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XANAX® XR, CIV Drug Interactions (alprazolam)


7.1 Drugs Having Clinically Important Interactions with XANAX XR

Table 4 includes clinically significant drug interactions with XANAX XR [see Clinical Pharmacology (12.3)].

Table 4: Clinically Significant Drug Interactions with XANAX XR
Clinical implicationThe 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 managementLimit 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)].
ExamplesMorphine, buprenorphine, hydromorphone, oxymorphone, oxycodone, fentanyl, methadone, alfentanil, butorpenol, codeine, dihydrocodeine, meperidine, pentazocine, remifentanil, sufentanil, tapentadol, tramadol.
CNS Depressants
Clinical implicationThe benzodiazepines, including alprazolam, produce additive CNS depressant effects when coadministered with other CNS depressants.
Prevention or managementLimit dosage and duration of XANAX XR during concomitant use with CNS depressants [see Warnings and Precautions (5.3)].
ExamplesPsychotropic medications, anticonvulsants, antihistaminics, ethanol, and other drugs which themselves produce CNS depression.
Strong Inhibitors of CYP3A (except ritonavir)
Clinical implicationConcomitant 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 (12.3)].
Prevention or managementConcomitant use of XANAX XR with a strong CYP3A4 inhibitor (except ritonavir) is contraindicated [see Contraindications (4), Warnings and Precautions (5.5)].
ExamplesKetoconazole, itraconazole, clarithromycin
Moderate or Weak Inhibitors of CYP3A
Clinical implicationConcomitant use of XANAX XR with CYP3A inhibitors may increase the concentrations of XANAX XR, resulting in increased risk of adverse reactions [see Clinical Pharmacology (12.3)].
Prevention or managementAvoid use and consider appropriate dose reduction when XANAX XR is coadministered with a moderate or weak CYP3A inhibitor [see Warnings and Precautions (5.5)].
ExamplesNefazodone, fluvoxamine, cimetidine, erythromycin
CYP3A Inducers
Clinical implicationConcomitant use of CYP3A inducers can increase alprazolam metabolism and therefore can decease plasma levels of alprazolam [see Clinical Pharmacology (12.3)].
Prevention or managementCaution is recommended during coadministration with alprazolam.
ExamplesCarbamazepine, phenytoin
Clinical implicationInteractions 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 managementReduce 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 [see Dosage and Administration (2.5)].
Concomitant use of XANAX XR with a strong CYP3A inhibitor, except ritonavir, is contraindicated [see Contraindications (4), Warnings and Precautions (5.5)].
Clinical implicationIncreased digoxin concentrations have been reported when alprazolam was given, especially in geriatric patients (>65 years of age).
Prevention or managementIn 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.

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