in
Digoxin: When multiple doses of digoxin and 10 mg atorvastatin were coadministered, steady-state digoxin concentrations increased slightly. Patients taking digoxin should be monitored appropriately.
Oral contraceptives: Coadministration of atorvastatin with an oral contraceptive produced increases in plasma concentrations of norethisterone and ethinyl estradiol.
Warfarin: In a clinical study in patients receiving chronic warfarin therapy, coadministration of atorvastatin 80 mg daily with warfarin caused a small decrease of about 1.7 seconds in prothrombin time during the first 4 days of dosing, which returned to normal within 15 days of atorvastatin treatment. Although only very rare cases of clinically significant anticoagulant interactions have been reported, prothrombin time should be determined before starting ATOZET in patients taking coumarin anticoagulants and frequently enough during early therapy to ensure that no significant alteration of prothrombin time occurs. Once a stable prothrombin time has been documented, prothrombin times can be monitored at the intervals usually recommended for patients on coumarin anticoagulants. If the dose of ATOZET is changed or discontinued, the same procedure should be repeated. Atorvastatin therapy has not been associated with bleeding or with changes in prothrombin time in patients not taking anticoagulants.
Table 1
Effect of Coadministered Medicinal Products on the Pharmacokinetics of Atorvastatin
Coadministered Medicinal Product and Dosing Regimen
Atorvastatin
ATOZET
Dose (mg)
Change in AUC&
Clinical Recommendation#
Tipranavir 500 mg BID/ Ritonavir 200 mg BID, 8 days (Days 14 to 21)
40 mg on Day 1, 10 mg on Day 20
↑ 9.4 fold
In cases where coadministration with ATOZET is necessary, do not exceed 10/10 mg ATOZET daily. Clinical monitoring of these patients is recommended
Ciclosporin 5.2 mg/kg/day, stable dose
10 mg OD for 28 days
↑ 8.7 fold
Lopinavir 400 mg BID/ Ritonavir 100 mg BID, 14 days
20 mg OD for 4 days
↑ 5.9 fold
In cases where coadministration with ATOZET is necessary, lower maintenance doses of ATOZET are recommended. At ATOZET doses exceeding 10/20 mg, clinical monitoring of these patients is recommended.
Clarithromycin 500 mg BID, 9 days
80 mg OD for 8 days
↑ 4.4 fold
Saquinavir 400 mg BID/ Ritonavir 300 mg BID from Days 5-7, increased to 400 mg BID on Day 8), Days 5-18, 30 min after atorvastatin dosing
40 mg OD for 4 days
↑ 3.9 fold
In cases where coadministration with ATOZET is necessary, lower maintenance doses of ATOZET are recommended. At ATOZET doses exceeding 10/40 mg, clinical monitoring of these patients is recommended.
Darunavir 300 mg BID/
Ritonavir 100 mg BID, 9 days
10 mg OD for 4 days
↑ 3.3 fold
Itraconazole 200 mg OD, 4 days
40 mg SD
↑ 3.3 fold
Fosamprenavir 700 mg BID/ Ritonavir 100 mg BID, 14 days
10 mg OD for 4 days
↑ 2.5 fold
Fosamprenavir 1400 mg BID, 14 days
10 mg OD for 4 days
↑ 2.3 fold
Nelfinavir 1250 mg BID, 14 days
10 mg OD for 28 days
↑ 1.7 fold^
No specific recommendation.
Grapefruit Juice, 240 mL OD*
40 mg SD
↑ 37%
Concomitant intake of large quantities of grapef |
