Published: 16 December 2013

Consultations

Changes to the Label Statements Database for codeine-containing medicines

To:
Product sponsors
Applicants for new and changed medicines
Regulatory affairs consultants

This letter is to:

• indicate proposed changes to the labelling requirements for codeine-containing medicines
• provide an opportunity for consultation on these changes
• provide a contact point for queries or feedback on the proposed changes.

Background

On 29 September 2012, Medsafe received a complaint from a healthcare professional about the use of “non-drowsy” on codeine-containing medicines, as drowsiness is one of the major side effects of codeine.

Medsafe investigated the complaint and reviewed available information from published literature, data from international regulators and affected sponsors. Medsafe then concluded that:

• sedation is a known side effect of opiate therapy and is listed as a common side effect of codeine treatment in all published New Zealand data sheets and consumer medicine information, including the data sheets for products containing less than 10 mg of codeine per tablet
• codeine is metabolised by CYP2D6 to morphine for its analgesic efficacy and many of its side effects. Medsafe considers that drowsiness is likely to be a dose-related side effect of codeine use that is dependent on morphine plasma levels. Due to differences in the expression of CYP2D6 there is substantial inter-individual variability in morphine plasma levels achieved for a given dose of codeine. In addition, age related changes in morphine sensitivity and body composition are also likely to affect both the efficacy and side effect profile of a given dose of codeine in elderly patients. Medsafe considers that significant drowsiness and consequent functional impairment (eg, driving ability) can be expected to occur in susceptible patients, even with codeine doses used in over-the-counter medicines.

Medsafe also considered whether there was justification for a non-drowsy statement when codeine was used in medicines containing a combination of codeine and phenylephrine. Medsafe concluded there is no evidence that the addition of phenylephrine to codeine-containing cough and cold products counteracts any drowsiness that might occur.

Given the potential for codeine to cause drowsiness in certain patients, Medsafe proposes that the following statements be added to the Label Statements Database for all codeine-containing medicines (including cough and cold medicines):

• this medicine may cause drowsiness
• be cautious about driving a vehicle or operating machinery within 8 hours of taking this medicine.

Next steps

Queries about, or comments on, the proposed changes described above should be sent to:
Laurence Holding
Medsafe
PO Box 5013
WELLINGTON

Email: askmedsafe@health.govt.nz

by Monday 3 March 2014.

Comment on the feedback received and any resulting adjustments to the new requirements will be provided through the Medsafe website (www.medsafe.govt.nz).

Yours sincerely,
Sarah Reader
Manager Product Regulation