In late June, an advisory panel to the US FDA narrowly recommended that the FDA should ban the prescription of Percocet (a combination of oxycodone and acetaminophen) and Vicodin (a combination of hydrocodone and acetaminophen), as well as seven other acetaminophen-narcotic combinations because of acetaminophen's role in hepatotoxicity.
The panel also voted — with somewhat broader support — to reduce the highest allowed dose of acetaminophen in over-the-counter pills like Tylenol to 325 milligrams from 500, and to reduce the maximum daily dosage to less than 4,000 milligrams.
Acetaminophen overuse is the leading cause of liver failure in the US, with more than 400 people dying and more than 40,000 hospitalized from overdoses annually.
The FDA doesn't have to follow the panel's recommendations, but it has historically shown an inclination to do so. Although the final FDA ruling is likely months away, neurologists who specialize in pain management are already anticipating its effects — with varying opinions.
“If you stay under four grams a day and the patient has no other medical problems, it's rare for acetaminophen to produce hepatic failure,” said Ronald Kanner, MD, chief of neurology at Long Island-Jewish Hospital and a pain medicine specialist.
Dr. Kanner acknowledged that in the best of all worlds, the acetaminophen and narcotic medications would be prescribed separately. “But we don't live in the best of all worlds. The more medications you prescribe, the less likely a patient is to follow the regimen,” he said. “There will be compliance problems, and prescribing problems. Any time you alter a prescribing practice to make it more complicated, you cut down on the number of prescriptions.”
“Taking them off the market is puritanical,” said Charles Argoff, MD, professor of neurology at Albany Medical College. “These are commonly used medications, which are effective for many patients, and extremely important tools for the prescriber. When used appropriately, they're used safely and with good outcomes.”
Dr. Argoff thinks that the over-the-counter use of acetaminophen is probably the biggest culprit in hepatotoxicity, not the narcotic-acetaminophen combinations.
“There is no control over how much acetaminophen a person takes if they take it alone,” said Dr. Argoff. “You don't know how much they're really taking. But if you're prescribing an agent which combines two effective analgesics, that can be controlled in a safe and effective manner.”
Dr. Argoff doesn't minimize the issue of hepatotoxicity. “This is really not trivial at all,” he said. “It's fair to say that chronic long-term use of maximal or supramaximal doses of over-the-counter analgesics may contribute not only to liver toxicity but also renal toxicity. And as prescribers, it's hard to know if patients are following our instructions not to combine over-the-counter acetaminophen with these combination drugs.”
But he believes that rather than an outright ban on the combinations, a better solution would be a national prescription monitoring program. These programs exist — at least in theory — in many states, but most are not operational due to lack of funds. “If you go into a pharmacy with a prescription for Percocet or Vicodin, the prescription monitoring program might alert the pharmacist that you had had another prescription for that drug and require them to call your doctor before issuing the drug.”
He also recommended more focus on over-the-counter acetaminophen. “One thing that's been done with cold medicines because of the concern about methamphetamine use has been to restrict sales to locked cases behind the counter, sold with ID,” he noted.
Or, more radically, Dr. Argoff suggested — the FDA could ban acetaminophen as an over-the-counter medication. “Although you could put out a huge public education effort about liver toxicity — in doctors' offices and ERs, direct-to-consumer mailings, TV ads, and so on, it's still like putting the candy jar in front of the kids,” he said.
A prescription requirement for Tylenol would be quite shocking, he admitted. “But having these little two-dose packs available everywhere and people using them like candy — that has tremendous health consequences. What would be wrong with a $2.50 prescription for 150 tablets, so use can be monitored?”
Pain specialist Misha-Miroslav Backonja, MD, professor of neurology, anesthesiology, and rehabilitation medicine at the University of Wisconsin School of Medicine and Public Health, doesn't see that as the solution. “Like everything else, acetaminophen if taken appropriately is safe and effective and has been for years. To make moms and grandmas and grandpas go to the doctor and get a prescription for every ache and pain would be unbearable for the medical system,” he said.
Should the FDA ban the acetaminophen-narcotic combinations, Dr. Backonja predicted, neurologists involved in pain management will not notice the change nearly as much as primary and perioperative care physicians. Because neurologists deal primarily with chronic disorders, including chronic pain disorders, they are more likely to use longer-acting single agents. “These combination therapies are probably not going to impact our chronic pain management significantly,” he said.
Indeed, Dr. Backonja suggested, there may be a side benefit to a ban for patients dealing with migraine and other chronic headaches. “This class of drugs has been identified as one of the major contributors to medication overuse headaches, so if nothing else, having restrictions or a ban on these medications might make that part of headache management simpler.”
Dr. Backonja doesn't favor an outright ban on the combination drugs. “Probably more strict regulation is appropriate, but it comes back to the whole community to address what's appropriate care of patients with pain problems,” he said.
But he believes that the debate over the FDA policy may bring the medical community to focus on an issue that has not garnered enough attention.
“In general, this class of drugs is probably not the best way to manage pain,” he said. “We have an unsolved issue of pain, especially chronic pain, and this whole class of drugs has become a crutch for a major problem. Pain is something that requires more education on diagnosis and aspects of pain management beyond Vicodin. Many doctors have been prescribing drugs that are probably not adequate or appropriate, so the whole community will have to address it more directly. The solution is not simple, because the problems the medication is addressing are much more complex than what we as a community think we are doing by prescribing them.”