Many drugs in short supply at hospitals, pharmacies

For a time this year, a psychiatric hospital run by the state of Maryland didn't have enough injectable drugs for schizophrenia patients who refused to take pills.

Doses of the most effective drug to boost blood pressure in patients at risk of dying from infection-related shock were low at Johns Hopkins Hospital. And some local pharmacists were having trouble filling prescriptions for attention deficit hyperactivity disorder.

The drugs are among hundreds that have been in short supply at the nation's hospitals, and more recently, community pharmacies. Pharmacists, doctors and advocacy groups say countless patients are getting less effective or more costly substitutes as a result. Occasionally, they may be receiving inappropriate drugs or doses — or no treatment at all.

"Every month we review what's not available to us," said Dr. Pamela Lipsett, a professor of surgery at Hopkins. "We get one [drug] back and lose another. And some diseases have only one drug. It's very frightening."

The U.S. Food and Drug Administration said shortages of prescription drugs have tripled during the last six years to a record high. There were 61 drug product shortages in 2005 and 178 in 2010. An association tracking shortages says the numbers are even higher, and show no sign of abating.

Federal officials say they are scrambling to alleviate shortfalls by working with manufacturers who cite no single reason for delays. They have asked for advance warning of manufacturing problems, specifically for "medically necessary" drugs, and have sought other sources of supply, sometimes even approving overseas purchases. Several lawmakers, meanwhile, have backed a bill to mandate an early warning system.

Many drugs in short supply are given through injections or intravenously at hospitals, according to the FDA. They include cancer drugs, anesthetics for surgery patients, emergency "crash cart" drugs and electrolytes for patients fed intravenously. But local drug store chains, including CVS, are reporting that shortages have recently become more pronounced for them too.

Officials at the Pharmaceutical Research and Manufacturers of America, or PhRMA, say they are already working with the government, suppliers and providers on the issue.

The industry blames the shortages on "myriad factors," including natural disasters, raw material shortages, changes in hospital and pharmacy contracts, changes to FDA protocols and discontinued medicines. The FDA and provider trade groups also say industry consolidation is a factor, as are makers who discontinue less profitable generic drugs or whose plants fail safety inspections.

Maintaining sterility during the manufacturing of injectable drugs can be particularly difficult, industry officials said.

"Regardless of the cause, in order to provide patients with uninterrupted access to medicines it is important for all of us … to work collaboratively to minimize unexpected disruptions in the supply of vital medicines," said PhRMA Deputy Vice President Karl Uhlendorf in a statement.

The drug shortages mean U.S. hospitals spend at least $200 million, or 11 percent, more a year on substitutes, according to a study of 228 hospitals, retail pharmacies and other care facilities by the Premier healthcare alliance, an information provider and purchasing agent for hospitals. The estimate doesn't include added labor for managing shortages or ensuring safety.

Nearly 90 percent of the hospitals reported a drug shortage in the second half of 2010 that may have caused a patient safety issue, resulted in procedure's delay or cancellation, required expensive substitutes or resulted in a pharmacist compounding a drug.

In those six months, more than 240 drugs were in short supply or unavailable and more than 400 generic drugs were back-ordered for five or more days. Shortages appear to be increasing, Premier said.

That alarms advocates. The Leukemia and Lymphoma Society said a shortage of Cytarabine emerged last fall, and of the three primary U.S. suppliers only one has resumed shipping. The FDA is considering using an overseas provider for the drug, the gold standard for treating several types of cancer.

Society officials contacted federal legislators, and Sen. Amy Klobuchar, a Minnesota Democrat, responded with the Preserving Access to Life-Saving Medications Act. It would require drug makers to notify the FDA of any event that could cause a shortage. The FDA would also have to say how it would address shortages and more quickly re-inspect plants cited by the agency for quality problems.

Sen. Barbara Mikulski, a Maryland Democrat, signed on and said: "The early warning system … makes sure providers and patients are the first to know when a drug shortage is about to occur. That advance notice will give them the time they need to adequately prepare and respond to a drug shortage."

Notice would help, especially when so many drugs are in short supply, said Jason M. Noel, an assistant professor at the University of Maryland School of Pharmacy. He helps staff the pharmacy at Spring Grove Hospital Center, a state-run psychiatric hospital in Catonsville.

Among the most difficult shortages for Spring Grove to cope with has been an injectable anti-psychotic medication used when patients are reluctant to take pills. Noel said alternatives for those with schizophrenia and other mental disorders are not as good.

Three of four manufacturers have discontinued making that drug, Haloperidol decanoate, or some forms in which it had been packaged, according to the American Society of Health-System Pharmacists, which has compiled a database of drugs in short supply.

"Therapeutically, if a patient were to continue taking the drug orally it would be okay, but there's a reason the person was on an injectable in the first place," Noel said. "These medications are for fairly severe conditions and potentially bad consequences can result from coming off them abruptly."

In another case, there has been a limited supply of the generic form of Adderal XR, used to treat attention deficit hyperactivity disorder. Noel said some insurance companies won't cover the brand name drug and some patients can't afford it. Pharmacists have been working with doctors and insurers in specific cases, he said.

John Lewin, division director for Hopkins' critical care and surgery pharmacies, said hospital officials participate in weekly conference calls to discuss shortages. He tracks about 120 drugs from week to week, some with no good alternatives.

He said drugs are rationed and substitutes used when possible. Officials are looking out for other pharmacists who may be hoarding drugs.

In some cases, a different pre-measured dose is available and providers must be alerted so a patient isn't inadvertently given too much or too little, he said. There are computer programs, notes and oral discussions to ensure safety.

With 2,000 doses of medications administered a day in critical care areas, Lewin said significant extra time and effort is needed for management and safety.

"There are so many layers where things can go wrong," he said. "Changes can impact safety. There needs to be a systematic process so patients don't get an overdose."

Worse, he said, is when a drug is not available at all. For months, that was the case with norepinephrine, considered the most effective drug to support blood pressure that drops in those in septic shock, a condition affecting some 750,000 Americans a year.

Lipsett, the Hopkins surgeon, said that could mean "life or death" for some patients. She said doctors customize other combinations of drugs, and she couldn't say if any patients suffered negative consequences.

Some of those drugs, including diuretics that remove extra fluid, were also in short supply and the only substitutes were more expensive.

Of the three makers of norepinephrine, one has discontinued manufacturing and one gave no reason for the shortage. The third is trying to cope with increased demand, according to the trade group tracking shortages.

Lipsett said doctors are stuck because there is only one drug for septic shock, and not enough new drugs in the pipeline to offer relief for this condition and others.

"Some patients aren't getting the drugs," she said. "And I'm sure there are mistakes."

Officials at the American Society of Health-System Pharmacists, which represents hospitals and health system pharmacists, say they continue to investigate causes and solutions involving supply, distribution, manufacturing and raw materials, as well as legislative and regulatory issues.

Specifically, the society is looking into faster approval for manufacturing plants and re-approval after a quality issue is identified, said Bona Benjamin, director of medication-use quality improvement. Other ideas include offering incentives for manufacturers to enter or re-enter the market for cheaper generics. And the group is exploring ways to speed up government approvals for new drugs, a process that can now take 12-15 years.

She said in some cases there are only one or two companies making a drug because of consolidation in the industry — a trend that increases the likelihood of a shortage.

"We understand there are variances in the manufacturing process and it's not uncommon to have issues that need to be resolved, and we understand that some drugs don't make money and manufacturers need to make a return on their investments," Benjamin said.

But she said public needs must be weighed. For now, she said, "I'd be reluctant to predict it's going to get better. It's a pretty serious situation. There have always been drug shortages, but we've never seen them this bad."



Tips for consumers:

•If your pharmacy is out of a drug, call around to others in or outside the area because shortages can be regional.

•Check the websites of the FDA and American Society of Health-System Pharmacists for alternative providers.

•Discuss alternatives with your doctor and insurer.

•Report life-threatening shortages to the FDA.

•When ordering a drug online, consult the National Association of Boards of Pharmacy for legitimate websites.

Drugs in short supply:

•Cytarabine, used to treat some types of cancers. Three manufacturers report higher-than-expected demand and manufacturing delays.

•Measles, mumps, rubella, and varicella vaccine, used for immunization of children. One manufacturer, which hasn't explained the shortage.

•Morphine injections, used for pain. Three manufacturers report increased demand.

•Norepinephrine injection, used to counteract low blood pressure during shock or cardiac arrest. Three manufacturers report increased demand and discontinued products.

•Penicillin G sodium injection, an antibiotic used to treat infection. Two manufacturers gave no reason for shortages.

•Propofol injection, used for sedation. Three manufacturers report higher demand and discontinued product lines.

Source: FDA and American Society of Health-System Pharmacist