Should thyroxine tablets be refrigerated? Have we got it wrong in Australia?

In reply: Sigma Australia acquired Oroxine (thyroxine sodium) from the original manufacturer in 1999, and launched Eutroxsig, an identical product, in 2002. During 2002–03, as a result of advances in analytical technology for some pharmaceutical products, product specifications, including shelf life and storage conditions, were updated, so that the product’s quality, safety and efficacy could be maximised or maintained throughout the claimed shelf life.

For Oroxine and Eutroxsig, the new stability data showed a loss of up to 10% of thyroxine sodium in the first 6 months when stored below 25°C, with some plateauing thereafter. As an interim measure, Sigma, in agreement with the Therapeutic Goods Administration (TGA), decided to immediately reduce the shelf life from 24 to 12 months (“store below 25°C”) and set the lower release to 98.0% (up from 92.5%), while investigating reasons behind the loss in potency.

The manufacturing process was confirmed to consistently yield tablets with very reproducible chemical and physical attributes in accordance with the release criteria. During manufacturing, however, about 2% of the thyroxine sodium is lost, with a corresponding similar increase in degradants.

The new stability studies support the storage of Oroxine and Eutroxsig in the refrigerator; however, repeated in-use handling may result in an increase in condensation and microbial contamination. This may lead to changes in the physical characteristics of these products, including the growth of mould. There may be a further increase in condensation if the lid is not tightly closed. One possible solution is for patients to place up to 4 weeks’ supply of tablets in a spare, previously used, Oroxine or Eutroxsig amber-coloured bottle and store out of the fridge (below 25°C) for current use, while keeping the remaining stock in the fridge. Sigma is looking at options to improve the packaging so that the above problems are minimised or eliminated.

Oroxine and Eutroxsig, manufactured by Sigma, are sold in Australia only. Sigma does not have access to formulation details, stability results and justification for the storage conditions used in other countries; therefore, we are unable to comment on such issues. As an Australian company, we are obliged to follow the regulatory guidelines of the Therapeutic Goods Act 1989 (Cwlth).

Sigma recommends that the label instructions regarding storage conditions after opening be strictly followed to maximise the quality, safety and efficacy of the product.