Drug Shortages Exist Across the Board

May 9, 2012

Ongoing shortages of several psychotropic medications have wreaked havoc among patients and their families, caused frustration and reluctant prescription switches among physicians, and prompted investigations by Congress.

Ongoing shortages of several psychotropic medications have wreaked havoc among patients and their families, caused frustration and reluctant prescription switches among physicians, and prompted investigations by Congress. Drug shortages reached an all-time high in 2011. According to the University of Utah Drug Information Service, 267 drugs-primarily injectables-were in short supply, up from 211 in 2010 and 58 in 2004.

While numerous press reports have publicized the shortage of medications for ADHD, there are also shortages of drugs for psychiatric disorders such as schizophrenia and addiction.

Ann Richards, PharmD, BCPP, a past President of the College of Psychiatric and Neurologic Pharmacists and the Pharmacy Director for the Texas Department of State Health Services, said that according to data collected by the American Society of Health-System Pharmacists, there are shortages of diazepam injection, diphenhydramine hydrochloride for injection, haloper-idol decanoate injection (Haldol), haloperidol lactate injection, lorazepam injection (Ativan), naltrexone oral tablets (Revia), and thiothixene capsules (Navane).1

Adelaide Robb, MD, Chair of the Pediatric Psychopharmacology Initiative of the American Academy of Child and Adolescent Psychiatry (AACAP), told Psychiatric Times, “We are having shortages of most if not all of the stimulants, and it’s nationwide.” Patients and their families are experiencing diffi-culty in obtaining mixed amphetamine salts (Adderall), methylphenidate immediate-release (Ritalin, Concerta, and Daytrana), and dexmethylphenidate (Focalin). “Even Dexedrine spansules [dextroamphetamine], which is one of the oldest ADHD drugs besides Ritalin, has been in short supply. The only one that is still fairly easy to get is Vyvanse [lisdexamfetamine], which is not available in a generic form,” says Robb.

A benzodiazepine shortage is causing problems for alcohol and substance abuse detoxification programs. Last year, there were shortages of such mood stabilizers as divalproex (Depakote) and lamotrigine (Lamictal), and of the first-generation antipsychotic haloperidol.

Ruth Hughes, PhD, psychologist and Chief Executive Officer of Children and Adults with Attention-Deficit/Hyperactivity Disorder (CHADD), a nonprofit educational and advocacy organization, said the shortages in ADHD medications that began with a shortage of short-acting generic versions of Adderall “have been going on for more than a year.”

A January survey of CHADD members revealed that nearly half (49.9%) of the 5500 respondents were having difficulty in getting their medications and of that group, 37% had to switch medications. “In our survey, every single stimulant medication, name-brand and generic, long-acting and short-acting, was named as a medication that was difficult to obtain,” said Hughes. With 15 million people who have ADHD in the United States, “we have a very significant segment of the population that can’t get their medications.”

Ramifications

The ADHD medication shortage has serious life ramifications for children and adults with the disorder, Hughes explained. CHADD has “received a dozen reports of adults who tried to tough it out without medication, made serious mistakes on their jobs and were subsequently fired,” she said. “We have reports of college students who were kicked out of school. We have reports of children with ADHD doing very poorly in school or being suspended or expelled, because their parents were unable to get their medication.” In addition, adolescents who are driving automobiles and are unable to get their ADHD medications are of great concern because they are 3 times more likely to have car accidents than are teens without ADHD and 4 times more likely to have fatal accidents.

Reports of price gouging have also emerged. “Some CHADD members have gone to pharmacies for generic ADHD medications and been told it would be more than $1000 for a month’s supply. Yet pharmaceutical manufacturers have told me they have not increased their prices,” said Hughes.

Medication shortages are influencing prescribing patterns. The best medication for the individual may not be the one that is being prescribed, according to both Robb and Richards.

In the DC metropolitan area (Washington, DC; Maryland; and Virginia), some parents of children with ADHD cannot get a 30-day supply of their child’s medicine at local pharmacies or a 90-day supply through large mail-order companies, Robb said. “So then we have to either switch medications or the parents have to run around to 5 or 6 different pharmacies, trying to find enough to fill a 30-day prescription,” she said.

The shortage of benzodiazepines has also caused a change in detoxification treatments for adolescents and young adults, Robb said. “Normally, what we would do is have a benzodiazepine taper and now those medicines are in short supply, so we have to use very old-fashioned medications like phenobarbital.”

Richards reported that most hospitals in her system “will use either diphenhydramine injection, lorazepam injection, haloperidol injection, or a combination of these products to treat adults experiencing behavioral emergencies. But all 3 drugs are in a shortage situation. Thus, we are looking for alternative treatments for these emergencies.”

Clinicians who would ordinarily prescribe haloperidol decanoate for a patient with adherence issues, she added, are forced to determine whether a switch to another long-acting injection might be more beneficial than prescribing oral haloperidol. “Switching to another long-acting injection can lead to therapeutic failure or side effects, but adherence is guaranteed if the medication is administered. On the other hand, switching to an oral product of the same medication ideally leads to a similar response, but if the individual has adherence issues, then the medication may not be taken as prescribed. Furthermore, the dosing of the oral product may be challenging, as the blood concentration of the long-acting medication will slowly decline.”

Causes of shortage

In response to the increasing frequency and severity of drug shortages in recent years, the FDA conducted a review, the results of which they published in October.2 The leading causes of drug shortages were quality problems-glass shards, fungi, or other contaminants-at a drug manufacturing facility (43%); delays in manufacturing or shipping (15%); and a shortage of the active pharmaceutical ingredient (10%).

Other causes included increases in demand, business choices, and other companies discontinuing the product lines.2 On the basis of 127 drug shortages between January 1, 2010, and August 26, 2011, the FDA review found that injectable medications accounted for 102 (80%) of the drugs in short supply.2

One of the companies with manufacturing problems is the injectable drugs manufacturer Ben Venue Laboratories, which has 4 factories in Bedford, Ohio. The Boehringer Ingelheim–owned company manufactures valproate sodium injection, haloperidol lactate injection, and buprenorphine injection, among other injectable drugs. Last year, Ben Venue voluntarily suspended manufacturing “to permit implementation of lasting corrective actions to address manufacturing-related issues as noted in FDA and other global regulatory agency inspections,” said spokesperson Jason Kurtz. He added that in the past 3 years, the company has invested more than $250 million to upgrade its facilities. A public statement posted on its Web site stated, “. . . no products manufactured in the North facility will be available to patients and healthcare professionals before the fourth quarter of 2012.3

In some cases, only one company manufactures a particular drug. For example, Hospira, the sole supplier of diazepam injection used to treat anxiety disorders (short-term) and alcohol withdrawal symptoms (among other disorders), is experiencing manufacturing delays. But according to the company spokesperson, Daniel Rosenberg, the company expects a full recovery by summer.

Obtaining active pharmaceutical ingredients for the manufacturing of controlled substances has been particularly challenging, according to manufacturers and others. In testimony before the House Committee on Energy and Commerce Subcommittee on Health last year, Jonathan Kafer, Vice President of Sales and Marketing for Teva Pharmaceuticals, described the dilemma as follows4:

From our work with the DEA [Drug Enforcement Agency] and FDA, we know that it is a difficult balancing act to ensure availability of controlled substances to patients in need while also striving to curb abuse and diversion. In an effort to control the supply of these medicines, the DEA makes yearly allocations of controlled drugs to the respective manufacturers of these products. In many instances, however, the use of a drug product changes over the year due to increased usage or shifting of markets. This can result in a shortage of these products, because without access to more of the controlled active ingredient, manufacturers are unable to increase supply. Currently, there are a number of controlled drugs on the American Society of Health-System Pharmacists shortage list.

Robb pointed to the DEA’s quota system for the shortages in ADHD medication as well as to demand outstripping supply: “Diagnosis and treatment with medication for ADHD in both pediatric and adult fields have increased in the last 5 years, so there is a larger demand for the products. But at the same time, the supply of ready materials to make the medications has not increased through the DEA.”

Jeffrey Scott, a DEA agent and spokesperson, said the quota for amphetamine salts has been “bumped up” for 2012 and that the quota can be revised mid-year. “Part of our mission is to ensure uninterrupted supply to meet legitimate medical and scientific needs, but we are only part of a chain that gets the medications to the public-the part that determines the quota of amphetamine salts used in ADHD medications. We develop the quota based on established medical need, retail consumption, manufacturers’ estimates, past quota history, etc. It is our best educated guess.”

Manufacturing companies that make decisions on how best to use their quota allocation, such as for brand-name versus generic forms of the drugs, are the next link in the chain, he added.

Amelioration efforts

On October 31, 2011, President Obama issued an Executive Order that directed the FDA, as well as the Department of Justice, to take action to reduce and prevent drug shortages through expedited reviews and to identify market participants who are stockpiling medications or pricing drugs exorbitantly.5 On the congressional front, the Committee on Energy and Commerce, Subcommittee on Health last fall examined drug shortages.

Several health care professional organizations (eg, AACAP, the American Psychiatric Association, and the American Academy of Pediatrics) along with several ADHD groups have formed an ADHD drug short-age coalition. The coalition has arranged visits to key congressional leaders and FDA officials, called for more transparency in the DEA quota-setting process, and recommended an interagency agreement between the FDA and DEA so that when a controlled-medication shortage is identified, the agencies can work together on an action plan.

[Editor's note: For further information, see FDA warns consumers about counterfeit version of Teva’s Adderall, published subsequent to this article.]

References:

References

1.

American Society of Health-System Pharmacists. Drug shortages: current drugs.

http://www.ashp.org/DrugShortages/Current

. Accessed March 30, 2012.

2.

US Food and Drug Administration. A review of FDA’s approach to medical product shortages. October 31, 2011.

http://www.fda.gov/DrugShortageReport

. Accessed March 30, 2012.

3.

Ben Venue Laboratories, Inc. Update on drug manufacturing. December 23, 2011.

http://www.benvenue.com/pages/release.html.

Accessed March 30, 2012.

4.

Testimony of Jonathan M. Kafer before the U.S. House of Representatives Committee on Energy and Commerce Subcommittee on Health. Examining the increase in drug shortages. September 23, 2011.

http://republicans.energycommerce.house.gov/Media/file/Hearings/Health/092311%20Drug%20Shortages/Kafer_Testimony.pdf

. Accessed March 30, 2012.

5.

The White House. Executive Order 13588-Reducing Prescription Drug Shortages.

http://www.whitehouse.gov/the-press-office/2011/10/31/executive-order-reducing-prescription-drug-shortages

. Accessed April 2, 2012.