What medications should I avoid with Zyrtec?

October 9, 2025 •

4 min read

While Zyrtec (cetirizine) is a common over-the-counter allergy medication, medical professionals generally advise caution when mixing it with other central nervous system (CNS) depressants due to increased sedation. To ensure your safety, it's crucial to understand what medications should I avoid with Zyrtec to prevent harmful interactions.

Quick Summary

Avoid combining Zyrtec with alcohol, other antihistamines, and central nervous system depressants like opioids, muscle relaxants, and sedatives. These combinations increase the risk of severe drowsiness and impaired coordination, impacting your ability to drive or operate machinery safely.

Key Points

Avoid Alcohol: Combining alcohol and Zyrtec intensifies sedative effects, increasing drowsiness and impairing judgment and coordination.
Do Not Double Up on Antihistamines: Avoid taking Zyrtec with other oral antihistamines (including Benadryl, Claritin, and Allegra) to prevent excessive side effects and overdose risk.
Beware of Central Nervous System Depressants: Exercise extreme caution with sleep aids, opioids, muscle relaxants, and certain psychiatric medications, as they can cause severe drowsiness when combined with Zyrtec.
Check Labels for Combination Products: Many cold and flu medications contain antihistamines, so always check the label and avoid taking them with Zyrtec.
Zyrtec-D Has Unique Risks: The decongestant in Zyrtec-D (pseudoephedrine) interacts dangerously with MAOIs and should be avoided with other decongestant products.
Consult a Healthcare Professional: Always speak with a doctor or pharmacist before combining Zyrtec with any other medication, especially if you have underlying health conditions.

Zyrtec, whose active ingredient is cetirizine, is a popular second-generation antihistamine used to relieve allergy symptoms such as sneezing, a runny nose, and watery eyes. Unlike first-generation antihistamines (like Benadryl), Zyrtec is generally considered non-drowsy. However, drowsiness is still a potential side effect for some individuals, and this risk is significantly heightened when Zyrtec is combined with other medications or substances that affect the central nervous system (CNS). Understanding these interactions is essential for preventing adverse effects and ensuring your safety.

The danger of mixing Zyrtec with CNS depressants

Central nervous system depressants are drugs that slow down brain activity. When you combine Zyrtec with other CNS depressants, the sedative effects can be amplified, leading to increased drowsiness, dizziness, and impaired cognitive function. This can significantly impact your ability to perform tasks requiring mental alertness and motor coordination, such as driving or operating heavy machinery. The risk of accidents and injury increases considerably with these combinations.

Alcohol

Consuming alcohol while taking Zyrtec is not recommended. Both substances can cause drowsiness, and when mixed, these sedative effects are intensified. The combination can lead to severe dizziness, headaches, blurred vision, and impaired judgment. Additionally, both Zyrtec and alcohol are metabolized by the liver, and their concurrent use can place additional strain on the organ. It is safest to avoid alcohol entirely while using Zyrtec.

Other Oral Antihistamines

Taking Zyrtec with another oral antihistamine is strongly discouraged unless specifically instructed by a healthcare provider. Doubling up on antihistamines, including other second-generation types like Claritin (loratadine) or Allegra (fexofenadine), can increase the risk of side effects like drowsiness and dizziness without providing any additional symptom relief. The same goes for older, first-generation antihistamines like Benadryl (diphenhydramine). This also includes combination cold and allergy products, so always check the label for active ingredients.

Sedatives, Tranquilizers, and Sleep Aids

Due to the risk of significant additive drowsiness, Zyrtec should not be combined with sedatives, tranquilizers, or sleep aids without medical supervision. This category includes both prescription medications and over-the-counter products.

Examples of these medications include:

Prescription sleep aids: Zolpidem (Ambien), eszopiclone (Lunesta)
Benzodiazepines: Alprazolam (Xanax), lorazepam (Ativan), diazepam (Valium)
Over-the-counter sleep aids: Diphenhydramine (found in ZzzQuil), doxylamine (found in Unisom)

Opioid Pain Relievers

Opioids are powerful CNS depressants used for pain relief. Combining them with Zyrtec can substantially increase the risk of severe drowsiness, dizziness, and slow breathing. A healthcare professional must determine if taking both is safe for you, as the risk level is different for everyone, especially older adults.

Muscle Relaxants

Muscle relaxants, such as cyclobenzaprine, are designed to relax muscles and can cause drowsiness on their own. Taking them with Zyrtec can significantly enhance this sedative effect.

Certain Psychiatric Medications

Several psychiatric medications, including some antidepressants and anti-anxiety drugs, can also cause drowsiness. Combining these with Zyrtec increases the likelihood of sedation and impaired cognitive function. Examples include trazodone and certain antipsychotics.

Important considerations for Zyrtec-D

Zyrtec-D is a combination product that contains both cetirizine and a decongestant called pseudoephedrine. The decongestant component introduces specific and serious drug interactions. You must not take Zyrtec-D if you have taken a monoamine oxidase inhibitor (MAOI) within the last 14 days, as a dangerous interaction can occur. Examples of MAOIs include isocarboxazid, phenelzine, and linezolid. You should also avoid other decongestant products when taking Zyrtec-D to prevent overdosage of pseudoephedrine.

Comparison of Zyrtec Interactions


Drug/Substance Class	Example(s)	Interaction Risk	Reason for Interaction
Alcohol	Beer, wine, liquor	High	Both are CNS depressants, leading to amplified sedation and impairment.
Other Oral Antihistamines	Benadryl, Allegra, Claritin, NyQuil	High	Duplication of active ingredients increases side effects and overdose risk.
Sedatives/Sleep Aids	Ambien, Xanax, Unisom	High	Significant additive CNS depression, causing excessive drowsiness.
Opioids	Oxycodone, hydrocodone	High	Compounding CNS depressant effects leading to severe sedation.
Muscle Relaxants	Cyclobenzaprine	High	Additive sedative effects, increasing drowsiness.
MAOIs (with Zyrtec-D)	Phenelzine, Linezolid	Very High	Dangerous and potentially fatal interaction with pseudoephedrine in Zyrtec-D.

Consulting a healthcare professional

Before starting any new medication, including over-the-counter drugs like Zyrtec, it is crucial to consult with a doctor or pharmacist. This is especially important if you have pre-existing conditions, particularly liver or kidney disease, which can affect how your body processes medication. Always provide your healthcare team with a full list of all medications, supplements, and herbal products you are taking to identify potential risks. A professional can help you navigate drug interactions and provide personalized advice for your specific health situation.

Conclusion

While Zyrtec is a safe and effective allergy treatment for many, it carries significant interaction risks with several common medications and substances. The most important rule is to avoid combining it with other central nervous system depressants, including alcohol, other antihistamines, sleep aids, and opioid pain relievers, due to the risk of severe drowsiness and impaired coordination. Always read the active ingredients on all medication labels, and exercise extra caution if using the Zyrtec-D variant, which has specific contraindications with MAOIs. By understanding these potential interactions and seeking advice from a healthcare professional, you can use Zyrtec safely and effectively to manage your allergies.

For more information on drug interactions, you can consult reliable sources such as the GoodRx website.

Frequently Asked Questions

No, it is best to avoid alcohol while taking Zyrtec. Combining the two can significantly increase drowsiness, dizziness, and impair your judgment and coordination due to their combined effect as CNS depressants.

You should not take Zyrtec and Benadryl (diphenhydramine) together. Both are antihistamines, and taking them at the same time can lead to excessive drowsiness, fatigue, and other side effects, with no added allergy relief benefit.

Combining Zyrtec with a sleep aid such as Ambien (zolpidem) can cause severe drowsiness and slowed brain function. The sedative effects of both drugs are amplified, increasing the risk of accidents and impairing mental alertness.

No, you should not take Zyrtec with opioid pain relievers like oxycodone without consulting a doctor first. The combination can lead to a significantly increased risk of severe drowsiness, dizziness, and potentially slow breathing.

No, you must not take Zyrtec-D (which contains pseudoephedrine) if you have taken an MAO inhibitor within the last 14 days. This combination can lead to a dangerous and potentially fatal drug interaction.

You should avoid any cold and flu products that contain an oral antihistamine. Always check the label for ingredients like diphenhydramine or doxylamine, as they will cause excessive drowsiness when combined with Zyrtec.

Yes, it is generally safe to take Zyrtec with acetaminophen (Tylenol) or ibuprofen (Advil, Motrin). However, you should avoid any combination products (e.g., Motrin PM or Tylenol Nighttime) that also contain an antihistamine.