UK Strengthens Addiction Warnings For Nonprescription Codeine Products

Warnings that long-term use of codeine and/or dihydrocodeine may lead to addiction will be added to product labeling for nonprescription analgesics that contain the ingredients, the Medicine & Healthcare products Regulatory Agency announced Aug. 15.

The joint effort on new labeling by the UK health authority and the nonprescription drug industry follows a review of the number of adverse events related to OTC drugs containing codeine.

The edited warnings will alert consumers to the "possible risk of addiction or medication overuse headache due to inappropriate use," the Proprietary Association of Great Britain said.

PAGB contributed to the review, which was presented to MHRA's Committee on Pharmacovigilance and Committee on Safety of Medicines (CSM) in March and June. The report included information from MHRA's Yellow Card adverse event reporting system.

The updated warnings will appear on both patient information leaflets and packaging labels and feature three statements, including: "If you need to use this medicine for more than three days at a time, see your doctor, pharmacist or health care professional."

Other statements are as follows: "Taking codeine regularly for a long time can lead to addiction, which might cause you to feel restless and irritable when you stop the tablets" and "Taking a painkiller for headaches too often or for too long can make them worse."

MHRA also is setting a size limit for all codeine-containing OTCs at a maximum of 32 tablets. However, PAGB noted the "majority" of nonprescription drugs containing codeine already are sold in pack sizes containing less than 32 tablets.

Products affected by the regulation change include Bayer's Feminax , Pfizer's Migraleve and GlaxoSmithKline's Panadol , PAGB said.

Other brands affected are Codis , Nurofen , Painex , Paracodol, Propain , Solpadeine , Syndol , Ultramol , Uniflu and Veganin .

Codeine and dihydrocodeine are Prescription-Only Medicines (POM) but are available behind the counter as Pharmacy (P) drugs when in low-dose form and combined with other analgesics such as aspirin, ibuprofen and paracetamol.

Maximum doses of the ingredients used in nonprescription drugs are codeine 20 mg and dihydrocodeine 10 mg.

The OTC drug industry will begin changing the warnings immediately, according to MHRA. The agency hopes to see the majority of products with updated labeling by June.

Despite requiring strengthened warnings, MHRA's review of the report on codeine-containing drugs did not prompt the agency to seek reclassification of products that are currently sold behind the counter.

"The number of reports of abuse of OTC codeine and dihydrocodeine is exceedingly small, compared to volume of sales," MHRA said.

CSM concluded that "the benefits of using these medicines justified the potential risks. . . [and] that there was no reason why these medicines should not continue under pharmacy supply."

PAGB also noted that combining codeine with paracetamol or ibuprofen "produces pain relief products which have been shown to be more effective than simple analgesics. They therefore play a useful role as over-the-counter medicines."

Misuse of codeine is not new, MHRA said, and most codeine-containing drugs already carry a warning statement.

However, PAGB pointed out that previous discussions of developing additional warnings have caused "worry" that "unless very carefully worded, warnings could attract some people to experiment with the products, whilst at the same time discouraging and alarming those who use the products correctly."

MHRA's codeine warnings come as the agency is in the midst of reviewing the safety profile of non-steroidal anti-inflammatory drugs.

The agency completed the first portion of its NSAID review by concluding that potential thrombotic risks posed by the drugs are not significant enough to require labeling changes (¹ (Also see "European Health Agency NSAID Review Recommends No Changes" - Pink Sheet, 8 Aug, 2005.), p. 6). MHRA will release its findings on gastro-intestinal safety of the drugs in September.