FDA Warns of Tramadol Suicide Link

Posted:5/28/2010

IMPORTANT DRUG WARNING

Dear Healthcare Professional:

PriCara®, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc., in cooperation with the US Food and Drug Administration (FDA), would like to inform you of important changes to the prescribing information for ULTRAM® (tramadol hydrochloride) tablets. The risks pertaining to these warnings are currently included in the ULTRAM® ER (tramadol hydrochloride) extended-release tablets prescribing information.

The following information has been added to the WARNINGS section of the USPI for ULTRAM® and is presented here in the same format (including boldface font) as it appears in the USPI:

Suicide Risk

• Do not prescribe ULTRAM® for patients who are suicidal or addiction-prone.
• Prescribe ULTRAM

The following prescribing information has been revised in the WARNINGS section of the USPI:

Risk of Overdosage

Patients taking tramadol should be warned not to exceed the dose recommended by their physician. Tramadol products in excessive doses, either alone or in combination with other CNS depressants, including alcohol, are a cause of drug-related deaths. Patients should be cautioned about the concomitant use of tramadol products and alcohol because of potentially serious CNS additive effects of these agents. Because of its added depressant effects, tramadol should be prescribed with caution for those patients whose medical condition requires the concomitant administration of sedatives, tranquilizers, muscle relaxants, antidepressants, or other CNS depressant drugs. Patients should be advised of the additive depressant effects of these combinations.

Serious potential consequences of overdosage with ULTRAM? (tramadol hydrochloride) tablets are central nervous system depression, respiratory depression and death. Some deaths have occurred as a consequence of the accidental ingestion of excessive quantities of tramadol alone or in combination with other drugs. In treating an overdose, primary attention should be given to maintaining adequate ventilation along with general supportive treatment (see OVERDOSAGE).

In addition, the following prescribing information has been revised in the DRUG ABUSE AND DEPENDENCE section of the USPI:

Abuse Tramadol has mu-opioid agonist activity. ULTRAM and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. 

Proper assessment of the patient and periodic re-evaluation of therapy are appropriate measures that help to limit the potential abuse of this product.

ULTRAM® is intended for oral use only.

Dependence

Tolerance is the need for increasing doses of drugs to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Physical dependence is manifested by withdrawal symptoms after abrupt discontinuation of a drug or upon administration of an antagonist (see also WARNINGS, Withdrawal).

The opioid abstinence or withdrawal syndrome is characterized by some or all of the following: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.
Generally, tolerance and/or withdrawal are more likely to occur the longer a patient is on continuous therapy with ULTRAM®.

PriCara® remains committed to providing you with the most current prescribing information for all of our products to help in the management of your patients. Please refer to the enclosed package insert for the full Prescribing Information as other sections of the prescribing information have also been revised.

Healthcare professionals should report all serious adverse events to 1-800-526-7736 or to FDA's MedWatch Adverse Event Reporting program online (at www.fda.gov/MedWatch/report.htm), by facsimile (1-800-FDA-0178), by telephone (1-800-FDA-1088), or by returning the postage-paid FDA form 3500 (which may be downloaded from www.fda.gov/MedWatch/getforms.htm) by mail (to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787).
For medical inquiries, please call the Customer Communications Center at 1-800-526-7736 or contact your PriCara® representative.

Sincerely,
Norman Rosenthal, MD
Chief Scientific Officer
© Ortho-McNeil-Janssen Pharmaceuticals, Inc. 2010 March 2010 01DR10001