Archived - Important Safety Information Regarding Carnitor® - Sigma-Tau Pharmaceuticals, Inc.

Important Drug Safety Information

2000 Ellesmere Road, Unit 16

Scarborough, Ontario

M1H 2W4

Telephone: 416-438-6727

Fax: 416-438-3179

September 10, 2001

Important Safety Information Regarding Carnitor®

Dear Healthcare Professional:

The purpose of this letter is to bring to your attention the recent addition to the Precautions Section of the Carnitor® (levocarnitine) Injection, Tablets and Oral Solution labeling a statement regarding the use of oral formulations of levocarnitine in End Stage Renal Disease (ESRD) patients on dialysis and patients with severely compromised renal function.

The basis for the labeling change arises from reports in the US of the unapproved use of oral formulations of levocarnitine in ESRD patients. Only the intravenous form has been approved for use in this patient population.

Sigma-Tau Pharmaceuticals, Inc., received approval on April 30, 2001 from the Therapeutic Products Programme (TPP) to market Carnitor Injection for the prevention and treatment of carnitine deficiency in patients with ESRD who are undergoing dialysis.

The statement added to the Precautions Section of all dosage forms is as follows:

Administration of high doses of the oral formulations of levocarnitine for long periods of time is not recommended in patients with severely compromised renal function or in ESRD patients on dialysis due to the fact that major metabolites formed following oral administration (trimethylamine [TMA] and trimethylamine-N-oxide [TMAO]) will accumulate since they can not be efficiently removed by the kidneys. This does not occur to the same extent following intravenous administration. TMA accumulation is not desirable since it increases the amount of nitrogenous waste to be removed in the dialysis procedure. In addition, increased levels of TMA in dialysis patients have been reported to be associated with possible neurophysiologic effects. Also, the inefficient removal of TMA may result in the development of 'fishy odor' syndrome. Only the intravenous form of levocarnitine is indicated for use in ESRD patients on hemodialysis.

Adverse events reported with Carnitor use include nausea, vomiting, body odor, gastritis and seizures. An incidence for these reactions is difficult to estimate due to the confounding effects of the underlying pathology. There are no reported contraindications or warnings.

Sigma-Tau does not promote or recommend the use of oral Carnitor in ESRD patients on dialysis.

The attached revised product monograph with the new information is provided for your information.

The identification, characterization, and management of drug-related adverse events are dependent on the active participation of health care professionals in adverse drug reaction reporting programs. Any occurrences of neurophysiological adverse events, 'fishy odor' syndrome or other serious and/or unexpected adverse events in patients receiving Carnitor should be reported to Sigma-Tau Pharmaceuticals or the Bureau of Licensed Product Assessment at the following addresses:

Sigma-Tau Pharmaceuticals, Inc.

2000 Ellesmere Road Unit 16

Scarborough, Ontario

M1H 2W4

Canada

Your professional commitment in this regard has an important role in protecting the well being of your patients by contributing to early signal detection and informed drug use.  

Further information may be obtained by calling 416-438-6727, extension 249.

original signed by

Les Szendrovits

Director - Scientific Affairs

Any suspected adverse drug reactions can also be reported to:

Canadian Adverse Drug Reaction Monitoring Program (CADRMP)

Bureau of Licensed Product Assessment

Therapeutic Products Directorate

Health Canada

Address Locator: 0201C2

Ottawa, Ontario, K1A 1B9

Tel: (613) 957-0337 or Fax: (613) 957-0335

Toll free for consumers and health professionals: Tel: 866 234-2345, Fax: 866 678-6789

cadrmp@hc-sc.gc.ca

The ADR Reporting Form can be found in The Canadian Compendium of Pharmaceuticals and Specialties, or on the TPD web site, along with the ADR Guidelines.