Interactions : אינטראקציות

7     DRUG INTERACTIONS

7.1 Drugs Having Clinically Important Interactions with XANAX XR
Table 4 includes clinically significant drug interactions with XANAX XR [see Clinical Pharmacology (12.2)].

Table 4: Clinically Significant Drug Interactions with XANAX XR
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 XANAX XR 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.
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 XANAX XR 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 XR 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 (12.2)].
Prevention or management Concomitant use of XANAX XR 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 XR with CYP3A inhibitors may increase the concentrations of XANAX XR, resulting in increased risk of adverse reactions [see Clinical Pharmacology
(12.2)].
Prevention or management Avoid use and consider appropriate dose reduction when XANAX XR is coadministered with a moderate or weak
CYP3A inhibitor [see Warnings and Precautions (5.5)].
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 (12.2)].
Prevention or management Caution is recommended during coadministration with alprazolam.
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 - 14 days),
CYP3A4 induction offsets this inhibition.
Alprazolam exposure was not meaningfully affected in the presence of ritonavir.
Prevention or management     Reduce XANAX XR dose when a patient is initiated with ritonavir and XANAX XR concomitantly, or when ritonavir is added to a regimen where XANAX XR is stabilized.

Increase XANAX XR dosage to the target dosage after 10 to 14 days of dosing ritonavir and XANAX XR concomitantly. No dosage adjustment of XANXR XR is necessary in patients receiving ritonavir for more than 10 to 14 days.

Concomitant use of XANAX XR with a strong CYP3A inhibitor, except ritonavir, is contraindicated [see
Contraindications (4), Warnings and Precautions (5.5)].
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 XANAX XR. Continue monitoring digoxin serum concentration and toxicity frequently. Reduce the digoxin dose if necessary.

7.2    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.