Interactions : אינטראקציות

DRUG INTERACTIONS

Drugs Having Clinically Important Interactions with Xanagis
Table 4 includes clinically significant drug interactions with [see Clinical Pharmacology].

Table 4: Clinically Significant Drug Interactions with Xanagis

Opioids
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 Xanagis and opioids, and monitor patients closely for respiratory depression and sedation [see Warnings and Precautions].
Examples                           Morphine, buprenorphine, hydromorphone, oxymorphone, oxycodone, fentanyl, methadone, alfentanil, butorpenol, codeine, dihydrocodeine, meperidine, pentazocine, remifentanil, sufentanil, tapentadol, tramadol.
CNS Depressants
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 Xanagis during concomitant use with CNS depressants [see Warnings and Precautions ].
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 Xanagis 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 ].


Prevention or management      Concomitant use of Xanagis with a strong CYP3A4 inhibitor (except ritonavir) is contraindicated [see Contraindications (4), Warnings and Precautions ].
Examples                      Ketoconazole, itraconazole, clarithromycin Moderate or Weak Inhibitors of CYP3A
Clinical implication          Concomitant use of Xanagis with CYP3A inhibitors may increase the concentrations of Xanagis, resulting in increased risk of adverse reactions of alprazolam [see Clinical Pharmacology ].
Prevention or management      Avoid use and consider appropriate dose reduction when Xanagis is coadministered with a moderate or weak CYP3A inhibitor [see Warnings and Precautions].
Examples                      Nefazodone, fluvoxamine, cimetidine, erythromycin CYP3A Inducers
Clinical implication          Concomitant use of CYP3A inducers can increase alprazolam metabolism and therefore can decease plasma levels of alprazolam [see Clinical
Pharmacology ].
Prevention or management      Caution is recommended during coadministration with Xanagis.
Examples                      Carbamazepine, phenytoin
Ritonavir
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 Xanagis dosage when ritonavir and Xanagis are initiated concomitantly, or when ritonavir is added to a regimen where Xanagis is stabilized.

Increase Xanagis dosage to the target dosage after 10 to 14 days of dosing ritonavir and Xanagis concomitantly. No dosage adjustment of Xanagis is necessary in patients receiving ritonavir for more than 10 to14 days [see Dosage and Administration ].

Concomitant use of Xanagis with a strong CYP3A inhibitor, except ritonavir, is contraindicated [see Contraindications, Warnings and
Precautions].
Digoxin
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 Xanagis. Continue monitoring digoxin serum concentration and toxicity frequently. Reduce the digoxin dose if necessary.
Drug/Laboratory Test Interactions

Although interactions between benzodiazepines and commonly employed clinical laboratory tests have occasionally been reported, there is no consistent pattern for a specific drug or specific test.