Q: On January 13, 2011 the FDA announced the intent to limit the strength of acetaminophen in prescription drug products to 325 mg per tablet, capsule, or other dosage unit to reduce the risk of liver toxicity in patients. This directive will go into effect on January 14, 2014. What will be the impact of this decision to CMOs that are producing these products?

—Eileen Bonilla Mercado, Shionogi, Inc.

A: As this is a prescription requirement, it could impact selection of comparator, meaning that the U.S. comparator would be a different strength to that available elsewhere in the world.

As patient safety is the primary concern, manufacturers will be working to ensure compliance. In preparation for the change some minor modifications to the formulation may be required with the more significant changes being on the label advisory. The allowable dose strength and number of doses available per pack for this product can vary from country to country as different approaches have been taken in order to address the potential for liver toxicity. Seeking specialist advice is recommended for those conducting global clinical trials that involve acetaminophen as a comparator or rescue medication.

For example, the UK has sought to limit the number of inadvertent deaths from paracetamol (acetaminophen) overdose by limiting the pack size to 32 tablets in pharmacies and 16 for other general sales outlets. This has had some success reported in a recent study: deaths fell by 43% in England and Wales in the 11 years since the law on pack sizes was changed.

—Helen Underwood, Fisher Clinical Services