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Drug Interactions between atazanavir and clarithromycin

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

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Interactions between your drugs

Moderate

clarithromycin atazanavir

Applies to: clarithromycin and atazanavir

ADJUST DOSE: Coadministration with atazanavir may significantly increase the plasma concentration of clarithromycin but decrease that of the active metabolite, 14-OH clarithromycin. The mechanism is atazanavir inhibition of CYP450 3A4, the isoenzyme responsible for the metabolism of clarithromycin. In 21 study subjects, atazanavir (400 mg once a day for 10 days) increased the mean steady-state peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of clarithromycin (500 mg once a day) by 50% and 94%, respectively, compared to administration of clarithromycin alone. In contrast, the Cmax and AUC of 14-OH clarithromycin were significantly reduced by 72% and 70%, respectively.

MANAGEMENT: Because increased plasma concentrations of clarithromycin may cause prolongation of the QT interval of the electrocardiogram, a dose reduction of clarithromycin by 50% is recommended for patients with moderate renal insufficiency (CrCl 30 to 60 mL/min) and a dose reduction by 75% is recommended for patients with severe renal insufficiency (CrCl less than 30 mL/min). The daily dose of clarithromycin should not exceed 1000 mg during concomitant use with protease inhibitors. In addition, because plasma concentrations of the active metabolite is significantly reduced, alternative therapy should be considered for indications other than infections due to Mycobacterium avium complex. Some authorities recommend avoiding the use of the fixed combination atazanavir-cobicistat with clarithromycin.

References

  1. (2003) "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb
  2. Cerner Multum, Inc. "Australian Product Information."

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Drug and food interactions

Moderate

atazanavir food

Applies to: atazanavir

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

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Minor

clarithromycin food

Applies to: clarithromycin

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.

References

  1. Cheng KL, Nafziger AN, Peloquin CA, Amsden GW (1998) "Effect of grapefruit juice on clarithromycin pharmacokinetics." Antimicrob Agents Chemother, 42, p. 927-9

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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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