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McCaskill sent letters to Purdue Pharma, Janssen Pharmaceuticals, Insys Therapeutics, Mylan, and Depomed, which she said make the top-five-selling prescription painkillers. She is seeking sales and marketing materials, any studies the companies might have conducted about the addictive properties of their drugs, information on compliance with legal settlements and figures on donations to advocacy groups.

McCaskill said she wants to know whether manufacturers have contributed to overuse and overprescribing of opioids. According to the Centers for Disease Control and Prevention, nearly 180,000 people have died of overdoses of prescription opioids since 2000 and tens of thousands more have succumbed to overdoses from heroin and fentanyl.

Most of the companies said Tuesday that they were reviewing McCaskill's request. A spokesman for Purdue Pharma issued a statement noting that its brand-name product, OxyContin, "accounts for only 2 percent of the opioid analgesic prescriptions nationally, but we are an industry leader in the development of abuse-deterrent technology and advocating for the use of prescription drug monitoring programs. We are reviewing Senator McCaskill's letter and will respond accordingly."

And in a separate statement, a spokeswoman for Janssen Pharmaceuticals said "we believe that we have acted appropriately, responsibly and in the best interests of patients regarding our opioid pain medications, which are FDA-approved and carry FDA-mandated warnings about the known risks of the medications on every product label." A spokeswoman for Mylan later added that "we very much hope that the Senator expands her interest to include the top ten suppliers of opioid drugs to the U.S. market. In 2016, Mylan ranked as the number 17 supplier of opioids sold in the U.S., representing approximately 1% of the entire U.S. opioid market."

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Earlier this month, McCaskill asked the Justice Department's inspector general to investigate why the Drug Enforcement Administration had delayed or blocked enforcement efforts against wholesale distributors of opioids accused of failing to follow laws designed to keep legal painkillers from reaching the black market. She cited reporting by The Washington Post that the efforts of DEA field investigators had been frustrated when attorneys at headquarters imposed higher burdens of proof for bringing cases, even as the overdose rate from those prescription drugs soared.

The city of Chicago and several U.S. counties have sued opioid manufacturers, demanding reimbursement for the expense of grappling with the drug crisis. The lawsuits contend that aggressive marketing by the companies has fueled the crisis.

Last year, Mylan was accused of price-gouging after it sharply raised the price of its lifesaving EpiPen injection medication for allergic reactions. The company released a lower-cost generic version of the device in response.