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Is there any risk of DEHP toxicity form giving amiodarone through regular Polyvinyl Chloride (PVC) tubing in Cardiology Patients? The injectable preparation of amiodarone is known to leach out plasticizers, such as di(2- ethylhexyl)phthalate (DEHP), from polyvinyl chloride (PVC) tubing. Although the toxic effects of DEHP have been well established in experimental animals, recent study showed that sensitive markers of anti-androgenic effects during development were in males in males (rat) exposed to the highest dose (405 mg/kg/day) .1 The ability of this compound to produce adverse effects in humans remains controversial.4 It is hypothesized that a DEHP found in plastic IV tubing may harm young children, specifically male reproductive system, based on animal data. 2 With these limits, the amount of DEHP exposure is expected to remain under the proposed tolerable intake of 0.6 to 0.8 mg/kg/day, without producing recommend by adverse effects in humans.3 The CDRH reports of exposure to DEHP during various procedures, but do not address particular drug, or device. CABG patient will receive approximately 1 mg/kg/day of DEHP total, comprising is much lower dose than neonatal patient who receive 22.6mg/kg/day during the blood transfusion. Dose of DEHP received by from device-related sources could be 20-fold greater than the dose of DEHP that is not expected to result in adverse effects following intravenous exposure. 4 The NTP concurrent draft brief recommends that concern could be warranted for male infants younger than 1 year and for the sons of women who underwent certain medical procedures while pregnant 2. It is well known that amiodarone adsorbs to polyvinyl chloride (PVC) tubing and the clinical trial dose administration schedule was designed to account for this adsorption. One study used amiodarone solution in 5% dextrose and used 1.8-m long polyvinyl chloride (PVC) IV administration set and 0.5ml/hr infusion rate amiodarone in the effluent decreased to approximately 82% from the initial concentration and remained at the concentration until all drug solution had been perfused, similar loses have been observed with nitroglycerin. Despite the study, all of the clinical trials were conducted using PVC tubing and its use is therefore recommended by the manufacture. The concentrations and rates of infusion provided in Dosage and Administration reflect doses identified in these studies.6 To minimize leaching and minimize loss of drug during the administration and absorption to the tubing, Wyeth (former original maker of Amiodarone), and Bedford Labs (generic company), currently used by Inova Health System recommend that a maximum concentration of 6 mg/ml and an infusion flow rate of at least 0.5 mg/min be used. In addition, it is recommended that infusions lasting longer than 2 hours be must be administered in glass or polyolefin bottles containing D5W. In neonates, the use of hard plastic syringes (rather than bags) and non-PVC tubing may help to minimize DEHP exposure 6,7,3.

Reference: 1. Anderson J.M et al.A dose-response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): effects on androgenic status, developmental landmarks and testicular histology in male offspring rats Toxicology. 2006 Aug 1;225(1):64-74 2. Barrett J.R. NTP Draft Brief on DEHP Environ Health Perspect. 2006 October; 114(10): A580–A581 3. Buck M.L. Pediatric Pharmacotherapy. A Monthly Newsletter for Health Care Professionals from the Children’s Medical Center at the University of Virginia Vol. 7 Num. 12 12/2001 4. Anonymous. Center for Devices and Radiological Health. Safety assessment of di(2-ethylhexyl)phthalate (DEHP) released from PVC medical devices. Rockville, MD: US Food and Drug Administration, 2001:3-4. 5. Weir SJ, at el. Sorption of amiodarone to polyvinyl chloride infusion bags and administration sets. Am J Hosp Pharm. 1985 Dec;42(12):2679-83. 6. Amiodarone. Product information package insert. Bedford Laboratories. May 2005. 7. Cordarone.Product information package insert. Wyeth Laboratories. August 2001.