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atorvastatin
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(a TOR va sta tin)

Drug Interactions

Atorvastatin is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity.

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: Potential pharmacokinetic interaction (variable increases in plasma atorvastatin concentrations); increased risk of myopathy. Carefully monitor patients for manifestations of unexplained muscle pain, tenderness, or weakness, particularly following initiation of atorvastatin therapy or an increase in dosage of either drug. (See Specific Drugs under Interactions.)

Inducers of CYP3A4: Potential pharmacokinetic interaction (variable reductions in plasma atorvastatin concentrations). (See Specific Drugs under Interactions.)

Specific Drugs

Drug Interaction Comments
Amlodipine Modest increase in atorvastatin exposure Not clinically relevant
Antacids Decreased plasma atorvastatin concentrations
Anticoagulants, oral (e.g., warfarin) Pharmacologic interaction (e.g., increased PT) unlikely
Azole antifungals

Itraconazole: 2.5 to threefold increase in atorvastatin AUC

Increased risk of myopathy

Consider using lower initial and maintenance dosages of atorvastatin
Bile acid sequestrants Decreased plasma atorvastatin concentrations Administer statins ≥1 hour before or at least 2–4 hours after the resin
Cyclosporine 8.7-fold increase in atorvastatin AUC; increased risk of myopathy and/or rhabdomyolysis

Carefully monitor patients for manifestations of unexplained muscle pain, tenderness, or weakness, particularly following initiation of atorvastatin therapy or an increase in dosage

Atorvastatin dosage should not exceed 10 mg daily

Digoxin Increased plasma digoxin concentrations Monitor appropriately
Diltiazem Increased plasma atorvastatin concentrations
Efavirenz Possible variable reductions in plasma atorvastatin concentrations
Fibric acid derivatives

Increased risk of myopathy

Fenofibrate: Decreased or increased AUC of atorvastatin reported

Concomitant use generally should be avoided; if used concomitantly, initiate atorvastatin at low or moderate dosages and consider using lower maintenance dosages of atorvastatin
Grapefruit juice (particularly >1.2 L daily) Increased bioavailability of atorvastatin
HIV protease inhibitors (combination of ritonavir plus saquinavir, combination of lopinavir plus ritonavir)

Combination of ritonavir plus saquinavir: Threefold increase in atorvastatin AUC and increased risk of myopathy

Combination of lopinavir plus ritonavir: 5.9-fold increase in atorvastatin AUC and increased risk of myopathy

Carefully monitor patients for manifestations of unexplained muscle pain, tenderness, or weakness, particularly following initiation of atorvastatin therapy or an increase in dosage of either drug

Consider using lower initial and maintenance dosages of atorvastatin

In patients receiving the combination of ritonavir and saquinavir, or the combination of lopinavir and ritonavir, use of atorvastatin dosages >20 mg daily requires appropriate clinical assessment to ensure that the lowest effective dosage is employed

Macrolide antibiotics (i.e., clarithromycin, erythromycin)

Clarithromycin: 4.4-fold increase in atorvastatin AUC and increased risk of myopathy

Erythromycin: Increased plasma atorvastatin concentrations and increased risk of myopathy

Carefully monitor patients for manifestations of unexplained muscle pain, tenderness, or weakness, particularly following initiation of atorvastatin therapy and an increase in dosage of either drug

Consider using lower initial and maintenance dosages of atorvastatin

In patients receiving clarithromycin, use of atorvastatin dosages >20 mg daily requires appropriate clinical assessment to ensure that the lowest effective dosage is employed

Niacin (antilipemic dosages) Increased risk of myopathy

Use low dosages of niacin and carefully monitor patients for manifestations of unexplained muscle pain, tenderness, or weakness, particularly following initiation of atorvastatin therapy or an increase in dosage of either drug

Consider using lower initial and maintenance dosages of atorvastatin

Oral contraceptives Increased bioavailability of norethindrone and ethinyl estradiol Caution when selecting an oral contraceptive
Rifampin Possible variable reductions in plasma atorvastatin concentrations Administer simultaneously, because delayed administration of atorvastatin following administration of rifampin associated with substantial reductions in plasma atorvastatin concentrations
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