Here is a fact that surprises most people: Ativan (lorazepam) skips the liver enzyme system that causes so many drug clashes. Most benzodiazepines, including Xanax and Valium, pass through the CYP450 enzymes first, so dozens of other medicines can speed them up or slow them down. Lorazepam goes straight to a simpler step called glucuronidation. That keeps the list of Ativan drug interactions shorter than you might expect.
Shorter does not mean safer. The interactions Ativan does have are mostly the dangerous kind: two or more substances that each slow the brain and breathing, stacked on top of each other. This guide walks through where you are likely to meet those interactions, from the pharmacy counter to the bar, and gives you a lookup table and a short script to take to your pharmacist.
Ativan drug interactions in one paragraph
Lorazepam interactions fall into two groups. The first and far bigger group is additive sedation: opioids, alcohol, sleep aids, gabapentin, sedating antihistamines, antipsychotics and other calming drugs all push the nervous system in the same direction, and together they can slow breathing to a dangerous degree. The second group is small and metabolic: a handful of drugs (valproate and probenecid are the main ones) block glucuronidation and raise lorazepam levels, while theophylline and some hormones may blunt or shorten its effect. Almost everything else on a typical medicine list does not change Ativan in a meaningful way.
The FDA prescribing information for Ativan lists these interactions in its drug interaction and boxed warning sections. If you want the bigger picture of what lorazepam does on its own, start with our overview of common and serious Ativan side effects, since many interactions simply make those effects stronger.
Where you’ll meet Ativan drug interactions
Interactions rarely announce themselves. They show up in ordinary places: a new prescription after surgery, a cold medicine grabbed at midnight, a glass of wine at dinner, a supplement a friend swore by. The sections below are organized by location, so you can picture the moment the risk appears.
At the pharmacy counter: prescription drugs
Prescription medicines cause the most serious Ativan drug interactions, because many of them are designed to calm, numb or sedate.
Opioid pain and cough medicines carry a boxed warning
Opioids are the single most important interaction. In August 2016 the FDA announced it would require boxed warnings on opioids and benzodiazepines about the risk of using them together. That covers pain pills such as oxycodone, hydrocodone, morphine and tramadol, plus prescription cough syrups that contain codeine or hydrocodone.
The Ativan label warns that the combination can cause profound sedation, slowed or stopped breathing, coma and death. It also says that when both are truly needed, prescribers should use the lowest doses for the shortest time and watch closely. Our guide to opioid safety, naloxone and secure storage covers how households with both drug types can lower the risk.
Buprenorphine and methadone need a careful balance
Buprenorphine (Suboxone and others) and methadone are opioids too, so the same breathing risk applies. But the FDA added an important nuance in September 2017: people in opioid addiction treatment should not be denied buprenorphine or methadone just because they also take a benzodiazepine. The agency’s 2017 FDA safety update on addiction medicines explains that untreated opioid addiction can be more dangerous than the combination, and that careful management by the care team lowers the risk.
In practice, that means telling every prescriber about both medicines and never stopping either one on your own. Our article on Suboxone induction and maintenance treatment explains how that care usually works.
Gabapentin and pregabalin can deepen breathing problems
Gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica) are often prescribed for nerve pain, seizures, and sometimes anxiety. In December 2019 the FDA issued a warning about breathing problems with gabapentinoids, noting that the risk is highest when they are combined with other central nervous system depressants, in older adults, and in people with lung disease such as COPD.
Ativan is one of those depressants. The pairing is sometimes prescribed on purpose, but it calls for extra caution, especially at night. Among Ativan drug interactions, this is one of the most often overlooked, because gabapentin feels mild to many people.
Clozapine and other antipsychotics
Clozapine (Clozaril) gets its own line on the Ativan label. The combination has been linked with marked sedation, heavy drooling, low blood pressure, unsteady walking, delirium and, rarely, respiratory arrest. People starting clozapine while already on a benzodiazepine are usually watched closely in the first weeks.
Other antipsychotics, such as olanzapine, quetiapine and haloperidol, add sedation and can lower blood pressure. The label lists antipsychotics among the CNS depressants that increase lorazepam’s effects.
Valproate and probenecid raise lorazepam levels
This is where Ativan’s liver pathway matters. Valproate (Depakote, used for seizures and bipolar disorder) and probenecid (used for gout) both interfere with glucuronidation, the step that clears lorazepam. Lorazepam then builds up in the blood and lasts longer.
The FDA label states that the lorazepam dose should be cut to roughly 50% when either drug is added. That is a decision for the prescriber, not a change to make at home, but it is a good reason to make sure every doctor knows about every medicine on your list.
Sedating antidepressants
Antidepressants are common partners for Ativan, often while a new SSRI is still kicking in. Most SSRIs, such as sertraline or fluoxetine, have little direct effect on lorazepam levels, though they can add mild drowsiness. The more sedating options deserve more attention: trazodone, mirtazapine, and older tricyclics like amitriptyline and doxepin. Our page on Prozac drug interactions shows how an SSRI’s own interaction list compares.
Other benzodiazepines and Z-drugs
Taking two benzodiazepines, or Ativan plus a “Z-drug” sleep medicine such as zolpidem (Ambien), eszopiclone (Lunesta) or zaleplon, doubles up on the same brain receptor. The effects stack: heavier sedation, more memory gaps, more falls. This sometimes happens by accident when a patient has prescriptions from two doctors. Our guide to Ambien drug interactions covers the sleep-aid side of this pairing, and Klonopin vs Ativan explains why switching between benzos is handled carefully.
Muscle relaxants
Cyclobenzaprine (Flexeril), methocarbamol, carisoprodol (Soma), tizanidine and baclofen all cause drowsiness. With lorazepam, that drowsiness can turn into confusion, poor coordination and slowed breathing. StatPearls specifically lists muscle relaxants among the CNS depressants that raise the risk of side effects with lorazepam.
Theophylline and aminophylline
Theophylline, an older asthma and COPD medicine, works in the opposite direction. The label says theophylline and aminophylline may reduce the sedative effect of benzodiazepines. That is usually not dangerous, but it can make Ativan seem weaker. If you start or stop theophylline, tell the prescriber who manages your lorazepam.
In the medicine cabinet: over-the-counter products
The riskiest OTC products are the ones that do not look risky, and they account for many surprise Ativan drug interactions. Many contain a sedating antihistamine, which the Ativan label specifically names as an additive depressant.
Sleep aids with diphenhydramine or doxylamine
Products labeled “PM” or “nighttime,” along with ZzzQuil, Unisom and plain Benadryl, use diphenhydramine or doxylamine to make you drowsy. On top of lorazepam, they can cause next-day grogginess, confusion and falls, and in older adults they add to memory problems. Our article on combining Ambien and Benadryl explains the same stacking problem with a different sleep drug.
Nighttime cold and flu medicines
NyQuil-type products usually combine a sedating antihistamine with dextromethorphan, acetaminophen, and sometimes alcohol in the liquid form. Each sedating piece adds to Ativan. A daytime, non-drowsy version or a single-ingredient product is often a better fit, but ask the pharmacist first. Our post on whether you can take NyQuil with tramadol breaks down what is inside these combination products.
Dextromethorphan combinations
Dextromethorphan (the “DM” in many cough syrups) is fairly safe at normal doses on its own, but it can cause dizziness and drowsiness. Combined with lorazepam, those effects grow, and at high doses dextromethorphan can cause confusion of its own. Stick to the labeled amount and avoid stacking several “DM” products.
Motion-sickness pills
Dimenhydrinate (Dramamine) and meclizine are antihistamines and can be quite sedating. Travelers sometimes take one along with Ativan for a flight, which can leave them much sleepier than planned. A scopolamine patch is a prescription alternative with its own side effects, so talk with the prescriber before a trip.
In the kitchen and at the bar
Alcohol is the most common dangerous pairing
Alcohol and lorazepam both act on the same calming receptor in the brain, so they multiply each other’s effects. The result can be blackouts, falls, car crashes and slowed breathing. The label warns about this directly, and MedlinePlus notes that alcohol can make lorazepam’s side effects worse. We cover the details, including timing questions, in can you drink alcohol on Ativan.
Caffeine works against Ativan
Caffeine is not dangerous with lorazepam, but it pushes in the opposite direction. Heavy coffee, energy drinks or caffeine pills can worsen anxiety and sleep, which may make Ativan seem less effective. Caffeine does not cancel out lorazepam’s effects on driving or coordination, so a strong coffee is not a way to “sober up.”
Grapefruit is not a big issue for Ativan
Grapefruit juice blocks CYP3A4, a gut and liver enzyme, which raises levels of drugs that depend on it. That is why grapefruit matters for alprazolam (Xanax), triazolam (Halcion) and midazolam. Lorazepam does not go through CYP3A4, so grapefruit is not expected to change its levels in a meaningful way. If you take other medicines that do use CYP3A4, though, the grapefruit warning may still apply to them.
On the supplement shelf
Supplements are the least studied corner of Ativan drug interactions, because research on them is thin. For most, the honest answer is “we know they can be sedating, but we do not have good data on how much they add to lorazepam.” That uncertainty is itself a reason to check first.
Kava
Kava has the clearest warning. The NIH page on kava safety advises against combining it with other sedating substances such as benzodiazepines or alcohol, and it notes rare but serious liver injury linked to kava products. Avoid kava while taking Ativan unless your prescriber specifically approves it.
Valerian, chamomile and other calming herbs
Valerian root, passionflower, lemon balm, hops and chamomile are marketed for sleep and stress. Their effects are usually mild, and studies on combining them with benzodiazepines are limited. Still, they may add drowsiness, and product strength varies widely between brands.
Melatonin
Melatonin is generally gentle, but it does cause sleepiness, and some people feel groggy the next morning. With Ativan, the main concern is extra drowsiness and next-day fog, particularly in older adults. Non-drug sleep habits, like a steady wake time and a dark, cool bedroom, do not add to sedation at all.
CBD and cannabis
THC-containing cannabis adds sedation, slows reaction time, and impairs memory, all of which overlap with lorazepam. CBD alone appears less sedating, but it can still cause drowsiness, and product labels are often inaccurate. Research on CBD with lorazepam specifically is sparse, so treat the combination with caution and do not drive.
Kratom
Kratom acts partly on opioid receptors. StatPearls notes that kratom combined with benzodiazepines can sharply raise the risk of severe CNS depression and says the pairing should be avoided.
St John’s wort
St John’s wort is a powerful enzyme inducer and matters a lot for drugs like Xanax. Because lorazepam is not cleared by those enzymes, it is less relevant for Ativan. It can still interact with many other medicines, including antidepressants, so do not start it without a pharmacist’s review.
Hormones and birth control
The Ativan label does not list hormonal birth control as an interaction. However, an older small study found that women taking combined oral contraceptives cleared lorazepam faster, apparently because estrogen speeds up glucuronidation. In theory, that could make lorazepam wear off a bit sooner.
The clinical meaning of this is uncertain, and lorazepam does not reduce the effectiveness of birth control. If you notice that Ativan seems to work for a shorter time after starting or stopping a pill, patch or ring, mention it to your prescriber rather than adjusting your own dose.
In the hospital
Anesthesia and procedural sedation
The label lists anesthetics among the drugs that add to lorazepam’s effects. Surgeons and anesthesia teams plan for this all the time, but only if they know. Tell them how much Ativan you take, how often, and when your last dose was. Do not skip doses before surgery unless the care team tells you to, because stopping suddenly can trigger withdrawal.
Flumazenil
Flumazenil is a hospital drug that reverses benzodiazepines. It sounds like the perfect antidote, but the label warns that in people who take lorazepam long term, it can trigger sudden withdrawal, including seizures. For that reason, it is used selectively and only in a monitored setting. Our guide to Ativan withdrawal explains why abrupt changes are risky.
Ativan interactions A to Z: lookup table
Use this table of Ativan drug interactions as a starting point for a conversation with your pharmacist, not as a final answer.
| Substance | Why it matters with lorazepam | What usually happens / what to ask |
|---|---|---|
| Alcohol | Same brain target; effects multiply | Avoid. Ask how long after a dose alcohol is still a concern. |
| Aminophylline / theophylline | May reduce sedative effect | Ativan may feel weaker. Report changes when starting or stopping. |
| Anesthesia | Additive sedation and breathing effects | Tell the surgical team your dose and last dose time. |
| Antipsychotics (olanzapine, quetiapine, haloperidol) | Additive sedation, low blood pressure | Ask about fall risk and dizziness on standing. |
| Buprenorphine / methadone | Opioid plus benzo breathing risk | Do not stop either. Ask for coordinated care and naloxone. |
| Cannabis (THC) / CBD | Added sedation and impairment | Do not drive. Ask whether any use is reasonable for you. |
| Clozapine | Marked sedation, drooling, low blood pressure, rare respiratory arrest | Usually needs close monitoring when started. |
| Cold and flu “nighttime” products | Sedating antihistamine, sometimes alcohol | Ask for a non-drowsy or single-ingredient option. |
| Dextromethorphan | Dizziness and drowsiness add up | Use only labeled amounts; avoid stacking DM products. |
| Diphenhydramine / doxylamine | Sedating antihistamines named on label | Avoid as sleep aids unless your prescriber approves. |
| Flumazenil | Reverses benzos; can provoke withdrawal seizures | Hospital use only, with monitoring. |
| Gabapentin / pregabalin | FDA warning on breathing problems with CNS depressants | Ask about nighttime dosing and lung disease risk. |
| Grapefruit | Lorazepam does not use CYP3A4 | Not expected to matter for Ativan; check your other drugs. |
| Kava | Sedating; NIH advises against mixing with benzos | Avoid. |
| Kratom | Opioid-like effects plus benzo | Avoid; severe CNS depression reported. |
| Melatonin | Mild added drowsiness | Ask about timing; watch for morning grogginess. |
| Motion-sickness pills (dimenhydrinate, meclizine) | Sedating antihistamines | Plan travel doses with your prescriber. |
| Muscle relaxants | Added sedation and confusion | Ask whether a lower dose or non-drug option fits. |
| Opioids (oxycodone, hydrocodone, tramadol, codeine) | Boxed warning: sedation, slowed breathing, death | Ask whether both are needed and about naloxone. |
| Oral contraceptives | May speed lorazepam clearance (small study) | Report if Ativan wears off sooner. |
| Other benzos and Z-drugs | Same receptor; effects stack | Make sure one prescriber sees the full list. |
| Sedating antidepressants (trazodone, mirtazapine, tricyclics) | Added drowsiness | Ask about bedtime timing and fall risk. |
| Valproate / probenecid | Block glucuronidation; raise lorazepam levels | Label suggests about a 50% lower lorazepam dose; prescriber decides. |
Why Ativan sidesteps grapefruit but not opioids
There are two ways one substance can change another. The first is a level interaction (pharmacokinetic): one drug changes how fast the other is cleared, so blood levels rise or fall. The second is an effect interaction (pharmacodynamic): both drugs act on the body in the same direction, so the combined effect is bigger even if blood levels do not change.
Grapefruit, St John’s wort, many antifungals and some antibiotics cause level interactions through the CYP enzymes. Lorazepam is cleared by glucuronidation instead, as the StatPearls lorazepam review describes, so most of those enzyme interactions pass it by. That is also why lorazepam is often preferred for people with liver disease.
Opioids, alcohol and sleep aids cause effect interactions. They do not need to change lorazepam levels at all. Each one quiets the brainstem centers that keep you breathing, and when several are on board at once, the brakes on breathing can fail. No liver pathway protects against that.
The takeaway for Ativan drug interactions: lorazepam’s clean metabolism makes it predictable, but it does nothing to make sedation stacking safer. That is also why it does not linger in an unusual way; see how long Ativan stays in your system for half-life details.
Who should be extra careful with Ativan drug interactions
- Older adults. Sedation and unsteadiness from lorazepam rise with age, according to the label. Add a second sedating drug and the risk of falls, hip fractures and confusion climbs quickly.
- People with sleep apnea or COPD. The label warns that lorazepam can worsen breathing in these conditions. The FDA’s gabapentinoid warning flags lung disease too, so combinations deserve extra scrutiny.
- People with liver or kidney disease. Lorazepam is easier on the liver than many benzos, but severe liver disease and kidney disease can still change how the body handles it and its metabolite. Expect closer monitoring.
- People in addiction treatment. Anyone taking buprenorphine or methadone, or recovering from alcohol use, needs a coordinated plan. That plan should include naloxone in the home if opioids are involved.
- People with several prescribers. Interactions often slip through when no single doctor sees the whole list. Using one pharmacy helps.
Bring this to your pharmacist: a 6-item script
MedlinePlus advises telling your doctor and pharmacist about every prescription, OTC product, vitamin and herbal supplement you take, and it calls out cough and pain medicines in particular. Here is a short script you can read out loud or show on your phone:
- “I take lorazepam (Ativan). Here is my full list, including vitamins, supplements and anything I take only sometimes.”
- “Do any of these add to sedation or slow my breathing?”
- “Is there anything here, like valproate or probenecid, that changes my lorazepam level?”
- “Which cold, allergy, or sleep products are safest for me to keep at home?”
- “Should I have naloxone at home, given my other medicines?”
- “What signs of too much sedation should my family watch for?”
The MedlinePlus lorazepam guide is a good plain-language companion to bring along.
Emergency signs of oversedation
Call 911 right away if someone taking Ativan with another sedating substance shows any of these signs:
- Cannot be woken up, or wakes only briefly and drifts off again
- Slow, shallow, irregular or noisy breathing (snoring or gurgling sounds)
- Blue or gray lips or fingertips
- Severe confusion, slurred speech or inability to stand
- Limp body or very slow heartbeat
Stay with the person and place them on their side if they are breathing but not alert. If opioids could be involved, give naloxone if you have it. Naloxone does not reverse lorazepam, but it can reverse the opioid part and it will not hurt someone who has no opioids in their system. For questions that are not emergencies, Poison Control is available 24/7 at 1-800-222-1222.
Frequently asked questions about Ativan drug interactions
What should you not take with Ativan?
The main things to avoid unless a prescriber has planned for them are opioids, alcohol, other benzodiazepines, Z-drug sleep aids, sedating antihistamines, kava and kratom. Valproate and probenecid need a dose review because they raise lorazepam levels.
Does Ativan interact with grapefruit?
Not in a meaningful way. Grapefruit blocks the CYP3A4 enzyme, and lorazepam does not use that enzyme. Some other benzodiazepines, like Xanax, are affected.
Can I take Ativan with an SSRI like sertraline or Lexapro?
Doctors commonly prescribe them together, often while an SSRI starts working. SSRIs do not usually change lorazepam levels, but both can add drowsiness, so follow your prescriber’s plan.
Is it safe to take Benadryl with Ativan?
Diphenhydramine is a sedating antihistamine, a group the Ativan label lists as an additive depressant. The combination can cause heavy drowsiness and confusion, especially in older adults. Ask your pharmacist for a non-sedating option.
Can I take Ativan and gabapentin together?
They are sometimes prescribed together, but the FDA warns that gabapentinoids can cause serious breathing problems when combined with other CNS depressants. Use the combination only as directed and report heavy sleepiness or breathing changes.
Does Ativan interact with birth control?
Ativan does not make birth control less effective. A small older study suggests the pill may clear lorazepam faster, which could shorten its effect. Talk to your prescriber if you notice a change.
What if I already took Ativan with something on this list?
If the person is alert and breathing normally, call Poison Control at 1-800-222-1222 or your pharmacist for advice. If they are hard to wake or breathing slowly, call 911.
Medical disclaimer
This article explains general patterns in how lorazepam interacts with other substances, and it cannot account for your health history, your exact medicine list or your doses. Treat it as background reading, and let your prescriber and pharmacist make any decision about starting, stopping or combining medicines.
