Plasma concentrations of phenylephrine spike to potentially risky 
levels when the drug is used in combination with acetaminophen, 
according to a letter in the New England Journal of Medicine. Drugs 
that combine phenylephrine and acetaminophen include over-the-counter 
cold medicines such as DayQuil and Tylenol Cold and Flu.

The letter’s authors, including drug company employees, report 
findings from three crossover trials: when healthy volunteers took 
phenylephrine (10 mg) in combination with acetaminophen (1000 mg), the 
maximal plasma concentration of phenylephrine was four times higher 
than when they took phenylephrine alone.

Combining the drugs increased phenylephrine exposure “beyond levels 
that were previously deemed to be safe and effective,” the authors 
write, thereby “increasing the potential risk of adverse events.” 
Among those potential events are “higher blood pressure, elevated 
heart rate and nervousness,” the New York Times reports.