FDA Patient Safety News: Show #30, August 2004

Taxotere Approved for Prostate Cancer

FDA has approved injectable Taxotere (docetaxel), in combination with prednisone, for the treatment of advanced, hormone-refractory metastatic prostate cancer. Taxotere inhibits the protein tubulin, which is essential to cell division.

This is the first drug approved for hormone-refractory prostate cancer that's shown a survival benefit. In a randomized clinical trial those treated with Taxotere and prednisone experienced a survival advantage of approximately 2.5 months compared with those treated with mitoxantrone and prednisone.

The most common adverse events reported with the Taxotere-prednisone combination were nausea, alopecia and bone marrow suppression. Less common but severe side effects are also possible with Taxotere, so be sure to read the complete labeling before prescribing.

Additional Information:

FDA Press Release: FDA Approves New Indication for Taxotere -- Prostate Cancer.

New Drug for Bone Marrow Disease

FDA recently approved the first effective treatment for patients with Myelodysplastic Syndrome (MDS), a collection of bone marrow disorders. The drug, called Vidaza, is azacytidine for injectable suspension, and it's distributed by Pharmion Corporation. Vidaza is believed to be cytotoxic to abnormal hematopoietic cells in the bone marrow, and thus may restore normal growth and differentiation in the marrow.

About 7,000 - 12,000 new cases of MDS are diagnosed every year. MDS can develop following treatment with drugs or radiation therapy for other diseases, or it can occur idiopathically. Some forms of MDS can progress to acute myeloid leukemia.

In clinical studies which included all subtypes of MDS, about 15% of MDS patients had complete or partial responses to azacytidine. Those who responded to the drug no longer needed transfusions. The most common adverse events reported in clinical trials included nausea, anemia, thrombocytopenia, diarrhea, fatigue, irritation at the injection site, and constipation.

Additional Information:

FDA Press Release: FDA Approves New Drug for Bone Marrow Disease.

Precautions in Prescribing Crestor

In a recent Public Health Advisory, FDA announced that Astra-Zeneca Pharmaceuticals has revised the European labeling for Crestor (rosuvastatin). The labeling used in Europe will now contain the same precautions about drug-related myopathy as the U.S. labeling.

The WARNING section of the labeling identifies patients who may be at increased risk for myopathy, including those who are over 65, or who have hypothyroidism or renal insufficiency. In announcing the change, FDA is re-emphasizing to U.S. physicians the importance of carefully following the recommendations in the current product label.

These are some of the safety messages in the label. First, base the patient dose on individual cholesterol goals and risks for side effects. Inform patients that statin drugs can cause muscle injury and, in rare, severe cases, kidney damage and other organ failure that can be life-threatening. And tell patients to promptly report muscle pain and weakness, malaise, fever, dark urine, nausea or vomiting.

Additional Information:

MedWatch 2004 Safety Summary: Crestor (rosuvastatin).

Drug Interactions with Desyrel

Bristol-Myers Squibb has notified healthcare professionals about important drug interactions that can increase or decrease plasma concentrations of the antidepressant drug Desyrel (trazodone hydrochloride).

One type of interaction occurs when Desyrel is given with CYP3A4 inhibitors such as ketoconazole, indinavir, and ritonavir. In these cases, the plasma concentration of trazodone may increase substantially, and patients could experience adverse effects such as nausea, hypotension and syncope. So if Desyrel is used with one of these CYP3A4 inhibitors, a lower dose of Desyrel should be considered.

Conversely, the plasma concentration of Desyrel may decrease when it's given with the anti-seizure drug carbamazapine. So patients who are taking both of these drugs should be closely monitored to see if their doses of Desyrel need to be increased.

Additional Information:

MedWatch 2004 Medical Product Safety Alerts.

Adverse Events from Infusing Local Anesthetics Directly into Wounds?

Here's a case where FDA needs information from you. In a recent issue of the journal “Anesthesiology,” an FDA article summarized 34 reports of serious adverse events associated with local anesthetics delivered directly into surgical wounds. They were administered using disposable infusion pumps that are designed for this purpose. These pumps are used to provide local pain relief following a variety of orthopedic, podiatric, gastrointestinal, OB/GYN and circulatory procedures. The adverse events included tissue necrosis, surgical wound infection and cellulitis.

At this point, FDA doesn't know whether these adverse events were actually caused by the infusion procedure. It's possible that the reports may represent nothing more than isolated incidents, and that the necrosis and cellulitis would have occurred without the anesthetic infusion. Reports like these are called “sentinel events,” meaning that they're early warnings that a problem may exist.

FDA isn't recommending that health care practitioners take any direct action right now, but is aking that they notify FDA if they've seen similar problems with these local anesthetic infusion systems in their own facilities. That will help to determine whether or not these systems represent a real problem. To report click on “Report a Problem.”

Additional Information:

Report a Problem.

Recall of Certain Tecan Clinical Workstations

Here's news for clinical laboratories about the recall of a multiple task diagnostic instrument called the Tecan Clinical Workstation, a product of Tecan US Inc. This workstation can be configured with different test systems, including the Roche Diagnostics Amplicor CT/NG test, which is used to detect chlamydia and gonorrhea.

Software problems in the Tecan Workstation may cause a mismatch among patient samples and test results, which could lead to false positive and false negative results. If your laboratory uses this workstation, go to our web site for more information about this recall, and about how laboratories can help solve the problem.

Additional Information:

Tecan US Press Release.

New Publication on Foodborne Illnesses

CDC has published a comprehensive report for physicians and other health care professionals on diagnosing and managing foodborne illnesses. It covers how to recognize, treat and report these illnesses, and it features detailed charts with each pathogen, the signs and symptoms of the illness it can cause, the foods that may be implicated, the lab tests that can help with diagnosis, and the treatment options. This document amounts to a real reference book that can help in treating patients.

Additional Information:

CDC Morbidity and Mortality Weekly Report: Diagnosis and Management of Foodborne Illnesses - A Primer for Physicians and Other Health Care Professionals.

Caution on Programming Certain IV Pumps

In a recent article, the Institute for Safe Medication Practices pointed out how the keypad design on some IV pumps can lead to dosing errors. ISMP reported on several cases where a nurse had inadvertently pressed the “zero” instead of the “decimal point” key when programming a dose, which caused a ten-fold dosing error.

These errors occurred because on some IV pumps, the zero and the decimal point keys are located close to each other. If you use pumps with this design, ISMP recommends that you alert staff to the potential for errors. Also, when you're giving high-alert medications, be sure to have a second person double-check the programmed dose. ISMP also points out that using so-called 'smart pumps' that recognize preset dose limits can alert staff to these errors before the infusion begins.

Additional Information:

ISMP Medication Safety Alert. May 6, 2004. IV pump keypad design causes confusion.

Sodium Hyaluronate Mix-ups

In a recent safety alert, the Institute for Safe Medication Practices described a case where a nurse preparing for a cataract procedure went to the refrigerator to get sodium hyaluronate, which is used in several types of eye surgery. Two brands of sodium hyaluronate were in the refrigerator, and she chose the one called Hyalgan.

When the surgeon tried to use it, he noticed that its viscosity was far different from what it should have been. The problem is that Hyalgan is an orthopedic product, intended for intraarticular injection in treating osteoarthritis. The sodium hyaluronate the nurse should have chosen is Healon, which is intended for ophthalmic use.

So this is a case where two drug products contain the same active ingredient, at the same concentration, and yet they differ in their physical properties and their uses. ISMP suggests that in facilities where both Hyalgan and Healon are available, this type of mixup can be prevented by adding auxiliary labels to the drug cartons that either say “ophthalmology” or “orthopedics.”

Additional Information:

ISMP Medication Safety Alert. May 6, 2004. Be careful where you inject these.

Warning Breast-Feeding Mothers about Domperidone

Here's a warning to pass on to patients who are breastfeeding their babies. FDA has received numerous reports of pharmacies compounding the drug domperidone and of lactating women using the drug to try to increase their milk production.

Domperidone isn't approved for that indication, and in fact it's not approved for any indication in this country. It's also not approved in any country for increasing breast milk production. (It’s been approved in several foreign countries, but only to treat certain gastric disorders.)

U.S. women using domperidone have been buying it from compounding pharmacies in this country, and also online from sources outside the U.S.

FDA is concerned that women may be risking their health if they use domperidone to try to increase milk production. There are reports of cardiac arrhythmias, cardiac arrest and sudden death in patients receiving an IV form of the drug, and in fact that form is no longer marketed.

At high oral doses, seizures and other neurologic side effects have been reported, and those are the doses that have been suggested for breastfeeding women. In addition, using certain other drugs, such as erythromycin, could raise blood levels of domperidone even further and increase the possibility of serious adverse effects. In several countries where the oral form of domperidone is marketed, the drug's labeling specifically warns that nursing mothers should not use it.

Using domperidone may place the infant at risk, too. That’s reflected in the labeling in many countries where the drug is approved for other purposes. The labeling notes that the drug is excreted in breast milk, and that could expose a breastfeeding infant to unknown risks.

The bottom line is to advise patients who are breastfeeding not to use domperidone to try to increase their milk supply.

Additional Information:

FDA Talk Paper: FDA Warns Against Women Using Unapproved Drug, Domperidone, to Increase Milk Production.

FDA Patient Safety News is available at www.fda.gov/psn