FDA acts to limit exposure to acetaminophen in combination products

Healthcare providers should stop prescribing combination drug products that contain more than 325 mg of acetaminophen (paracetamol) per dosage unit because of the increased risk of liver injury, the US Food and Drug Administration has said.1

Many prescription drugs for pain on the market combine acetaminophen with an opioid, such as codeine, oxycodone, or hydrocodone. Such prescription products containing acetaminophen combinations make up 20% of the acetaminophen market and include some of the most widely prescribed drugs in the United States.

Inadvertent overdoses from acetaminophen combination products account for nearly half of 1600 acetaminophen related cases of liver failure seen each year in the US, the FDA said.

In recommendations issued on 14 January the FDA said, “There are no available data to show that taking more than 325 mg of acetaminophen per dosage unit provides additional benefit that outweighs the added risks for liver injury. Further, limiting the amount of acetaminophen per dosage unit will reduce the risk of severe liver injury from inadvertent acetaminophen overdose, which can lead to liver failure, liver transplant, and death.”

The agency also urged pharmacists who receive prescriptions for combination products containing more than 325 mg of acetaminophen per dosage unit to contact the prescriber to discuss switching to a product with a lower dose of the drug.

Although a two tablet or two capsule dose may still be prescribed if appropriate, the FDA said that lower doses per dosage unit should reduce the risk of a patient taking more than the maximum recommended dose of 4000 mg per day.

Acetaminophen related liver injury is typically seen in patients who took more than the prescribed dose in 24 hours or who took more than one product containing acetaminophen at the same time, or who drank alcohol while taking acetaminophen products, the FDA said.

In 2011 the FDA asked manufacturers to limit the amount of acetaminophen in their products to no more than 325 mg per tablet or capsule by 14 January 2014.2 At the time, several brands contained 650 mg per dosage unit and one contained 750 mg.

More than half of manufacturers have complied, but some products containing more than 325 mg per dosage unit remain available.

“In the near future we intend to institute proceedings to withdraw approval of prescription combination drug products containing more than 325 mg of acetaminophen per dosage unit that remain on the market,” the FDA said.

It added that in a separate regulatory action it would review the acetaminophen content of the many over-the-counter products for pain, fever, and coughs and colds that contain acetaminophen. “Many consumers are often unaware that many products (both prescription and [over-the-counter]) contain acetaminophen, making it easy to accidentally take too much,” the FDA said.