Atorvastatin drug interactions: Difference between revisions

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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 inhibitor]]s, and [[itraconazole]]) [see Warnings and Precautions, Skeletal Muscle (5.1) and Clinical Pharmacology (12.3)].
====Strong Inhibitors of CYP 3A4====
Atorvastatin is metabolized by cytochrome P450 3A4. Concomitant administration of Atorvastatin 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 Atorvastatin 80 mg with [[clarithromycin]] (500 mg twice daily) compared to that of Atorvastatin alone [see Clinical Pharmacology (12.3)]. Therefore, in patients taking [[clarithromycin]], caution should be used when the Atorvastatin dose exceeds 20 mg [see Warnings and Precautions, Skeletal Muscle (5.1) and Dosage and Administration (2.6)].
====Combination of Protease Inhibitors====
Atorvastatin AUC was significantly increased with concomitant administration of Atorvastatin with several combinations of HIV protease inhibitors, as well as with the hepatitis C protease inhibitor telaprevir, compared to that of Atorvastatin alone [see Clinical Pharmacology (12.3)]. Therefore, in patients taking the [[HIV protease inhibitor]] [[tipranavir]] plus [[ritonavir]], or the [[hepatitis C]] protease inhibitor [[telaprevir]], concomitant use of Atorvastatin should be avoided. In patients taking the [[HIV protease inhibitor]] [[lopinavi]]r plus [[ritonavir]], caution should be used when prescribing Atorvastatin and the lowest dose necessary should be used. In patients taking the [[HIV protease inhibitors]] [[saquinavir]] plus [[ritonavir]], [[darunavi]]r plus [[ritonavir]], [[fosamprenavir]], or [[fosamprenavir]] plus ritonavir, the dose of Atorvastatin should not exceed 20 mg and should be used with caution [see Warnings and Precautions, Skeletal Muscle (5.1) and Dosage and Administration (2.6)]. In patients taking the HIV protease inhibitor [[nelfinavir]] or the [[hepatitis C]] protease inhibitor [[boceprevir]], the dose of Atorvastatin should not exceed 40 mg and close clinical monitoring is recommended.
====[[Itraconazole]]====
Atorvastatin AUC was significantly increased with concomitant administration of Atorvastatin 40 mg and [[itraconazole]] 200 mg [see Clinical Pharmacology (12.3)]. Therefore, in patients taking [[itraconazole]], caution should be used when the Atorvastatin dose exceeds 20 mg [see Warnings and Precautions, Skeletal Muscle (5.1) and Dosage and Administration (2.6)].
====[[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 Atorvastatin 10 mg and [[cyclosporine]] 5.2 mg/kg/day compared to that of Atorvastatin alone [see Clinical Pharmacology (12.3)]. The co-administration of Atorvastatin with cyclosporine should be avoided [see Warnings and Precautions, Skeletal Muscle (5.1)].
====[[Gemfibrozil]]====
Due to an increased risk of myopathy/rhabdomyolysis when [[HMG-CoA reductase]] inhibitors are co-administered with gemfibrozil, concomitant administration of Atorvastatin with [[gemfibrozil]] should be avoided [see Warnings and Precautions (5.1)].
====Other [[Fibrates]]====
Because it is known that the risk of [[myopathy]] during treatment with [[HMG-CoA reductase]] inhibitors is increased with concurrent administration of other fibrates, Atorvastatin should be administered with caution when used concomitantly with other fibrates [see Warnings and Precautions (5.1)].
====[[Niacin]]====
The risk of skeletal muscle effects may be enhanced when Atorvastatin is used in combination with niacin; a reduction in Atorvastatin dosage should be considered in this setting [see Warnings and Precautions (5.1)].
====[[Rifampin]] or other Inducers of Cytochrome P450 3A4====
Concomitant administration of Atorvastatin 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 Atorvastatin with rifampin is recommended, as delayed administration of Atorvastatin after administration of rifampin has been associated with a significant reduction in atorvastatin plasma concentrations.
====[[Digoxin]]====
When multiple doses of Atorvastatin and [[digoxin]] were co-administered, steady state plasma digoxin concentrations increased by approximately 20%. Patients taking digoxin should be monitored appropriately.
==== [[Oral Contraceptive]]s====
Co-administration of Atorvastatin and an oral contraceptive increased AUC values for norethindrone and [[ethinyl estradiol]] [see Clinical Pharmacology (12.3)]. These increases should be considered when selecting an oral contraceptive for a woman taking Atorvastatin.
====[[Warfarin]]====
Atorvastatin had no clinically significant effect on [[prothrombin time]] when administered to patients receiving chronic warfarin treatment.
====[[Colchicine]]====
Cases of [[myopathy]], including [[rhabdomyolysis]], have been reported with atorvastatin co-administered with [[colchicine]], and caution should be exercised when prescribing atorvastatin with [[colchicine]].


==Major Interactions==
==Major Interactions==

Revision as of 18:03, 30 January 2014

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


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 (12.3)].

Strong Inhibitors of CYP 3A4

Atorvastatin is metabolized by cytochrome P450 3A4. Concomitant administration of Atorvastatin 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 Atorvastatin 80 mg with clarithromycin (500 mg twice daily) compared to that of Atorvastatin alone [see Clinical Pharmacology (12.3)]. Therefore, in patients taking clarithromycin, caution should be used when the Atorvastatin dose exceeds 20 mg [see Warnings and Precautions, Skeletal Muscle (5.1) and Dosage and Administration (2.6)].

Combination of Protease Inhibitors

Atorvastatin AUC was significantly increased with concomitant administration of Atorvastatin with several combinations of HIV protease inhibitors, as well as with the hepatitis C protease inhibitor telaprevir, compared to that of Atorvastatin alone [see Clinical Pharmacology (12.3)]. Therefore, in patients taking the HIV protease inhibitor tipranavir plus ritonavir, or the hepatitis C protease inhibitor telaprevir, concomitant use of Atorvastatin should be avoided. In patients taking the HIV protease inhibitor lopinavir plus ritonavir, caution should be used when prescribing Atorvastatin and the lowest dose necessary should be used. In patients taking the HIV protease inhibitors saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, or fosamprenavir plus ritonavir, the dose of Atorvastatin should not exceed 20 mg and should be used with caution [see Warnings and Precautions, Skeletal Muscle (5.1) and Dosage and Administration (2.6)]. In patients taking the HIV protease inhibitor nelfinavir or the hepatitis C protease inhibitor boceprevir, the dose of Atorvastatin should not exceed 40 mg and close clinical monitoring is recommended.

Itraconazole

Atorvastatin AUC was significantly increased with concomitant administration of Atorvastatin 40 mg and itraconazole 200 mg [see Clinical Pharmacology (12.3)]. Therefore, in patients taking itraconazole, caution should be used when the Atorvastatin dose exceeds 20 mg [see Warnings and Precautions, Skeletal Muscle (5.1) and Dosage and Administration (2.6)].

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 Atorvastatin 10 mg and cyclosporine 5.2 mg/kg/day compared to that of Atorvastatin alone [see Clinical Pharmacology (12.3)]. The co-administration of Atorvastatin with cyclosporine should be avoided [see Warnings and Precautions, Skeletal Muscle (5.1)].

Gemfibrozil

Due to an increased risk of myopathy/rhabdomyolysis when HMG-CoA reductase inhibitors are co-administered with gemfibrozil, concomitant administration of Atorvastatin with gemfibrozil should be avoided [see Warnings and Precautions (5.1)].

Other Fibrates

Because it is known that the risk of myopathy during treatment with HMG-CoA reductase inhibitors is increased with concurrent administration of other fibrates, Atorvastatin should be administered with caution when used concomitantly with other fibrates [see Warnings and Precautions (5.1)].

Niacin

The risk of skeletal muscle effects may be enhanced when Atorvastatin is used in combination with niacin; a reduction in Atorvastatin dosage should be considered in this setting [see Warnings and Precautions (5.1)].

Rifampin or other Inducers of Cytochrome P450 3A4

Concomitant administration of Atorvastatin 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 Atorvastatin with rifampin is recommended, as delayed administration of Atorvastatin after administration of rifampin has been associated with a significant reduction in atorvastatin plasma concentrations.

Digoxin

When multiple doses of Atorvastatin and digoxin were co-administered, steady state plasma digoxin concentrations increased by approximately 20%. Patients taking digoxin should be monitored appropriately.

Oral Contraceptives

Co-administration of Atorvastatin and an oral contraceptive increased AUC values for norethindrone and ethinyl estradiol [see Clinical Pharmacology (12.3)]. These increases should be considered when selecting an oral contraceptive for a woman taking Atorvastatin.

Warfarin

Atorvastatin had no clinically significant effect on prothrombin time when administered to patients receiving chronic warfarin treatment.

Colchicine

Cases of myopathy, including rhabdomyolysis, have been reported with atorvastatin co-administered with colchicine, and caution should be exercised when prescribing atorvastatin with colchicine.

Major Interactions

Moderate Interactions

Minor Interactions



Adapted from the FDA Package Insert.

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