Doral (Quazepam) Drug Interactions: What to Avoid and What to Tell Your Doctor

Drug interactions are one of the most important safety considerations when taking Doral (quazepam). Because quazepam is a CNS depressant with a very long half-life, interactions with other medications can produce effects that are more serious — and longer-lasting — than with shorter-acting sleep aids. This guide walks through the major interaction categories and what patients need to communicate with their healthcare team.

The Most Dangerous Interaction: Opioids

The FDA's boxed warning for quazepam explicitly addresses the combination with opioid pain medications. This is the most serious drug interaction associated with Doral.

Combining quazepam with opioids (such as oxycodone, hydrocodone, fentanyl, morphine, codeine, buprenorphine, tramadol) can cause:

• Profound, extreme sedation
• Dangerous respiratory depression (breathing slows or stops)
• Coma
• Death

If you take an opioid medication for any reason — including after surgery, for injury pain, or for chronic pain — you must inform every prescriber that you take quazepam. This interaction continues for several days after you stop taking quazepam due to its long half-life.

Absolutely contraindicated: Sodium oxybate (Xyrem) and calcium/magnesium/potassium/sodium oxybates — combining these with quazepam is considered contraindicated due to additive CNS depression.

Alcohol: Never Mix With Quazepam

Alcohol is a CNS depressant. When combined with quazepam, the effects of both are dramatically amplified. Even one alcoholic drink the same evening as quazepam can cause extreme sedation, impaired breathing, and significantly increased risk of accidents or death. Alcohol must be completely avoided while taking quazepam.

Other CNS Depressants: Use Extreme Caution

Any medication that slows down the brain or central nervous system can interact with quazepam. This includes:

• Antihistamines (diphenhydramine/Benadryl, hydroxyzine) — additive CNS depression; avoid OTC sleep aids containing diphenhydramine
• Other benzodiazepines (lorazepam, diazepam, clonazepam) — additive sedation and respiratory depression risk; generally do not combine
• Antipsychotics (quetiapine, olanzapine, risperidone) — additive sedation; monitor closely if combined
• Muscle relaxants (cyclobenzaprine, baclofen, carisoprodol) — additive CNS and respiratory depression
• Anticonvulsants (gabapentin, pregabalin, valproate) — additive CNS depression; combination with gabapentinoids and benzodiazepines has been associated with increased overdose deaths
• Sedating antidepressants (mirtazapine, trazodone, amitriptyline) — additive sedation; discuss with doctor before combining

CYP Enzyme Interactions: Medications That Affect Quazepam Blood Levels

Quazepam is primarily metabolized by CYP3A4 liver enzymes. Medications that inhibit or induce this enzyme can significantly change quazepam blood levels:

• CYP3A4 inhibitors (increase quazepam levels — use caution): itraconazole, ketoconazole, HIV protease inhibitors (ritonavir, darunavir), clarithromycin, nefazodone, conivaptan, grapefruit juice
• CYP3A4 inducers (decrease quazepam levels — may reduce efficacy): rifampin, apalutamide, carbamazepine, phenytoin, St. John's Wort

CYP2B6: Medications That Quazepam Can Affect

Importantly, quazepam itself inhibits the CYP2B6 enzyme, meaning it can increase blood levels of other drugs metabolized by CYP2B6:

• Bupropion (Wellbutrin): Quazepam may increase bupropion levels, potentially increasing the risk of bupropion toxicity including seizures
• Efavirenz (Sustiva): May increase efavirenz levels, potentially increasing CNS toxicity

If you take either of these medications, inform your prescriber before starting quazepam.

Supplements and OTC Products to Watch

• St. John's Wort: A CYP3A4 inducer; can reduce quazepam effectiveness
• Valerian root, kava, melatonin: May add to CNS depressant effects; use caution
• OTC sleep aids (diphenhydramine/Benadryl): Do not combine with quazepam — additive sedation
• Grapefruit juice: Inhibits CYP3A4 in the gut wall, potentially increasing quazepam absorption; avoid grapefruit around the time of dosing

What to Tell Every Doctor You See

Keep an updated medication list and share it at every appointment, especially:

• Before any surgery or procedure where sedation or pain management is planned
• When starting any new medication — even OTC or herbal supplements
• When visiting an urgent care clinic, ER, or specialist who may not have access to your full medication history

For more information on quazepam side effects and safety, see our Doral side effects guide.

If you're having trouble finding your quazepam prescription filled, medfinder can call pharmacies near you to find which ones can fill it.