Did you know that promethazine with codeine cough syrup had a high risk of diversion and high risk of addiction? I didn’t.

From my experience, this is the only effective prescription cough medicine available. Sure, you can prescribe what is essentially over-the-counter dextromethorphan. But be ready when the patient throws a fit because that’s what they’ve been using for the last several days or weeks, and it wasn’t effective. Tessalon Perles help some people but not many and not very well. But codeine cough syrup does work well.

This medication is taken orally and processed in the liver by the cytochrome P450 system. The enzymes in the liver convert codeine, which is really a prodrug and has very little activity itself, to its metabolites, norcodeine, and morphine. Occasionally, there is also a little hydrocodone produced. So don’t jump to conclusions when your Tylenol #3 or cough syrup patient tests weakly positive for this unprescribed medication. This process is called O-demethylation.

If I remember correctly, the textbook is up to date, and Bard didn’t lie. A certain percentage of the population will not be able to carry out this transformation, and codeine really won’t work well for them. These people are called poor metabolizers. In studies I’ve seen, this can be as much as one in six of some patient populations. It’s the morphine that is really getting the work done.

Most doctors know that morphine is an amazing antitussive. We use codeine because while straight morphine might work just as well, it would hit faster and not last as long. That’s because the extra step going from codeine to morphine creates a flatter curve, almost like a time-release medication, as the enzymes can only work at a specific rate. There is or was a medication called Hycotuss. This was made with hydrocodone, and in my experience, was not very effective at all, and I don’t use it. Again, it’s the morphine doing the work.

This cough syrup is usually dispensed in 5 cc doses every four to six hours as needed. 5 cc of this medication contains 10 mg of codeine and 6.25 mg of promethazine. My MME calculator tells me that 10 mg of codeine up to six times a day (every 4 to 6 hours) comes out to 9 MME. That seems pretty mild to me.

This medication has been used since the 1950s at variable duration. For a few days for a minor cough, perhaps a week for something like pneumonia, and chronically for someone suffering from a significant chronic cough. Severe chronic cough can have many causes, from almost any inflammatory lung condition to allergies and even gastroesophageal reflux. Smoking, of any kind, is, of course, a major cause. And in someone vaping, we must now worry about heavy metal and other less well-defined causes of lung injury.

But no matter what caused your cough, when OTC failed, codeine with promethazine was the go-to medication. Then, it became popular in the rap community. I did not know this, not being an aficionado of that music genre or any music genre, in fact. I listen to news podcasts and audiobooks. Most of the books are science, medicine, or science fiction. My kids love it, I’m sure.

I missed the fact that mixing this innocuous cough syrup with alcohol had become a thing. Now, people weren’t dropping dead from it or showing up in droves at methadone clinics crying out for “lean,” but the fact that this behavior was perceived to be more common in a community of higher melanin production was enough to set off the alarm bells at the DEA. And, while it did not show up on any of my hundreds of hours of pain and addiction medicine CME, it suddenly became a focus of prosecution.

Physicians and advanced practice nurses all over the U.S. were suddenly called on the carpet for prescribing this medication. Or actually charged with a crime. In 2013, the FDA restricted its use to adults over the age of 18 and added labeling changes reflecting this in 2018. But how can it be a crime to prescribe a medication approved for cough to a patient complaining of a cough? And, with the recent Ruan ruling, it seems that there would need to be criminal intent, but the Supreme Court’s decision didn’t even slow the prosecutors down. They argued instead that prescribers were “willfully blind” to the high risk of addiction and diversion with this medication. I have a problem with that.

Promethazine with codeine cough syrup is still listed as Schedule V. Schedule IV is defined by the DEA’s own website as “drugs with a low potential for abuse and low risk of dependence,” and Schedule V is listed as “drugs with lower potential for abuse than Schedule IV.” So, while the FDA lists the risk of addiction and diversion of this medication as lower than low, when doctors are prosecuted, DEA agents, as well as paid medical experts, routinely tell the jury that the medication has “a high risk of diversion and addiction.” Shouldn’t someone tell the FDA? So they could adjust the Schedule up, maybe to Schedule III as they did with hydrocodone going from III to II? Otherwise, we have one branch of the federal government telling us something is a lower-than-low risk for addiction and diversion, while another branch is prosecuting us for believing it.

Interestingly, I have been reviewing a lot of cases, and I’m having trouble finding many doctors who weren’t prosecuted for prescribing this medication to Black people. Maybe you could help me. What has been your experience with this medication? And do you think it should be moved from Schedule V to Schedule III?

L. Joseph Parker is a distinguished professional with a diverse and accomplished career spanning the fields of science, military service, and medical practice. He currently serves as the chief science officer and operations officer, Advanced Research Concepts LLC, a pioneering company dedicated to propelling humanity into the realms of space exploration. At Advanced Research Concepts LLC, Dr. Parker leads a team of experts committed to developing innovative solutions for the complex challenges of space travel, including space transportation, energy storage, radiation shielding, artificial gravity, and space-related medical issues. 

He can be reached on LinkedIn and YouTube.