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Drug Interactions between Norvir and Xanax

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

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Interactions between your drugs

Major

ALPRAZolam ritonavir

Applies to: Xanax (alprazolam) and Norvir (ritonavir)

ADJUST DOSE: The coadministration of ritonavir with alprazolam may result in increased concentrations of the latter. The mechanism is decreased clearance of alprazolam due to inhibition of CYP450 3A4 activity by ritonavir. Coadministration of alprazolam with potent CYP450 3A4 inhibitors ketoconazole and ritonavir have been shown to increase serum alprazolam concentrations by 3.98- and 2.70-fold, respectively. Increased serum concentrations of alprazolam may lead to prolonged and/or increased pharmacologic effects of benzodiazepines, including sedation and respiratory depression. According to the manufacturer, ritonavir may increase alprazolam plasma concentrations when both are initiated together or when ritonavir is added to stable alprazolam therapy.

MANAGEMENT: The manufacturer of alprazolam recommends reducing the alprazolam dose by 50% if both alprazolam and ritonavir are initiated together or when ritonavir is initiated in patients on a stable alprazolam dose. Dosage reduction is not considered necessary in patients taking ritonavir for at least 10 to 14 days.

References

  1. (2002) "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn
  2. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical
  3. Michalets EL (1998) "Update: clinically significant cytochrome P-450 drug interactions." Pharmacotherapy, 18, p. 84-112
  4. Greenblatt DJ, vonMoltke LL, Harmatz JS, Durol ALB, Daily JP, Graf JA, Mertzanis P, Hoffman JL, Shader RI (2000) "Alprazolam-ritonavir interaction: Implications for product labeling." Clin Pharmacol Ther, 67, p. 335-41
View all 4 references

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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

ritonavir food

Applies to: Norvir (ritonavir)

ADJUST DOSING INTERVAL: Administration with food may modestly affect the bioavailability of ritonavir from the various available formulations. When the oral solution was given under nonfasting conditions, peak ritonavir concentrations decreased 23% and the extent of absorption decreased 7% relative to fasting conditions. Dilution of the oral solution (within one hour of dosing) with 240 mL of chocolate milk or a nutritional supplement (Advera or Ensure) did not significantly affect the extent and rate of ritonavir absorption. When a single 100 mg dose of the tablet was administered with a high-fat meal (907 kcal; 52% fat, 15% protein, 33% carbohydrates), approximately 20% decreases in mean peak concentration (Cmax) and systemic exposure (AUC) were observed relative to administration after fasting. Similar decreases in Cmax and AUC were reported when the tablet was administered with a moderate-fat meal. In contrast, the extent of absorption of ritonavir from the soft gelatin capsule formulation was 13% higher when administered with a meal (615 KCal; 14.5% fat, 9% protein, and 76% carbohydrate) relative to fasting.

MANAGEMENT: Ritonavir should be taken with meals to enhance gastrointestinal tolerability.

References

  1. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical

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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

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