Why Drug Interactions Matter with Nayzilam

Nayzilam (Midazolam nasal spray) is a rescue medication for seizure clusters. Because it's a benzodiazepine that affects the brain and respiratory system, mixing it with certain other medications or substances can be dangerous — even life-threatening.

People with epilepsy often take multiple medications, making it especially important to know which ones can interact with Nayzilam. This guide covers the major interactions you and your doctor need to be aware of. For a general overview of the medication, see What Is Nayzilam?

The Most Dangerous Interaction: Opioids

Nayzilam carries an FDA boxed warning — the most serious type of drug safety alert — about its interaction with opioids. Taking Nayzilam while on opioid medications can cause:

• Profound sedation
• Respiratory depression (dangerously slow breathing)
• Coma
• Death

Common opioid medications include:

• Oxycodone (OxyContin, Percocet)
• Hydrocodone (Vicodin, Norco)
• Morphine
• Fentanyl
• Codeine
• Tramadol
• Methadone

If you or your loved one takes any opioid medication, make sure your neurologist and all caregivers know. Your doctor may still decide Nayzilam is appropriate, but extra monitoring is essential.

Other CNS Depressants

Opioids aren't the only concern. Any substance that depresses the central nervous system (CNS) can add to Nayzilam's sedating and respiratory effects. These include:

• Alcohol — Even small amounts can increase sedation and breathing risks
• Other benzodiazepines — such as Lorazepam, Diazepam, Alprazolam, or Clonazepam. Some epilepsy patients take a daily benzodiazepine, so your doctor needs to account for this.
• Barbiturates — such as Phenobarbital, which is sometimes used as a seizure medication
• Sleep medications — such as Zolpidem (Ambien), Eszopiclone (Lunesta)
• Muscle relaxants — such as Cyclobenzaprine, Baclofen
• Certain antihistamines — sedating ones like Diphenhydramine (Benadryl)

The combined effect of these medications with Nayzilam can lead to excessive sedation, difficulty breathing, and loss of consciousness beyond what's expected from Nayzilam alone.

CYP3A4 Inhibitors: Medications That Increase Nayzilam's Effects

Midazolam (the active ingredient in Nayzilam) is broken down in the body by an enzyme called CYP3A4. Medications that block or slow this enzyme can cause Midazolam to stay in your body longer and at higher levels, leading to stronger and more prolonged sedation.

Moderate to strong CYP3A4 inhibitors include:

• Antifungal medications: Ketoconazole, Itraconazole, Fluconazole
• Antibiotics: Erythromycin, Clarithromycin
• HIV medications: Ritonavir, Nelfinavir
• Grapefruit juice — Yes, even grapefruit can inhibit CYP3A4 and increase Midazolam exposure

If you take any of these medications, tell your neurologist. They may adjust your seizure rescue plan or provide additional monitoring guidance to your caregivers.

CYP3A4 Inducers: Medications That May Reduce Nayzilam's Effectiveness

On the flip side, some medications speed up CYP3A4, causing your body to break down Midazolam faster. This can make Nayzilam less effective at stopping seizure clusters.

CYP3A4 inducers include:

• Rifampin — an antibiotic used for tuberculosis
• Carbamazepine (Tegretol) — a common seizure medication
• Phenytoin (Dilantin) — another common seizure medication
• St. John's Wort — an herbal supplement

This is particularly important because Carbamazepine and Phenytoin are seizure medications. If you take one of these daily and also have Nayzilam as a rescue medication, your doctor needs to consider that Nayzilam might be less effective for you. They may recommend a different rescue medication or adjust your plan. Learn about alternative rescue medications that might be options.

What About Epilepsy Medications?

Since Nayzilam is used alongside daily epilepsy medications, here's a quick reference:

• Carbamazepine (Tegretol) and Phenytoin (Dilantin) — May reduce Nayzilam's effectiveness (CYP3A4 inducers)
• Phenobarbital — Adds to CNS depression; use with caution
• Clobazam (Onfi) — Another benzodiazepine; combined use increases sedation risk
• Levetiracetam (Keppra), Lamotrigine (Lamictal), Valproate (Depakote) — No major direct interactions with Nayzilam reported, but always inform your doctor of all medications

What to Tell Your Doctor and Caregivers

Before your doctor prescribes Nayzilam, make sure they know about:

1. All prescription medications — especially opioids, other benzodiazepines, seizure medications, antibiotics, and antifungals
2. Over-the-counter medications — including sleep aids, antihistamines, and cold medications
3. Herbal supplements — especially St. John's Wort
4. Alcohol use — be honest about how much and how often
5. Recreational drug use — any substances that could affect the brain or breathing

Caregivers should also keep a list of the patient's medications with the Nayzilam, so emergency responders can see it if needed.

What If You're Not Sure About an Interaction?

If you start a new medication or supplement and aren't sure whether it interacts with Nayzilam:

• Ask your pharmacist — Pharmacists are experts in drug interactions and can check quickly
• Call your neurologist's office — They can advise on whether any changes to your rescue plan are needed
• Use a drug interaction checker — Websites like Drugs.com have free interaction checkers, though they should supplement (not replace) professional advice

Key Takeaways

• The most dangerous interaction is with opioids — this can cause respiratory depression, coma, or death
• Alcohol and other CNS depressants add to Nayzilam's sedation and breathing risks
• CYP3A4 inhibitors (like Ketoconazole, Erythromycin, grapefruit juice) can make Nayzilam's effects stronger and last longer
• CYP3A4 inducers (like Carbamazepine, Phenytoin, Rifampin) may make Nayzilam less effective
• Tell your doctor about all medications, supplements, and substances you use

For more about managing your Nayzilam prescription, including side effects to watch for and how to save money, explore our other guides. Use MedFinder to find Nayzilam in stock near you.