5 Lorazepam (Ativan) Interactions and How to Manage Them

Drug interactions can affect the safety and effectiveness of your medications. This applies to prescription medications, over-the-counter (OTC) products, and supplements alike.

Lorazepam (Ativan) is no exception. It’s a benzodiazepine medication that treats anxiety. Benzodiazepines aren’t typically first-choice options due to interactions and side effects, but they can be effective options when needed.

Lorazepam works in your brain by affecting a natural chemical called gamma-aminobutyric acid (GABA). GABA causes your brain and spinal cord to slow down. While this can help anxiety, this is also the reason that lorazepam has many interactions. Several other interactions can affect how much lorazepam stays in your body, too.

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Let’s explore five types of lorazepam interactions and some helpful tips to manage them.

1. Opioids

Opioids are a common treatment option for moderate-to-severe pain. You may be familiar with several opioids, such as hydrocodone / acetaminophen, morphine (MS Contin), and oxycodone (OxyContin). 

However, combining opioids with lorazepam can result in extreme sleepiness and slow, shallow breathing. This can be life-threatening in some cases. Lorazepam carries a boxed warning regarding this drug interaction. A boxed warning is the FDA’s most serious medication warning.

Your prescriber and pharmacist should be aware of all medications you’re taking, including lorazepam and any opioids. What’s more, if you receive these medications from different prescribers, make sure each one is in the loop about everything you’re taking. They might change your pain medication or lorazepam prescription to an alternative.

2. CNS depressants

Many medications that treat mental health conditions have a similar effect on your brain — namely, slowing brain and spinal cord activity. This is often referred to as central nervous system (CNS) depression.

CNS depressants can amplify lorazepam-induced CNS depression, potentially exacerbating side effects. Symptoms of slowed brain and spinal cord activity may include:

• Slurred speech

• Uncoordinated movements

• Confusion

• Drowsiness

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CNS depressant examples

Many medications and substances are considered CNS depressants. This includes antidepressants, antipsychotics, barbiturates, and more. 

While not an exhaustive list, CNS depressants to use with caution with lorazepam are listed below.

Antidepressants such as:

• Fluoxetine (Prozac)

• Sertraline (Zoloft)

• Amitriptyline

• Mirtazapine (Remeron)

• Zuranolone (Zurzuvae)

• Esketamine (Spravato)

Antipsychotics such as:

• Quetiapine (Seroquel)

• Risperidone (Risperdal)

• Clozapine (Clozaril)

• Haloperidol (Haldol)

• Olanzapine (Zyprexa)

Sedatives and sleeping pills such as:

• Ketamine (Ketalar)

• Zolpidem (Ambien)

• Eszopiclone (Lunesta‌)

• Zaleplon (Sonata)

Muscle relaxers such as:

• Cyclobenzaprine (Amrix)

• Carisoprodol (Soma)

• Metaxalone

• Tizanidine (Zanaflex)

Barbiturates such as:

• Phenobarbital

• Pentobarbital

• Primidone (Mysoline)

Other substances, including:

• Cannabis

• Alcohol

• Kava

• Kratom

• Valerian root

In several cases, your prescriber may OK an interacting combination, but they’ll follow up with you regularly to see how you’re doing.

3. Certain over-the-counter products

Many OTC medications and supplements may cause drowsiness too. However, they aren’t typically considered CNS depressants. They work in your brain in a different way that doesn’t cause slowed brain activity. Still, these products can add onto lorazepam’s effects and contribute to excessive sleepiness.

First-generation antihistamines, such as diphenhydramine (Benadryl) and dimenhydrinate (Dramamine), are common culprits. Several cold medicines, such as NyQuil (acetaminophen / dextromethorphan / doxylamine) may also be to blame. Dietary supplements such as melatonin and tryptophan may also contribute to sleepiness. 

Make sure your prescriber and pharmacist are aware of all of the medications and supplements you take. Based on your situation, they can tell you if a certain combination is safe or if any medication adjustments are necessary. And always report any symptoms of excessive sleepiness to them without delay.

4. Valproic acid

Valproic acid is a common anti-seizure medication. But it interacts with several medications, including lorazepam.

Valproic acid can increase lorazepam levels in your blood. This combination is sometimes prescribed intentionally for seizures and certain mental health conditions. But the combination may still worsen lorazepam side effects, such as sleepiness, fatigue, and dizziness. Your prescriber may want to lower your lorazepam dose if you’re prescribed both medications.

Let your prescriber know if you’re still experiencing lorazepam side effects after a dosage adjustment. It can be tricky to change up an anti-seizure regimen — especially if it's working well — so they may switch you to a different anxiety medication. 

5. Probenecid

Probenecid is a prescription medication used for gout prevention. It also interacts with lorazepam.

Probenecid prevents your body from clearing lorazepam effectively. This causes it to stick around longer than it normally would. Again, this may cause lorazepam levels to rise in your blood and worsen side effects. 

Your prescriber will likely reduce your lorazepam dose in half if you’re taking both medications together. Alternatively, they may recommend a different gout prevention medication — one that doesn’t interact with lorazepam.

Are there any lorazepam interactions with antibiotics?

Lorazepam doesn’t interact with most common antibiotics. This isn’t true for all benzodiazepines though. Alprazolam (Xanax) interacts with a few of them.

This interaction happens because alprazolam is broken down by specific liver enzymes (proteins). Clarithromycin (Biaxin XL) and erythromycin (Ery-Tab) are two antibiotics that interfere with these enzymes. They can slow the breakdown of alprazolam, increasing alprazolam levels in your blood. This may result in new or worsening severe alprazolam side effects.

Lorazepam is not broken down by these same liver enzymes. Your liver inactivates lorazepam in a different way.

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Written by:

Mandeep Sohal, PharmD

Mandeep Sohal, PharmD, has more than 7 years of experience in the pharmaceutical industry and is licensed in California. In his career, he’s had experience with specialty pharmacy, community pharmacy, pharmacy benefit management, and pharmaceutical manufacturers.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Renad Abu-Sawwa, PharmD, BCPPS

Renad Abu-Sawwa, PharmD, BCPPS, is an associate professor and associate discipline director of clinical pharmacology at Rush Medical College with a practice site as a clinical pharmacy specialist practitioner at RUSH Children's Hospital in the Pediatric Epilepsy Clinic.

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