A normal therapeutic course for Mildronate is 4 to 6 weeks, per labeling. It was first prescribed for Sharapova 10 years ago.
And why was a tennis star taking meldonium?
An anti-ischemic agent that is used outside the U.S. for treatment of angina and circulation disorders in the brain and to improve neurologic ischemic conditions, is now the center of a controversy gripping the world of professional tennis.
Maria Sharapova said she took the drug Mildronate (meldonium), which was recently identified as a performance-enhancing drug and added to the World Anti-Doping Agency's list of prohibited substances.
Because the drug is not approved in the U.S., the FDA declined requests for comment.
"This is the kind of drug that would be used in someone who has cardiac disease, specifically congestive heart failure," said Robert Glatter, MD, an emergency physician at Lenox Hill Hospital in New York City. "There would be absolutely no indication for a young, healthy athlete to be on this medication unless they had underlying cardiomyopathy or a history of heart failure, which is highly unlikely."
Made by Latvian drug company Grindex, meldonium was designed to treat ischemia, or a lack of blood flow to the heart or other organs. It's for patients with "angina pectoris, chronic heart failure, brain circulation disorders," according to the company website, which also says the drug "improves physical capacity and mental function" in healthy people.
Grindeks told MedPage Today it will fight to get the drug removed from the WADA prohibited substances list.
"As far as there have been no clinical studies providing scientific evidence that acute or chronic use of meldonium increases the athlete's physical ability, any suggestions to include meldonium in the prohibited list have no scientific basis and are not justified," the company said in an email to MedPage Today, adding that it is not aware of adverse events occurring in athletes who use Mildronate.
The drug works to help reduce oxygen consumption by increasing and improving blood flow, Glatter said.
"If it's used in excess there's a chance that it could lead to adverse outcomes," Glatter said, explaining that the drug causes dilation of the coronary vasculature. Because it lowers blood pressure, a healthy person taking it could "potentially risk passing out, especially under higher doses or use more frequently."
The World Anti-Doping Agency added meldonium to its list of prohibited substances in September, and it was officially prohibited starting Jan. 1, 2016. The drug was on WADA's monitoring program throughout 2015, Ben Nichols, a WADA spokesman, told MedPage Today.
"Meldonium was added [to the Prohibited List] because of evidence of its use by athletes with the intention of enhancing performance," Nichols said, explaining that he can't comment further until the International Tennis Federation reached its decision regarding Sharapova.
Sharapova explained at a press conference this week that her doctor prescribed the drug to her 10 years ago because she was getting the flu "every couple of months," and had irregular electrocardiogram results as well as "indications of diabetes with a family history of diabetes." She explained that she didn't know the drug was banned and only learned upon receiving a letter from the International Tennis Federation informing her that she'd failed a drug test at the Australian Open.
"For 10 years, this medicine was not on WADA's ban list, and I had been legally taking the medicine for the past 10 years," she said.
Grindex told MedPage Today that a normal therapeutic course for the drug is 4 to 6 weeks.
"Depending on the patient's health condition, treatment course of meldonium preparations may vary from four to six weeks. Treatment course can be repeated twice or thrice a year," the company told MedPage Today. "Only physicians can follow and evaluate patient health condition and state whether the patient should use meldonium for a longer period of time or not according to the information provided in the patient leaflet and summary of product characteristics."
Glatter said Mildronate is likely used for longer periods of time when it is used off-label.
The most recent Mildronate clinical trial ended in 2010 at Xijing Hospital in China. In that study the drug was tested in patients with ischemic stroke, according to clinicaltrials.gov. Another at the same hospital was recruiting in 2013, but its status has not been updated in 2 years. Those are the only two Mildronate trials that appear on clinicaltrials.gov.
Since Mildronate has been on the market in the former USSR since 1984, it was grandfathered into approval in Latvia once it joined the European Union in 2004 without fresh clinical trials, the company said. But getting FDA-approval would be more complicated.
"To register Mildronate in the USA through the FDA, a marketing authorization applicant has to conduct full cycle clinical trials in the US prior to submit an application adequate to contemporary requirements," Grindeks told MedPage Today, adding that this would take time and resources, but wouldn't be ideal because the product lost its patent protection a decade ago.
Mildronate has also been studied in rodents in the hopes of using it for patients with Parkinson's disease and Alzheimer's disease to improve mood and improve cognition, Glatter said.