FDA Patient Safety News: Show #56, October 2006

Warning on Combining Triptans and SSRIs/SNRIs

FDA has alerted healthcare professionals about a possible life-threatening condition that can occur when triptans (e.g., Imitrex) are taken concomitantly with SSRIs (e.g., Paxil and Prozac) or SNRIs (e.g., Cymbalta)

All of these drug increase serotonin and if they are taken together, they can produce excessively high serotonin levels. This can lead to serotonin syndrome, which is a rare, but serious and sometimes fatal condition that can result in wide variety of signs and symptoms including changes in mental status, autonomic instability, neuromuscular abnormalities and gastrointestinal symptoms. The risk of developing the syndrome is greatest immediately after a new serotonergic drug is started or the dose is increased.

SSRIs and SNRIs are both used to treat depression and other mood disorders, and triptans are used to treat migraines. So a patient might be regularly taking an antidepressant, and then intermittently taking a triptan to treat a migraine episode. In fact, drug usage data suggest that over a one year period, about 20% of people prescribed a triptan might also be taking an SSRI.
Physicians prescribing a triptan, SSRI or SNRI should:
• keep in mind that triptans are often used intermittently and that either the triptan, SSRI or SNRI may be prescribed by a different physician
• weigh the potential risk of serotonin syndrome with the expected benefit of using a triptan with an SSRI or SNRI
• discuss the possibility of serotonin syndrome with patients if a triptan and an SSRI or SNRI will be used together
• follow patients closely if a triptan and an SSRI or SNRI are used together, particularly during treatment initiation, with dose increases, or with the addition of another serotonergic medication
• instruct patients who take a triptan and an SSRI or SNRI together to seek medical attention immediately if they experience the symptoms of serotonin syndrome (described above). Patients should also talk to their physician before stopping their medication.

Additional Information:

FDA MedWatch Safety Alert 2006 – 5-Hydroxytryptamine Receptor Agonists (Triptans); Selective Serotonin Reuptake Inhibitors (SSRIs); Selective Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs). July 19, 2006.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm150748.htm


Recall of Ultravist Contrast Agent

In July, Berlex, Inc. recalled all lots of Ultravist (iopromide) Injection 370mgl/mL, an intravenous contrast agent. These products could contain particulate matter along with crystals. If administered to patients, they could cause vascular thrombosis, thromboembolism or injury to the heart, kidney or brain.

This recall only affects Ultravist Injection 370 mgI/mL and not other concentrations of Ultravist (150mgI/mL, 240mgI/mL, 300 mgI/mL). Hospitals, imaging centers and other healthcare facilities that have the recalled product should not use it. Instead, immediately quarantine the product and return it to the company. For more information on this recall, call the company at 1-866-BERLEX-5.

Additional Information:

FDA MedWatch Safety Alert 2006 - Ultravist (iopromide) Injection 370 mgl/mL, 125 mL. July 31, 2006.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm150799.htm


Caution on Cleaning and Sterilizing Ultrasound Biopsy Equipment

FDA has issued a Public Health Notification about the importance of adequately cleaning and sterilizing reusable ultrasound biopsy transducer assemblies between patients. These assemblies are used to obtain biopsy samples guided by an ultrasound image. This often involves placing the transducer in a body cavity where it will contact blood or feces. It is vital to thoroughly clean and sterilize these devices after each use so residual material remaining on the device from one patient won't infect the next patient.

The FDA notification stresses that in order for the reprocessing of any reusable device to be effective, it must be thoroughly cleaned before it is sterilized, and that brushes are often required to clean these assemblies. Failure to brush the lumens of the needle guides may have been associated with patient infections in the past, and the FDA has reports of visible residue in the biopsy needle guide channels in one reprocessed transducer assembly.

The FDA notification provides a number of specific recommendations to avoid contamination and patient infection, and you can find them on our web site.

But the most important recommendation is to follow the manufacturer's instructions for reprocessing these transducer assemblies. The operator's manual should give detailed instructions for that particular brand and model. If anything in the instructions is not clear, contact the manufacturer. As the notification says, “Make no assumptions.”

Additional Information:

FDA MedWatch Safety Alert 2006 - Reprocessing of Reusable Ultrasound Transducer Assemblies Used for Biopsy Procedures. June 19, 2006.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm151526.htm


Caution on Cleaning and Sterilizing Ultrasound Biopsy Equipment

FDA has issued a Public Health Notification about the importance of adequately cleaning and sterilizing reusable ultrasound biopsy transducer assemblies between patients. These assemblies are used to obtain biopsy samples guided by an ultrasound image. This often involves placing the transducer in a body cavity where it will contact blood or feces. It is vital to thoroughly clean and sterilize these devices after each use so residual material remaining on the device from one patient won't infect the next patient.

The FDA notification stresses that in order for the reprocessing of any reusable device to be effective, it must be thoroughly cleaned before it is sterilized, and that brushes are often required to clean these assemblies. Failure to brush the lumens of the needle guides may have been associated with patient infections in the past, and the FDA has reports of visible residue in the biopsy needle guide channels in one reprocessed transducer assembly.

The FDA notification provides a number of specific recommendations to avoid contamination and patient infection, and you can find them on our web site.

But the most important recommendation is to follow the manufacturer's instructions for reprocessing these transducer assemblies. The operator's manual should give detailed instructions for that particular brand and model. If anything in the instructions is not clear, contact the manufacturer. As the notification says, “Make no assumptions.”

Additional Information:

CDC - MMWR WeeklyPseudomonas aeruginosa Infections Associated with Transrectal Ultrasound-Guided Prostate Biopsies --- Georgia, 2005. July 21, 2006. / 55(28); 776-777.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5528a3.htm?s_cid=mm5528a3_e


Mix-up Prompts Azathioprine Recall

In July, Roxane Laboratories recalled one lot of 50 mg Azathioprine tablets because the bottles in this lot may actually contain Methotrexate. Azathioprine is used to help prevent rejection in kidney transplant patients, and can also be used to manage severe rheumatoid arthritis.

If Methotrexate is taken instead of Azathioprine, serious toxic effects may occur, such as decreased resistance to infection, reduced blood counts, or liver, kidney or lung injury. Deaths have also been reported at high doses of Methotrexate - the kinds of doses that might result from substituting of Methotrexate 2.5 mg tablets for Azathioprine 50 mg tablets.

The affected lot number is 558470A (Expiration date – March 2009). One bottle from this lot was discovered to contain 2.5 mg Methotrexate tablets instead of Azathioprine.

Roxane Laboratories says that pharmacists and wholesalers who have any bottles of Azathioprine from this lot should stop distributing them. Pharmacists who may have dispensed Azathioprine from this lot should contact the affected patients to assure they didn't receive Methotrexate tablets.

Patients who have been notified by their pharmacist that they may have received medication from the recalled lot should return the Azathioprine to their pharmacist. Patients who aren't notified should visually inspect their Azathioprine tablets. If the tablets are marked with the number 54 323, patients should not take them and immediately contact the pharmacist or physician. For more information, contact Roxane Laboratories Technical Product Information at
800-962-8364.

Additional Information:

FDA MedWatch Safety Alert 2006 – Azothioprine. July 13, 2006.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm150499.htm


Warning on Intracranial Hemorrhage with Aptivus

Boehringer Ingelheim is alerting healthcare professionals about a new black box warning for the company's antiretroviral drug Aptivus (tipranavir). The warning describes reports of both fatal and non-fatal intracranial hemorrhage (ICH) in patients receiving Aptivus, co-administered with ritonavir.

The company's letter says that there were 14 reports of intracranial hemorrhage events, including 8 fatalities, in clinical trials of over 6,800 HIV-1 infected patients receiving Aptivus as part of combination antiretroviral therapy. Many of the patients who experienced hemorrhage had other medical conditions. They included CNS lesions, head trauma, recent neurosurgery, coagulopathy, hypertension and alcohol abuse. Some patients were receiving concomitant medications that may have caused or contributed to the hemorrhaging, including anticoagulants and antiplatelet agents.

The patients receiving Aptivus who suffered ICH did not have abnormal coagulation parameters, either in general or before the hemorrhage occurred. So routine measurement of coagulation parameters isn't currently indicated in managing patients on Aptivus. The company says that Aptivus/ritonavir combination therapy should be used with caution in patients who may be at increased risk of bleeding from trauma, surgery or other medical conditions, or who are receiving antiplatelet agents or anticoagulants.

Additional Information:

FDA MedWatch Safety Alert 2006 - Aptivus (tipranavir). June 30, 2006.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm150415.htm


Nostril Errors with Nasal Sprays

The Institute for Safe Medication Practices recently alerted practitioners that although many nasal sprays are intended to be administered in both nostrils, there are some medications meant to be sprayed into just one nostril. These include calcitonin salmon, butorphanol, desmopressin, sumatriptan and zolmitriptan. If a patient misunderstands the directions and sprays the prescribed amount of one of these drugs into each nostril, he or she could be getting a two-fold overdose.

Patient error may be only a part of the problem. Some electronic prescribing systems are preprogrammed to print directions saying "spray in each nostril" whenever a nasal spray is prescribed. ISMP says that for nasal sprays intended for one nostril, the patient needs explicit verbal directions and written instructions in order to prevent "double spraying."

Additional Information:

ISMP Medication Safety Alert – One or Both Nostrils? June 29, 2006.
http://www.ismp.org/newsletters/acutecare/articles/20060629_2.asp


Easier-to-Use Format for Prescription Drug Labeling

Over the years, the package inserts that provide information to health care practitioners on prescription drugs have been getting longer and more complex because there is more and more information that has to be conveyed. Now, this prescribing information is getting a new look which will make it easier to read and to locate specific information.

The new labeling will be required for drugs that were submitted for FDA approval after June 2006 (the effective date of the new regulation) and also for any drug that was approved within the five years prior to that date. In addition, if a drug with an approval date greater than five years has a major change, such as a new indication, then that drug will be required to have the new labeling as well. Of course, manufacturers of older drugs are encouraged to change their labeling into the new format and they can do so at any time.

Many of the changes in the prescribing information have to do with the way the information is formatted and arranged. For example, at the very beginning of the insert there is a new section called "Highlights of Prescribing Information."
This “Highlights” section is a concise summary of the information that is most important to prescribers. The “Highlights” section also refers to the corresponding sections in the "Full Prescribing Information" where more information can be obtained.

The information in the “Highlights” section includes the uses for the drug, the dosage and the major risks, the year the drug was approved (so new products can be more easily identified), and a toll-free number for reporting adverse events. The “Highlights” will also include a list of all substantive recent changes made within the year, to ensure healthcare professionals have immediate access to the most up-to-date information about the product before prescribing it. The new information will also be highlighted in the “Full Prescribing Information” section with a vertical line in the margin.

The information practitioners refer to most frequently and consider most important (e.g. Boxed Warning, Indications and Usage, Dosage and Administration, and Dosage Forms and Strengths (separated from Storage and Handling) will be located at the front of the prescribing information. In addition, risk information (Warnings, Precautions, Adverse Reactions) will be consolidated in one location.

Finally, there is a new section called "Patient Counseling Information" that will advise prescribers on what to tell the patient about concerning this particular drug. Also, if there are FDA-approved medication guides, patient package inserts and instructions for use, those will have to be included in the new labeling, or accompany it by June 2007.

FDA also continues to work on electronic methods of communicating drug information. One of the most important ones is called Daily Med. Daily Med is an online clearinghouse accessed through the National Library of Medicine that provides free, one-stop shopping for drug information which is updated constantly.

Additional Information:

New Requirements for Prescribing Information.
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/LawsActsandRules/ucm084159.htm


Easier-to-Use Format for Prescription Drug Labeling

Over the years, the package inserts that provide information to health care practitioners on prescription drugs have been getting longer and more complex because there is more and more information that has to be conveyed. Now, this prescribing information is getting a new look which will make it easier to read and to locate specific information.

The new labeling will be required for drugs that were submitted for FDA approval after June 2006 (the effective date of the new regulation) and also for any drug that was approved within the five years prior to that date. In addition, if a drug with an approval date greater than five years has a major change, such as a new indication, then that drug will be required to have the new labeling as well. Of course, manufacturers of older drugs are encouraged to change their labeling into the new format and they can do so at any time.

Many of the changes in the prescribing information have to do with the way the information is formatted and arranged. For example, at the very beginning of the insert there is a new section called "Highlights of Prescribing Information."
This “Highlights” section is a concise summary of the information that is most important to prescribers. The “Highlights” section also refers to the corresponding sections in the "Full Prescribing Information" where more information can be obtained.

The information in the “Highlights” section includes the uses for the drug, the dosage and the major risks, the year the drug was approved (so new products can be more easily identified), and a toll-free number for reporting adverse events. The “Highlights” will also include a list of all substantive recent changes made within the year, to ensure healthcare professionals have immediate access to the most up-to-date information about the product before prescribing it. The new information will also be highlighted in the “Full Prescribing Information” section with a vertical line in the margin.

The information practitioners refer to most frequently and consider most important (e.g. Boxed Warning, Indications and Usage, Dosage and Administration, and Dosage Forms and Strengths (separated from Storage and Handling) will be located at the front of the prescribing information. In addition, risk information (Warnings, Precautions, Adverse Reactions) will be consolidated in one location.

Finally, there is a new section called "Patient Counseling Information" that will advise prescribers on what to tell the patient about concerning this particular drug. Also, if there are FDA-approved medication guides, patient package inserts and instructions for use, those will have to be included in the new labeling, or accompany it by June 2007.

FDA also continues to work on electronic methods of communicating drug information. One of the most important ones is called Daily Med. Daily Med is an online clearinghouse accessed through the National Library of Medicine that provides free, one-stop shopping for drug information which is updated constantly.

Additional Information:

Daily Med (National Library of Medicine) Current Medication Information.
http://dailymed.nlm.nih.gov/dailymed/about.cfm


Easier-to-Use Format for Prescription Drug Labeling

Over the years, the package inserts that provide information to health care practitioners on prescription drugs have been getting longer and more complex because there is more and more information that has to be conveyed. Now, this prescribing information is getting a new look which will make it easier to read and to locate specific information.

The new labeling will be required for drugs that were submitted for FDA approval after June 2006 (the effective date of the new regulation) and also for any drug that was approved within the five years prior to that date. In addition, if a drug with an approval date greater than five years has a major change, such as a new indication, then that drug will be required to have the new labeling as well. Of course, manufacturers of older drugs are encouraged to change their labeling into the new format and they can do so at any time.

Many of the changes in the prescribing information have to do with the way the information is formatted and arranged. For example, at the very beginning of the insert there is a new section called "Highlights of Prescribing Information."
This “Highlights” section is a concise summary of the information that is most important to prescribers. The “Highlights” section also refers to the corresponding sections in the "Full Prescribing Information" where more information can be obtained.

The information in the “Highlights” section includes the uses for the drug, the dosage and the major risks, the year the drug was approved (so new products can be more easily identified), and a toll-free number for reporting adverse events. The “Highlights” will also include a list of all substantive recent changes made within the year, to ensure healthcare professionals have immediate access to the most up-to-date information about the product before prescribing it. The new information will also be highlighted in the “Full Prescribing Information” section with a vertical line in the margin.

The information practitioners refer to most frequently and consider most important (e.g. Boxed Warning, Indications and Usage, Dosage and Administration, and Dosage Forms and Strengths (separated from Storage and Handling) will be located at the front of the prescribing information. In addition, risk information (Warnings, Precautions, Adverse Reactions) will be consolidated in one location.

Finally, there is a new section called "Patient Counseling Information" that will advise prescribers on what to tell the patient about concerning this particular drug. Also, if there are FDA-approved medication guides, patient package inserts and instructions for use, those will have to be included in the new labeling, or accompany it by June 2007.

FDA also continues to work on electronic methods of communicating drug information. One of the most important ones is called Daily Med. Daily Med is an online clearinghouse accessed through the National Library of Medicine that provides free, one-stop shopping for drug information which is updated constantly.

Additional Information:

FDA Press Release - FDA Announces New Prescription Drug Information Format to Improve Patient Safety. January 18, 2006.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108579.htm



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