Israel Health Ministry to investigate handling of drug's side effects
Among the Eltroxin are an underactive thyroid, overactive thyroid and allergic reactions; four class-action suits have been brought in four different courts on the matter.
On Thursday, the Health Ministry decided on the unusual step of establishing a committee to probe the ministry's handling of information about patients' side effects from Eltroxin, used to treat an underactive thyroid.
Among the side effects, which in some cases require hospitalization, are underactive thyroid, overactive thyroid and allergic reactions. Four class-action suits have been brought in four different courts on the matter.
On February 16, the composition of the drug Eltroxin, which has been available in Israel since 1981, was changed. A similar change was made in some 20 countries where the drug is marketed. Although the active ingredients were not altered, the change in the inactive ingredients apparently helped change the drug's ability to be absorbed into the bloodstream and caused the side effects.
The Health Ministry had initially directed the company that markets the drug, Perrigo, to report only to medical personnel on the risk of side effects, and only gradually, between March and June this year.
On April 27, the Health Ministry received its first report of a patient whose thyroid condition became unstable after taking Eltroxin. The ministry's initial investigation revealed that the information was reported to the firm marketing the drug and to the manufacturer, the company Aspen.
In early May, the ministry received information of similar cases in New Zealand and Denmark after Eltroxin's ingredients were changed.
In early July, after the ministry received some 100 reports on side effects, it decided to treat the case as "extraordinary." The ministry then called a meeting to order Perrigo to inform patients of the change.
Only on August 4 did the Ministry instruct Perrigo to affix a sticker to Eltroxin's packaging warning patients of possible side effects and see their doctors if necessary.
Some 200,000 Israelis are being treated with Eltroxin, most of them women. According to the Health Ministry, more than 1,500 units are sold every day in Israel. But only this month did the Health Ministry release public warnings on the matter.
Sources in the Health Ministry's pharmacy department are calling the affair "an earthquake." So far, more than 450 complaints in Israel have been documented on side effects after using the product, some requiring hospitalization. Most of the complaints came this month after the ministry issued the public warning on October 9.
On Thursday, ministry director general Roni Gamzu announced the appointment a special investigative committee, to include outside experts.
The committee was set up, according to a Health Ministry statement, "in light of the complexity of the event" and "in keeping with the Patients Rights Law to fully investigate the matter and the way decisions were made."
Israel has no requirement for doctors and medical institutions to report to the health authorities on side effects of prescription drugs, as is common in Western countries.
Only last year did the Health Ministry create a website for physicians to report on extraordinary side effects from medications, but such reporting is voluntary. That may be the reason why so much time passed before the Health Ministry realized the extent of the problem.
In New Zealand, with a population of 4.5 million, Eltroxin was changed in early 2008, after which, over five months, 1,309 reports on side effects were filed.
One question is why the Health Ministry, which was aware of the reports from abroad, did not consider them a warning when it approved the change in the composition of Eltroxin marketed in Israel.
Britain's Medicines and Healthcare Products Regulatory Agency launched an investigation into the cases in New Zealand and the agency issued a report in 2009.
According to an article in the British Medical Journal in January 2010, the media panic in New Zealand after the change in the drug's composition stemmed mainly from the fact that many patients were unaware of the change in Eltroxin's composition and no alternative drug was available. There were also concerns that the change was made to save money.
Perrigo said this week the drug's composition in Israel was changed with the Health Ministry's approval.
An initial investigation by the ministry revealed that the request to register the new composition was discussed in the consulting committee for registration in the ministry's pharmacy department as far back as 2009. But it is unclear whether the side effects reported in New Zealand were taken into consideration at the time. It is also unclear why the ministry decided at the time to report the change only to medical personnel.
"In no country was a report made to the public about the change in the drug's composition," the Health Ministry said in a statement, adding that when the application was made to change the composition, the manufacturer submitted test results proving that the product was sound. "We assume that it will not be long before patients using the new drug will be balanced by adjusting the dosage to the medication marketed in Israel."
Among the countries where Eltroxin's composition was changed, beginning in 2006, are Germany, the Netherlands, Switzerland, Poland, the Czech Republic, Colombia, Thailand, Singapore, Egypt and Israel.
Extensive reports on side effects have been filed only in New Zealand, Israel and Denmark - where the drug's composition was changed in 2008.
A document released by Aspen states that the side effects in New Zealand and Denmark have been investigated; the company believes they stemmed from mistakes in usage. The company said it believed the drug's new composition was safe for use.
The Health Ministry decided recently, following the Eltroxin affair, on a new procedure in crisis management involving medications. According to a draft document, drug manufacturers, importers and pharmacy owners involved in a crisis stemming from a defect will have to take part in crisis management.
They will have to report to the Health Ministry and ensure the public's health even before the Health Ministry issues directives. Meanwhile, the Health Ministry's pharmacy department and medical administration will establish a crisis management team if needed.
The Patients Rights Organization has recently approached the ministry to require health maintenance organizations to report to patients on changes in the composition of drugs that have led to severe side effects.
The ministry issued a directive on October 16 that treatment with Eltroxin should not be changed without consulting a physician. The directive states that blood tests should be performed one month to six weeks after beginning use of the drug in its new composition.
Meanwhile, the health care system is importing two medications as possible alternatives to Eltroxin.
Although the two medications are not registered for use in Israel, the Health Ministry has granted special permission for them to be imported.
The Clalit HMO was the first to import the drug Eutirox, which Clalit will be gradually introducing beginning this week. The manufacturer, Merck Serono, said the drug would be available at all HMOs beginning in November. HMOs have also begun talks with U.S. drugmaker Abbott to import another medicine, Synthroid.
According to Dr. Nicky Lieberman, head of Clalit's community medicine department, "if the replacement of Eltroxin had been properly managed from the outset, there would not have been a problem, nor would there have been if this had happened in a country where panic did not reach the headlines. In Israel, hysteria over health-related issues is extreme, so I decided ahead of time to bring a large quantity of alternative drugs that would be enough for many patients, because the panic can be predicted."
But Lieberman added that alternative drugs are only needed for a small number of patients, mainly babies who need the medication crushed, and patients who develop side effects. Most patients only need their dosage raised, because the new composition slightly reduces the availability of the active ingredient in the bloodstream, Lieberman said.