Lipitor Side Effects
Generic Name: atorvastatin
Please note - some side effects for Lipitor may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.
Side Effects of Lipitor - for the Consumer
Lipitor
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Lipitor:
Seek medical attention right away if any of these SEVERE side effects occur when using Lipitor:Diarrhea; joint pain; mild sore throat; nausea; runny or stuffy nose; stomach upset.
Severe allergic reactions (rash; hives; itching; difficulty breathing or swallowing; tightness in the chest; swelling of the mouth, face, lips, throat, or tongue); change in the amount of urine produced; dark urine; muscle pain, tenderness, or weakness (with or without fever or fatigue); painful, difficult, or frequent urination; pale stools; persistent loss of appetite; persistent pain, soreness, redness, or swelling of a tendon or joint; red, swollen, blistered, or peeling skin; severe or persistent nausea, vomiting, or stomach pain; unusual tiredness; yellowing of the eyes or skin.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
TopLipitor Side Effects - for the Professional
Lipitor
The following serious adverse reactions are discussed in greater detail in other sections of the label:
Rhabdomyolysis and myopathy [see Warnings and Precautions (5.1)]
Liver enzyme abnormalities [see Warnings and Precautions (5.2)]
Clinical Trial Adverse Experiences
Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical studies 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 16,066 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.
| Adverse Reaction* | Any dose N=8755 |
10 mg N=3908 |
20 mg N=188 |
40 mg N=604 |
80 mg N=4055 |
Placebo N=7311 |
|---|---|---|---|---|---|---|
|
||||||
| Nasopharyngitis | 8.3 | 12.9 | 5.3 | 7.0 | 4.2 | 8.2 |
| Arthralgia | 6.9 | 8.9 | 11.7 | 10.6 | 4.3 | 6.5 |
| Diarrhea | 6.8 | 7.3 | 6.4 | 14.1 | 5.2 | 6.3 |
| 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 |
| Dyspepsia | 4.7 | 5.9 | 3.2 | 6.0 | 3.3 | 4.3 |
| Nausea | 4.0 | 3.7 | 3.7 | 7.1 | 3.8 | 3.5 |
| Musculoskeletal pain | 3.8 | 5.2 | 3.2 | 5.1 | 2.3 | 3.6 |
| Muscle Spasms | 3.6 | 4.6 | 4.8 | 5.1 | 2.4 | 3.0 |
| Myalgia | 3.5 | 3.6 | 5.9 | 8.4 | 2.7 | 3.1 |
| Insomnia | 3.0 | 2.8 | 1.1 | 5.3 | 2.8 | 2.9 |
| Pharyngolaryngeal pain | 2.3 | 3.9 | 1.6 | 2.8 | 0.7 | 2.1 |
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 (14.1)] 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 (14.1)] 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 (14.1)] 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 × 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 × 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 (14.1)] 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 × ULN twice within 4–10 days) in the atorvastatin group (0.9%) compared to placebo (0.1%). Elevations of CK (>10 × 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 (5.5)].
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%).
Postmarketing Experience
The following adverse reactions have been identified during postapproval 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, fatigue, tendon rupture, fatal and non-fatal hepatic failure, dizziness, depression, peripheral neuropathy, and pancreatitis.
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).
Pediatric Patients (ages 10–17 years)
In a 26-week controlled study in boys and postmenarchal girls (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 was generally similar to that of placebo [see Clinical Studies (14.6) and Use in Special Populations, Pediatric Use (8.4)].
Side Effects by Body System - for Healthcare Professionals
General
In general, atorvastatin has been well tolerated. Less than 2% of patients in premarketing clinical studies discontinued treatment due to adverse effects.
Gastrointestinal
Gastrointestinal side effects have been the most commonly reported. These have been reported in less than 4% of patients and have included constipation, flatulence, dyspepsia, and abdominal pain. Diarrhea has been reported in up to 5.3% of patients and may be dose-related. Other gastrointestinal side effects observed with HMG-CoA reductase inhibitors have included pancreatitis, anorexia, and vomiting. Most effects tended to be mild and transient.
Hepatic
In clinical trials, liver enzyme elevations returned to pretreatment levels upon discontinuation or dose reduction of atorvastatin. Nawrocki and colleagues reported elevated bilirubin levels in 2/30 patients and elevated AST and ALT levels in 1/30 patients.
Hepatic side effects including altered liver function have been observed with all HMG-CoA reductase inhibitors. In premarketing clinical trials, up to 0.7% of patients experienced persistent, elevated AST and/or ALT values greater than three times the upper normal limits on two or more occasions. Elevations of liver enzymes may be dose-related. Other hepatic side effects of the HMG-CoA class have included hepatitis, cholestatic jaundice, fatty changes in the liver, cirrhosis, fulminant hepatic necrosis, and liver failure.
Musculoskeletal
HMG-CoA reductase inhibitors (statins) have been associated with rare cases of severe myopathy and rhabdomyolysis, accompanied by increases in creatine kinase, myoglobinuria, proteinuria, and renal failure. Concomitant use with gemfibrozil (fibric acid derivatives), niacin, cyclosporine, erythromycin (macrolides) or azole antifungals may increase the incidence and severity of musculoskeletal side effects. Other variables associated with an increased risk of statin-induced myopathy include, advanced age, small body stature, female gender, renal and/or hepatic dysfunction, perioperative periods, hypothyroidism, diabetes mellitus, and alcoholism.
A case of atorvastatin-induced early-onset (after 4 doses) rhabdomyolysis has been reported in a patient with nephrotic syndrome. The authors suggest that the patient's underlying renal dysfunction may have predisposed the patient to rhabdomyolysis.
Musculoskeletal side effects have included uncomplicated myalgia and arthralgia. Milder forms of myotoxicity (i.e., myalgia) are commonly reported and occur in approximately 5% to 7% of patients taking a statin drug. Rhabdomyolysis and myopathy related to HMG-CoA reductase inhibitor use have been reported rarely. One case of atorvastatin-induced dermatomyositis has been reported. Tendon rupture has been reported in postmarketing surveillance.
Hematologic
Hematologic side effects including hemolytic anemia, thrombocytopenia, and leukopenia have occurred with HMG-CoA reductase inhibitors. These effects may be manifestations of a hypersensitivity reaction.
Nervous system
Nervous system side effects of headache and weakness have occurred with HMG-CoA reductase inhibitors. In addition, at least one case of polyneuropathy attributed to atorvastatin use has also been reported. Other nervous system side effects reported with HMG-CoA reductase inhibitors have included dizziness, drowsiness, fatigue, cranial nerve dysfunction, tremor, vertigo, memory loss, decline in cognitive function, paresthesias, peripheral neuropathy, and peripheral nerve palsy.
Renal
Renal side effects including acute renal failure secondary to rhabdomyolysis have been reported with HMG-CoA reductase inhibitors.
Endocrine
Endocrine side effects associated with the use of other HMG-CoA reductase inhibitors have included hypospermia, gynecomastia, and thyroid dysfunction. In addition, acid maltase deficiency (the genetic disorder also referred to as Pompe's Disease) has been revealed following HMG-CoA therapy in at least one presymptomatic patient.
Hypersensitivity
Hypersensitivity reactions have been observed rarely with HMG-CoA reductase inhibitors. Symptoms have included anaphylaxis, angioedema, allergic reaction, urticaria, fever, chills, flushing, malaise and dyspnea. Bullous rashes including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have occurred.
Psychiatric
Psychiatric side effects of HMG-CoA reductase inhibitors have included decreases in libido, anxiety, depression, and insomnia. In addition, nightmares have been associated with atorvastatin use.
Genitourinary
A 77-year-old female with a history of hypercholesterolemia experienced hemorrhagic cystitis coincident with atorvastatin therapy. She presented with gross hematuria of approximately 4 weeks duration. She had been given atorvastatin 5 mg daily approximately 1 week before the onset of her hematuria. Urinalysis showed grossly bloody urine with too-numerous-to-count red cells on microscopic examination. Biopsy of the affected areas of the bladder showed congestion of superficial mucosal vessels and mild infiltration of the epithelium and lamina propria with polymorphonuclear leukocytes and lymphocytes, consistent with benign, acute, and chronic inflammatory process. The patient discontinued atorvastatin therapy but continued with her other medication regimen. Her hematuria resolved within 1 week of discontinuing therapy with atorvastatin. At the insistence of her prescriber, she once again was given atorvastatin, with a rapid recurrence of her hematuria. She once again discontinued atorvastatin, and her hematuria rapidly resolved.
Genitourinary adverse effects associated with other HMG-CoA reductase inhibitors have included erectile dysfunction, impotence, and testicular pain. At least one case of hemorrhagic cystitis has been reported.
Dermatologic
Dermatologic reactions have occurred rarely. In premarketing trials, up to 3.8% of patients complained of a rash. Phototoxicity has been associated with atorvastatin. A case of dermatomyositis has also been reported.
Cardiovascular
Analysis of study data has shown an increased risk of hemorrhagic stroke in patients treated with atorvastatin who had a stroke or TIA within 6 months preceding treatment compared to placebo.
Cardiovascular side effects occurring since market introduction have included angioneurotic edema, peripheral edema, and chest pain. Atorvastatin may also increase the incidence of hemorrhagic stroke in patients with a history of recent stroke or TIA.
Respiratory
Respiratory symptoms reported since market introduction have included bronchitis, rhinitis, pharyngitis, and sinusitis.
Ocular
Ocular side effects including a case of reversible ophthalmoplegia as well as a case of ocular myasthenia have been reported.
A 60-year-old woman with hypercholesterolemia treated with atorvastatin developed painless horizontal diplopia, vertigo, blurry vision, elevated anti-acetylcholine receptor (anti-AchR) antibodies levels, ataxia, and paresthesia of the upper extremities. No other medications were reported. Neurological exam revealed generalized hyperreflexia and finger-nose and gait ataxia. Ptosis was present in both upper eyelids. Discontinuation of atorvastatin resulted in symptom resolution and anti-AchR levels within normal limits.
A 67-year-old women treated for hypercholesterolemia with atorvastatin developed myogenic ptosis and variable incomitant horizontal and vertical strabismus consistent with ocular myasthenia. Following discontinuation of atorvastatin, the patient experienced significant clinical improvement with only mild residual aponeurotic ptosis after 2 months.
Immunologic
Immunologic side effects including a possible case of atorvastatin-induced reversible positive antinuclear antibodies have been reported.
Other
Other side effects reported during clinical trials (in more than 2% of patients) have included infection, accidental injury, flu syndrome, abdominal pain, and back pain. Fatigue and tendon rupture have been reported in postmarketing studies with atorvastatin.
TopMore Lipitor resources
- Lipitor Prescribing Information (FDA)
- Lipitor Monograph (AHFS DI)
- Lipitor Advanced Consumer (Micromedex) - Includes Dosage Information
- Lipitor Consumer Overview
- Lipitor MedFacts Consumer Leaflet (Wolters Kluwer)
- Atorvastatin Prescribing Information (FDA)
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