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

Tranxene (clorazepate) interacts with a wide range of medications, supplements, and substances. Some of these interactions are mild and require only monitoring, while others carry serious risks including respiratory depression, coma, and death. This guide covers the most important interactions you need to know — and what to tell every healthcare provider you see.

The Most Dangerous Interaction: Opioids

The FDA has issued a boxed warning — its most serious level of drug warning — about the combination of benzodiazepines and opioids. When clorazepate is combined with any opioid medication (such as oxycodone, hydrocodone, fentanyl, morphine, codeine, or buprenorphine), the result can be:

Profound sedation

Respiratory depression (dangerously slow or stopped breathing)

Coma

Death

If you're taking Tranxene and need an opioid pain medication — for surgery, a dental procedure, or injury treatment — it is essential that every provider involved in your care knows about your clorazepate prescription. This combination should be avoided if alternatives exist, and when necessary, must be used at the lowest effective doses with close monitoring.

Alcohol: Never Combine With Tranxene

Alcohol is a central nervous system depressant, just like clorazepate. Combining them multiplies the sedative and respiratory depressant effects of both substances. Even small amounts of alcohol can significantly increase drowsiness, dizziness, and the risk of respiratory depression when combined with Tranxene. Do not drink alcohol while taking clorazepate. This is true even at low doses of alcohol.

Other CNS Depressants

Any medication or substance that depresses the central nervous system will have additive effects when combined with clorazepate. This includes:

Other benzodiazepines (alprazolam, lorazepam, diazepam, clonazepam) — additive sedation and respiratory risk

Barbiturates (phenobarbital) — additive CNS depression, also accelerates clorazepate metabolism

Antipsychotics (chlorpromazine, quetiapine, haloperidol) — enhanced CNS depression

Sleep medications (zolpidem, eszopiclone, zaleplon) — increased sedation and respiratory risk

Antihistamines (diphenhydramine/Benadryl, hydroxyzine) — additive sedation

Muscle relaxants (cyclobenzaprine, carisoprodol) — additive CNS depression

CYP3A4 Inhibitors: Drugs That Increase Clorazepate's Effect

Clorazepate (via its active metabolite nordiazepam) is metabolized partly by the liver enzyme CYP3A4. Drugs that inhibit this enzyme can increase nordiazepam blood levels, potentially increasing side effects:

Azole antifungals (ketoconazole, itraconazole, fluconazole)

Macrolide antibiotics (erythromycin, clarithromycin)

Cimetidine (Tagamet) — inhibits benzodiazepine metabolism

Fluoxetine (Prozac) — inhibits clorazepate metabolism

Disulfiram (Antabuse) — inhibits metabolite breakdown

Isoniazid (tuberculosis treatment) — slows clorazepate metabolism

CYP3A4 Inducers: Drugs That Reduce Clorazepate's Effect

Conversely, drugs that speed up CYP3A4 activity can reduce nordiazepam blood levels, potentially making clorazepate less effective:

Rifampin (rifampicin) — powerful inducer, significantly reduces benzodiazepine levels

Phenytoin (Dilantin) — anticonvulsant that induces metabolism

Carbamazepine (Tegretol) — anticonvulsant that accelerates clorazepate breakdown

Apalutamide (Erleada) and enzalutamide (Xtandi) — strong CYP3A4 inducers used in prostate cancer treatment

Other Notable Interactions

Valproic acid (Depakote): May affect clorazepate metabolism; monitor for increased sedation

Probenecid: Can slow clorazepate metabolism, increasing drug levels

Levodopa: Clorazepate may reduce levodopa's effectiveness in Parkinson's disease

Oral hormonal contraceptives: May affect clorazepate metabolism; monitor for changes in effect

Theophylline: May reduce benzodiazepine effectiveness

What to Tell Every Healthcare Provider

Every time you see any healthcare provider — a dentist, a surgeon, an urgent care provider, a new doctor — tell them you take Tranxene (clorazepate). This is especially critical before any procedure involving sedation or pain management with opioids. Carry a medication card in your wallet listing your medications and doses. For more on managing Tranxene's effects, see our guide on Tranxene side effects.