Clonazepam Interactions You Need to Know About

Clonazepam (brand name Klonopin) can interact with a surprising number of other medications, supplements, and even certain foods. Some of these interactions are merely inconvenient — extra drowsiness, for example. Others can be life-threatening.

Whether you're starting Clonazepam for the first time or adding a new medication to your routine, this guide will help you understand what to watch for and what to discuss with your doctor.

How Drug Interactions Work with Clonazepam

Clonazepam interactions generally fall into two categories:

1. Additive CNS depression: Other medications that slow down brain activity can stack on top of Clonazepam's effects, leading to excessive sedation, slowed breathing, or even coma. This is the most common — and most dangerous — type of interaction.
2. Metabolic interactions: Clonazepam is broken down in your liver by an enzyme called CYP3A4. Medications that speed up or slow down this enzyme can change how much Clonazepam stays in your blood, making it either less effective or more potent than expected.

Major Drug Interactions — Avoid or Use Extreme Caution

These interactions carry the highest risk and are flagged in Clonazepam's prescribing information:

Opioid Pain Medications (FDA Boxed Warning)

This is the most dangerous interaction. Combining Clonazepam with opioids can cause fatal respiratory depression — your breathing slows or stops entirely. The FDA has placed a Boxed Warning on all benzodiazepines about this risk.

Opioids to be especially aware of:

• Fentanyl (Duragesic, Subsys)
• Oxycodone (OxyContin, Percocet)
• Hydrocodone (Vicodin, Norco)
• Morphine (MS Contin, Kadian)
• Codeine (Tylenol with Codeine)
• Tramadol (Ultram)

If you're prescribed both an opioid and Clonazepam, your doctor should use the lowest effective doses and monitor you closely.

Alcohol

Alcohol is a central nervous system depressant, just like Clonazepam. Together, they significantly increase the risk of:

• Extreme drowsiness
• Loss of coordination
• Respiratory depression
• Loss of consciousness

Do not drink alcohol while taking Clonazepam. Even small amounts can be dangerous.

Other Benzodiazepines

Taking Clonazepam with another benzodiazepine — such as Alprazolam (Xanax), Lorazepam (Ativan), or Diazepam (Valium) — adds up the sedation and respiratory depression risks. This combination should be avoided unless specifically directed by a specialist.

Barbiturates and Sedative-Hypnotics

Medications like Phenobarbital and sleep aids like Zolpidem (Ambien) or Eszopiclone (Lunesta) compound the sedating effects of Clonazepam. The combination increases the risk of dangerous oversedation.

Strong CYP3A4 Inhibitors

These medications slow down the enzyme that breaks down Clonazepam, causing it to build up in your blood to potentially toxic levels:

• Ketoconazole (antifungal)
• Itraconazole (Sporanox — antifungal)
• Clarithromycin (Biaxin — antibiotic)

If you must take one of these with Clonazepam, your doctor may reduce your Clonazepam dose.

CYP3A4 Inducers

These do the opposite — they speed up Clonazepam metabolism, potentially making it less effective:

• Rifampin (Rifadin — antibiotic for tuberculosis)
• Carbamazepine (Tegretol — anticonvulsant)
• Phenytoin (Dilantin — anticonvulsant)

If you take any of these, your doctor may need to increase your Clonazepam dose or choose an alternative.

Moderate Drug Interactions — Use with Caution

These interactions may not be life-threatening but can significantly increase side effects:

Antidepressants (SSRIs and SNRIs)

Medications like Sertraline (Zoloft), Fluoxetine (Prozac), Escitalopram (Lexapro), Venlafaxine (Effexor), and Duloxetine (Cymbalta) can increase sedation when combined with Clonazepam. Many patients take both, but your doctor should monitor for excessive drowsiness.

Antihistamines

Over-the-counter allergy and sleep medications containing Diphenhydramine (Benadryl) or Doxylamine (Unisom) can add to Clonazepam's drowsiness. Even "non-drowsy" antihistamines like Cetirizine (Zyrtec) can contribute to fatigue in combination with Clonazepam.

Muscle Relaxants

Cyclobenzaprine (Flexeril), Baclofen, and Tizanidine (Zanaflex) cause additive CNS depression when combined with Clonazepam.

Antipsychotics

Medications like Quetiapine (Seroquel), Olanzapine (Zyprexa), and Risperidone (Risperdal) increase sedation and respiratory depression risk when taken with Clonazepam.

Valproic Acid (Depakote)

This anticonvulsant may increase Clonazepam blood levels, potentially intensifying both therapeutic effects and side effects.

Supplements and OTC Medications to Watch

Don't assume that "natural" means safe to combine with Clonazepam. These supplements can interact:

• Kava — acts on GABA receptors similarly to Clonazepam; combining them can cause excessive sedation
• Valerian root — also enhances GABA activity and can increase drowsiness
• Melatonin — while generally mild, it can add to Clonazepam's sedating effects
• St. John's Wort — may affect CYP3A4 metabolism and alter Clonazepam levels
• Diphenhydramine (Benadryl) — commonly overlooked because it's OTC, but it's a significant sedation amplifier

Food and Drink Interactions

Alcohol

Worth repeating: avoid alcohol completely. This is the single most important food/drink interaction to remember.

Grapefruit and Grapefruit Juice

Grapefruit inhibits CYP3A4, the enzyme that metabolizes Clonazepam. Drinking grapefruit juice or eating grapefruit can increase Clonazepam levels in your blood, potentially making side effects worse. While the interaction isn't as severe as with some other medications, it's best to limit or avoid grapefruit products.

What to Tell Your Doctor

Before starting Clonazepam — or adding any new medication to your routine — make sure your doctor knows about:

• Every prescription medication you take, including those from other doctors
• All over-the-counter medications, including pain relievers, allergy pills, and sleep aids
• All supplements and herbal products
• Your alcohol consumption — be honest, even if it's occasional
• Any recreational substance use
• Any recent changes to your medication list

Pharmacists are also an excellent resource. When you fill your Clonazepam prescription, your pharmacist will automatically check for interactions with other medications on file. But they can only catch interactions with drugs they know about — so make sure your pharmacy has a complete medication list.

Final Thoughts

Clonazepam is a safe and effective medication when used properly, but its interactions with other substances require real attention. The most critical rule: never combine Clonazepam with opioids or alcohol without explicit guidance from your doctor.

For more about Clonazepam's side effects or general information, explore our other guides. And if you need help finding Clonazepam at a pharmacy near you, Medfinder can help.