8 Antihistamine Interactions: Alcohol, Sleep Aids, and More

Antihistamines are commonly used to manage allergy symptoms. But they have several other uses. They’re taken for motion sickness, hives, and occasional sleep troubles. And they’re very accessible. Many are available over the counter (OTC).

Antihistamines can be split into two types: older and newer. First-generation (older) antihistamines have a greater risk of side effects. Second- and third-generation (newer) antihistamines have a lower risk. Notable side effects include drowsiness, dizziness, and dry mouth.

Some medications, substances, and even foods can raise the risk of these side effects. For instance, taking antihistamines with opioids can cause severe drowsiness or dizziness. Below, we dig deeper into eight common antihistamine interactions.

Good to know: Histamine-2 (H2) blockers are a type of antihistamine used for heartburn. They work differently from histamine-1 (H1) antihistamines, which are used for allergies. This article will focus on H1 antihistamines and their interactions.

1. Alcohol

Alcohol slows down activity in the brain. This affects balance and coordination. It can also make you sleepy and lightheaded. Antihistamines, especially older ones, can also cause these side effects.

Mixing alcohol with antihistamines can worsen these effects. It can also raise the risk of falls, especially in older adults. This interaction is riskier with older antihistamines, such as diphenhydramine (Benadryl, ZzzQuil). But there are still risks with newer ones like cetirizine (Zyrtec).

No amount of alcohol is safe to drink with antihistamines, so it’s best to avoid this combination. But you can talk with a healthcare professional about what a safer amount might be if you choose to drink.

2. Other antihistamines

It’s common for people to take more than one allergy medication. But it’s important to know which ones are safe to take together. In general, you shouldn’t use more than one antihistamine at a time.

Taking multiple antihistamines can worsen sleepiness, dizziness, and dry mouth. And in rare cases, an antihistamine overdose is possible. Symptoms of an overdose include agitation, rapid heartbeat, and hallucinations.

Antihistamines come in different dosage forms. The table below provides examples of antihistamine formulations.

Unless a healthcare professional tells you otherwise, don’t use more than one antihistamine of the same dosage form. For example, you shouldn’t take two oral antihistamines at the same time.

And be sure to ask a healthcare professional before mixing different forms. For instance, double check before using an oral antihistamine with an antihistamine nasal spray. These combinations haven’t been well studied for safety.

EXPERT PICKS: WHAT TO READ NEXT

• All about side effects: Many antihistamine interactions raise the risk of side effects. Read about notable antihistamine side effects here.

• Combining allergy medications: Pharmacists explain which allergy medications you can safely take together.

• Alcohol and antihistamines: Here’s why you shouldn’t drink alcohol while taking antihistamines.

3. Sleep aids

It’s not recommended to take older antihistamines with sleep aids. Older antihistamines typically cause drowsiness. Combining them with sleep aids can lead to excessive drowsiness or dizziness.

Examples of sleep aids include:

• “Z-drugs,” such as zolpidem (Ambien)

• Ramelteon (Rozerem)

• Orexin receptor antagonists, such as daridorexant (Quviviq)

• OTC sleep aids, such as ZzzQuil and Unisom SleepTabs

• Melatonin

It’s best to avoid taking any antihistamine with sleep aids. But if you need to take an antihistamine, look for ones labeled “nondrowsy.” They’re generally safer because they have a lower risk of drowsiness than older antihistamines.

4. Opioids

Avoid combining opioids and older antihistamines.

Opioids are a class of prescription-only pain relievers. They slow down activity in the brain. This causes side effects like sleepiness and dizziness. Taking them with older antihistamines could make these side effects worse.

Examples of opioids include:

• Oxycodone (Roxicodone, OxyContin)

• Tramadol (ConZip)

• Hydrocodone (Hinsingla ER)

• Fentanyl

It’s a good idea to avoid taking antihistamines if you take opioids. But if you need to take both, a newer antihistamine would be safer.

5. Other medications that cause drowsiness

You should also avoid taking antihistamines with other medications that cause drowsiness. This combination can worsen sleepiness or dizziness.

Other medications that cause drowsiness include:

• Benzodiazepines, such as alprazolam (Xanax)

• Muscle relaxers, such as cyclobenzaprine (Amrix)

• Anti-seizure medications, such as gabapentin (Neurontin)

• Barbiturates, such as phenobarbital

As discussed above, this interaction is riskier with older antihistamines. But there’s a risk with any antihistamine. If you can’t avoid the combination, consider taking a nondrowsy antihistamine.

6. Anticholinergic medications, such as dicyclomine

You should also avoid taking older antihistamines with anticholinergic medications. Examples include tiotropium (Spiriva), oxybutynin, and dicyclomine.

Anticholinergics treat several conditions, including Parkinson’s disease and overactive bladder. They work by blocking a chemical in the body called acetylcholine.

Blocking acetylcholine causes several side effects. These are called anticholinergic side effects. Examples include:

• Dry mouth

• Constipation

• Dry eye

• Trouble urinating

While they’re not considered anticholinergics, older antihistamines also block acetylcholine. So combining them with anticholinergics raises the risk of these side effects. In rare cases, taking too many medications that block acetylcholine can cause serious side effects. Examples include confusion, flushing, and fever.

Newer antihistamines have less of an effect on acetylcholine. So it may be safe to combine one with an anticholinergic. But it’s a good idea to double check with your healthcare team first.

7. Certain antidepressants, such as amitriptyline

Older antihistamines also interact with certain antidepressants. Many antidepressants cause drowsiness. Mixing them with older antihistamines may make sleepiness more likely.

Examples of antidepressants that can cause drowsiness include:

• Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac)

• Serotonin and norepinephrine reuptake inhibitors (SNRIs), such as duloxetine (Cymbalta)

• Trazodone

• Tricyclic antidepressants (TCAs), such as amitriptyline

TCAs also cause anticholinergic side effects. So taking one with an older antihistamine can raise the risk of these effects and drowsiness.

Taking newer antihistamines with the above antidepressants is less likely to cause an issue.

8. Fruit juice with fexofenadine

Most antihistamines don’t interact with fruit juice. But fexofenadine (Allegra) interacts with apple, orange, and grapefruit juice. These juices lower the amount of fexofenadine that your body absorbs. This means it may not work as well.

But don’t worry. You don’t have to completely avoid these beverages. Just be sure to separate fexofenadine from fruit juice by at least 4 hours.

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Written by:

Kristina D. Carter, PharmD, MBA, MHA

Kristina D. Carter, PharmD, MBA, MHA, has over 25 years of experience working in healthcare. She is registered as a licensed pharmacist in Georgia, Indiana, and Tennessee.

Edited by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

Reviewed by:

Austin Ulrich, PharmD, BCACP

Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. In his early career, he provided direct patient care in a variety of settings, including hospital and community pharmacies, and in a primary care clinic as a clinical pharmacist.

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