Taking Zofran (Ondansetron) With Nyquil

Answer

There is no listed or reported interaction between Zofran (ondansetron) and the common ingredients in nighttime cold medications (including NyQuil). They are generally considered to be safe to be taken together. 

However, there is a theoretical risk of serotonin syndrome when combining dextromethorphan, the cough suppressant in NyQuil, and Zofran, but this risk is thought to be very minimal in those not taking any other interacting drugs.

I discuss this in more detail below.

What Is In NyQuil?

NyQuil contains the following ingredients:

• Acetaminophen (analgesic)
• Doxylamine (sedating antihistamine)
• Dextromethorphan (cough suppressant)

The ingredients in many generic cough/cold products can vary but the above are the most common ones included. Some do contain a nasal decongestant (e.g., phenylephrine) and an expectorant (e.g., guaifenesin) as well.

What Is Zofran?

Zofran (ondansetron) is a medication used to treat/prevent nausea and vomiting.

It works by antagonizing a specific serotonin receptor that is widely distributed throughout the body. Antagonizing this receptor is thought to decrease serotonin signal transmission to the central nervous system, lessening the symptoms of nausea and vomiting. The duration of action of Zofran is reported to be around 6 to 8 hours.

It should be noted that although there is no interaction (aside from what is discussed below) between Zofran and Nyquil, both can cause sedation and fatigue. It is important to only dose them together at bedtime.

Doxylamine, the sedating antihistamine in many cough/cold products begins to work in 30-60 minutes. Zofran similarly begins to work in about 30 minutes. Therefore you can expect the onset of sedation to begin rather quickly after taking the products together.

Dextromethorphan (From NyQuil), Zofran, And Serotonin Syndrome

There is a potential interaction between Zofran and high doses of dextromethorphan, the cough suppressant in Nyquil.

There is a theoretical risk of serotonin syndrome when both drugs are used together.

Symptoms of serotonin syndrome include:

• Confusion
• Hallucinations
• Sweating
• Chills
• Hyperthermia
• Hypertensive crisis

Serotonin syndrome is a rare but serious disorder that results from excess serotonin levels in the brain. If you ever experience symptoms of serotonin syndrome, you should seek medical attention right away. Those susceptible include individuals who are taking a combination of serotonergic drugs.

Dextromethorphan, while not acting directly to increase serotonin, has documented cases of increased serotonin levels when used in supra-therapeutic dosages (i.e. dosages more than indicated on product labeling). 

Zofran, although not a serotonin agonist, blocks serotonin binding to receptors, which could theoretically increase unbound/available serotonin, which may then bind to other serotonin receptors.

There are no case reports of serotonin syndrome between Zofran and dextromethorphan. Nevertheless, it is important to be aware of this theoretical interaction, especially if taking additional serotonergic medications or high doses of each (e.g., such as certain antidepressants, like Zoloft).

Final Words

I hope you found this helpful!

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