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Drug Interactions between atazanavir / cobicistat and glycopyrrolate / indacaterol

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Minor

atazanavir indacaterol

Applies to: atazanavir / cobicistat and glycopyrrolate / indacaterol

Coadministration with inhibitors of CYP450 3A4 and/or P-glycoprotein may increase the systemic exposure to indacaterol following oral inhalation, as it is a substrate of both the isoenzyme and efflux transporter. When a single 300 mcg dose of indacaterol inhalation powder was administered in combination with the potent dual CYP450 3A4/P-glycoprotein inhibitor, ketoconazole (200 mcg twice daily for 7 days), indacaterol peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.3- and 1.9-fold, respectively. These changes probably reflect the impact of maximal combined inhibition. Similarly, verapamil 80 mg three times a day for 4 days increased indacaterol Cmax by 1.5-fold and AUC by 2-fold, while erythromycin 400 mg four times a day for 7 days increased indacaterol Cmax by 1.2-fold and AUC by 1.4-fold. Ritonavir 300 mg twice daily for 7.5 days had no effect on the Cmax of indacaterol, but increased its AUC by 1.7-fold. Indacaterol oral inhalation powder has been evaluated in clinical trials for up to one year at doses up to 600 mcg. No dosage adjustment is necessary at the 75 mcg dose when used with CYP450 3A4 and P-glycoprotein inhibitors.

References

  1. "Product Information. Arcapta Neohaler (indacaterol)." Novartis Pharmaceuticals (2011):

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Minor

indacaterol cobicistat

Applies to: glycopyrrolate / indacaterol and atazanavir / cobicistat

Coadministration with inhibitors of CYP450 3A4 and/or P-glycoprotein may increase the systemic exposure to indacaterol following oral inhalation, as it is a substrate of both the isoenzyme and efflux transporter. When a single 300 mcg dose of indacaterol inhalation powder was administered in combination with the potent dual CYP450 3A4/P-glycoprotein inhibitor, ketoconazole (200 mcg twice daily for 7 days), indacaterol peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.3- and 1.9-fold, respectively. These changes probably reflect the impact of maximal combined inhibition. Similarly, verapamil 80 mg three times a day for 4 days increased indacaterol Cmax by 1.5-fold and AUC by 2-fold, while erythromycin 400 mg four times a day for 7 days increased indacaterol Cmax by 1.2-fold and AUC by 1.4-fold. Ritonavir 300 mg twice daily for 7.5 days had no effect on the Cmax of indacaterol, but increased its AUC by 1.7-fold. Indacaterol oral inhalation powder has been evaluated in clinical trials for up to one year at doses up to 600 mcg. No dosage adjustment is necessary at the 75 mcg dose when used with CYP450 3A4 and P-glycoprotein inhibitors.

References

  1. "Product Information. Arcapta Neohaler (indacaterol)." Novartis Pharmaceuticals (2011):

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Drug and food interactions

Moderate

atazanavir food

Applies to: atazanavir / cobicistat

ADJUST DOSING INTERVAL: Administration of atazanavir with food enhances oral bioavailability and reduces pharmacokinetic variability. According to the manufacturer, administration with a light meal increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single 400 mg dose of atazanavir by 57% and 70%, respectively, relative to the fasting state. Administration with a high-fat meal resulted in a mean increase of 35% in atazanavir AUC and no change in Cmax compared to fasting. The coefficient of variation of AUC and Cmax decreased by approximately one-half when given with either a light or high-fat meal compared to the fasting state.

MANAGEMENT: To ensure maximal oral absorption, atazanavir should be administered with or immediately after a meal.

References

  1. "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb (2003):

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Moderate

glycopyrrolate food

Applies to: glycopyrrolate / indacaterol

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

References

  1. Linnoila M "Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol." Eur J Clin Pharmacol 6 (1973): 107-12

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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