Levothyrox: indictment of Merck, summary of the scandal

LEVOTHYROX CASE. The Merck laboratory, which markets the new formula of Levothyrox, is indicted for 'aggravated deception' and ordered to pay 1,000 euros to each of the 3,329 patients who filed a complaint for 'lack of information' on the side effects of Levothyroxine. medication.

[Updated October 19, 2022 at 9:00 a.m.] Wednesday October 19, 2022, the French subsidiary of the German pharmaceutical laboratory Merck (who markets the Levothyrox ) announced, via a press release, his indictment for 'aggravated deception' as part of the change in formula of the drug Levothyrox. Indeed, several thousand patients treated with the new formula of the drug Levothyrox , indicated in the treatment of disorders of the thyroid ( hypothyroidism ) , I know have complained of heavy side effects (headaches, dizziness, insomnia...) and have filed a complaint against Merck at first instance, in March 2019. At the end of this first trial, the judges had not recognized any fault on the part of the laboratory. Convinced otherwise, 3,329 patients appealed and demanded compensation of 10,000 per person. Finally, the Court of Cassation rejected, on March 16, 2022, the appeal of the German pharmaceutical company Merck. The laboratory, which markets the new formula of Levothyrox® is therefore well ordered to pay 1,000 euros to each of the plaintiffs for 'non-pecuniary damage', indicated their lawyer, Maître Christophe Leguevaques . In his stop , the Court of Cassation confirms that 'when the composition of a drug changes and this change in formula is not explicitly indicated in the leaflet, the manufacturer and the operator may be blamed for a lack of information' , can 'causing moral harm' . Dates, unfolding of events... Back to the Levothyrox affair.

What are the key dates in the Levothyrox scandal?

  Photo of the new Levothyrox formula

It all starts in mars 2017 . Merck Lab commercializes its new Levothyrox® formula following the request of the National Safety and Medicines Agency. Administered to people with thyroid disorders, Levothyrox® can replace the thyroxine natural when it is no longer secreted in sufficient quantity by the thyroid (in case of hypothyroidism for example). But why did you change the formula ? The active ingredient remains the same. Only the lactose was replaced by mannitol, another excipient, in order 'to guarantee a greater stability of the content of active substance (levothyroxine) throughout the shelf life of the medicinal product (because there could be differences in levothyroxine content from one batch to another or over time for the same batch)', attests the drug agency in a press release. And ensure that ' these modifications do not change the efficacy or the tolerance profile of the drug '. However, as a precautionary measure, the ANSM advises certain patients (those whose therapeutic balance is particularly difficult to achieve, those suffering from a thyroid cancer or cardiovascular disease, children and the elderly) to carry out a TSH assay 6 to 8 weeks after the start of the new formula in order to adjust the dosage if necessary, and to report any side effects on the site of the Ministry of Health. Finally, the format and colors of the medicine boxes have been changed to better inform patients.

Patients complain of side effects.

► April-May-June 2017. While tolerating the old formula well, thousands of patients on the new formula Levothyrox® complain of side effects ( fatigue, weight gain, hair loss, digestive problems , leg pain, vision problems, memory loss or depression). In an open letter to Agnès Buzyn, Minister of Health, and a online petition launched in June gathering over 40,000 signatures, patients are calling for a return to the old form of treatment. The ANSM is clear: it does not intend to modify the formula again and qualifies the change in composition as 'final'.

► August 2017, the Medicines Agency is reassuring and publishes on its website a series of questions/answers on the new Levothyrox formula for patients and healthcare professionals. Regarding the adverse effects, the ANSM justifies itself: 'A dose readjustment is sometimes necessary with the new formula but the balance once reached will be maintained'.

► September 2017 . the Minister of Health at the time, Agnès Buzyn, expressed 9,000 complaints from patients on Levothyrox ®. The actress Annie Duperey testifies in Le Parisien, to deplore the appearance of side effects from which she suffers since she takes the new formula of Levothyrox. 'There is no fraud, no conspiracy, there is no error' reassures the Minister. 'There was one patient information problem . Patients found themselves surprised at a formulation that had changed. Many side effects would be related to the dosage of the drug' , she justifies. The petition calling for the return to the old formula has more than 250,000 signatures. A Preliminary investigation is in progress at the public health center of the tribunal de grande instance of Marseille.

  Photo de Euthyrox, l'ancienne formule du Levothyrox
Photo of Euthyrox, the old formula of Levothyrox

► October 2017. Availability of the drug Euthyrox® whose composition is identical to the old formula of Levothyrox®.

► January 2018. More than 17,000 reports of adverse effects are attributed to the new Levothyrox® formula, according to a new pharmacovigilance report unveiled on Tuesday January 30 by the ANSM, including 19 death cases . Surprisingly, two-thirds of patients report adverse effects even though their dosages of TSH are within the expected standards (without thyroid imbalances). If no explanation has been put forward to date, the authors of the study recommend the establishment of a working group to analyze these data.

Traces of heavy metals in the new Levothyrox formula.

► 6 mars 2018. A judicial investigation against X has been opened for 'aggravated deception, involuntary injury and endangerment of others ' as part of the Levothyrox® case. 7,000 complaints have been filed. Patients are demanding medical expertise and hope 'a formula that suits everyone' .

► April 2018. Levothyroxine Medicine Monitoring Committee says it has found traces of heavy metals in the new formula of Levothyrox and in particular the presence of ' nanoparticles and iron-chromium, chromium-nickel, iron-chromium-silicon and ferrochrome-aluminum alloys, while only a few steel scraps are detected in the old formula' says the French Association of Thyroid Patients (AFMT). The AFMT considers that the very small quantities of heavy metals are insufficient to consider changing treatment for whom the drug is well tolerated.

► June 14, 2018. ANSM confirms the presence of traces of heavy metals in the new formula but they 'do not in themselves represent a quality defect nor a health risk insofar as the concentrations are below the safety thresholds established by the scientific community at the international level for drugs'.

► July 5, 2018. The ANSM maintains its positions: 'The information questioning the quality of the new Levothyrox formula is unfounded.' And points out that Europe has issued a favorable opinion on the launch of the new Levothyrox® formula in 21 out of 28 countries in 2019.

► September 2018. A report on improving drug information is submitted to the Minister of Health. It points to gaps in information and communication, such as 'the absence of anticipation and support', the 'artisanal' and 'insufficiently coordinated' crisis communication or the 'minimization of the feelings of the patients'. The authors claim a ' increased effort of transparency ', as well as the launch of a 'popularized drug' information site and better consideration of complaints on social networks. In response to this report, Agnès Buzyn promises information ' more accessible, clear and responsive ' on medicines and the establishment of a single, official source of public information on medicines. This will be sante.fr.

The Medicines Agency accused of having concealed several information.

► September 28, 2018 , a petition launched by the AFMT, submitted to the Minister of Health, accuses the ANSM of having concealed several pieces of information - including the name of the company and the place of manufacture of the active ingredient of Levothyrox, a new formula - from counsel for several plaintiffs. The ANSM denies in a press release (dating from the same day) published on its website. Patients who reported health problems to the ANSM because of Levothyrox® new formula, via the pharmacovigilance form, are today 30,000 .

► October 31, 2018. ANSM confirms availability in France in 2019 de l'Euthyrox® (medication equivalent to the old formula of Levothyrox). These boxes, imported by Germany, are given priority to patients who have not found a lasting solution. The Merck France laboratory has thus insisted on the transitional nature of this old formula .

► December 3, 2018. The Levothyrox civil lawsuit opens in Villeurbanne (Auvergne-Rhône-Alpes). In total, 4,113 complainants accuse the pharmaceutical company Merck of a ' lack of information ' at the time of the marketing of the new formula of the drug in the spring of 2017. The victims are each claiming a lump sum compensation of 10,000 euros in damages in guise of 'moral prejudice'.

► Mars 2019. The Lyon District Court finds that Merck made no errors in the information given to patients and explains that ' the quality and therapeutic value of the new formula drug ' were ' some '. The 4,113 victims will therefore not be compensated .

► June 2019. The rapport final of a study commissioned by the Ministry of Health is published on the website of the National Agency for Health and Medicine (ANSM). ' The results of this study do not provide any argument in favor of specific toxicity of the new formula of Levothyrox® ' he concludes. This study - which involved 2,075,106 people treated with Levothyrox® and aged 18 to 85 - therefore did not show an increased risk of serious health problems (hospitalizations, deaths, work stoppages...) during the months following the initiation of the new formula of thyroid treatment. On the other hand, the survey concluded that there was an increase in recourse to outpatient care (+2%) and certain medications such as benzodiazepines , anxiolytics that act on the nervous system and on sleep disorders.

► Wednesday, January 8, 2020: The Ministry of Health announces that the drug Euthyrox ® which corresponds to the old formula of Levothyrox ® and which was available since the end of 2017 in France, will be permanently withdrawn from the market in September 2020 . Currently 110,000 French are treated with, or 3.7% of the 3 million patients on levothyroxine. They are invited 'to consult their doctor to analyze their situation, change treatment in good conditions and avoid potential supply stress situations' indicates the ministry. From September 2020, patients will have no choice but to adapt to the new formulas.

► Thursday, June 25, 2020: During the appeal trial, the Merck laboratory was finally ordered to pay 1,000 euros to each patient who continued the complaint procedure. The judges of the Lyon Court of Appeal having recognized that the laboratory had committed 'a fault' when changing the formula of its treatment.

► Wednesday, March 16, 2022 : The Court of Cassation rejects the appeal of the pharmaceutical laboratory. In his stop , the highest civil law court confirms that 'when the composition of a drug changes and this change in formula is not explicitly indicated in the leaflet, the manufacturer and the operator may be blamed for a lack of information' , can 'causing moral harm' . The appeal body 'declared admissible the appeal of the civil parties and (...) found that Merck had committed a fault. The court considers that there was a moral prejudice suffered by all the parties' , said their lawyer, Christophe Lèguevaques, to the press.

► Wednesday 19 October 2022: Indictment of the Merck laboratory. In a press release, the pharmaceutical laboratory indicates that ' the president of Merck in France was heard ' the day before at the health center of the Marseilles court. A hearing at the end of which ' the investigating judge decided to put the Merck company under investigation '.

What are the indications for Levothyrox?

Levothyrox is recommended in the following situations:

  • in case of hypothyroidism (insufficient secretion of thyroid gland ),
  • In the event of circumstances associated or not with hypothyroidism where it is necessary to curb the secretion of TSH (hormone that stimulates the thyroid gland).

What does the new Levothyrox formula contain?

The active substance in Levothyrox is Levothyroxine sodium . Other components are added to ensure the stability and good absorption of the drug (excipients): Mannitol, corn starch, gelatin, croscarmellose sodium, magnesium stearate, citric acid anhydrous.

► Levothyrox comes in the form of a white scored tablet , in boxes containing 25, 28, 30, 50, 90 or 100 tablets.

What are the side effects of the new Levothyrox formula?

Like all medicines, this medicine can cause side effects, although not everyone gets them. These side effects can be:

  • Worsening of heart disease ( angina pectoris, heart failure, heart rhythm disturbances ),
  • Signs of hyperthyroidism (palpitations, insomnia, excitability, tremors, increased temperature, sweating, rapid weight loss, diarrhea): in this case, consult your doctor,
  • In children, possibility of hypercalciurie (too high calcium level in the urine),
  • Possible allergic reactions (hypersensitivity). The most common signs and symptoms are: rash, hives, itching, swelling of the neck and face, difficulty breathing and redness.

If you get any side effects, talk to your doctor or pharmacist. This also applies to any undesirable effect not mentioned in this leaflet. You can also report adverse effects directly via the ANSM's national reporting system: www.signalement-sante.gouv.fr

What are the contraindications of Levothyrox?

Levothyrox is contraindicated:

  • if you are allergic (hypersensitive) to the active substance or to any of the other ingredients of this medicine.
  • if you suffer from hyperthyroidism (set of disorders caused by excessive activity of the thyroid gland), apart from hyperthyroidism treated with synthetic antithyroid drugs, iodine 131 or surgery and requiring replacement therapy with thyroid hormones (for example in the case of long-term treatment of Maladie by Basedow by the combination of synthetic antithyroid drug + levothyroxine).
  • In case of acute coronary syndrome or acute myocarditis (inflammation of the heart muscle).
  • If you adrenal glands are not working properly (adrenal insufficiency) and you do not have adequate replacement therapy for it.
Source journaldesfemmes.fr