McKesson Corp., one of the largest U.S. drug distributors, sent pharmacies prescription opioids that had been removed from their bottles and replaced with over-the-counter painkillers, the Food and Drug Administration said.

In a warning letter to Chief Executive Officer John Hammergren dated Feb. 7, the FDA said inspections of McKesson’s headquarters in San Francisco and a distribution facility in Oregon last year found the company had failed to respond adequately after being notified by regulators and drugstore customers about the tampered bottles. McKesson also failed to keep proper records of its internal investigation of the matter, the FDA said.

McKesson’s alleged violations show how the legitimate drug-supply chain can be exploited to divert opioids to the illegal market, FDA Commissioner Scott Gottlieb said in an interview Tuesday. “Anyone who is taking custody of controlled substances through the supply chain bears responsibility of ensuring the integrity of the products,” he said.

In September 2016, Rite Aid Corp. notified McKesson that one of its Milford, Michigan, pharmacies had received a bottle of 100 tablets of prescription painkiller oxycodone hydrochloride, which was manufactured by Mallinckrodt Plc. The seal had been broken and the bottle no longer contained the opioid, but rather held 15 tablets of naproxen, the generic name for Aleve.

Rite Aid pharmacies in Warren and Waterford, Michigan, also received tampered bottles of prescription painkillers that no longer contained oxycodone. The FDA letter said McKesson’s investigation into the three incidents suggests that the oxycodone was likely “replaced with other product while the packages were in the possession or control of McKesson.”

The FDA contacted McKesson on July 3 and received responses from the company on July 25, Sept. 25 and Nov. 4. McKesson’s responses demonstrated “a lack of understanding” of the issue, according to the warning letter.

“McKesson takes this situation very seriously,” spokeswoman Kristin Chasen said in an email. “We have been in communication with the FDA over the past several months to respond to their questions and we are in the process of providing additional procedural detail and documentation, including enhancements recently made in response to the FDA’s initial feedback. We are committed to the security of the supply chain and are taking steps to help ensure we comply fully with FDA’s track-and-trace laws for all pharmaceutical products.”

McKesson shares rose 2.6 percent to $133.84 at 2:06 p.m. in New York. The stock has fallen 11 percent in the past 12 months.

Given the severity of the U.S. opioid crisis, Gottlieb said the FDA will focus new efforts on securing potential vulnerabilities in the supply chain. The agency is also developing new guidance on opioids, outlining the risks created by illicit use as well as the safety and effectiveness of new drugs. The report will be published later this year.

“This is a new area of focus for us,” said Gottlieb, noting that legally sold opioids are often subject to theft. “This is a part of a broader vision for trying to make sure we’re providing appropriate vigilance over the legitimate supply chain.”