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Drug Interaction Report

3 potential interactions and/or warnings found for the following 2 drugs:

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Interactions between your drugs

Major

ALPRAZolam atazanavir

Applies to: Xanax (alprazolam), Reyataz (atazanavir)

GENERALLY AVOID: Coadministration with protease inhibitors (PI) such as saquinavir, nelfinavir, atazanavir, fosamprenavir or amprenavir may significantly increase the plasma concentrations and pharmacologic effects of alprazolam. The proposed mechanism is PI-mediated inhibition of intestinal and hepatic CYP450 3A4, the isoenzyme responsible for the first-pass and hepatic metabolism of alprazolam. Coadministration of alprazolam with the potent CYP450 3A4 inhibitor and protease inhibitor, ritonavir, has been shown to increase serum alprazolam concentrations by 2.7-fold. Increased serum concentrations of alprazolam may lead to prolonged and/or increased pharmacologic effects of benzodiazepines, including sedation and respiratory depression.

MANAGEMENT: Given the potential for prolonged and/or increased sedation and respiratory depression associated with excessive benzodiazepine blood levels, concomitant use of PI with alprazolam should generally be avoided. If the combination is unavoidable, alprazolam dosage reduction as well as clinical and laboratory monitoring may be appropriate.

References

  1. (2002) "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn
  2. (2001) "Product Information. Invirase (saquinavir)." Roche Laboratories

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Drug and food interactions

Moderate

ALPRAZolam food

Applies to: Xanax (alprazolam)

GENERALLY AVOID: The pharmacologic activity of oral midazolam, triazolam, and alprazolam may be increased if taken after drinking grapefruit juice. The proposed mechanism is CYP450 3A4 enzyme inhibition. In addition, acute alcohol ingestion may potentiate CNS depression and other CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MANAGEMENT: The manufacturer recommends that grapefruit juice should not be taken with oral midazolam. Patients taking triazolam or alprazolam should be monitored for excessive sedation. Alternatively, the patient could consume orange juice which does not interact with these drugs. Patients should be advised to avoid alcohol during benzodiazepine therapy.

References

  1. (2002) "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn
  2. (2002) "Product Information. Valium (diazepam)." Roche Laboratories
  3. (2001) "Product Information. Halcion (triazolam)." Pharmacia and Upjohn
  4. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  5. Kupferschmidt HHT, Ha HR, Ziegler WH, Meier PJ, Krahenbuhl S (1995) "Interaction between grapefruit juice and midazolam in humans." Clin Pharmacol Ther, 58, p. 20-8
  6. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ (1995) "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther, 58, p. 127-31
  7. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
View all 7 references

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Moderate

atazanavir food

Applies to: Reyataz (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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Therapeutic duplication warnings

No duplication 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.

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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.

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Further information

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