitant use with atorvastatin.
3. In patients taking saquinavir plus ritonavir, daranavir plus ritonavir, fosamprenavir, fosamprenavir plus ritonavir, elbasvir plus grazoprevir or letermovir, do not exceed LIPITOR 20 mg.
4. In patients taking nelfmavir, do not exceed LIPITOR 40 mg [see DOSAGE AND ADMINISTRATION].
5. Consider the risk/benefit of concomitant use of ledipasvir plus sofosbuvir with LIPITOR.
6. Monitor all patients for signs and symptoms of myopathy particularly during initiation of therapy and during upward dose titration of either drug.
|Examples:||Tipranavir plus ritonavir, glecaprevir plus pibrentasvir, lopinavir plus ritonavir, simeprevir, saquinavir plus ritonavir, daranavir plus ritonavir, fosamprenavir, fosamprenavir plus ritonavir, elbasvir plus grazoprevir, letermovir, nelfmavir, and ledipasvir plus sofosbuvir.|
|Select Azole Antifungals or Macrolide Antibiotics|
|Clinical Impact:||Atorvastatin plasma levels were significantly increased with concomitant administration of LIPITOR with select azole antifungals or macrolide antibiotics, due to inhibition of C YP3A4 and/or transporters [see CLINICAL PHARMACOLOGY].|
|Intervention:||In patients taking clarithromycin or itraconazole, do not exceed LIPITOR 20 mg [see DOSAGE AND ADMINISTRATION]. Consider the risk/benefit of concomitant use of other azole antifungals or macrolide antibiotics with LIPITOR. Monitor all patients for signs and symptoms of myopathy particularly during initiation of therapy and during upward dose titration of either drug.|
|Examples:||Erythromycin, clarithromycin, itraconazole, ketoconazole, posaconazole, and voriconazole.|
|Clinical Impact:||Cases of myopathy and rhabdomyolysis have been observed with concomitant use of lipid modifying dosages of niacin (≥1 gram/day niacin) with LIPITOR.|
|Intervention:||Consider if the benefit of using lipid modifying dosages of niacin concomitantly with LIPITOR outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitor patients for signs and symptoms of myopathy particularly during initiation of therapy and during upward dose titration of either drag.|
|Fibrates (other than Gemfibrozil)|
|Clinical Impact:||Fibrates may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of fibrates with LIPITOR.|
|Intervention:||Consider if the benefit of using fibrates concomitantly with LIPITOR outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitor patients for signs and symptoms of myopathy particularly during initiation of therapy and during upward dose titration of either drag.|
|Clinical Impact:||Cases of myopathy and rhabdomyolysis have been reported with concomitant use of colchicine with LIPITOR.|
|Intervention:||Consider the risk/benefit of concomitant use of colchicine with LIPITOR. If concomitant use is decided, monitor patients for signs and symptoms of myopathy particularly during initiation of therapy and during upward dose titration of either drug.|
|Clinical Impact:||Grapefruit juice consumption, especially excessive consumption, more than 1.2 liters/daily, can raise the plasma levels of atorvastatin and may increase the risk of myopathy and rhabdomyolysis.|
|Intervention:||Avoid intake of large quantities of grapefruit juice, more than 1.2 liters daily, when taking LIPITOR.|
Drug Interactions That May Decrease Exposure To LIPITOR
Table 4 presents drug interactions that may decrease exposure to LIPITOR and instructions for preventing or managing them.
Table 4: Drug Interactions that may Decrease Exposure to LIPITOR
|Clinical Impact:||Concomitant administration of LIPITOR with rifampin, an inducer of cytochrome P450 3A4 and inhibitor of OATP1B1, can lead to variable reductions in plasma concentrations of atorvastatin. Due to the dual interaction mechanism of rifampin, delayed administration of LIPITOR after administration of rifampin has been associated with a significant reduction in atorvastatin plasma concentrations.|
|Intervention:||Administer LIPITOR and rifampin simultaneously.|
LIPITOR Effects On Other Drugs
Table 5 presents LIPITOR's effect on other drugs and instructions for preventing or managing them.
Table 5: LIPITOR Effects on Other Drugs
|Clinical Impact:||Co-administration of LIPITOR and an oral contraceptive increased plasma concentrations of norethindrone and ethinyl estradiol [see CLINICAL PHARMACOLOGY].|
|Intervention:||Consider this when selecting an oral contraceptive for patients taking LIPITOR.|
|Clinical Impact:||When multiple doses of LIPITOR and digoxin were co-administered, steady state plasma digoxin concentrations increased [see CLINICAL PHARMACOLOGY].|
|Intervention:||Monitor patients taking digoxin appropriately.|
Read the entire FDA prescribing information for Lipitor (Atorvastatin Calcium)
© Lipitor Patient Information is supplied by Cerner Multum, Inc. and Lipitor Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.
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