Important New Safety Information for Colchicine [Colcrys]: Potentially Fatal Drug/Drug Interactions at PGP and CYP3A4

July 31, 2009
July 30, 2009 – Today, the American Food and Drug Administration  (FDA) released the following Safety Alert concerning the potential for fatal drug/drug interactions when Colchicine [Colcrys] is used in combination with strong inhibitors of P-glycoprotein (PGP) or CYP3A4. Following suit is the  text of the Safety Alert  by the FDA.

FDA has now approved the first single-ingredient oral colchicine product, Colcrys, for the treatment of Familial Mediterranean Fever (FMF) and acute gout flares.  Oral colchicine has been used for many years as an unapproved drug with no FDA-approved prescribing information, dosage recommendations, or drug interaction warnings.

During the drug application review, FDA identified two previously uncharacterized safety concerns associated with the use of colchicine (marketed as Colcrys).

First, FDA analyzed safety data for colchicine from adverse events reported to the Agency, the published literature, and company-sponsored pharmacokinetic and drug interaction studies. This analysis revealed cases of fatal colchicine toxicity reported in certain patients taking standard therapeutic doses of colchicine and concomitant medications that interact with colchicine, such as clarithromycin. These reports suggest that drug interactions affecting the gastrointestinal absorption and/or hepatic metabolism of colchicine play a central role in the development of colchicine toxicity.

Second, data submitted supporting the safety and efficacy of Colcrys in acute gout flares demonstrated that a substantially lower dose of colchicine was as effective as the higher dose traditionally used. Moreover, patients receiving the lower dose experienced significantly fewer adverse events compared to the higher dose.

Based on this information, FDA is highlighting important safety considerations found in the approved prescribing information to assure safe use of Colcrys.

FDA recommends:

  • Healthcare professionals not use P-glycoprotein (P-gp) or strong CYP3A4 inhibitors in patients with renal or hepatic impairment who are currently taking colchicine.
  • Healthcare professionals consider a dose reduction or interruption of colchicine treatment in patients with normal renal and hepatic function if treatment with a P-gp or a strong CYP3A4 inhibitor is required.
  • Healthcare professionals prescribe the FDA-approved Colcrys dose for the treatment of acute gout flares: 1.2 mg followed by 0.6mg in 1 hour (total 1.8mg).
  • Healthcare professionals refer to Colcrys’ approved prescribing information for specific dosing recommendations and additional drug interaction information.
  • Patients review the Medication Guide for important safety information
This information reflects FDA’s current analysis of data available to FDA concerning this drug. FDA intends to update this sheet when additional information or analyses become available.

Look here for additional information, particularly on the drug/drug interaction  issue. To report any unexpected adverse or serious events associated with the use of this drug, please contact the FDA MedWatch online ( MedWatch Online]) or by regular mail using the postage-paid FDA Form 3500.

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Public Health Advisory: The FDA recommends that consumers should not use body building products marketed as containing steroids or steroid-like substances

July 29, 2009

July 28, 2009 – The American Food and Drug Administration (FDA) has today released a Public Health Advisory concerning body building supplements that contain so-called steroid like ingredients. Read here below the full text of the advisory.

The FDA is notifying the public about new safety information concerning products marketed for body building and increasing muscle mass.  The FDA has sent a Warning Letter to a manufacturer of body building supplements that claim to contain steroid-like ingredients, but in fact contain synthetic steroids.  The products named in the Warning Letter are marketed by American Cellular Laboratories, Inc., and include “TREN-Xtreme,” “MASS Xtreme,” “ESTRO Xtreme,” “AH-89-Xtreme,” “HMG Xtreme,” “MMA-3 Xtreme,” “VNS-9 Xtreme,” and “TT-40-Xtreme.”

The FDA has received reports of serious adverse events associated with the use of these products and other similar products.  Products like these are frequently marketed as alternatives to anabolic steroids for increasing muscle mass and strength and are sold both online and in retail stores.  They are often promoted to athletes to improve sports performance and to aid in recovery from training and sporting events.  Although products containing synthetic steroids are frequently marketed as dietary supplements, they are NOT dietary supplements, but instead are unapproved new drugs that have not been reviewed by the FDA for safety and effectiveness.

Adverse event reports received by the FDA for body building products that are labeled to contain steroids or steroid alternatives involve men (ages 22-55) and include cases of serious liver injury, stroke, kidney failure and pulmonary embolism (blockage of an artery in the lung).

Due to the potentially serious health risks associated with using these types of products, the FDA recommends that consumers immediately stop using all body building products that claim to contain steroids or steroid-like substances.  Consumers should consult their health care professional if they are experiencing symptoms possibly associated with these products, particularly nausea, weakness or fatigue, fever, abdominal pain, chest pain, shortness of breath, jaundice (yellowing of the skin or whites of the eyes) or brown/discolored urine.  The FDA also recommends that consumers talk with their health care professional about any body building supplements they are taking or planning to take, particularly if they are uncertain about a product’s ingredients.

Health care professionals are advised to ask their patients about any over-the-counter products they may be using, including products marketed as dietary supplements. Additionally, health care professionals should be alert to patients presenting with the warning signs that may be associated with the use of steroids or steroid-like substances, including liver injury, kidney failure, stroke, and hormone-associated adverse effects, such as blood clots, including pulmonary embolism and deep vein thrombosis.

Health care professionals and consumers are encouraged to report any adverse events related to the use of these products to FDA’s MedWatch Adverse Event Reporting program, either online, by regular mail or by fax, using the contact information at the bottom of this page.

For more details about these products see FDA’s Consumer Information piece (Consumer Update) Warning on Body Building Products Marketed as Containing Steroids or Steroid-Like Substances.

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FDA: Boxed Warning on Serious Mental Health Events to be Required for the Smoking Cessation Drugs Varenicline [Chantix] and Bupropion [Zyban]

July 1, 2009

July 01, 2009 – Please find here the minimally adapted text of a today’s news release by the American Food and Drug Administration (FDA) concernings drugs that contain the pharmacologically active ingredients varenicline and bupropion.

The U.S. Food and Drug Administration today announced that it is requiring manufacturers to put a Boxed Warning on the prescribing information for the smoking cessation drugs Varenicline [Chantix] and Bupropion [Zyban]. The warning will highlight the risk of serious mental health events including changes in behavior, depressed mood, hostility, and suicidal thoughts when taking these drugs.

“The risk of serious adverse events while taking these products must be weighed against the significant health benefits of quitting smoking,” said Janet Woodcock, M.D., director, the FDA’s Center for Drug Evaluation and Research. “Smoking is the leading cause of preventable disease, disability, and death in the United States and we know these products are effective aids in helping people quit.”

Similar information on mental health events will be required for Bupropion marketed as the antidepressants [Wellbutrin], [Wellbutrin SR],  [Wellbutrin XL], and for various generic versions of [Bupropion]. These drugs already carry a Boxed Warning for suicidal behavior in treating psychiatric disorders.

Woodcock said health care professionals who prescribe Chantix and Zyban should monitor their patients for any unusual changes in mood or behavior after starting these drugs. She added that patients should immediately contact their health care professional if they experience such changes.

The FDA’s request for the additional warnings is based on a review of reports submitted to the agency’s Adverse Event Reporting System since the time the products were marketed and on an analysis of information from clinical trials and scientific literature. The analyses revealed that some who have taken Chantix and Zyban have reported experiencing unusual changes in behavior, become depressed, or had their depression worsen, and had thoughts of suicide or dying. In many cases, the problems began shortly after starting the medication and ended when the medication was stopped. However, some people continued to have symptoms after stopping the medication. Also, in a few cases, the problems began after the medication was stopped.

Neither Chantix nor Zyban contain nicotine and some of these symptoms may be a response to nicotine withdrawal. People who stop smoking may experience symptoms such as depression, anxiety, irritability, restlessness, and sleep disturbances. However, some patients who were using these products experienced the reported adverse events while they were still smoking.

In addition to the Boxed Warning, the FDA also is requesting more information in the Warnings section of the prescribing information and updated information in the Medication Guide for patients that further discuss the risk of mental health events when using these products. Manufacturers also will be required to conduct a clinical trial to determine how often serious neuropsychiatric symptoms occur in patients using various smoking cessation therapies, including patients who currently have psychiatric disorders. The FDA’s review of adverse events for patients using nicotine patches did not identify a clear link between those medications and suicidal events.

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For your information, please find here, in addition to the above news release by the FDA, the text of the current Boxed Warning to be found in the drug labeling document of Bupropion [Wellbutrin]:

“Suicidality and Antidepressant Drugs: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of WELLBUTRIN or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. WELLBUTRIN is not approved for use in pediatric patients. (See WARNINGS: Clinical Worsening and Suicide Risk, PRECAUTIONS: Information for Patients, and PRECAUTIONS: Pediatric Use.)”

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