ADULT PEDIATRIC APPROVAL MASMAP PMAP Approved by: PMAP November 14, 2013 Peds P&T January 20, 2014 Professional Involved: Physicians, Nurses, Pharmacists Key Words: Amiodarone, Cardiac arrest, Ventricular tachycardia, Supraventricular tachycardia Title: Amiodarone Route: IV/IO MUHC Policy #: Reserved Section Effective Date: January 20, 2014 Updated: January 28, 2015 Date for Revision: High Risk Medication: Associated practice related to medication: 1. PURPOSE (This is not a medical order) To provide a guideline for decision-making related to the administration of IV Amiodarone. This protocol does not apply to the administration of PO Amiodarone. 2. SCOPE The administration of this medication is restricted to Critical care areas (paediatric intensive care unit (PICU), Neonatal intensive care unit (NICU), and the Emergency department), where one to one monitoring and expertise are provided within the paediatric sites at the MUHC. Clinicians administering this medication are required to be PALS certified or similarly trained and familiar with this protocol prior to administration. All monitoring requirements must be adhered to and documented. 3. PROTOCOL SEE ATTACHED PROTOCOL 4. PREPRINTED ORDER FORMS / RÉGLE DE SOINS INFIRMIERS - SEE ATTACHED 5. POLICY SEE BELOW 5.1.1 INDICATIONS As per PALS algorithm is recommended for the treatment of: Ventricular fibrillation (VF) or Ventricular tachycardia (VT) cardiac arrest Perfusing arrhythmias such as VT with pulse Supraventricular Tachycardia (SVT) Any other ventricular arrhythmias where Cardiology recommends the use of this agent (eg. Junctional ectopic tachycardia). 5.1.2 CONTRAINDICATIONS Known hypersensitivity to Amiodarone or to any of its components, including iodine and polysorbate (Tween 80) Severe sinus node dysfunction Second or third-degree atrioventricular block Marked sinus bradycardia Severe bradycardia causing syncope Cardiogenic shock Acute hepatitis or pulmonary interstitial abnormalities Known congenital long QT syndrome Medication Administration Policy - Pediatric Amiodarone Final Update January 28, 2015 Page 1 of 7
5.1.3 PRECAUTIONS Hepatic impairment Cardiac devices (e.g. Implantable cardioverter defibrillators, pacemakers) Concurrent therapy with drugs metabolized by CYP enzymes, and drugs with QT prolongation potential Hypo or hyperthyroidism Neonates: use with caution as Amiodarone 50 mg/ml injectable contains 20.2 mg/ml of benzyl alcohol. Benzyl alcohol (equal to or greater than 99 mg/kg/day) has been associated with gasping syndrome in neonates. 5.1.3.1 ADVERSE REACTIONS CVS: Bradycardia and AV blocks, cardiac arrhythmias, cardiogenic shock, hypotension CNS: Tremors, poor coordination, abnormal gait/ataxia Respiratory: Pulmonary toxicity Endocrine & metabolic: Hyperthyroidism, hypothyroidism Hematologic: Coagulation abnormalities Local: Phlebitis 5.2 PREGNANCY AND LACTATION Amiodarone and its active metabolite Cross the placenta and may cause fetal harm, leading to congenital goiter and hypo- or hyperthyroidism. Enter breast milk.. Breastfeeding is not recommended. 5.3 PHARMACOKINETICS IV: Rapid redistribution with a decrease to 10% of peak values within 30-45 minutes after completion of infusion. Highly protein bound. Mainly metabolized in the liver by CYP450 cytochromes and form active metabolite (N-desethylamiodarone). Half-life for single IV dose: 20-47 days; for N-desethylamiodarone (active metabolite) it is 14-75 days. Half-life may be shortened in children. Elimination via biliary excretion. Amiodarone and its metabolites are NOT dialyzable. 5.4 ADMINISTRATION Prepare Amiodarone at the standard 2 mg/ml Adjust administration rate to patient s clinical condition and urgency Loading dose may be given as 1 mg/kg aliquots Maximum bolus infusion rate: 15 mg/min, does not apply in a cardiac arrest situation Administer continuous IV infusion with a volumetric pump at a rate not exceeding 0.25 mg/kg/min, unless clinically indicated A 0.2 micron in-line filter is recommended for continuous IV infusion Infusion exceeding 2 hours must be mixed in a polyolefin (non-pvc) bag Central line is the preferred route of administration to decrease risk of superficial phlebitis, however a large peripheral vein may be used if central access is not immediately available Hypokalemia or hypomagnesaemia must be corrected prior to treatment with Amiodarone IV due to the risk of torsade de pointes Refer to Table 1 and 2 for Amiodarone Dose and Administration Refer to Appendix 1 for Amiodarone infusion preparation 5.4.1 STORAGE Store between 20 and 25 C. Protect from light and excessive heat. Discard unused portion. Diluted solutions do not require protection from light during IV administration. 5.4.2 SUPPLIES Vial 50 mg/ml (3 ml) Medication Administration Policy - Pediatric Amiodarone Final Update January 28, 2015 Page 2 of 7
5.4.3 COMPATIBILITY Amiodarone is stable in D5W at a 1 6 mg/ml at room temperature for: 24 hours in a polyolefin (Non-PVC) bag 2 hours in a PVC bag Y-Site Compatible (non-exhaustive list): atropine, calcium chloride, calcium gluconate, EPINEPHrine, norepinephrine, potassium chloride up to 40 mmol/l, vasopressin Y-Site incompatibility (non-exhaustive list): Aminophylline, cefazolin, digoxin, heparin, magnesium sulfate, sodium bicarbonate 5.4.4 DOSE Filter is not required Maximum infusion rate does not apply ALERT - IN CARDIAC ARREST SITUATION Table 1. Amiodarone Dose and Administration for Cardiac Arrest Neonates/Infants/Children/Adolescents Indication Dose Dilution Infusion Rate Pulseless VT/VF (Cardiac Arrest) 5 mg/kg IV/IO Maximum single dose: 300 mg IV/IO Dilute dose in a total of 20 ml D5W or NS Rapid IV/IO push by physician 15 mg/kg IV/IO up to 2.2 g/day Adults Indication Dose Dilution Infusion Rate Pulseless VT/VF (Cardiac Arrest) 300 mg IV/IO Supplemental dose: 150 mg IV, if pulseless VT or VF continues or recurs after subsequent defibrillation attempt Dilute dose in total of 20 ml D5W or NS Rapid IV/IO push by physician 2.2 g/day Medication Administration Policy - Pediatric Amiodarone Final Update January 28, 2015 Page 3 of 7
Table 2. Amiodarone Dose and Administration for SVT, VT with Pulses Neonates/Infants/Children/ Adolescents Indication Dose Dilution Infusion Rate Ventricular Arrhythmias (VT with Pulse) and SVT with a pulse Loading dose: 5 mg/kg IV/IO Maximum single dose: 300 mg May repeat initial loading dose if no conversion 15 mg/kg or 2.2 g/day Dilute to a 2 mg/ml with D5W (empty polyolefin bag) Infuse over 20 60 minutes May be given as 1 mg/kg aliquots over 5-10 minutes Maintenance infusion: Initial: 5 mcg/kg/min IV Usual range: 5-15 mcg/kg/min Maximum 15 mcg/kg/min 2.2 g/day (bolus AND infusion) Dilute 500 mg in total of 250 ml D5W for a 2 mg/ml (empty polyolefin bag) see Appendix 1 for Infusion preparation Use a 0.2 micron in-line filter * Please consult Cardiology for further dosing recommendations Adults Initial dose of 1050 mg over the first 24 hours given in a 3-phase sequence: rapid loading phase, slow loading phase, and maintenance infusion phase (see below). Indication Dose Dilution Infusion Rate Ventricular Arrhythmias (VT with Pulse) and SVT with a pulse 1. Rapid loading phase 150 mg IV 2. Slow loading phase 360 mg IV over 6 hours Dilute in 75 ml D5W (2 mg/ml) Dilute in 180 ml D5W for a 2 mg/ml (empty polyolefin bag) Infuse over 10 minutes (15 mg/min) then, Infuse at 1 mg/min (30 ml/h) for 6 hours then, Use a 0.2 micron in-line filter. 3. Maintenance infusion 540 mg IV over 18 hours * Please consult Cardiology for further dosing recommendations Dilute in 270 ml D5W for a 2 mg/ml (empty polyolefin bag) Infuse at 0.5 mg/min (15 ml/h) for 18 hours Use a 0.2 micron in-line filter. Medication Administration Policy - Pediatric Amiodarone Final Update January 28, 2015 Page 4 of 7
5.5 MONITORING Prior to administration obtain: Baseline vital signs Correct any electrolytes imbalances in particular hypokalemia and hypomagnesaemia 12 lead ECG with a rhythm strip if the clinical condition of the patient allows it Consultation with Cardiology should be sought when considering Amiodarone if the clinical condition of the patient allows it Continuous cardiac monitoring is mandatory throughout therapy Document blood pressure, heart rate, respiratory rate, oxygen saturation, q 5 minutes x 3, q 15 minutes x 3, then q 1h or more frequently, as clinically indicated Hypotension and bradycardia during IV infusion can usually be managed by reduction of the drug infusion rate A second large bore IV access should be available for possible fluid resuscitation Observe for bradycardia, AV blocks, torsade de pointe hypotension, and clinical signs of worsening heart failure Monitoring parameters: serum electrolytes (especially potassium and magnesium), liver enzymes, ECG as per physician order (risk of prolonged QT interval), INR if interacting medications If peripheral IV Amiodarone infusion, monitor IV site q 1h for signs of phlebitis for the duration of peripheral infusion. Cardiologist consult required to monitor pacing or defibrillation thresholds in patient with implanted cardiac devices ALERT A defibrillator with the capacity of external pacing must be in proximity to the bedside during IV Amiodarone administration with appropriate patient size external pacing pads Physician in charge should be familiar in activating the pacing function of the defibrillator Physician in charge of the patient should be familiar with how to start external pacing if required Medication Administration Policy - Pediatric Amiodarone Final Update January 28, 2015 Page 5 of 7
REFERENCES: Taketomo, C.K., Hodding, J.H., Kraus, M.D. (2012-2013) Pediatric and Neonatal Dosage Handbook, 19th edition Lexicomp Ottawa Hospital Parenteral Drug Therapy Manual, 31 st edition. 2010 Kleinman M.E., Chameides L, Schexnayder S.M et al. Pediatric Advanced Life Support:2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Pediatrics,126(5): e1361-99 Sandoz Canada (2005). Product Monograph: Amiodarone hydrochloride for injection. Retrieved on Aug 21, 2013 from: http://webprod5.hc-sc.gc.ca/dpd-bdpp/info.do?code=66036&lang=eng Perry JC., Fenrich AL, Hulse JE, et al. Pediatric use of intravenous amiodarone : efficacy and safety in critically ill patients from a multicenter protocol. J Am Coll Cardiol, 1996, 27(5): 1246-50 MAIN AUTHORS: Nora Ruo, B. Pharm, M.Sc, Pediatric intensive care pharmacist Denise Kudirka, Cadre conseil en soins infirmiers spécialisés urgence pédiatrique CONSULTANTS: Marie Antonacci, BSc.N. Gabrielle Girard, B. Pharm, M.Sc, Neonatal intensive care pharmacist Dr Adrian Dancea, Cardiologist Dr Samara Zavalkoff, Pediatric Intensivist Dr Dubravka Diksic, Pediatric Emergentologist Marjorie Friesen, Pharmacist at Drug information center Michel Sergerie, Cadre conseil en soins infirmiers spécialisés cardiologie Medication Administration Policy - Pediatric Amiodarone Final Update January 28, 2015 Page 6 of 7
Appendix 1 SVT, VT with Pulses: PREPARATION of INFUSION for Neonates/Infants/Children/ Adolescents Concentration: Prepare an infusion at a 2 mg/ml Solution: Dilute 500 mg of amiodarone (10 ml) in 240 ml D5W For a final volume of 250 ml at a final 2 mg/ml (2000 mcg/ml) CALCULATION of RATE rate = dose (mcg/kg/min) X weight (kg) X 60 minutes (ml/h) (ml/h) concentration (mcg/ml) EXAMPLE: medical order : 5 mcg/kg/min for a 30 kg child rate = 5 mcg/kg/min X 30 kg X 60 minutes (ml/h) rate = 4.5 ml/h (ml/h) 2000 mcg/ml Medication Administration Policy - Pediatric Amiodarone Final Update January 28, 2015 Page 7 of 7