Hot Summer Threatens Efficacy of Mail-Order Medications

Melted capsules. Cloudy insulin. Pills that may no longer work.

Doctors and pharmacists say the scorching temperatures enveloping the country could be endangering people’s health in an unexpected way: by overheating their medications.

Millions of Americans now receive their prescription medications through mail-order shipments, either for convenience or because their health plans require it. But the temperatures inside the cargo areas of delivery trucks can reach 150 degrees Fahrenheit in the summer, according to drivers — far exceeding the range of 68 to 77 degrees recommended by the national organization that sets standards for drug handling.

Mail-order pharmacies say that their packaging is weather resistant and that they take special precautions when medication “requires specific temperature control.” But in a study published last year, independent pharmaceutical researchers who embedded data-logging thermometers inside simulated shipments found that the packages had spent more than two-thirds of their transit time outside the appropriate temperature range, “regardless of the shipping method, carrier, or season.”

Extreme temperatures can alter the components in many medications, from pancreatic enzymes to the thyroid replacement drug levothyroxine to oral contraceptives, medical experts say.

Dr. Mike Ren, a primary care physician and an assistant professor in the department of family and community medicine at the Baylor College of Medicine, said that liquid medications like insulin or AUVI-Q, the epinephrine injection for allergic reactions, are often at heightened risk of degradation because excessive heat exposure can cause the evaporation of liquid components that were compounded at precise ratios. Aerosolized medications, too, are uniquely vulnerable because of the risk of pressure changes in the canister.

“It’s really a double whammy,” he said, since liquids and aerosolized drugs also happen to be the fast-acting medications most often needed in an emergency.

“A rescue inhaler or an EpiPen — those things are not like a daily blood pressure pill,” he said. “They need to work immediately.”

Bryan Rabakon, senior vice president of supply chain and engineering for OptumRx, said in an interview that the company used “a range of technologies from predictive analytics to packaging innovations to protect the integrity of the medications on their journey from the pharmacy to our patients’ homes.”

OptumRx monitors the duration of the shipment, he said, and if a medication is in transit for longer than the number of hours allowed, a new package is automatically reshipped. But he said the company did not monitor the temperatures inside packages in transit.

“We did have tags in the past,” Rabakon said, referring to low-cost slips that indicate exposure to extreme heat, “but they had a lot of false positives, so we actually discontinued them.”

Representatives from Cigna did not respond to questions regarding processes at its mail-order pharmacy, Express Scripts. In an investigation by NBC into mail-order drugs, Wendy Barnes, then the head of home delivery for Express Scripts, said the company did not use special packaging or disposable temperature tags inside most room-temperature shipments.

The Food and Drug Administration provides strict guidelines for packaging and storing drugs and transporting them between manufacturers, wholesalers and pharmacies, but the rules do not apply to transportation to patients. A spokesperson for the agency said in a statement that those mail-order procedures fall under the jurisdiction of the states. The statement also noted that “medicines that are not stored properly may not work as well or may cause harm, even if they are not expired,” and advised: “Avoid exposing medicines to extreme high or low temperatures.”

What Happens in Heat

The New York Times spoke to more than a dozen patients who had received medications they suspected were damaged by heat and humidity during transportation, some of whom experienced serious medical issues after consuming the drugs. Most said they had received their medications in manila envelopes or plastic shipping bags with no additional insulation. They spoke about finding pill bottles in metal mailboxes or tossed onto their front porches, leaving them unsure of how long the drugs had been baking in the sun. Others said they routinely stayed home to watch for drop-offs but found that the medications arrived already warm to the touch.

When customers called pharmacists at the mail-order companies, they said, they were often told that if the medications did not show physical signs of degradation — such as misshapen syringes; melted, gummy capsules; or foggy-looking vials — they were safe to use. But various studies have shown that medications can degrade from heat exposure without discoloration.

“I certainly wouldn’t rely on it just because it looks OK,” Ren said.

In Missouri, Loretta Boesing received a shipment of a liquid immunosuppressant medication for her son, who had a liver transplant, in 102-degree weather in only a plastic envelope. Soon after, his health began waning, and his body began to reject the liver. During a two-week hospital stay, he began receiving the medications from the hospital pharmacy instead and began to recover.

Several years after the ordeal, Boesing’s insurance changed, and the new services were administered by CVS Caremark. She filed several appeals to the company to allow her to continue picking up the medication at the hospital pharmacy. But the request was denied, she said, and the medication again arrived without an ice pack, warm. She said her son’s liver lab tests had begun to elevate again.

She wept on a call with a CVS Caremark representative, which she recorded and shared with the Times. “I am begging you right now: Please do not let me lose my son,” she says on the call.

Michael DeAngelis, a spokesperson for CVS Health, said he was not able to comment on the specific case because of patient privacy laws but added that the company customizes its packaging using a “sophisticated algorithm” that accounts for both FDA and manufacturer data.

“There are hundreds of different possible packaging combinations that we can use to help mitigate weather and temperature issues,” he said.

Boesing went on to start the nonprofit group Unite for Safe Medications.

Rebecca Nierengarten, 39, of Maplewood, Minnesota, was in medical school when she fell ill with a dangerous autoimmune disease that causes extreme muscle weakness. She said her insurance company had forced her to switch from hospital infusions of an immunoglobulin product called Privigen to home delivery of the drug, and every summer, her condition worsened so drastically that she could not stand up from a chair without assistance and struggled to swallow.

“It’s a protein medication — proteins denature with heat,” she said. “If you have a biology degree, you know that.”

Extreme temperatures can be an issue in the winter months as well. Cheri Hicks, 55, an interior designer in Grand Rapids, Michigan, who has Type 2 diabetes, noticed one day in November that her blood sugar had skyrocketed, even though she had kept up her diet and good hydration. After her doctor gave her a sample insulin pen, her blood sugar fell, suggesting that the mail-order pack — which had been delivered three days late because of a snowstorm — had most likely frozen and then thawed, damaging the insulin.

An Old Problem, Exacerbated

Researchers have been aware of potential effects of heat exposure on medications since at least the 1990s. Between June and August of 1996, United States Pharmacopeia — the nonpartisan group that sets national standards for drug handling — packaged and mailed electronic temperature and humidity indicators to various parts of the country to determine whether drugs were being subjected to worrisome conditions.

The results, shared with a task force of the National Association of Boards of Pharmacy, showed that more than 90% had exceeded the appropriate temperature range and that more than a quarter of those had been exposed to what was considered “excessive heat,” above 104 degrees Fahrenheit. The packages were also exposed to significant spikes in humidity.

But representatives from the Pharmaceutical Care Management Association, which lobbies for the pharmacy benefit managers that oversee drug benefits for many insurance plans, were present at the meeting, and the task force decided against acting.

In the more than two decades since, global temperatures have risen, and so have the number of people who receive medications by mail through the big pharmacy benefit managers, many of which are owned by companies that also own mail-order pharmacies.

When three federal agencies — the Justice Department, the Health and Human Services Department and the Federal Trade Commission — put out a request for public comments on how consolidation in health care was affecting Americans, comments poured in from people worried about the heat.

“This drug has arrived with capsules melted together. How many times have the capsules not been melted, yet the medication was altered enough so it was less effective?” one wrote. “Is my disease progressing because of this? ”

“I have a partner who takes around 15 pills a day across 7 different prescriptions,” another commented. “Regulations, specifically temperature regulations, are a must on these mail order pharmacies.”

“PBMs often force mail order as the only option, constantly exposing our meds to destructive temperatures way outside the manufacturer’s specifications for days on end,” another wrote.

Temperature Rules Blocked in Oklahoma

Four years ago, Marty Lee Hendrick, executive director of Oklahoma’s pharmacy board, wrote up a relatively vague rule regarding the transporting of medications in his state and sent it to the Legislature, where it passed with ease. But when Hendrick saw worrisome new data on drug package temperatures in 2022, he put together a task force that drafted much more specific language, requiring that the drugs be kept in the temperature ranges recommended by USP.

A group of lobbyists argued that the board’s proposed rule “micromanages the type of packaging used to deliver the drugs and the temperature in which those packages must be stored.”

The trade association representing PBMs also submitted a letter arguing that the proposed rule was “not grounded in science and evidence” but was “based on speculation and an attempt to resolve a perceived issue.” Lobbyists argued that mail-order pharmacies already use vigorous processes to “ensure the integrity and stability” of drug deliveries but that the new rules would drive up the cost of each prescription package by an estimated $23.

The rule was eventually abandoned.

In some states, pharmacy boards have “no appetite” for stronger rules, Hendrick said. Others have contacted him about framing their own proposals. He said he had advised them to brace for the lobbyists.

“I hate to say this, but we’re really probably one big tragedy away from people realizing how serious this is,” Hendrick said. “Our time will come. I know it will. But these battles end up being wars.”

This article originally appeared in The New York Times .