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

Like all medications, Valtoco (diazepam nasal spray) can interact with other drugs, supplements, and substances. Some of these interactions are dangerous. This guide outlines the most important Valtoco drug interactions, what to avoid, and what information to share with your healthcare team.

Most Dangerous Interaction: Opioids (Boxed Warning)

The most serious drug interaction for Valtoco is with opioid medications. The FDA has issued a

Boxed Warning about the risks of using benzodiazepines with opioids. This combination can cause:

Profound sedation

Respiratory depression (slowed or stopped breathing)

Coma

Death

Opioids that can interact with Valtoco include: codeine, tramadol, hydrocodone, oxycodone, morphine, fentanyl, buprenorphine, methadone, and others. If you take any opioid medication for chronic pain or other conditions,

tell your doctor before using Valtoco. Your prescriber should weigh the risks and benefits carefully.

Alcohol and CNS Depressants

Combining Valtoco with alcohol or other central nervous system (CNS) depressants increases sedation and the risk of breathing problems. Avoid alcohol completely while using Valtoco. Other CNS depressants to discuss with your doctor include:

Other benzodiazepines (e.g., lorazepam, clonazepam, alprazolam)

Sleep aids (zolpidem, eszopiclone)

Antihistamines with sedating effects (diphenhydramine)

Antipsychotics (quetiapine, olanzapine)

Muscle relaxants (cyclobenzaprine, baclofen)

General anesthetics

CYP2C19 and CYP3A4 Inhibitors (Increase Diazepam Exposure)

Diazepam is metabolized primarily by the liver enzymes CYP2C19 and CYP3A4. Medications that inhibit these enzymes can slow the breakdown of diazepam, leading to higher and more prolonged blood levels—increasing the risk of side effects:

CYP2C19 inhibitors: Fluconazole, omeprazole, esomeprazole, fluvoxamine, fluoxetine, ticlopidine

CYP3A4 inhibitors: Ketoconazole, itraconazole, clarithromycin, erythromycin, ritonavir, diltiazem

If you take any of these medications, your doctor may need to adjust your Valtoco dose or monitor you more carefully.

CYP2C19 and CYP3A4 Inducers (Decrease Diazepam Exposure)

Conversely, medications that induce (speed up) CYP2C19 or CYP3A4 can reduce diazepam blood levels, potentially making Valtoco less effective:

CYP3A4 inducers: Rifampin, carbamazepine (Tegretol), phenytoin (Dilantin), phenobarbital, St. John's Wort

Note: Several of these inducers are also commonly used antiepileptic drugs. If you take carbamazepine, phenytoin, or phenobarbital as daily seizure medications, discuss with your neurologist how this may affect Valtoco's efficacy as a rescue medication.

What to Tell Your Doctor Before Using Valtoco

Before your prescriber finalizes a Valtoco prescription, provide a complete medication history including:

All prescription medications (especially opioids, sleep aids, antidepressants, antifungals, antibiotics)

Over-the-counter medications (including antihistamines and cough/cold medicines)

Herbal supplements (especially St. John's Wort, valerian, kava)

Alcohol use history

History of substance use disorder

Any history of suicidal thoughts or depression

Contraindications: Who Should NOT Use Valtoco

Valtoco is contraindicated (should not be used) in patients with:

Acute narrow-angle glaucoma (note: open-angle glaucoma patients may use Valtoco with monitoring)

Known hypersensitivity to diazepam or any ingredient in Valtoco

Neonates and infants (Valtoco is not approved for this age group)

For more on Valtoco's side effect profile, see: Valtoco Side Effects: What to Expect and When to Call Your Doctor.