Side effects from Eltroxin® - status January 2010

The Danish Medicines Agency has recorded an increase in the number of reported side effects from Eltroxin®. The increase is observed after the manufacturer changed the excipients contained in Eltroxin®. The new excipients are commonly used in medicines.

Current status

• The Danish Medicines Agency has analysed the two strengths of Eltroxin® and has found no deviations from the approved specifications.
• We have received the manufacturer's analyses of the reported data and conclude that there is no immediate case for requesting further analyses from the manufacturer.
• We will continue our close monitoring of side effect reports submitted for Eltroxin®.

Levothyroxine-containing products on the Danish market
Eltroxin® has for many years been the only levothyroxine-containing product sold in Denmark. On 28 December 2009, Euthyrox® entered the market in the strengths 25, 50 and 100 micrograms. Euthyrox® tablets have a scoreline so that they can be divided into equal parts. You can find Danish summaries of product characteristics for Eltroxin® and Euthyrox® in the factbox to the right.

Precautionary measures to be taken by doctors
When patients switch between different levothyroxine-containing products or formulations, it is very important that a doctor monitors the level of thyroid stimulating hormone (TSH), in particular with respect to patients who experience side effects. However, due to the long half life of levothyroxine (approx. 7 days), the TSH level should not be measured until approx. 5-6 weeks after the patient has started taking the new product or the new formulation or has had the dose adjusted.

Compassionate use permits
The number of compassionate use permits for alternatives to Eltroxin® increased from 304 as at 18 August 2009 to 1,333 as at 10 December 2009. Compassionate use permits have been issued to patients who experience side effects from Eltroxin®. They have been granted as individual compassionate use permits to general practitioners and general compassionate use permits to endocrine and medical departments and specialists in endocrinology.
Some of these compassionate use permits were issued for Euthyrox®, which was put on the Danish market on 28 December 2009 in the strengths 25, 50 and 100 micrograms. Consequently, a compassionate use permit is no longer needed for the dispensing of Euthyrox®.

Side effects
In the past two years and until 31 October 2009, inclusive, the Danish Medicines Agency has received a total of 846 reports of suspected adverse reactions from Eltroxin®. The reports were primarily submitted in the period March 2009 to October 2009. A single adverse reaction report may contain several adverse reactions, and altogether 4,643 suspected adverse reactions have thus been reported in the past two years up to and including 31 October 2009. The 10 most common adverse reactions reported during this period are displayed in the table below. These adverse reactions are all suggestive of overmedication or undermedication with Eltroxin®.

In the period from 1 August 2009 to 31 October 2009, we received 488 reports describing 2,669 suspected adverse reactions. The reports that we receive now primarily contain adverse reactions that have been experienced before. In November 2009, we received 101 reports describing 575 suspected adverse reactions.
It is not possible to distinguish between suspected adverse reactions from the new or old formulation of Eltroxin®, but it is assumed that most of the adverse reaction reports concern the new formulation.

Please be aware that

• The Danish Medicines Agency’s pharmacovigilance database only contains side effects from Denmark.
• Not all side effects are reported to the Danish Medicines Agency.
• Information about the occurrence of side effects from a medicine should always be compared to the consumption of the medicine concerned. You can see the actual consumption in the Register of Medicinal Product Statistics at www.medstat.dk.
• In the two-year period from 1 November 2007 to 31 October 2009, 112,216 persons were treated with Eltroxin®. In the three months from 1 August 2009 to 31 October 2009, 82,003 persons were treated with Eltroxin®.

Use the information cautiously
The information in the pharmacovigilance database does not reflect the risk of adverse reactions related to the individual medicines. First and foremost, the information indicates whether a specific medicine requires increased attention or not. The information may therefore cause further examination.

An adverse reaction report is not the same as a true adverse reaction
An adverse reaction report contained in the pharmacovigilance database does not mean that there is a connection between the medicinal product and the adverse reaction. Adverse reactions are reported to and registered in the database, even if it is only suspected that there might be a connection between the medicine and the adverse reaction. Known side effects from Eltroxin® are listed in the summary of product characteristics, which is available via the factbox to the right.

For further information, please contact Mette Winkelmann on tel.: +45 4488 9226 or Helle Harder on tel.: +45 4488 9659.

Danish Medicines Agency, 7 January 2010