Report: Off-label prescriptions can compromise safety

A three-part investigative series by Knight Ridder Newspapers claims that patients nationwide are being injured as doctors routinely prescribe drugs off-label.

Based on data from the U.S. Food and Drug Administration (FDA), the report estimates that at least 8,000 people became seriously ill last year after taking some of the nation’s most popular drugs for off-label purposes. Among the report’s findings on prevalence of off-label prescribing:

  • 21% of the prescriptions examined were for off-label uses.
  • 115 million off-label prescriptions for the drugs analyzed by Knight Ridder were written in the United States last year, nearly double the number of five years ago.
  • As many as 90% of the prescriptions for some drugs were off-label uses.
  • Three-quarters of antiseizure medications are prescribed off-label, as are nearly two-thirds of antipsychotics and about one-quarter of antidepressants.

To calculate how often drugs are prescribed off-label, Knight Ridder analyzed the three top-selling drugs in 15 classes of medications, comparing what doctors said they prescribed them for with the FDA’s approval for each. The analysis looked at 900 million prescriptions written in 1998 and 2003 for more than 1,000 different ailments. Its estimate of the prevalence of off-label prescribing excluded cancer treatments or pediatric off-label uses. The investigative reporters also interviewed patients, doctors, researchers, and drug companies, and reviewed thousands of records from lawsuits, government hearings, regulatory actions, medical records, and scientific studies.


FDA: Difference in infections among leading RA treatments

Data from the U.S. Food and Drug Administration’s (FDA) adverse events reporting system (AERS) suggest the number of granulomatous infections, such as tuberculosis and pneumonia, in patients treated with etanercept for rheumatoid arthritis (RA) may be substantially lower than patients treated with infliximab, according to data presented at the American College of Rheumato-logy 67th Annual Scientific meeting.

These data suggest there may be biologically and medically important differences in the safety profiles of different marketed tumor necrosis factor (TNF)-inhibitors with respect to rate of infection.

Of the total (755) granulomatous infections reported, substantial differences between the etanercept group and infliximab group were reported (155 vs. 547, respectively) through June 2002. Additionally, the number of Pneumocystis carinii pneumonia cases reported was also lower for etanercept group vs. the infliximab group (four vs. 44, respectively). At an FDA advisory meeting in March 2003, it was reported that approximately 400,000 patients had been treated with infliximab and 150,000 patients with etanercept through December 2002.

Researchers say that further studies are needed to determine the exact differences in mechanism of action between etanercept and infliximab that may be leading to these clinically important differences in infection rates.


Be aware of common dispensing errors

Health care professionals are being warned of two dispensing errors that could have serious adverse effects on patients.

First, UCB Pharma is warning of dispensing errors between levetiracetam (Keppra) tablets and oral solution and lopinavir/ritonavir (Kaletra) capsules and oral solution.

Keppra, an antiepileptic, is available as tablets and oral solution. Keppra tablets, 250 mg are blue, 500 mg are yellow, and 750 mg are orange, oblong-shaped, scored, film-coated tablets debossed with "ucb" and "strength" on one side. They are supplied in containers of 120 tablets. Keppra oral solution is a clear, colorless, grape-flavored liquid supplied in 16 fl oz white HDPE bottles containing 500 mg levetiracetam per 5 mL.

Kaletra, an antiretroviral, is available as capsules or oral solution. Kaletra 133.3 mg lopinavir/33.3 mg ritonavir capsules are orange soft gelatin capsules imprinted with the Abbott corporate logo and "PK." It is available in bottles of 180 capsules. Kaletra oral solution is a light-yellow to orange liquid supplied in amber-colored 160 mL glass bottles containing 400 mg lopinavir/100 mg ritonavir per 5 mL.

In addition, Elan Biopharmaceuticals is warning that serious adverse events and deaths have resulted from accidental overdose of high concentration morphine sulfate oral solutions. In most of these cases, morphine oral solutions ordered in milligrams were mistakenly interchanged for milliliters of the product, resulting in twentyfold overdoses. For example, a prescribed dose of 5 mg was mistakenly administered as 5 mL (100 mg) of the morphine sulfate concentrated solution.

Elan currently distributes three concentrated morphine sulfate oral solutions:

• Roxanol CII (morphine sulfate) Concentrated Oral Solution (20 mg/mL), available in 30 mL and 120 mL bottles with calibrated dropper.

• Roxanol-T CII (morphine sulfate) Concentrated Oral Solution (20 mg/mL) — tinted, flavored; available in 30 mL and 120 mL bottles with calibrated dropper.

• Roxanol 100 CII (morphine sulfate) Concen-trated Oral Solution (20 mg/mL), available in a 240 mL bottle with calibrated patient spoon.

Prescribers and dispensers should be aware that these and other concentrations of morphine sulfate are available from various manufacturers with the concentration expressed in mg/tablespoon (5 mL).


Researchers report bone loss from oral diabetes drug

Scientists at the University of Arkansas for Medical Sciences (UAMS) in Little Rock report that a widely used oral drug for Type 2 diabetes may pose a significant risk of bone loss.

The researchers say in a laboratory study, the antidiabetic compound rosiglitazone (Avandia) caused a significant decrease in total body bone mineral density, suggesting that the therapy may pose a significant risk of adverse skeletal effects in humans.

The UAMS scientists used microcomputed tomography to analyze the bones of healthy mice that received doses of rosiglitazone over seven weeks. The doses that mice received were the same doses mice received in earlier studies that demonstrated the compound’s effectiveness for Type 2 diabetes. The researchers next plan to test the effects of the drug on mice and rats with diabetes.

The results of the study were published in the Sept. 18 issue of the journal Endocrinology.