Flurazepam Drug Interactions: What to Avoid and What to Tell Your Doctor

Flurazepam has a complex interaction profile. Because it works by depressing central nervous system activity, combining it with other substances that also depress the CNS — including many common medications, alcohol, and even some supplements — can amplify its effects to a dangerous or even life-threatening degree. Understanding these interactions is essential for anyone taking flurazepam.

An important note: Because flurazepam's active metabolite has a half-life of 40–114 hours, interactions don't just apply while you're actively taking the drug. The risk of dangerous interactions continues for several days after your last dose.

Contraindicated Combinations (Never Use Together)

Sodium oxybate / GHB (Xyrem, Lumryz, Avafi): Absolute contraindication. Both flurazepam and sodium oxybate are powerful CNS depressants. Combining them can cause life-threatening CNS and respiratory depression. Never use together.

Black Box Warning: Opioid Combinations

The FDA requires a Boxed Warning (the most serious type) for flurazepam regarding its interaction with opioid medications. This combination can cause:

Profound sedation

Respiratory depression (breathing slows or stops)

Coma

Death

Opioids that trigger this warning include all prescription pain medications: oxycodone, hydrocodone, morphine, fentanyl, tramadol, codeine, and others. Cough medicines containing codeine also qualify. If you are prescribed an opioid and already taking flurazepam, your prescriber should be explicitly aware and closely monitoring you.

High-Risk Interactions: Avoid or Use Extreme Caution

Alcohol: Dramatically increases CNS depression. Even moderate alcohol consumption on the day after taking flurazepam can cause dangerous sedation and impaired coordination — because flurazepam's metabolite is still active. Avoid alcohol during treatment and for several days after stopping.

Buprenorphine (Suboxone, Subutex, Brixia): Combining flurazepam with buprenorphine — used for opioid use disorder — significantly increases respiratory depression risk and has been associated with coma and death. Many fatalities involving buprenorphine have included concurrent benzodiazepine use.

Other benzodiazepines: Additive CNS depression. Using multiple benzodiazepines together is generally not recommended and increases overdose risk substantially.

Intranasal olopatadine (Patanase) and intranasal metoclopramide: Both increase risk of CNS depression when combined with flurazepam. Avoid or use an alternative.

Moderate Interactions: Use With Caution

Tricyclic antidepressants (amitriptyline, nortriptyline, imipramine): Additive CNS depression. May need dose adjustments.

Antihistamines (diphenhydramine, cetirizine, chlorpheniramine): Over-the-counter allergy medications can add to sedation. Avoid taking Benadryl or NyQuil-type products while on flurazepam.

CYP3A4 inhibitors (ritonavir, ketoconazole, fluconazole, mifepristone, tucatinib): These medications slow the breakdown of flurazepam in the liver, increasing drug levels and prolonging sedation. A dose reduction may be needed.

CYP3A4 inducers (carbamazepine, rifampin, phenobarbital, primidone, apalutamide): These speed up flurazepam's metabolism, reducing its effectiveness. Your prescriber may need to adjust your dose.

Muscle relaxants (carisoprodol, cyclobenzaprine): Additive sedative and muscle relaxant effects. Increases fall and CNS depression risk.

What to Tell Your Doctor Before Starting Flurazepam

Before you fill your flurazepam prescription, make sure your prescriber knows about:

All opioid medications you take — including those prescribed by other providers

All other prescription medications, especially antidepressants, antifungals, anticonvulsants, and HIV medications

Over-the-counter medications including antihistamines, sleep aids, and cough/cold products

Any supplements or herbal products (kava, valerian root, and similar substances can increase CNS depression)

Your alcohol use — even occasional drinking

For a complete overview of side effects, read our Flurazepam Side Effects guide. If you need help locating flurazepam at a pharmacy, medfinder can help you search near you.