In the six months since pharmaceutical giant Merck KGaA reformulated a thyroid hormone replacement drug distributed in France, patients there have filed dozens of lawsuits. Hundreds of thousands signed a petition to reverse the change, and around 9,000 reported illnesses and side-effects, some dramatic. They complain of hair loss, cramps, weight gain, extreme fatigue, headaches, diarrhea, dizziness, memory loss, and heart palpitations.

The outcry has created a political and media blitz. Rumors and conspiracy theories have flown, including that Merck switched production of the drug to a plant in China to cut costs. (The drug, which has no competition in France, is produced in Europe.)

Bowing to the intense backlash, the French government began investigating and last week made the unprecedented request that Merck restore the old drug formulation to the market, Science reported. On Tuesday, French police searched the drug maker’s plant in Lyon, Reuters reported. Authorities are investigating whether Merck is guilty of “aggravated deceit, involuntary attacks on the physical integrity and endangering the lives of others,” according to a translated report by Le Monde.

On the surface, it may seem like a simple case of a catastrophic failure in quality control or just a rotten formulation. But health experts are puzzled by the kerfuffle. Merck didn’t change the active ingredient in the drug—it simply switched an excipient, a filler, that improved the drug’s shelf-life and stability. And it did so because France's National Agency for Medicines and Health Products Safety (ANSM) requested the change.

The United States, Brazil, China, and other countries have requested the same change, according to Luciano Rossetti, global head of research and development at Merck, who spoke to Science.

Fussy formula

The drug, Levothyrox, was stabilized with lactose in the past. Taken by about 3 million people in France alone, the drug replaces the hormone thyroxine in patients with the metabolic condition, hypothyroidism. The new version replaced the lactose with citric acid and mannitol, a sugar alcohol. Both are widely used as excipients in medicines.

A randomized bioequivalence study that Merck performed prior to introducing the new formula on the market showed that the switch improved shelf life and didn’t alter the activity of the drug in people. The amount of active ingredient fell in the range of 95 to 105 percent in each tablet over the whole shelf life. And the drug had the same blood peak levels and clearance in patients.

Experts are mostly stumped as to why the reformulation caused such a fracas and such serious side-effect reports. A press officer for the ANSM told Science: There is “no scientific explanation at this point for the surge in observed effects.”

Some endocrinologists and experts have speculated that dosing could be at the heart of the most serious health problems. With a more stable form of the drug, the effective dose of the new drug could be stronger than that of the old lactose version. Such seemingly small differences in the amount of the hormone could cause side-effects like the ones reported. And, it can take months to work out the correct dosage of a thyroxine treatment.

The situation was likely worsened by the media storm and the poor communication about the switch from Merck and doctors, according to Le Monde. Patients may have panicked and attributed other health problems or perceived side-effects—the nocebo effect—to the new drug.

For its part, Merck said it is cooperating fully with the French investigation and authorities there have promised to temporarily import versions of the drug from other manufacturers. The old Merck formulation of the drug will be available to French patients until those alternatives are available.