What is the interaction between alprazolam (Xanax) and hydromorphone (Dilaudid)?

From the Guidelines

The combination of alprazolam and Dilaudid should be avoided whenever possible due to the increased risk of potentially fatal overdose, as concurrent use can lead to severe central nervous system depression and decreased respiratory drive 1.

Key Considerations

• Benzodiazepines and opioids, such as alprazolam and Dilaudid, both cause central nervous system depression and can decrease respiratory drive, putting patients at greater risk for potentially fatal overdose 1.
• The concurrent use of these medications is associated with a near quadrupling of the risk for overdose death compared with opioid prescription alone 1.
• Clinicians should consider whether the benefits outweigh the risks of concurrent use of these drugs and should check the prescription drug monitoring program (PDMP) for concurrent controlled medications prescribed by other clinicians.

Management and Tapering

• If tapering is required to reduce the risk for fatal respiratory depression, it might be safer and more practical to taper opioids first, given the greater risks of benzodiazepine withdrawal relative to opioid withdrawal 1.
• Benzodiazepines should be tapered gradually if discontinued, as abrupt withdrawal can be associated with severe symptoms, including rebound anxiety, hallucinations, seizures, and delirium tremens 1.
• A commonly used tapering schedule is a reduction of the benzodiazepine dose by 25% every 1–2 weeks, and cognitive behavioral therapy (CBT) can increase tapering success rates 1.

From the FDA Drug Label

7 DRUG INTERACTIONS

Table 1 includes clinically significant drug interactions with hydromorphone hydrochloride Table 1: Clinically Significant Drug Interactions with Hydromorphone Hydrochloride Benzodiazepines and other Central Nervous System (CNS) Depressants Clinical Impact:Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death Intervention:Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation [see Warnings and Precautions (5. 6)]. Examples:Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol.

The interaction between alprazolam (a benzodiazepine) and dilaudid (hydromorphone) can increase the risk of:

• Hypotension
• Respiratory depression
• Profound sedation
• Coma
• Death Due to the additive pharmacologic effect of these two CNS depressants. It is recommended to reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate, and to limit dosages and durations to the minimum required. Patients should be followed closely for signs of respiratory depression and sedation 2.

From the Research

Interaction between Alprazolam and Dilaudid

• The interaction between alprazolam (a benzodiazepine) and Dilaudid (a brand name for hydromorphone, an opioid) is a concern due to the potential for increased risk of respiratory depression and other adverse events 3, 4.
• Studies have shown that the concomitant use of opioids and benzodiazepines increases the risk of mortality and severe adverse respiratory events 3.
• The risk of harm and benefit of the drug combination strongly correlates to its context, and there are situations where benefits may outweigh the risks, such as in hospice settings 3.
• Patients with chronic pain who use opioid analgesics along with benzodiazepines and/or alcohol are at higher risk for fatal/nonfatal overdose and have more aberrant behaviors 4.
• Coadministration of these agents produces a defined increase in rates of adverse events, overdose, and death, warranting close monitoring and consideration when treating patients with pain 4.
• There is no specific study on the interaction between alprazolam and Dilaudid, but the general principles of opioid and benzodiazepine combination apply 5, 6, 7.