Atorvast-Natrapharm Drug Interactions

Overview: Pharmacokinetic interaction studies conducted with drugs in healthy subjects may not detect the possibility of a potential drug interaction in some patients due to differences in underlying diseases and use of concomitant medications (see Precautions).
Concomitant Therapy with Other Lipid Metabolism Regulators: Based on post-marketing surveillance, gemfibrozil, fenofibrate, other fibrates and lipid-modifying doses of niacin (nicotinic acid) may increase the risk of myopathy when given concomitantly with HMG-CoA reductase inhibitors, probably because they can produce myopathy when given alone (see Precautions). Therefore, combined drug therapy should be approached with caution; lower starting and maintenance doses of atorvastatin should be considered.
Cytochrome P-450-Mediated Interactions: Atorvastatin is metabolized by the CYP450 isoenzyme, CYP3A4. Erythromycin, a CYP3A4 inhibitor, increased atorvastatin plasma levels by 40%. Co-administration of CYP3A4 inhibitors eg, grapefruit juice, some macrolide antibiotics (ie, erythromycin, clarithromycin), immunosuppressants (cyclosporine), azote antifungal agents (ie, itraconazole, ketoconazole), protease inhibitors or the antidepressant, nefazodone, have the potential to increase plasma concentrations of HMG-CoA reductase inhibitors, including atorvastatin (see Interactions). Concomitant use of strong inhibitors of CYP3A4 with atorvastatin should be used with caution. If such use must be instituted, lower starting and maintenance doses of atorvastatin should be considered and patients should be monitored closely for musculoskeletal effects (see Dosage & Administration and Precautions).
Transporter Inhibitors: Atorvastatin and atorvastatin-metabolites are substrates of the organic anion-transporting polypeptide (OATP1B1) transporter. Inhibitors of the OATP1B1 (eg, cyclosporine) can increase the bioavailability of atorvastatin (see Pharmacology: Pharmacokinetics under Actions).
Inducers of Cytochrome P-450 3A: Concomitant administration of atorvastatin with inducers of CYP3A4 (eg, efavirenz, rifampin) can lead to variable reductions in plasma concentrations of atorvastatin. Due to the dual interaction mechanism of rifampin, (CYP3A4 induction and inhibition of hepatocyte uptake transporter OATP1B1), simultaneous co-administration of atorvastatin with rifampin resulted in a mean increase in C_max and AUC of atorvastatin of 12% and 190%, respectively. In contrast, a delayed administration of atorvastatin after administration of rifampin has been associated with a significant reduction (approximately 80%) in atorvastatin plasma concentrations.
Drug-Drug Interactions: The drugs listed in Table 2a and 2b are based on either drug interactions studies, case reports or potential interactions due to the expected magnitude and seriousness of the interaction (ie, those identified as contraindicated). Interactions with other drugs have not been established. (See Table 2a and 2b.)

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Drug-Food Interactions: Co-administration of grapefruit juice has the potential to increase plasma concentrations of HMG-CoA reductase inhibitors, including atorvastatin. The equivalent of 1.2 L/day resulted in a 2.5-fold increase in AUC of atorvastatin. Consumption of excessive grapefruit juice with atorvastatin is not recommended.
Drug-Herb Interactions: Interactions with herbal products have not been established.
Drug/Laboratory Test Interactions: Atorvastatin may elevate serum transaminase and CK levels (from skeletal muscle). In the differential diagnosis of chest pain in a patient on therapy with atorvastatin, cardiac and noncardiac fractions of these enzymes should be determined.