7 DRUG INTERACTIONS
7.1 Drugs Having Clinically Important Interactions with XANAX
Table 4 includes clinically significant drug interactions with XANAX [see Clinical Pharmacology (12.3)].
|Clinical implication||The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at gamma-aminobutyric acid(GABAA) sites and opioids interact primarily at mu receptors. When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists.|
|Prevention or management||Limit dosage and duration of concomitant use of XANAX and opioids, and monitor patients closely for respiratory depression and sedation [see Warnings and Precautions (5.1)].|
|Examples||Morphine, buprenorphine, hydromorphone, oxymorphone, oxycodone, fentanyl, methadone, alfentanil, butorpenol, codeine, dihydrocodeine, meperidine, pentazocine, remifentanil, sufentanil, tapentadol, tramadol.|
|Clinical implication||The benzodiazepines, including alprazolam, produce additive CNS depressant effects when coadministered with other CNS depressants.|
|Prevention or management||Limit dosage and duration of XANAX during concomitant use with CNS depressants [see Warnings and Precautions (5.3)].|
|Examples||Psychotropic medications, anticonvulsants, antihistaminics, ethanol, and other drugs which themselves produce CNS depression.|
|Strong Inhibitors of CYP3A (except ritonavir)|
|Clinical implication||Concomitant use of XANAX with strong CYP3A inhibitors has a profound effect on the clearance of alprazolam, resulting in increased concentrations of alprazolam and increased risk of adverse reactions [see Clinical Pharmacology (12.3)].|
|Prevention or management||Concomitant use of XANAX with a strong CYP3A4 inhibitor (except ritonavir) is contraindicated [see Contraindications (4), Warnings and Precautions (5.5)].|
|Examples||Ketoconazole, itraconazole, clarithromycin|
|Moderate or Weak Inhibitors of CYP3A|
|Clinical implication||Concomitant use of XANAX with CYP3A inhibitors may increase the concentrations of XANAX, resulting in increased risk of adverse reactions of alprazolam [see Clinical Pharmacology (12.3)].|
|Prevention or management||Avoid use and consider appropriate dose reduction when XANAX is coadministered with a moderate or weak CYP3A inhibitor [see Warnings and Precautions (5.5)].|
|Examples||Nefazodone, fluvoxamine, cimetidine, erythromycin|
|Clinical implication||Concomitant use of CYP3A inducers can increase alprazolam metabolism and therefore can decease plasma levels of alprazolam [see Clinical Pharmacology (12.3)].|
|Prevention or management||Caution is recommended during coadministration with XANAX.|
|Clinical implication||Interactions involving ritonavir and alprazolam are complex and time dependent. Short term administration of ritonavir increased alprazolam exposure due to CYP3A4 inhibition. Following long term treatment of ritonavir (>10 to 14 days), CYP3A4 induction offsets this inhibition.|
Alprazolam exposure was not meaningfully affected in the presence of ritonavir.
|Prevention or management||Reduce XANAX dosage when ritonavir and XANAX are initiated concomitantly, or when ritonavir is added to a regimen where XANAX is stabilized.|
Increase XANAX dosage to the target dosage after 10 to 14 days of dosing ritonavir and XANAX concomitantly. No dosage adjustment of XANAX is necessary in patients receiving ritonavir for more than 10 to14 days [see Dosage and Administration (2.6)].
Concomitant use of XANAX with a strong CYP3A inhibitor, except ritonavir, is contraindicated [see Contraindications (4), Warnings and Precautions (5.5)].
|Clinical implication||Increased digoxin concentrations have been reported when alprazolam was given, especially in geriatric patients( >65 years of age).|
|Prevention or management||In patients on digoxin therapy, measure serum digoxin concentrations before initiating XANAX. Continue monitoring digoxin serum concentration and toxicity frequently. Reduce the digoxin dose if necessary.|