Health Min. slams its handling of thyroid drug change
An investigation panel found a clear circumstantial link between the distribution of the reformulated drug in Israel and a rise in reports of side effects.
The Health Ministry's investigation into what has come to be known as "the Eltroxin affair" criticizes senior ministry officials and pharmaceutical companies involved in handling the reformulation of the synthetic thyroid hormone replacement and its implications for Israeli patients. The investigation team was headed by Health Ministry Director General Dr. Roni Gamzu.
The pharmaceutical manufacturer GlaxoSmithKline changed the composition of Eltroxin (Levothyroxine ), reformulating the inactive ingredients used in the pill, in February 2011. No changes were made to the active ingredients, but it was not until August that the patient information leaflet included with the medication was updated with a warning instructing patients to have their thyroid levels checked because of the reformulation.
Since the new pills were introduced hundreds of Israelis who take Eltroxin to regulate their thyroid function have complained of side effects thought to be the result of the change. The ministry's pharmaceutical division has recorded 798 such reports, mainly from women with the average age of 53. Most of the complaints were filed in October (370 ) and November (246 ), after the affair was disclosed in Haaretz.
The investigation committee rated 15 of the complaints as "severe." They included the cases of three pregnant women who had miscarriages and three cases involving hospitalization, but the ministry did not receive a comprehensive report on the current medical condition of the patients who complained of side effects. No deaths were reported as a result of the reformulation.
GSK has marketed Eltroxin in Israel since 1981. In March 2008 it applied to register a new formulation of the drug with the Health Ministry, permission for which was issued in March 2010. In September 2009 the company transferred its production line for Eltroxin to Aspen Global in Germany; Perrigo Israel became the Israeli distributor of the drug.
The investigation panel found a clear circumstantial link between the distribution of the reformulated drug in Israel and a rise in reports of side effects.
"The fact that there were no alternative drugs available when the distribution of the new formula began presumably contributed to the sharp rise in reports [of side effects]", the report said.
The report states that GSK did not convey up-to-date information to the Health Ministry on the events in New Zealand during the processing of its request to change the composition of the drug.
Perrigo, the pharmaceutical company that markets the drug, only provided a periodic update for 2011 about the drug - after the Health Ministry approached it following the incidents.
The committee said the Health Ministry was also at fault in the matter. "Preparation and decision-making of the pharmacy department was impaired due to a lack of clear and unequivocal early information from the companies on the unusual incidents of similar extent in New Zealand and Denmark".
The report says some of the doctors administering the drug did not know how to deal with the patients' complaints, despite the claim by Perrigo that it had briefed the doctors twice about the changes in the drug's composition. "The conduct of the Health Ministry, drug companies and HMOs did not adequately reflect the patients' distress." The report recommends issuing a procedure to monitor the drug's side effects. As Haaretz reported, the Health Ministry has already started preparing this procedure. It also recommends increasing doctors' awareness of the need to report drugs' side effects and managing the risks posed by drugs,
Following the affair the HMOs started importing Eutirox and Synthroid for Eltroxin patients who complained of side effects.
At least five class action suits have been filed to various courts in Israel following the affair. The Health Ministry and drug companies' responsibility is expected to be a major issue in the hearings related to these suits.
A spokesperson for Perrigo commented that "Perrigo learned of the report's completion for the first time from the media, and has not received a copy of it from the committee. However, the company stresses that it began informing doctors and pharmacists, in coordination with the Health Ministry, about the change in the drug's composition immediately as it began its marketing.