Print | Need Larger Text? | Share

Important Safety Information on Amiodarone Intravenous-Sabex Inc.

Date: 2001-07-04

Help on accessing alternative formats, such as Portable Document Format (PDF), Microsoft Word and PowerPoint (PPT) files, can be obtained in the alternate format help section.

(PDF Version - 24 K)

Contact
BCANS Enquiries

IMPORTANT DRUG SAFETY INFORMATION

July 4, 2001

Dear Health Care Professional:  

Re: Important Safety Information on Amiodarone Intravenous

Sabex Inc. would like to make you aware of two recent changes being made to the Amiodarone Hydrochloride for Injection prescribing information (i.e. Amiodarone Hydrochloride for Injection Product Monograph). The safety and efficacy of Amiodarone Hydrochloride for Injection in the pediatric population has not been established; therefore, its use in pediatric patients is not recommended. Nevertheless, Sabex Inc. is aware that Amiodarone Hydrochloride for Injection is used off-label to treat arrhythmias in pediatric patients.

The first addition to the text will be in the DOSAGE AND ADMINISTRATION section of the Product Monograph/Package Insert. Text will be added that states, "Amiodarone Hydrochloride for Injection has been found to leach out plasticizers, such as DEHP [di-(2-ethylhexyl) phthalate] from intravenous tubing (including PVC tubing). The degree of leaching increases when infusing amiodarone at higher concentrations and lower flow rates than provided in DOSAGE AND ADMINISTRATION". DEHP is used in various plastic medical devices, generally to increase flexibility.

An expert panel concluded that, based on data from animal studies, there was concern that exposure to DEHP may adversely affect male reproductive tract development during fetal, infant and toddler stages of development if the exposure in these immature stages is several fold higher than in adults, a situation that might be associated with intensive medical procedures such as those used in critically ill infants.¹
Although a no-observable-adverse-effect level (NOAEL) by the oral route was identified for sexually mature rats (3.7-14 mg/kg per day), a NOAEL was not identified for rats in the postnatal stage. The maximum anticipated exposure to DEHP following amiodarone intravenous administration under conditions of pediatric administration was calculated to be about 1.9 mg/kg per day for a 3-kg infant, which produces a safety margin of between about twofold and sevenfold.

The second addition relates to the PRECAUTIONS, Use in Pediatrics section of the Product Monograph/Package Insert. Text will be added that describes a "gasping syndrome" in neonates, which may be fatal, following the administration of intravenous solutions containing the preservative benzyl alcohol. The text states, "Amiodarone Hydrochloride for Injection contains the preservative benzyl alcohol. There have been reports of fatal "gasping syndrome" in neonates (children less than one month of age) following the administration of intravenous solutions containing the preservative benzyl alcohol. Signs and symptoms included: metabolic acidosis progressing to respiratory distress.^{2, 3}

There are no approved dosing recommendations for amiodarone in children. If, in the opinion of the treating physician, the benefits of using this product outweigh the risks, alternative methods of dosing and administration may be considered (e.g., bolus dosing in 1-mg/kg aliquots given over 5 to 10 minutes as described by Perry et al⁴). This method of administration has not been evaluated by Health Canada. The study of Perry et al included only critically ill pediatric patients with a potentially life-threatening cardiac arrhythmia who had not responded to conventional therapy. Although the method used by Perry et al will potentially reduce exposure to plasticizers, it will not prevent exposure to benzyl alcohol which is a non-medicinal ingredient of Amiodarone Hydrochloride for Injection.

Sabex Inc. continues to work actively with Health Canada to monitor adverse event reporting and to ensure that up-to-date information regarding the use of amiodarone is available. Revisions to the existing product monograph with respect to the information provided above have been requested by Health Canada. Copies of the current product monograph for amiodarone are available on request from the manufacturer. Health Care Professionals will be advised of the revisions as soon as possible.

Reporting rates determined on the basis of spontaneously reported post-marketing adverse events are generally presumed to underestimate the risks associated with drug treatments.

The identification, characterization, and management of drug-related adverse events are dependent on the active participation of healthcare professionals in adverse drug reaction reporting programmes. Any occurrences of serious and/or unexpected adverse events should be reported to the manufacturer and to the Bureau of Licensed Product Assessment.

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.

Please contact Sabex' Drug Information Support at 1-800-343-8839 ext: 2179 if you have any questions.

Sincerely,

Leonor Ferreira, M.Sc., M.B.A. Director, Regulatory Affairs

References: