The Food and Drug Administration has backed off from a warning letter it sent to several manufacturers and decided to allow an unapproved version of high-concentrate morphine sulfate oral solution to remain on the market.

Objections from pain specialists, hospice workers, and patients convinced the FDA that there is no good alternative for some patients who need the immediate-release morphine sulfate oral concentrate solution 20 mg/mL for pain control, Dr. Douglas Throckmorton of the FDA's Center for Drug Evaluation and Research said at a press briefing.

The decision will benefit patients at the end of their lives who cannot easily be administered opiates intravenously or through other routes and cannot swallow well. They may need a high morphine dose—several hundred milligrams—and an approved, less-concentrated morphine sulfate elixir would require a large volume of liquid, putting them at risk of aspirating the liquid.

As part of an ongoing crackdown on unapproved drugs in the United States, the FDA on March 30 had written to nine companies warning them to stop making and marketing 14 unapproved narcotic products, believing that acceptable alternatives were available.

The March 30 action alarmed members of four organizations in the Palliative Care Coalition, whose leaders communicate regularly and who quickly drafted a letter apprising the FDA of the medical necessity for the concentrated morphine elixir.

In addition to use in patients near the end of life, the elixir is used to manage pain in “patients who are not dying but [are] going through very traumatic treatment for head and neck cancer, which is likely to be curative but very difficult to get through,” Dr. Diane E. Meier said in an interview. She is director of the Center to Advance Palliative Care at Mount Sinai School of Medicine, New York. The Palliative Care Coalition consists of her organization and the American Academy of Hospice and Palliative Medicine, the Hospice and Palliative Nurses Association, and the National Hospice and Palliative Care Organization.

In response to the outcry, the FDA sent follow-up letters on April 9 to six companies that offer the concentrated morphine sulfate elixir, saying they could continue to market the drug formulation. This should especially help some patients in hospitals and hospices, Dr. Throckmorton acknowledged.

“Both those populations sometimes experience severe pain at the end of life and want to be able to be managed at their homes whenever possible. The use of this elixir enables that,” he said. “That's an important part of the decision that we made today.”

The reversal surprised and delighted observers. “I don't think we expected a response” from the FDA to the coalition's letter, Dr. Meier said, “so to get one was really gratifying and made us very optimistic that this will be the beginning of an effective professional dialogue.”

Mike Cohen, president of the nonprofit Institute for Safe Medication Practices in Horsham, Pa., commented on Twitter.com

The concentrated morphine elixir products were marketed before the 1938 Federal Food, Drug, and Cosmetic Act regulations took effect, and were allowed on the market without formal approval under a grandfather clause. The FDA today believes few drugs are entitled to grandfather status, Mr. Cohen wrote in the institute's April 9 newsletter.

The FDA is willing to fast-track an approval application from any company for the concentrated morphine sulfate elixir, Dr. Throckmorton said. If one gets approved, any companies making unapproved versions will have 180 days to cease manufacturing and marketing their formulations. Until one is approved, however, they can continue to supply the product.

The other unapproved drugs that were targeted in the original warning on March 30 must still be taken off the market within 90 days. These include immediate-release hydromorphone and oxycodone tablets. Failure to comply could result in seizure of these drugs.

Dr. Meier says the coalition remains concerned about those drugs being taken off the market, too. “There is a nationwide shortage of opioids,” she said. “In New York City you can't find many of these drugs, even before this shutdown has taken place. My colleagues report this to be true across the country.”

Dr. Meier and others planned to participate in an invitation-only meeting with FDA officials on May 4 to discuss Risk Evaluation and Mitigation Strategies (REMS) for drugs including opioids. Coalition members are concerned that REMS requirements could further decrease patient access to pain medications, but are hoping that the flexibility shown by the FDA regarding the morphine elixir bode well for future talks.

“I found the responsiveness and timeliness of the FDA to be really wonderful. It reinforced the FDA's obligation to not only reduce harm but [also] to ensure access to beneficial medications,” Dr. Meier said.

The companies that received the April 9 letter allowing them to continue offering morphine sulfate oral solution 20 mg/mL are Lannett Co., Lehigh Valley Technologies, Mallinckrodt Inc. Pharmaceuticals Group, Xanodyne Pharmaceuticals Inc., Boehringer Ingelheim Roxane Inc., and Cody Laboratories Inc.

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'I found the responsiveness and timeliness of the FDA to be really wonderful.' DR. MEIER

Unapproved Narcotic Gets Reprieve From FDA