DRUG INTERACTIONS
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) [see
Warnings and Precautions, Skeletal Muscle (5.1)
and
Clinical Pharmacology
].
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.
Clarithromycin: Atorvastatin AUC was significantly
increased with concomitant administration of LIPITOR 80 mg with clarithromycin
(500 mg twice daily) compared to that of LIPITOR alone [see
Clinical Pharmacology
].
Therefore, in patients taking clarithromycin, caution should be used when the
LIPITOR dose exceeds 20 mg [see
Warnings and
Precautions, Skeletal Muscle
and
Dosage and Administration
]. Combination of Protease Inhibitors: Atorvastatin AUC
was significantly increased with concomitant administration of LIPITOR 40 mg
with ritonavir plus saquinavir (400 mg twice daily) or LIPITOR 20 mg with
lopinavir plus ritonavir (400 mg + 100 mg twice daily) compared to that of
LIPITOR alone [see
Clinical Pharmacology
]. Therefore, in patients taking HIV protease inhibitors,
caution should be used when the LIPITOR dose exceeds 20 mg [see
Warnings and Precautions, Skeletal Muscle
and
Dosage and
Administration
]. Itraconazole: Atorvastatin AUC was significantly
increased with concomitant administration of LIPITOR 40 mg and itraconazole 200
mg [see
Clinical Pharmacology
]. Therefore, in patients taking itraconazole, caution should
be used when the LIPITOR dose exceeds 20 mg [see
Warnings and Precautions, Skeletal Muscle
and
Dosage and Administration
].
Grapefruit Juice
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).
Cyclosporine
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 [see
Clinical Pharmacology
]. In cases where
co-administration of LIPITOR with cyclosporine is necessary, the dose of LIPITOR
should not exceed 10 mg [see
Warnings and
Precautions, Skeletal Muscle
].
Rifamprin or other Induceder of Cytochrome P450 3A4
Concomitant administration of LIPITOR with inducers of cytochrome
P450 3A4 (e.g., efavirenz, rifampin) can lead to variable reductions in 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.
Digoxin
When multiple doses of LIPITOR and digoxin were coadministered,
steady state plasma digoxin concentrations increased by approximately 20%.
Patients taking digoxin should be monitored appropriately.
Oral Contraceptives
Co-administration of LIPITOR and an oral contraceptive increased
AUC values for norethindrone and ethinyl estradiol [see
Clinical Pharmacology
]. These increases should
be considered when selecting an oral contraceptive for a woman taking
LIPITOR.
Warfarin
LIPITOR had no clinically significant effect on prothrombin time
when administered to patients receiving chronic warfarin treatment.
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