Key takeaways:
Zyrtec (cetirizine) is an over-the-counter antihistamine used to treat allergy symptoms. Its active ingredient is also available as a prescription infusion called Quzyttir.
Zyrtec interacts with alcohol, other oral antihistamines, and opioids. It also interacts with sleep medications and certain cold medications. Many Zyrtec interactions raise the risk of side effects such as severe drowsiness and dizziness.
Zyrtec can make certain medications, such as Wakix (pitolisant) and gabapentin (Neurontin, Horizant, Gralise), less effective. Your healthcare team can tell you about potential interactions.
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Zyrtec (cetirizine) is an over-the-counter (OTC) antihistamine. It is used to treat allergy symptoms, such as runny nose and sneezing.
Before taking Zyrtec, ask your healthcare team about potential interactions. Zyrtec generally causes mild or no side effects when taken as directed. But certain medications and substances can raise the risk of side effects, such as drowsiness, when combined with Zyrtec.
Here, we’ll discuss what you should know about Zyrtec interactions.
Zyrtec interactions at a glance
OTC Zyrtec comes in several forms, including tablets, capsules, and liquid syrup. Cetirizine, the active ingredient in Zyrtec, is also available by prescription as an IV infusion called Quzyttir. The interactions discussed below apply to cetirizine taken by mouth or IV.
Keep in mind: Cetirizine is also available as a prescription-only eye drop called Zerviate. Zerviate is used to treat allergy symptoms that affect the eyes. Since Zerviate is applied directly to the eyes, only a small amount of cetirizine is potentially absorbed into the bloodstream. Because of this, Zerviate is unlikely to cause interactions.
The following substances and medications can interact with Zyrtec:
Other oral antihistamines, such as Benadryl (diphenhydramine)
Many “nighttime” cold medications, such as NyQuil (acetaminophen / dextromethorphan / doxylamine)
Opioids, such as oxycodone (Roxicodone, OxyContin)
Sleeping medications, such as zolpidem (Ambien)
Other medications that cause drowsiness, such as muscle relaxers
Gabapentin (Neurontin, Gralise, Horizant)
Wakix (pitolisant)
This isn’t a complete list. So be sure to check with your healthcare team before starting a new medication with Zyrtec. It’s a good idea to share a medication list with them too. This can help your healthcare team manage interactions.
Below, we’ll dig deeper into eight Zyrtec interactions and how to manage them.
1. Other oral antihistamines
It’s common to take more than one allergy medication. But not all combinations are safe. Don’t take Zyrtec with other antihistamines unless a healthcare professional says it’s OK.
Examples of other antihistamines include:
Allegra (fexofenadine)
Chlorpheniramine
Claritin (loratadine)
Dramamine (dimenhydrinate)
Hydroxyzine (Vistaril)
Xyzal (levocetirizine)
Antihistamines can cause side effects, such as drowsiness, dry mouth, and headache. Taking more than one at a time can raise the risk of experiencing these effects. Rarely, combining antihistamines can lead to an antihistamine overdose. Symptoms may include hallucinations, fever, and a racing heart.
If you want to switch from Zyrtec to a different antihistamine, wait 24 hours after your last dose of Zyrtec.
Important to note: There isn’t enough research on combining Zyrtec and nonoral antihistamines, such as Pataday (olopatadine eye drops) and Astepro (azelastine nasal spray). For example, much of the research on combination treatments for allergic rhinitis look at antihistamines used with other types of allergy medications, such as corticosteroid nasal sprays, rather than two antihistamines used together. Ask a healthcare professional before taking Zyrtec while using a nonoral antihistamine.
2. Certain cold medications, such as NyQuil
Combination cold medications can be convenient. But they’re not always safe to take if you also take Zyrtec.
As mentioned, it’s not recommended to take Zyrtec with other antihistamines. Many “nighttime” cold medications contain an antihistamine that causes drowsiness. For example, antihistamines such as doxylamine and triprolidine are found in some combination cold products.
Popular cold medications that can interact with Zyrtec include:
NyQuil (acetaminophen / dextromethorphan / doxylamine)
Coricidin HBP Maximum Strength Night Cold & Flu (acetaminophen / dextromethorphan / doxylamine)
Delsym Nighttime Cough (acetaminophen / dextromethorphan / triprolidine)
Mucinex Nightshift Cold and Flu (acetaminophen / dextromethorphan / triprolidine)
Robitussin Maximum Strength Nighttime Cough DM (dextromethorphan / doxylamine)
Be sure to read the OTC label before taking a medication. If you see an antihistamine listed as an active ingredient, avoid it while taking Zyrtec. If you’re unsure whether your medication contains an antihistamine, ask a pharmacist. They can recommend a product that’s safe to combine with Zyrtec.
3. Opioids
Ask a healthcare professional before taking Zyrtec and an opioid, such as oxycodone. Opioids can cause drowsiness and dizziness. Combining them with Zyrtec can raise the risk of these side effects.
Keep in mind that a healthcare professional may tell you it’s OK to take both Zyrtec and an opioid. But everyone’s risks with this combination are different. For instance, you may be more sensitive to this interaction’s effects if you’re age 65 or older. A healthcare professional can help you decide if it’s OK for you to take both Zyrtec and an opioid.
4. Sleep medications
Ask your healthcare team if you can take Zyrtec with sleeping medications. Zyrtec can cause drowsiness on its own. Taking it with a sleep aid can make drowsiness more severe.
Examples of sleep medications include:
“Z-drugs,” such as zolpidem
Rozerem (ramelteon)
Orexin receptor antagonists, such as Quviviq (daridorexant)
OTC sleep aids, such as ZzzQuil (diphenhydramine) and Unisom SleepTabs (doxylamine)
As with opioids, your healthcare team may give you the OK to take both Zyrtec and a sleep medication. But it’s best to check with them before combining these medications on your own.
5. Other medications that cause drowsiness
There are many sedatives (medications that cause drowsiness) that can interact with Zyrtec. Taking Zyrtec with any of them can make sleepiness more severe. Always ask a healthcare professional before combining them.
Examples of other medications that cause drowsiness include:
Muscle relaxers, such as cyclobenzaprine
Some antidepressants, such as trazodone and doxepin (Silenor)
Other anti-seizure medications, such as oxcarbazepine (Trileptal)
Benzodiazepines, such as alprazolam (Xanax)
Ask your healthcare team if it’s OK for you to take Zyrtec with other medications that cause drowsiness. Be sure to watch for excessive sleepiness if they say you can take both.
6. Alcohol
It’s best to avoid alcohol while taking Zyrtec. Alcohol slows down your central nervous system (brain and spinal cord). This can make you feel sleepy and less coordinated. Zyrtec can also cause drowsiness as a side effect. Taking Zyrtec with alcohol can worsen these side effects.
Completely avoiding alcohol is recommended when taking Zyrtec. But this may not be realistic for you. Ask a healthcare professional if it’s OK for you to consume an occasional drink while taking Zyrtec. If needed, your healthcare team can also help you safely reduce or stop drinking alcohol.
7. Gabapentin
Gabapentin is a medication that treats nerve pain and seizures. Zyrtec can interact with gabapentin in two different ways.
Gabapentin commonly causes drowsiness and dizziness. Taking gabapentin with Zyrtec may worsen these side effects. And certain people, such as older adults, may have a greater risk of this when taking both medications.
Zyrtec can also lower gabapentin levels in your body. This means that gabapentin may not work as well as expected. And if you’re taking gabapentin for seizure management, this interaction could trigger seizures.
Ask a healthcare professional before combining Zyrtec and gabapentin to make sure it’s safe for you.
8. Wakix
Wakix treats excessive daytime sleepiness in people living with narcolepsy. It works by attaching to certain histamine receptors (binding sites) in the brain. It also raises levels of histamine. So you should avoid taking antihistamines that attach to these same receptors.
Zyrtec is able to bind to these histamine receptors in the brain. This means it may stop Wakix from working as well as it should. So it’s recommended to avoid this combination.
Make sure your prescriber knows if you take Zyrtec before you start Wakix. They’ll likely recommend an alternative to Zyrtec to help you avoid this interaction.
Frequently asked questions
Yes, you can take Zyrtec and ibuprofen (Advil, Motrin) together. In fact, this combination may be helpful if your allergy symptoms include sinus headaches.
Just be sure to read the OTC label of your products carefully. Ibuprofen is sometimes combined with an antihistamine in a single product. One example is Motrin PM (ibuprofen / diphenhydramine). It’s best to avoid taking combination products that contain an antihistamine and Zyrtec at the same time. It can raise your risk of side effects such as drowsiness and dry mouth.
Yes, you can take Zyrtec and Tylenol (acetaminophen) together. These medications don’t interact.
But there are many products that combine Tylenol’s active ingredient with other antihistamines. For example, Tylenol Nighttime Severe Cough + Sore Throat (acetaminophen / dextromethorphan / doxylamine) contains an antihistamine called doxylamine. You should avoid taking these products with Zyrtec since taking multiple antihistamine medications can increase your risk of side effects. These side effects can include dizziness, headache, and constipation.
Yes, you can take Zyrtec and ibuprofen (Advil, Motrin) together. In fact, this combination may be helpful if your allergy symptoms include sinus headaches.
Just be sure to read the OTC label of your products carefully. Ibuprofen is sometimes combined with an antihistamine in a single product. One example is Motrin PM (ibuprofen / diphenhydramine). It’s best to avoid taking combination products that contain an antihistamine and Zyrtec at the same time. It can raise your risk of side effects such as drowsiness and dry mouth.
Yes, you can take Zyrtec and Tylenol (acetaminophen) together. These medications don’t interact.
But there are many products that combine Tylenol’s active ingredient with other antihistamines. For example, Tylenol Nighttime Severe Cough + Sore Throat (acetaminophen / dextromethorphan / doxylamine) contains an antihistamine called doxylamine. You should avoid taking these products with Zyrtec since taking multiple antihistamine medications can increase your risk of side effects. These side effects can include dizziness, headache, and constipation.
The bottom line
Zyrtec (cetirizine) is an over-the-counter antihistamine that treats allergy symptoms. The active ingredient in Zyrtec, cetirizine, is also available as a prescription IV infusion called Quzyttir, which has the same interaction risks.
Zyrtec interacts with many medications and substances, such as alcohol, opioids, and other antihistamines. It also interacts with sleep aids and certain cold medications. These interactions can increase your risk of side effects such as drowsiness. Zyrtec can also prevent certain medications, such as Wakix (pitolisant), from working as well as they could.
If you’re concerned about a Zyrtec interaction, talk to your healthcare team. They can help you avoid or manage Zyrtec interactions.
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References
Costa, A. C. C., et al. (2020). Cetirizine reduces gabapentin plasma concentrations and effect: Role of renal drug transporters for organic cations. The Journal of Clinical Pharmacology.
Harmony Biosciences. (2026). Wakix- pitolisant hydrochloride tablet, film coated [package insert]. DailyMed.
Kong, W., et al. (2024). High-risks drug adverse events associated with Cetirizine and Loratadine for the treatment of allergic diseases: A retrospective pharmacovigilance study based on the FDA adverse event reporting system database. Clinical and Translational Allergy.
Naqvi, A., et al. (2024). Cetirizine. StatPearls.
Renko, A., et al. (2022). Unintentional cetirizine overdose causing anticholinergic syndrome. The American Journal of Emergency Medicine.
Zhang, Y., et al. (2025). Efficacy and safety of combined pharmacotherapies in moderate-to-severe allergic rhinitis: A network meta-analysis. International Forum of Allergy & Rhinology.
