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Drugstore giant CVS has reached a $3.5 million settlement with the federal government after investigators found that pharmacists in Massachusetts and New Hampshire filled hundreds of forged prescriptions for painkillers at the height of the opioid crisis, the US attorney’s office announced Thursday.

It is the largest such settlement in Massachusetts history, federal authorities believe.

They faulted CVS for its pharmacists’ failures to recognize signs that prescriptions were fake and then alert the authorities.

As part of the settlement, CVS Health Corp. pledged to improve training of employees to recognize signs of forged prescriptions. The company, headquartered in Woonsocket, R.I., said it settled to avoid the cost and inconvenience of further legal proceedings.

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The settlement, announced by US Attorney Carmen Ortiz’s office, followed two Drug Enforcement Administration investigations into whether CVS pharmacists ignored red flags, including computer system bans on individuals receiving addictive drugs.

“It makes clear to other pharmacies that we will be investigating, we will be monitoring, and we will be vigilant as to how they distribute the controlled substances they are responsible for,” Ortiz said.

Investigators alleged that pharmacists in 50 CVS stores violated the Controlled Substances Act by filling forged prescriptions more than 500 times — mostly for addictive painkillers.

The DEA estimated the total value of the pills involved at more than $1 million.

One DEA investigation examined CVS stores across Massachusetts and New Hampshire, while the other focused on Boston-area stores.

Those inquiries were triggered in part by physicians’ reports of stolen prescription pads, Ortiz said.

The forged prescriptions, written between 2011 and 2014, came from a handful of individuals, including a woman identified only as “P.R.” She signed a dentist’s name on 56 of 59 oxycodone prescriptions that were filled at five CVS locations.

Those prescriptions were filled even though CVS had banned P.R. in 2011. She was able to circumvent the ban by creating a new patient profile, using a different last name.

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Another forger presented prescriptions from an emergency room physician at Brigham and Women’s Hospital who did not work at the Boston hospital. That customer filled fake prescriptions for hydrocodone and methadone more than 200 times, according to federal authorities. Yet another forger listed a Massachusetts address for a dentist who had moved to Maine.

In a statement, CVS spokesman Gary Serby said the company is committed to the highest standards of ethics and business practices and is dedicated to reducing prescription drug abuse and diversion.

“Since the covered time period, we have implemented enhanced policies, procedures, and tools to help our pharmacists properly exercise their corresponding responsibility to determine whether a controlled substance prescription was issued for a legitimate medical purpose before filling it,” the statement read.

Ortiz praised CVS for updating its programs even before the settlement was reached.

Pharmacists have “a very clear and defined responsibility” under state and federal laws to detect false prescriptions, said Carmen Catizone, executive director of the National Association of Boards of Pharmacy, of which Massachusetts is a member. The curriculum in pharmacy schools helps students learn about signs of prescription abuse, Catizone said.

“How much CVS and Walgreens train a pharmacist to familiarize them to try and remember [red flags] is going to vary from store to store, but that doesn’t remove the responsibility that they have to know them,” he said.

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But health care specialists and law enforcement officials acknowledged that pharmacists can’t stem forged prescriptions on their own.

Physicians hold equal responsibility for checking the statewide Prescription Monitoring Program database to ensure patients are not “doctor-shopping” so that they can fill multiple prescriptions, said Dr. Daniel Alford, an addiction specialist at Boston University’s School of Medicine.

Ideally, pharmacists would check the veracity of every prescription, but that isn’t feasible, he said.

“The prescription can look totally normal, totally legit, and does it mean every time you get a prescription for a controlled substance you [as a pharmacist] need to then call the doctor’s office?” Alford said. “Where are you going to find the time?”

If pharmacists are on alert for red flags, Catizone said, they would need to contact doctors only for suspicious prescriptions.

Ortiz acknowledged that prescription forgery is a multifaceted problem and called the crackdown on pharmacists “just one line of the defense.”

Dr. James Gessner, president of the Massachusetts Medical Society, said everyone involved with prescribing potentially addictive medication needs to be vigilant.

“Physicians must prescribe with care, pharmacists must dispense responsibly, and patients must take the medicines as directed,” Gessner said.

CVS’s oversight has been challenged before. In 2015, the company paid $450,000 to settle similar allegations of negligence at several pharmacies in its home state.

Previously, the largest such settlement in Massachusetts involved Massachusetts General Hospital last year, related to lax control of its drug supply, which allowed doctors and nurses to steal thousands of pain pills, Ortiz said.

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Officials in Ortiz’s office said the settlement money will go to the Department of Justice but has not been designated for any particular use.

John McGahan, president of the Gavin Foundation, a Boston nonprofit fighting substance abuse, said he hopes the money will be used to ensure people never need to forge prescriptions in the first place.

“We’re on the back end of this epidemic,” McGahan said. “We’d hope the proceeds go toward prevention.”


Vivian Wang can be reached at vivian.wang@globe.com. Follow her on Twitter @vwang3.