ADVERSE REACTIONS
LIPITOR is generally well-tolerated. Adverse reactions have usually been mild and transient. In controlled clinical studies of 2502 patients, <2% of patients were discontinued due to adverse experiences attributable to atorvastatin. The most frequent adverse events thought to be related to atorvastatin were constipation, flatulence, dyspepsia, and abdominal pain.
Clinical Adverse Experiences
Adverse experiences reported in ≥2% of patients in placebo-controlled clinical studies of atorvastatin, regardless of causality assessment, are shown in Table 8.
TABLE 8. Adverse Events in Placebo-Controlled Studies (% of Patients) | BODY SYSTEM/Adverse Event | Placebo
N = 270 | Atorvastatin
10 mg
N = 863 | Atorvastatin
20 mg
N = 36 | Atorvastatin
40 mg
N = 79 | Atorvastatin
80 mg
N = 94 |
|---|
| BODY AS A WHOLE | | | | | |
| Infection | 10.0 | 10.3 | 2.8 | 10.1 | 7.4 |
| Headache | 7.0 | 5.4 | 16.7 | 2.5 | 6.4 |
| Accidental Injury | 3.7 | 4.2 | 0.0 | 1.3 | 3.2 |
| Flu Syndrome | 1.9 | 2.2 | 0.0 | 2.5 | 3.2 |
| Abdominal Pain | 0.7 | 2.8 | 0.0 | 3.8 | 2.1 |
| Back Pain | 3.0 | 2.8 | 0.0 | 3.8 | 1.1 |
| Allergic Reaction | 2.6 | 0.9 | 2.8 | 1.3 | 0.0 |
| Asthenia | 1.9 | 2.2 | 0.0 | 3.8 | 0.0 |
| | | | | | |
| DIGESTIVE SYSTEM | | | | | |
| Constipation | 1.8 | 2.1 | 0.0 | 2.5 | 1.1 |
| Diarrhea | 1.5 | 2.7 | 0.0 | 3.8 | 5.3 |
| Dyspepsia | 4.1 | 2.3 | 2.8 | 1.3 | 2.1 |
| Flatulence | 3.3 | 2.1 | 2.8 | 1.3 | 1.1 |
| | | | | | |
| RESPIRATORY SYSTEM | | | | |
| Sinusitis | 2.6 | 2.8 | 0.0 | 2.5 | 6.4 |
| Pharyngitis | 1.5 | 2.5 | 0.0 | 1.3 | 2.1 |
| | | | | | |
| SKIN AND APPENDAGES | | | | |
| Rash | 0.7 | 3.9 | 2.8 | 3.8 | 1.1 |
| | | | | | |
| MUSCULOSKELETAL SYSTEM | | | | |
| Arthralgia | 1.5 | 2.0 | 0.0 | 5.1 | 0.0 |
| Myalgia | 1.1 | 3.2 | 5.6 | 1.3 | 0.0 |
Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)
In ASCOT (see CLINICAL PHARMACOLOGY, Clinical Studies) involving 10,305 participants 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 PHARMACOLOGY, Clinical Studies) involving 2838 subjects with type 2 diabetes treated with LIPITOR 10 mg daily (n=1428) or placebo (n=1410), there was no difference in the overall frequency of adverse events or serious adverse events 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 PHARMACOLOGY, Clinical Studies) involving 10,001 subjects with clinically evident CHD treated with LIPITOR 10 mg daily (n=5006) or LIPITOR 80 mg daily (n=4995), there were more serious adverse events and discontinuations due to adverse events 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 PHARMACOLOGY, Clinical Studies) involving 8,888 subjects 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 events or serious adverse events between the treatment groups during a median follow-up of 4.8 years.
The following adverse events were reported, regardless of causality assessment in patients treated with atorvastatin in clinical trials. The events in italics occurred in ≥2% of patients and the events in plain type occurred in <2% of patients.
Body as a Whole: Chest pain, face edema, fever, neck rigidity, malaise, photosensitivity reaction, generalized edema.
Digestive System: Nausea, gastroenteritis, liver function tests abnormal, colitis, vomiting, gastritis, dry mouth, rectal hemorrhage, esophagitis, eructation, glossitis, mouth ulceration, anorexia, increased appetite, stomatitis, biliary pain, cheilitis, duodenal ulcer, dysphagia, enteritis, melena, gum hemorrhage, stomach ulcer, tenesmus, ulcerative stomatitis, hepatitis, pancreatitis, cholestatic jaundice.
Respiratory System: Bronchitis, rhinitis, pneumonia, dyspnea, asthma, epistaxis.
Nervous System: Insomnia, dizziness, paresthesia, somnolence, amnesia, abnormal dreams, libido decreased, emotional lability, incoordination, peripheral neuropathy, torticollis, facial paralysis, hyperkinesia, depression, hypesthesia, hypertonia.
Musculoskeletal System: Arthritis, leg cramps, bursitis, tenosynovitis, myasthenia, tendinous contracture, myositis.
Skin and Appendages: Pruritus, contact dermatitis, alopecia, dry skin, sweating, acne, urticaria, eczema, seborrhea, skin ulcer.
Urogenital System: Urinary tract infection, hematuria, albuminuria, urinary frequency, cystitis, impotence, dysuria, kidney calculus, nocturia, epididymitis, fibrocystic breast, vaginal hemorrhage, breast enlargement, metrorrhagia, nephritis, urinary incontinence, urinary retention, urinary urgency, abnormal ejaculation, uterine hemorrhage.
Special Senses: Amblyopia, tinnitus, dry eyes, refraction disorder, eye hemorrhage, deafness, glaucoma, parosmia, taste loss, taste perversion.
Cardiovascular System: Palpitation, vasodilatation, syncope, migraine, postural hypotension, phlebitis, arrhythmia, angina pectoris, hypertension.
Metabolic and Nutritional Disorders: Peripheral edema, hyperglycemia, creatine phosphokinase increased, gout, weight gain, hypoglycemia.
Hemic and Lymphatic System: Ecchymosis, anemia, lymphadenopathy, thrombocytopenia, petechia.
Postintroduction Reports
Adverse events 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, and hepatic failure.
Pediatric Patients (ages 10–17 years)
In a 26-week controlled study in boys and postmenarchal girls (n=140), the safety and tolerability profile of LIPITOR 10 to 20 mg daily was generally similar to that of placebo (see CLINICAL PHARMACOLOGY, Clinical Studies section and PRECAUTIONS, Pediatric Use).
|
