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Drug Interactions between clarithromycin and darunavir

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

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Interactions between your drugs

Moderate

clarithromycin darunavir

Applies to: clarithromycin and darunavir

ADJUST DOSE: Coadministration with darunavir/ritonavir may increase the plasma concentrations of clarithromycin. The mechanism is inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of clarithromycin. In 17 study subjects, administration of clarithromycin (500 mg twice a day) with darunavir/ritonavir (400 mg/100 mg twice a day) increased the peak plasma concentration (Cmax), area under the concentration-time curve (AUC) and trough plasma concentration (Cmin) of clarithromycin by 26%, 57% and 174%, respectively, compared to administration without darunavir/ritonavir. Clarithromycin had no significant effect on the pharmacokinetics of darunavir.

MANAGEMENT: No dosage adjustment of clarithromycin or darunavir is required during coadministration in patients with normal renal function. However, clarithromycin dosage should be reduced by 50% in patients with moderate renal impairment (CrCl 30 to 60 mL/min) and 75% in patients with more severe renal impairment (CrCl below 30 mL/min).

References

  1. (2006) "Product Information. Prezista (darunavir)." Ortho Biotech Inc

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Drug and food interactions

Moderate

darunavir food

Applies to: darunavir

ADJUST DOSING INTERVAL: Food enhances the absorption and oral bioavailability of darunavir administered in combination with low-dose ritonavir. The mechanism is unknown. When administered with food, the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of darunavir were approximately 30% higher than when administered in the fasting state. Darunavir exposure was similar for the range of meals studied. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 grams fat) to 928 Kcal (56 grams fat).

MANAGEMENT: To ensure maximal oral absorption, darunavir coadministered with ritonavir should be taken with food. The type of food is not important.

References

  1. (2006) "Product Information. Prezista (darunavir)." Ortho Biotech Inc

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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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