Does diphenhydramine interact with Luvox? (+3 precautions)

In this article, we will discuss whether or not diphenhydramine interacts with Luvox, the possible side effects and risks when diphenhydramine and Luvox are combined, safe substitutes for diphenhydramine, and precautions while taking diphenhydramine with Luvox.

Does diphenhydramine interact with Luvox?

Yes, diphenhydramine does interact with Luvox (fluvoxamine). Diphenhydramine may increase the risk of adverse effects when combined with Luvox. Diphenhydramine can decrease the metabolism of fluvoxamine. (1)

Diphenhydramine is an antihistamine and sedative. It is used to treat nasal discharge brought on by allergies, hay fever, or the common cold; It can also relieve red irritated eyes, cough, and sneezing. (2)

Fluvoxamine is an antidepressant that is marketed under the trade names Luvox and Faverin. It is a member of the SSRI (Selective Serotonin Reuptake Inhibitors) drug class. Luvox works by increasing and enhancing the amount of serotonin levels in the brain. It is mainly used to treat OCD (Obsessive Compulsive Disorder) and SAD (Social Anxiety Disorder). (3)

Combining both diphenhydramine and Luvox may result in serious interactions and side effects, especially in the elderly. Both diphenhydramine and Luvox are contraindicated in the elderly (above 65 years). Consult your healthcare provider about combining diphenhydramine with Luvox or with any other antidepressant. 

How does diphenhydramine interact with Luvox?

Diphenhydramine can increase the levels of fluvoxamine (Luvox) in your body. The CYP450 enzyme in the liver extensively metabolizes fluvoxamine. Luvox is broken down by this enzyme into inactive metabolites, which the kidneys then excrete. (4)

Nevertheless, several drugs such as diphenhydramine have the ability to stimulate or inhibit CYP activity, which can change how Luvox is metabolized and impact the body’s levels of the drug. Diphenhydramine may raise the body’s levels of Luvox and raise the possibility of adverse consequences. 

As a result, it’s crucial to let your healthcare provider know if you’re taking diphenhydramine along with Luvox since they might need to change your dosage or keep a closer eye out for any negative effects.

What are the side effects of combining diphenhydramine with Luvox?

There are several side effects that can result from combining diphenhydramine and Luvox. Examples include: (3), (5)

Common side effects

  • Dizziness.
  • Insomnia (inability to sleep).
  • Dry mouth.
  • Nausea and vomiting.
  • Diarrhea and constipation.
  • Stomach pain and indigestion.
  • Sexual dysfunction (can occur while taking fluvoxamine).

Serious adverse effects

  • Long-lasting confusion and difficulty concentrating.
  • Numbness or tingling sensation.
  • Tachycardia (fast heartbeats) and arrhythmia (irregular heartbeats).
  • Face, eyes, nose, tongue, throat, or ears swelling.
  • Bleeding from any part of your body such as bleeding gums, coughing up blood, blood in urine or feces.
  • Muscle stiffness.
  • Difficulty breathing.
  • Seizures.

If you encounter any of these life-threatening adverse effects, seek medical attention immediately. 

Which antihistamines are safe to take with Luvox?

The second-generation antihistamines are comparatively safer than the first-generation antihistamines when used with Luvox. That’s because diphenhydramine as well as other first-generation antihistamines can cause drowsiness and have adverse effects on the CVS (Cardio-Vascular System) when combined with SSRIs such as citalopram and fluvoxamine.

Examples of the 2nd generation antihistamines include

  • Fexofenadine.
  • Loratadine.
  • Cetirizine.

 These antihistamines were also shown to be safe in certain patient populations, such as young children and the elderly. (6)

Important precautions when taking diphenhydramine with Luvox

There are several precautions that should be followed when taking diphenhydramine with Luvox such as: (1), (2), (3), (7)

  • If you use diphenhydramine and Luvox together and experience any CNS-related side effects such as impaired motor coordination or disorientation, contact your healthcare provider immediately. 
  • Alcohol should be avoided as it raises the possibility of CNS side effects when taking both medications together.
  • Avoid doing tasks that call for mental alertness such as driving until you know how the drugs affect you.
  • When taking diphenhydramine and Luvox together, use caution particularly in the elderly (65 years of age or older).
  • Inform your healthcare provider about any concurrent medications you are taking or any underlying medical conditions you have.
  • Space out the time of your doses. You should take each medication two hours before or four hours after the other.
  • In order to avoid withdrawal symptoms, you should never abruptly discontinue the use of Luvox without the consultation of your physician. Your physician will gradually reduce your medication dose.


Based on my knowledge and research, diphenhydramine can interact with Luvox and cause several side effects. In my opinion, taking 2nd generation antihistamines with Luvox instead of diphenhydramine will reduce the likelihood of adverse effects.

However, following the precautions while taking diphenhydramine with Luvox will help reduce the CNS and CVS-related side effects.










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Luvox Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing – WebMD [Internet]. Available from:


Diphenhydramine (including Nytol Original & Histergan): drowsy antihistamine [Internet]. 2018. Available from:,also%20stop%20working%20as%20well. 


Philpot EE. Safety of Second Generation Antihistamines. Allergy and Asthma Proceedings. 2000 Jan 1;21(1):15–20. Available from:,including%20pediatric%20and%20elderly%20patients 


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