Pharmaceutical

Pediatric deaths lead to new black box warning on codeine

fda logo Pediatric deaths lead to new black box warning on codeine Drugs containing codeine now have a black box warning notifying doctors and consumers that the medication may cause breathing difficulties and deaths in children who are given codeine to relieve pain following surgery to have their tonsils or adenoids removed. These adverse events have resulted even when the medication was given in recommended dosages.

The danger exists for children who are “ultra-rapid metabolizers” of codeine, meaning that their liver converts codeine to morphine in higher than normal amounts. The Food and Drug Administration (FDA) first warned of this danger in August 2012. Since then, the agency has conducted a comprehensive safety review of codeine use in children and determined that all codeine drugs should contain a boxed warning.

The FDA Adverse Event Reporting System (AERS) database from 1969 to May 2012 identified 10 deaths and three overdoses associated with codeine. Many of these children were recovering from tonsillectomies or adenoidectomies.

Codeine is an opioid pain reliever used to treat mild to moderate pain. It is also used to reduce coughing, usually in combination with other medications. Codeine is converted to morphine in the liver by an enzyme. Some people have genetic variations that make this enzyme overactive. This causes the codeine to be converted to morphine faster and more completely than in people who do not have the enzyme. High levels of morphine can cause respiratory depression, which can be fatal.

The new warnings will be added to the safety labels of the following medications:

  • Codiene Sulfate Solution
  • Codeine Sulfate Tablets, 15mg, 30 mg, and 60 mg.
  • Fioricet with Codeine (butalbital, acetaminophen, caffeine, and codeine phosphate) Capsules
  • Fiorinal with Codeine (butalbital, aspirin, caffeine, and codeine phosphate, USP) Capsules
  • Promethazine and Codeine Syrup
  • Promethazine, Phenylephrine and Codeine Syrup
  • Soma Compound with Codeine (carisoprodol, aspirin, and codeine phosphate) Tablets
  • SynalgosDC (dihydrocodeine bitartrate, aspirin and caffeine) Capsules

Any side effects with drugs containing codeine should be reported to the FDA’s MedWatch AERS at www.FDA.gov/MedWatch/Report.htm.

Source: FDA