An Unexpected Discovery: Maxiclear

Our R&D team made an unexpected discovery during clinical trials being conducted in Jordan as part of the development of a new product.

Many over the counter cold and flu products combine phenylephrine and acetaminophen (paracetamol). We found that when combined with acetaminophen, the level of phenylephrine is effectively twice what it should be.

This is because the standard dose of phenylephrine in over-the-counter cold and flu products is 10mg. That is all regulatory authorities have allowed. But unbeknown to everyone (including the regulators), when phenylephrine and acetaminophen are taken together in this dose, the concentration of phenylephrine spikes to roughly 20mg because of the way the human body processes both drugs together.

In short, AFT’s research showed that, inadvertently, people had been been taking the equivalent of double the recommended levels of phenylephrine.

AFT’s discovery was then published in the prestigious New England Journal of Medicine1 and received considerable media interest, including a feature in The New York Times.

The reason for this interest lay in the sheer size of the over-the-counter flu market. There are over 1300 such products used around the world.

It also lay in the fact that the US Food and Drug Administration (FDA) had previously declined to increase the permitted dose of phenylephrine from 10 milligrams to 25 milligrams on the basis that safety might be reduced. Yet, in effect, this was the dosage people were receiving anyway.

A number of regulatory agencies, including the FDA, have taken an interest in the findings. A subsequent clinical trial2 has confirmed this unknown pharmacokinetic interaction between acetaminophen and phenylephrine.

1: Hartley C. Atkinson, Ioana Stanescu, and Brian J. Anderson (2014), “Increased Phenylephrine Plasma Levels with Administration of Acetaminophen”, New England Journal of Medicine 370;12, 1171-1172

2. Hartley C. Atkinson, Ioana Stanescu, Isam I. Salem, Amanada L. Potts, and Brian J. Anderson (2015) “Increased bioavailability of phenylephrine by co-administration of acetaminophen: results of four open-label, crossover pharmacokinetic trials in healthy volunteers”, European Journal of Clinical Pharmacology 71;2, 151-158.