After hundreds of users lodged complaints about side effects resulting from changes in the composition of the drug, the Eltroxin affair has taken a dramatic turn.
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Internal correspondence and documents which have reached Haaretz indicate that the Perrigo company, which markets the Eltroxin drug in Israel, relayed an incorrect report to the Health Ministry about changes in the composition of the thyroid medication. The ministry, Haaretz has learned, is considering taking criminal action against Perrigo.
In response to this report, Perrigo said it "categorically denies allegations made against it," adding that it "did not conceal information from the Health Ministry."
The Health Ministry responded: "The changes in the concentration of components were never reported to the ministry at any stage ..." The ministry added, though: "It has not been proven that the change in the agents' concentration levels are the cause of unwanted side effects."
In the Eltroxin affair, 800 users of the medication lodged complaints about side effects after February 11, the date when the drug's components were altered. Eltroxin announced the change in its composition only once, far in advance of this date; the drug's packages carried only one announcement about the change, in August 2011.
Eltroxin is a popular drug, with the Health Ministry estimating that some 250,000 Israelis use it for thyroid conditions. Last week, the Israel Hayom newspaper disclosed that the ministry had learned that the Aspen company in Germany, which produces Eltroxin under a new manufacturing arrangement, had instituted changes not only in the drug's outer coating, but also in its actual medical ingredients. Eltroxin's local marketing agent, the Perrigo company, had claimed that the changes were purely cosmetic, and not related to its key pharmaceutical components.
Internal company documents obtained by Haaretz indicate that the drug's active agents include components four times greater in concentration than what was present in the drug's original version. Internal company correspondence shows that on December 26, 2011, after the affair's initial disclosure and after the Health Ministry had established an investigation committee, Perrigo's chief pharmacist said the new Eltroxin contained various components in enlarged concentrations. Yet in registration materials sent to the ministry by the company regarding the drug's new version (in compliance with a registration procedure established by the ministry in 2008 ), Perrigo reported that these components were now present in a lower concentration.
Relaying an answer provided by the Aspen company in December 2011, Perrigo explained that the facts cited in this registration document about low concentration levels were relayed "for informational purposes" only. This Perrigo explanation stated that there "is no change in the concentration levels" of the drug's "active agents."
According to the Health Ministry, Perrigo waited until January 12 to admit that active agents used in the production of Eltroxin's new version differed from those used in the medicine's previous version, and that the concentration levels of various components had been altered. Documents indicate that Dr. Rami Kariv, head of the Health Ministry's GMP (good manufacturing practice ) bureau, concluded that "the manufacturer's behavior concerning the changes [in Eltroxin] was irregular, and was tainted by the provision of incomplete, if not incorrect, information; there remains a question of what actions ought to be taken by the Health Ministry in response to this [questionable] behavior."
A senior Health Ministry official told Haaretz that the change in the new drug's components "was discovered thanks to the alert diligence of the ministry's staff. The change was not detected in any other country in which the drug is marketed. Though there is no proof that the change in the component's concentration is what led to the reported side effects, the false reports disclosed by the company are a very grave matter."
It bears mentioning that neither the ministry nor Perrigo notified the public about changes that had been uncovered in the concentration of Eltroxin's components - not even HMO physicians and pharmacists were informed of the changes. Ministry officials explain that there was no cause to issue such an announcement - the ministry was already monitoring the use of the thyroid drug by patients.
In this period - after the changes in the new drug's composition were known to the ministry and Perrigo, but not to the public - Kariv informed the company that the report it had relayed to the ministry "is not relevant with regard to the product which is being manufactured today." Kariv told Perrigo that it would have to produce a new report about Eltroxin, and that the ministry would make its decision about registering the new drug on the basis of this new report. In response, Perrigo relayed on January 18 a letter detailing changes instituted in the composition of the new Eltroxin drug.
Perrigo stated in response: "The Perrigo company categorically denies allegations made against it. Perrigo, which markets the drug in Israel, did not conceal information from the Health Ministry. It relayed to the ministry all relevant information it had regarding the drug, information it received from the medicine's producer, the Aspen company. Perrigo operates in compliance with Health Ministry guidelines relating to disclosure of medical and pharmaceutical information."
The Health Ministry states in response to this report: "The changes in the concentration of components were never reported to the ministry at any stage, just as (to the best of our knowledge ) reports were not disclosed to any health agency around the world; the manufacturer related to these changes as though they were a matter to be monitored internally, without disclosure to outside regulators.
"Following a series of questions and clarifications [made by the ministry] it became clear that the concentration of active agents had been changed by the manufacturer. This information was obtained as the ministry's investigation committee was concluding its work. It would not have been possible to detect the changes earlier, since the manufacturer did not issue reports about them. A laboratory examination of such components cannot detect alterations of concentration levels once the components are assembled in a tablet form.
"After the changes in component levels were uncovered, a professional team [established by the ministry] went to review the manufacturing process in Germany. It has not been proven that the change in the agents' concentration levels are the cause of unwanted side effects."