The risk of myopathy during treatment with drugs of this class is increased with concurrent administration of
cyclosporine, fibric acid derivatives, niacin (nicotinic acid), erythromycin, azole antifungals.
Antacid: When atorvastatin and MaaloxÒ TC suspension were coadministered,
plasma concentrations of atorvastatin decreased approximately 35%. However, LDL-C reduction was not altered.
Antipyrine: Because atorvastatin does not affect the pharmacokinetics of antipyrine, interactions with
other drugs metabolized via the same cytochrome isozymes are not expected.
Colestipol: Plasma concentrations of atorvastatin decreased approximately 25% when colestipol and
atorvastatin were coadministered. However, LDL-C reduction was greater when atorvastatin and colestipol were
coadministered than when either drug was given alone.
Cimetidine: Lipitor plasma concentrations and LDL-C reduction were not altered by coadministration of
Digoxin: When multiple doses of atorvastatin and digoxin were coadministered, steady-state plasma digoxin
concentrations increased by approximately 20%. Patients taking digoxin should be monitored appropriately.
Erythromycin: In healthy individuals, plasma concentrations of atorvastatin increased approximately 40%
with coadministration of atorvastatin and erythromycin, a known inhibitor of cytochrome P450 3A4.
Oral Contraceptives: Coadministration of atorvastatin and an oral contraceptive increased AUC values for
norethindrone and ethinyl estradiol by approximately 30% and 20%. These increases should be considered when selecting
an oral contraceptive for a woman taking atorvastatin.
Warfarin: Lipitor had no clinically significant effect on prothrombin time when administered to
patients receiving chronic warfarin treatment.
HMG-CoA reductase inhibitors interfere with cholesterol synthesis and theoretically might blunt adrenal and/or
gonadal steroid production. Clinical studies have shown that atorvastatin does not reduce basal plasma cortisol
concentration or impair adrenal reserve. The effects of HMG-CoA reductase inhibitors on male fertility have not been
studied in adequate numbers of patients. The effects, if any, on the pituitary-gonadal axis in premenopausal women
are unknown. Caution should be exercised if an HMG-CoA reductase inhibitor is administered concomitantly with drugs
that may decrease the levels or activity of endogenous steroid hormones, such as ketoconazole, spironolactone, and
Brain hemorrhage was seen in a female dog treated for 3 months at 120 mg/kg/day. Brain hemorrhage and optic nerve
vacuolation were seen in another female dog that was sacrificed in moribund condition after 11 weeks of escalating
doses up to 280 mg/kg/day. The 120 mg/kg dose resulted in a systemic exposure approximately 16 times the human plasma
area-under-the-curve (AUC, 0-24 hours) based on the maximum human dose of 80 mg/day. A single tonic convulsion was
seen in each of 2 male dogs (one treated at 10 mg/kg/day and one at 120 mg/kg/day) in a 2-year study. No CNS lesions
have been observed in mice after chronic treatment for up to 2 years at doses up to 400 mg/kg/day or in rats at doses
up to 100 mg/kg/day. These doses were 6 to 11 times (mouse) and 8 to 16 times (rat) the human AUC (0-24) based on the
maximum recommended human dose of 80 mg/day.
CNS vascular lesions, characterized by perivascular hemorrhages, edema, and mononuclear cell infiltration of
perivascular spaces, have been observed in dogs treated with other members of this class. A chemically similar drug
in this class produced optic nerve degeneration (Wallerian degeneration of retinogeniculate fibers) in clinically
normal dogs in a dose-dependent fashion at a dose that produced plasma drug levels about 30 times higher than the
mean drug level in humans taking the highest recommended dose.