What medications cannot be taken with Dilaudid?

October 10, 2025 •

3 min read

According to the FDA, the concurrent use of opioids with other central nervous system (CNS) depressants, such as alcohol or benzodiazepines, carries a serious and potentially fatal risk of profound sedation, respiratory depression, coma, and even death. For this reason and others, understanding what medications cannot be taken with Dilaudid is a critical safety measure for anyone prescribed this potent opioid.

Quick Summary

Taking Dilaudid with certain drugs like CNS depressants, MAOIs, or other opioids can cause life-threatening respiratory depression, sedation, or a dangerous condition called serotonin syndrome. This guide outlines the most important drug-drug and drug-substance interactions to avoid.

Key Points

CNS Depressants: Combining Dilaudid with alcohol, benzodiazepines, muscle relaxants, or other opioids can cause profound sedation, respiratory depression, and death.
MAOI Interactions: Monoamine Oxidase Inhibitors (MAOIs) should not be used with Dilaudid due to the risk of serotonin syndrome or opioid toxicity.
Serotonin Syndrome: Mixing Dilaudid with serotonergic drugs like SSRIs and SNRIs can lead to a dangerous and potentially fatal buildup of serotonin.
Avoid Mixed Opioids: Do not take Dilaudid with mixed agonist/antagonist opioids (e.g., butorphanol) as this can reduce effectiveness or cause withdrawal.
Monitor for Anticholinergic Effects: Concurrent use with anticholinergic drugs increases the risk of severe constipation and urinary retention.
Inform Your Doctor: Always provide your healthcare provider with a complete list of all medications, including over-the-counter and herbal supplements like St. John's Wort.
Dosing Accuracy is Critical: Errors in measuring doses of Dilaudid can result in an accidental, fatal overdose, especially in children.

Critical drug interactions to avoid

Central Nervous System (CNS) Depressants

One of the most dangerous interactions involving Dilaudid (hydromorphone) is with other CNS depressants. These substances amplify the depressant effects on the nervous system, which can lead to severe breathing problems, coma, and death. Because Dilaudid also depresses the central nervous system, the combined effect is far greater than the sum of its parts.

Common CNS depressants to avoid include:

Alcohol: Consumption of alcohol with Dilaudid is extremely dangerous and can lead to a fatal overdose, especially with extended-release formulations.
Benzodiazepines: Medications for anxiety and insomnia, such as alprazolam (Xanax), diazepam (Valium), and lorazepam (Ativan), can significantly increase the risk of respiratory depression. The FDA requires a boxed warning on opioids regarding this interaction.
Sedatives and Hypnotics: This includes sleep aids like zolpidem (Ambien) and barbiturates like amobarbital.
Muscle Relaxants: Combining Dilaudid with muscle relaxants such as cyclobenzaprine (Flexeril) or baclofen can enhance respiratory depression.
Other Opioids: Taking Dilaudid with other opioids, like oxycodone or hydrocodone, can lead to dangerous additive effects.
Certain Antihistamines: Some antihistamines, particularly first-generation types like diphenhydramine (Benadryl), cause significant drowsiness and can interact with Dilaudid.

Monoamine Oxidase Inhibitors (MAOIs)

Monoamine Oxidase Inhibitors (MAOIs) are a class of antidepressants that should not be taken with Dilaudid. This combination can cause severe, unpredictable reactions, including serotonin syndrome or opioid toxicity. Patients must not take Dilaudid if they have taken an MAOI within the past 14 days.

Examples of MAOIs include:

Isocarboxazid (Marplan)
Phenelzine (Nardil)
Tranylcypromine (Parnate)
Linezolid (antibiotic)
Methylene blue (dye)

Serotonergic Drugs

Combining Dilaudid with other drugs that increase serotonin levels in the brain raises the risk of a potentially fatal condition called serotonin syndrome. This can occur with a variety of medications and cause symptoms like agitation, hallucinations, rapid heartbeat, and high blood pressure.

Serotonergic drugs to be cautious with include:

SSRIs (e.g., fluoxetine, sertraline)
SNRIs (e.g., duloxetine, venlafaxine)
Tricyclic Antidepressants (TCAs) (e.g., amitriptyline)
Triptans for migraines
Other Opioids with serotonergic activity (e.g., tramadol)

Mixed Agonist/Antagonist Opioids

Using Dilaudid with mixed opioid analgesics can reduce the pain-relieving effects of Dilaudid or, more dangerously, precipitate withdrawal symptoms in a physically dependent patient.

Examples of these opioids include:

Butorphanol
Nalbuphine
Pentazocine
Buprenorphine

Anticholinergic Drugs

Anticholinergic medications can increase the risk of severe constipation and urinary retention when taken with Dilaudid. Dilaudid already has a constipating effect, so adding an anticholinergic can worsen this significantly and may lead to a dangerous intestinal blockage called paralytic ileus.

Examples of anticholinergic drugs include:

Atropine
Scopolamine
Certain medications for bladder control like oxybutynin
Some medications for Parkinson's disease, like benztropine

Herbal Supplements and Other Considerations

Some herbal supplements and other non-prescription substances can also interact with Dilaudid. St. John's Wort, an herbal supplement often used for depression, and tryptophan are noted for potential interactions. Always inform your healthcare provider of all supplements and over-the-counter medications you are taking.

Summary of Drug Interactions with Dilaudid


Drug/Class	Examples	Type of Interaction	Potential Risk
CNS Depressants	Alcohol, Benzodiazepines (Xanax, Valium), Sleep Aids (Ambien), Muscle Relaxants (Flexeril), Other Opioids	Additive depressant effect	Profound sedation, severe respiratory depression, coma, death
Monoamine Oxidase Inhibitors (MAOIs)	Isocarboxazid, Phenelzine, Tranylcypromine, Linezolid	Potentiation of hydromorphone effects	Serotonin syndrome, opioid toxicity, coma
Serotonergic Drugs	SSRIs, SNRIs, TCAs, Triptans	Increase serotonin levels	Serotonin syndrome (agitation, rapid heart rate, confusion)
Mixed Opioid Agonist/Antagonists	Butorphanol, Nalbuphine, Buprenorphine	Counteractive opioid effects	Reduced pain relief, precipitated withdrawal symptoms
Anticholinergics	Atropine, Scopolamine, Oxybutynin	Increased gastrointestinal and urinary side effects	Severe constipation, urinary retention, paralytic ileus
Certain Herbal Supplements	St. John's Wort, Tryptophan	Potential unknown interactions	Not well-documented, but caution is advised

Conclusion

Dilaudid is a powerful and effective pain medication, but its use comes with significant risks, particularly when combined with other substances. The interactions with CNS depressants, MAOIs, and serotonergic drugs are especially dangerous and can lead to life-threatening complications. Always have a complete and honest conversation with your healthcare provider about all medications, supplements, and lifestyle choices, including alcohol consumption, to ensure your safety. Never start, stop, or change a medication without consulting your doctor or pharmacist. Understanding and respecting these serious drug interactions is the best way to prevent adverse events and use Dilaudid safely and effectively. For more information, consult the FDA prescribing information for Dilaudid.

Frequently Asked Questions

No, you should never drink alcohol while taking Dilaudid. This combination significantly increases the risk of profound sedation, severe respiratory depression, and death.

Taking Dilaudid with benzodiazepines such as Xanax, Valium, or Ativan can lead to extreme drowsiness, dangerously slowed breathing, coma, and death. The combination is extremely dangerous and should be avoided.

You should not take Dilaudid with Monoamine Oxidase Inhibitors (MAOIs) and should avoid most other serotonergic antidepressants, such as SSRIs and SNRIs, due to the risk of a severe reaction called serotonin syndrome.

Combining Dilaudid with other opioids, especially mixed agonist/antagonist types like buprenorphine or butorphanol, can either enhance the depressant effects or trigger withdrawal symptoms.

Many OTC medications can interact with Dilaudid. For example, certain antihistamines and herbal supplements like St. John's Wort should be avoided. Always consult your pharmacist or doctor before taking any new medication.

Serotonin syndrome is a potentially life-threatening condition caused by too much serotonin in the brain. It can occur when Dilaudid is combined with other serotonergic drugs, and symptoms include agitation, hallucinations, rapid heart rate, and confusion.

If you suspect you or someone else is experiencing a severe drug interaction, seek emergency medical attention immediately. This is especially important for symptoms like difficulty breathing, extreme sedation, or signs of serotonin syndrome.