Pharma: June 2009 Archives


June 30, 2009

The standard first-line opioid painkillers, Vicodin and Percocet, are actually both combination medications containing an opioid (hydrocodone for Vicodin and oxycodone for Percocet) with acetaminophen. The theoretical advantage here is supposed to be that you get better pain suppression with the combination than with either alone. The disadvantage here is that acetaminophen has a relatively narrow therapeutic index, and overdoses cause acute liver damage. [I suppose there's an argument that this is an advantage, since it makes it hard to get enough opioid to get high without risking liver damage.] According to Wikipedia, acetaminophen poisoning is the most common cause of acute liver failure [*].

Because of concerns over liver damage, the FDA's Advisory Panel has recommended eliminating them:

The two drugs combine a narcotic with acetaminophen, the ingredient found in popular over-the-counter products like Tylenol and Excedrin. High doses of acetaminophen are a leading cause of liver damage, and the panel noted that patients who take Percocet and Vicodin for long periods often need higher and higher doses to achieve the same effect.

Acetaminophen is combined with different narcotics in at least seven other prescription drugs, and all of these combination pills will be banned if the Food and Drug Administration heeds the advice of its experts. Vicodin and its generic equivalents alone are prescribed more than 100 million times a year in the United States.

Laureen Cassidy, a spokeswoman for Abbott Laboratories, which makes Vicodin, said, "The F.D.A. will make a final determination and Abbott will follow the agency's guidance."

The question I have is what will replace these meds in common use. There appear to be a number of combination hydrocodone formulations (with aspirin, ibuprofen, chlorpheniramine, ...), but with the first two you need to worry about allergies and chlorpheniramine doesn't have any painkilling effect so you just have to accept the unnecessary antihistamine side effects. I'm not sure if there are any hydrocodone-only formulations—I've never been prescribed one. While there are oxycodone-only formulations, doctors typically start with vicodin and then move up to percocet if that doesn't work, so it's not clear what this does to the front line. Moreover, as I said earlier, if you prescribe non-combination formulations you need to worry more about abuse, since there's nothing stopping the patient from just upping the dosage.

Obviously, preventing people from overdosing is an important consideration, but we also need to make sure we have a solution for pain that doesn't respond to OTC medications (NSAIDs and acetaminophen).