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Home , Extravasation, Pentamidine, Sodium thiosulfate

10/30/2019

Extravasation Management: A Hot Problem With Cold Solutions

Graham Klink, PharmD PGY2 Oncology Pharmacy Resident Huntsman Cancer Institute Graham Klink, PharmD November 2, 2019

Disclosure Pharmacist Learning Objectives

Relevant Financial Conflicts of Interest  Define vesicant, vesicant‐like, irritant, and non‐vesicant and their unique management when oCE Presenter, Graham Klink, PharmD extravasated. o None oCE Mentor, Erik Harrington, MS, PharmD, BCOP o None  Recognize risk factors for extravasation including iatrogenic causes, patient factors, and high‐risk oCE Mentor, Nannette Sageser, PharmD agents. o None  Recall the pharmacology of agents used in the treatment of extravasation reversal.  Off‐Label Uses of ◦ ◦ Phentolamine  Construct an appropriate treatment regimen including both pharmacologic and non‐pharmacologic ◦ Hyaluronidase options for the management of vesicant extravasation. ◦ Dimethyl sulfoxide ◦ ◦ Terbutaline  Design an appropriate counseling and monitoring plan for patients following extravasation events.

Lexicomp. Wolters Kluwer, Inc. (2019)

Technician Learning Objectives Extravasation

 Identify used in the treatment of extravasation. Efflux of solutions from a vessel or direct infiltration into the surrounding tissues during intravenous infusion  Distinguish the appropriate storage and handling of antidotes commonly used in the management of extravasation.

 Recognize the proper compounding technique and appropriate dispensing of medications utilized in the management of various extravasation events.

Image: https://bit.ly/2mJ3hZV Goutos I et al. JHS (2014) 39E:08‐18.

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Incidence and Outcomes Classification of agents  Vesicant – capable of producing , pain, erythema, and potentially .Extravasation of cytotoxic agents occurs at a rate of 0.01‐6.5% tissue ischemia and blistering . Incidence of non‐cytotoxic agent extravasation is largely unknown  Vesicant‐like – usually classified as irritants but may cause local .Majority occur in peripheral intravenous catheters (PIV) blistering, pain, and potential necrosis . Less common with central venous catheters (CVC)  Irritant – transitory effect characterized by burning sensation, pain, and .Lesions may continue to expand and typically heal slowly redness during the infusion or extravasation . Ulceration may require plastic surgery or skin grafts . Superimposed infection may occur . Pain may persist for up to 1‐2 weeks after extravasation  Non‐irritant ‐ no local reactions, potentially mild or sensation of discomfort

Goutos I et al. JHS (2014) 39E:08‐18. Goutos I et al. JHS (2014) 39E:08‐18. Le A, et al. Annals of Pharma (2014)48(7):870‐86. Kreidieh F, et al. WJCO (2016) 7(1) 87‐97.

Classification of agents Norepinephrine ≥ 0.4 Epinephrine Platinums mg/mL Dobutamine Dopamine Calcium chloride 10% Phenylephrine Adrenergic Dextrose 10% Hyperosmolar Vesicants Vesicant‐like Irritants Non‐vesicants agents Potassium chloride ≥ 2 mEq/mL Sodium bicarbonate ≥ 8.4% ≥ 3% Vinca alkaloids Taxanes Platin Salts Arsenic Total Parenteral Nutrition Anthracyclines Anti‐tumor antibiotics II Asparaginase Mitomycin inhibitors Dactinomycin Alkylating agents Alkylating agents Antimetabolites Vesicants Alkylating agents Anti‐tumor antibiotics Monoclonal antibodies Interferon Antitumor Other Acyclovir Topoisomerase I antibiotics Adrenergic agents inhibitors Monoclonal antibodies Phenytoin Promethazine Hyper/hyposmolar Antibiotics Bortezomib agents Antiarrhythmics Antibiotics Liposomal Anthracyclines Doxorubicin Antimetabolites Daunorubicin Idarubicin Anthracyclines Vinca Alkaloids Vincristine Vinblastine Vinorelbine

Fidalgo J, et al. Annals of Oncol (2012) 23 (7) 167‐73. Fidalgo J, et al. Annals of Oncol (2012) 23 (7) 167‐73. Kreidieh F, et al. WJCO (2016) 7(1) 87‐97. Kreidieh F, et al. WJCO (2016) 7(1) 87‐97. Le A, et al. Annals of Pharma (2014) 48(7) 870‐86.

Cladribine Arsenic Cytarabine Bleomycin Mitoxantrone Other Bortezomib Fluorouracil Brentuximab Methotrexate Etoposide Topoisomerase I Oxaliplatin Bendamustine Antimetabolite Inhibitors

Daunorubicin liposomal Topotecan Doxorubicin liposomal Irinotecan Daunorubicin liposomal‐ Vesicant- cytarabine liposomal Irritants like Ado‐ Liposomal Docetaxel trastuzumab Antibiotics Ganciclovir Anthracyclines emtansine Nafcillin

Paclitaxel Busulfan (conventional Carboplatin ≥ 10 Alkylating Cabazitaxel Platin Salts Carmustine & albumin mg/mL Agents Cyclophosphamide bound) Cisplatin < 0.4 mg/mL Ifosfamide Melphalan

. Fidalgo J, et al. Annals of Oncol (2012) 23 (7) 167‐73. Kreidieh F, et al. WJCO (2016) 7(1) 87‐97. Kreidieh F, et al. WJCO (2016) 7(1) 87‐97. Le A, et al. Annals of Pharma (2014) 48(7) 870‐86. Le A, et al. Annals of Pharma (2014) 48(7) 870‐86.

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Azacitidine Risk Factors Asparaginase Decitabine Patient Specific Factors Iatrogenic Causes Alemtuzumab Bevacizumab Fragile, small, or mobile veins Inexperienced personnel Monoclonal Antimetabolites Ipilimumab Antibodies Pertuzumab Sclerosed veins Multiple attempts at cannulation Rituximab Multiple courses of Cannulation at an unsuitable site Non- Trastuzumab vesicants Obesity Infusion pumps Impaired or altered circulation Improper cannulation Cefepime Difficulty with communication Prolonged infusion Ceftriaxone Ceftazidime side effects Pressure bag use Antibiotics Interferon

Boulanger J, et al. Sup Care Canc (2015) 23: 1459‐71. Kreidieh F, et al. WJCO (2016) 7(1) 87‐97. Le A, et al. Annals of Pharma (2014) 48(7) 870‐86. Goutos I et al. JHS (2014) 39E:08‐18.

Preventing extravasation Preventing extravasation  Proper administration of vesicant drugs  Medical, pharmacy, and nursing team education and coordination  Use central line when possible  Appropriate vascular access  Recent placement of line Midline Catheter  Appropriate cannula and needle selection  Avoid dorsum of hand or near joints

  Institution guidelines for extravasation Do not cover cannula entry site  Do not test with cytotoxic drug

 Flush line every 2‐3 minutes

Image: https://shutr.bz/2nYEhyp Image: https://bit.ly/2oii7qU Ener R.A., et al. Annals of Oncol (2004) 15; 858‐62. Kreidieh FY et al. WJCO. (2016) 7:1. Kreidieh FY et al. WJCO. (2016) 7:1.

Preventing extravasation Diagnosis of Extravasation  Patient Education Patient symptoms • Tingling, burning, discomfort, pain, swelling or redness  Risk of extravasation

 Accurate history of previous extremity manipulation Nursing staff education • Frequently monitoring for swelling, redness, blanching, absence of  Report discomfort, pain, redness or swelling immediately return, or resistance during bolus administration

 Understand risk associated with PIV versus CVC Differential Diagnosis •LocalLocal skin reactions reaction vs. chemicalChemical phlebitis phlebitis vs. extravasation Asparaginase Doxorubicin Carmustine Gemcitabine Cisplatin Fludarabine Cisplatin Vinorelbine

Ener R.A., et al. Annals of Oncol (2004) 15; 858‐62. Daunorubicin Melphalan 5‐FU Kreidieh FY et al. WJCO. (2016) 7:1. Fidalgo P et al. Annals o Oncol (2012) 23(7):167‐173.

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• Blanched skin •Same as Grade 1 •Edema < 1 inch •Edema 1‐6 inches • Cool to touch • With or without pain Management Principles of Extravasation

Immediate Management Grade 1 Grade 2 General Management Staging of Extravasation Specific Management Grade 4 Grade 3

• Tight, leaking skin • Blanched or translucent • Discolored, bruised, or skin deep pitting edema •Edema > 6 inches •Moderate to severe pain • Mild to moderate pain • Circulatory impairment • Possible numbness • Irritant or vesicant Image: https://bit.ly/2nYPK0V Reynolds P, et al. Pharma (2014) 34(6) 617‐32.

Immediate Management of PeripheralPeripheral IV Extravasation Immediate Management of Central IV Extravasation

STOP the infusion AND DISCONNECT the infusion set STOP the infusion AND DISCONNECT the infusion set

LEAVE the needle in place and ASPIRATE as much fluid as possible LEAVE the central line in place and ASPIRATE extravasated fluid

URGENT Chest X‐ray or thoracic computed topography (CT) imaging DO NOTREMOVE removethe needle cannula for cisplatinand MARK ≥0.4the mg/mL extravasated or bendamustine area and CONSULT surgery

Goutos I et al. JHS (2014) 39E:08‐18. Fidalgo P et al. Annals o Oncol (2012) 23(7):167‐173.

General Management

MONITOR every 5‐10 minutes for altered mental status and Contact the Provider any significant skin changes Immediately APPLY DRY compresses for 15 minutes every 6 hours

Localize and neutralize Disperse and dilute Anthracyclines, antibiotics, taxanes, cisplatin ≥0.4 mg/mL, Vinca alkaloids, oxaliplatin, and sympathomimetic agents and alkylating agents

Image: https://bit.ly/1T9Llil Fidalgo P et al. “ESMO”. Annals o Oncol (2012) 23(7):167‐173.

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General Management – Documentation General Management – Documentation

Erythema, Presence or Record Pain Patient Name Date and Time Name of Drug Swelling, and Absence of Management and MRN Extravasation and Diluent Induration Pain Steps

Description of Amount of Location and Include Continue to Other Agents Intravenous Drug Size of Photographs if Document Administered Access Extravasated Extravasation Possible Progression

Fidalgo P et al. Annals of Oncol (2012) 23(7):167‐173. Fidalgo P et al. Annals of Oncol (2012) 23(7):167‐173. Mullin S, et al. Hospital Pharmacy (2000) 35:57‐76. Mullin S, et al. Hospital Pharmacy (2000) 35:57‐76.

Pharmacology Specific Management Extravasation of Sympathomimetic Agents

Local stimulation of ⍺‐adrenergic Mechanism 1. Vasoconstriction/ Ischemic Necrosis receptors may lead to tissue ischemia

2. Direct Toxicity Dobutamine, Dopamine, Epinephrine, Agents Norepinephrine, and Phenylephrine 3. Osmotic Damage

4. Extrinsic Mechanical Compression Specific Warm compress, Phentolamine, Management Terbutaline, and Nitroglycerin Ointment

Goutos I et al. JHS (2014) 39E:08‐18. Le A, et al. Annals of Pharma (2014) 48(7) 870‐86.

Extravasation of Sympathomimetic Agents Antidotes for Sympathomimetic Agents - Phentolamine Age < 2 years old Age ≥ 2 years old Non‐specific ⍺‐receptor antagonist, competes with catecholamines to reverse ischemia

Nitroglycerin Phentolamine ointment

Phentolamine

Use terbutaline/ nitroglycerin only Terbutaline α2 receptor when on shortage or contraindicated α1 receptor

Le A, et al. Annals of Pharma (2014) 48(7) 870‐86. Plum M et al. Pharm and Thera (2017) 42(9) 581‐85. Le A, et al. Annals of Pharma (2014) 48(7) 870‐86.

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Antidotes for Sympathomimetic Agents - Antidotes for Sympathomimetic Agents - Phentolamine Terbutaline

Adults: 5‐10 mg subcutaneously in multiple small injections Selective β2‐receptor agonist, vasodilatory effect Children: 0.1‐0.2 mg/kg subcutaneously (5 mg max) attenuates vasoconstriction

Prepare by diluting 1 mL of phentolamine solution in 10 mL of sodium chloride 0.9% Terbutaline

Administer as soon as possible but within 12 hours β2 Repeat assessment of distal circulation at site

Image: https://bit.ly/2pn3uD1 Le A, et al. Annals of Pharma (2014) 48(7) 870‐86. Plum M et al. Pharm and Thera (2017) 42(9) 581‐85.

Antidotes for Sympathomimetic Agents - Antidotes for Sympathomimetic Agents – Terbutaline Topical Nitroglycerin

Adults (≥ 2 years old) 1 mg (1 mg/ 10 mL) subcutaneously formation leads to smooth muscle Do not use in pediatrics < 2 years old relaxation and vasodilation of capillaries

Prepare dilution using 9 mLs of sodium chloride 0.9% Adult: Apply 1‐inch strip to site of extravasation Dosage is different for intravenous vasopressor extravasation than digital epinephrine injection Pediatric (<2 y.o.): Apply 4 mm/kg to site (max 1 inch)

May repeat once after 15 minutes May repeat every 8 hours for up to 2 additional doses Administer subcutaneously into the area of extravasation Use nitroglycerin 2% ointment

Le A, et al. Annals of Pharma (2014) 48(7) 870‐86. Le A, et al. Annals of Pharma (2014) 48(7) 870‐86. Plum M et al. Pharm and Thera (2017) 42(9) 581‐85. Plum M et al. Pharm and Thera (2017) 42(9) 581‐85.

Extravasation of Highly Acidic/Alkali Agents Acidic and Basic Agents Exposure to alkaline or acidic solutions Mechanism pH ≤ 3 pH 3-5 pH 5-7 pH ≥ 7 (pH <5 or >9) causes tissue damage Midazolam Amiodarone Amphotericin Acyclovir Vancomycin Gentamicin Ceftriaxone Ampicillin Cefepime Azathioprine Agents See pH specific table Labetalol Clindamycin Chlorothiazide Lorazepam Ondansetron Lidocaine Ganciclovir Specific Warm dry compress and avoid Oxytocin Meropenem Phenytoin Promethazine Metronidazole Propofol Management neutralization Nafcillin Valproic Acid

Le A, et al. Annals of Pharma (2014) 48(7) 870‐86. Reynolds P, et al. Pharma (2014) 34(6) 617‐32. Le A, et al. Annals of Pharma (2014) 48(7) 870‐86.

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Extravasation of Hyperosmolar Solutions Hyperosmolar Agents

Exert osmotic pressure and cause a shift Mechanism ≥ 290-500 mOsm/kg ≥ 501 mOsm/kg of intracellular fluid into interstitial space Ampicillin Mannitol Lipids Dextrose ≥ 10% TPN, see hyperosmolar agents table Agents Metronidazole Calcium Chloride 10% Nafcillin Sodium Bicarbonate ≥ 8.4 mEq Phenytoin Potassium Chloride ≥ 2 mEq/mL Specific Cold compress, hyaluronidase, and Vancomycin Sodium Chloride ≥ 3% Management potential fasciotomy

Banks V, Shaw A. NHS. (2019). Vol 1. Le A, et al. Annals of Pharma (2014) 48(7) 870‐86. Le A, et al. Annals of Pharma (2014) 48(7) 870‐86. Plum M et al. Pharm and Thera (2017) 42(9) 581‐85.

What if my extravasated drug is acidic and What if my extravasated drug is alkali and hyperosmolar? hyperosmolar?

Vancomycin Phenytoin

pH 2.5‐ Warm compress pH 12 Warm compress 4.5

~350 Do not administer Conc. Hyaluronidase, if mOsm/kg hyaluronidase Dependent refractory

Hurst S, et al. Dimens Crit Care Nurs (2004) 23, 125‐8. Hurst S, et al. Dimens Crit Care Nurs (2004) 23, 125‐8. Le A, et al. Annals of Pharma (2014) 48(7) 870‐86. Le A, et al. Annals of Pharma (2014) 48(7) 870‐86. Plum M et al. Pharm and Thera (2017) 42(9) 581‐85 Plum M et al. Pharm and Thera (2017) 42(9) 581‐85

Extravasation of Vinca alkaloids for Hyperosmolar and Vinca Alkaloids - Hyaluronidase Direct cellular damage, may have Mechanism delayed erythema but intense pain Modifies permeability of connective tissue increasing distribution and absorption

Vinblastine, vincristine, and Epithelial cells Agents Hyaluronidase vinorelbine Basement Hyaluronic acid membrane Chondroitin sulphate

Specific Circulation Management Warm compress, Hyaluronidase

Ener R.A., et al. Annals of Oncol (2004) 15; 858‐62. Kreidieh FY et al. WJCO. (2016) 7:1. Le A, et al. Annals of Pharma (2014) 48(7) 870‐86.

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Antidote for Hyperosmolar and Vinca Alkaloids - Preparation of Antidotes – Hyaluronidase Hyaluronidase Preparation Adult: 150 units/mL in 5 separate 0.2 mL subcutaneous injections Differs by Product Pediatric: 15 units/mL in 5 separate 0.2 mL subcutaneous injections

Subcutaneous – Administer at leading edge of extravasation site Vitrase Hylenex Be careful of product used, preparation instructions differ

150 unit/mL = 15 unit/mL = 1 mL Administer as soon as possible within 60 minutes 150 unit/mL = use 15 unit/mL = 1 mL 0.75 mL solution (150 unit/mL solution as solution + NaCl + NaCl 0.9% 0.25 solution) + NaCl Vinca alkaloids use 1 mL for each 1 mL of extravasated drug provided 0.9% 9 mLs mL 0.9% 9 mLs

Hylenex recombinant (hyaluronidase human) prescribing info, Halozyme. Le A, et al. Annals of Pharma (2014) 48(7) 870‐86. Vitrase Ovine (hyaluronidase) prescribing info, ISTA.

Extravasation of Anthracyclines and Mitoxantrone Antidote for Anthracycline Agents + Mitoxantrone - Dexrazoxane Cellular uptake causes continuous Mechanism 1. Binds topoisomerase II and prevents formation of free radicals cycles of tissue damage 2. Binds free and bound iron to displace anthracycline‐iron complexes and reduce oxidative stress to cardiac tissue

Daunorubicin, Doxorubicin, Day 1: 1000 mg/m2 IV in 1000 mL NaCl 0.9% over 1‐2 hours Agents 2 Idarubicin, Mitomycin, Mitoxantrone Day 2: 1000 mg/m IV in 1000 mL NaCl 0.9% over 1‐2 hours Day 3: 500 mg/m2 IV in 1000 mL NaCl 0.9% over 1‐2 hours Use DMSO 99% only when Dexrazoxane on shortage or Give ASAP but within 6 hours of extravasation in opposite arm from extravasation Specific Cold compresses, Dexrazoxanecontraindicated OR Management Dimethyl sulfoxide (DMSO 99%) Remove compress 15 min before and after completing the infusion Reduce dose by 50% if CrCl < 40 mL/min

Ener R.A., et al. Annals of Oncol (2004) 15; 858‐62. Fidalgo P, et al. Annals of Oncol (2012) 23(7) 167‐73. Kreidieh FY et al. WJCO. (2016) 7:1. Kreidieh FY et al. WJCO. (2016) 7:1.

Antidote for Anthracycline Agents + Mitoxantrone – Extravasation of (some) Alkylating Agents Dimethyl Sulfoxide (DMSO) 99% Leads to direct tissue damage through 1. Increases permeability of tissue by vasodilation Mechanism the cross linking of double stranded DNA 2. Neutralizes free radicals

Cisplatin (≥ 0.4 mg/mL) and Adult/Pediatric: Apply DMSO 99% topically, covering twice the Agents affected area every 6 hours for 14 days Bendamustine

Give ASAP but within 10 minutes of extravasation Specific Cold compress, Saturate swab prior to application and do NOT use occlusive dressing Management May cause local irritation, redness, sensation of heat and garlic breath

Boulanger J, et al. Sup Care Canc (2015) 23: 1459‐71. Boulanger J, et al. Sup Care Canc (2015) 23: 1459‐71. Kreidieh FY et al. WJCO. (2016) 7:1. Wickham R, et al. Oncol Nurs Forum (2006) 33(6): 1732‐35.

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Antidote for Cisplatin and Bendamustine - Preparation of Antidotes – Sodium Thiosulfate Sodium Thiosulfate Preparation Differs by Prevents tissue damage by providing a substrate for alkylation in Concentration subcutaneous tissue

Inject 2 mL, of 1/6 molar solution, for every 100 mg of cisplatin extravasated OR 10% 25% Inject 2 mL for every 1 mg of bendamustine extravasated

Administer ASAP or within 1 hour of extravasation 1/6 molar = 4 1/6 molar = 1.6 Preparation varies dependent on concentration of solution mLs solution + mLs solution + Keep catheter in place to administer; may administer subcutaneously 6 mLs SWFI 8.4 mLs SWFI

Boulanger J, et al. Sup Care Canc (2015) 23: 1459‐71. Wickham R, et al. Oncol Nurs Forum (2006) 33(6): 1732‐35. Nithiodote (sodium thiosulfate) prescribing info, Cangene BioPharma.

Extravasation of Oxaliplatin Extravasation of Other Anti-Neoplastics

Longer duration of DNA inhibition which May lead to erythema, Mechanism Mechanism may lead to prolonged vesicant potential tenderness, and swelling

Docetaxel, Paclitaxel, Cabazitaxel, Agents Oxaliplatin Agents Ado‐trastuzumab, etc.

Specific Warm compress, Dexamethasone 8 mg Specific Cold compress, no specific Management IV or PO twice daily for up to 14 days Management antidote

Kennedy KG, et al. Clin Oncol. (2003) 15(5):237‐39. Kreidieh FY et al. WJCO. (2016) 7:1.

Follow-Up Management Additional Interventions Hyperbaric  Maintain communication in the outpatient setting Saline Surgical oxygen flush out debridement therapy  Plastic surgery consult if continuing symptoms

 Counsel patient on use of extremity after symptoms resolve Squeeze Liposuction  Counsel patient on specific antidote instructions and wound care technique

Goutos I et al. JHS (2014) 39E:08‐18. Goutos I et al. JHS (2014) 39E:08‐18.

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Storage of Antidotes Storage of Antidotes

Protect from Light Protect from Light • Vasopressors •Pharmacy/ •Pharmacy/ •Pharmacy •Pharmacy/ •Pharmacy administered Vasopressors Vasopressors storage only Oncology storage Only 99% •Various size administered administered • Multiple units • Room tubes of 2% •Reconstitute • Remember strength vials • Multiple temperature topical with 1 mL of to dilute available strength vials •Reagent Thiosulfate DMSO Terbutaline available ointment sterile further • Room grade Dexrazoxane Nitroglycerin temperature • Room chemical • Room Phentolamine • Room • Room temperature temperature temperature temperature available from biochemical

Sodium supplier

Goutos I et al. JHS (2014) 39E:08‐18. Goutos I et al. JHS (2014) 39E:08‐18.

Storage of Antidotes – Hyaluronidase Patient Case

KP is a 79 y.o. male with anaplastic T cell lymphoma admitted for right upper extremity (RUE) cellulitis after Stage 3 extravasation of while receiving his first cycle of •Store on • Preparation differsProtect between from Light products: BV‐CHP (brentuximab, cyclophosphamide, doxorubicin, and prednisone) therapy. Oncology PMH: PAD, depression, hearing loss, acid reflux, anxiety and Crohn’s disease units/ • Vitrase (ovine hyaluronidase solution) Pharmacy/ •Use 200 mg/2 mL product for Nurse noted at the time of discharge from clinic RUE bulging near PIV site. Patient went to Pediatric preparation the bathroom while Brentuximab was infusing and likely extravasated at this time. Although floors unsure which agent extravasated. •Protect from light •Refrigerate Hyaluronidase both Five days later KP presents with increased redness, swelling, and blistering despite elevating products • Hylenex (recombinant human and icing the site four times daily. Per plastic surgery consult the patient was started on hyaluronidase solution) intravenous antibiotics (cefepime and vancomycin) due to concern for cellulitis.

Hylenex recombinant (hyaluronidase human) prescribing info, Halozyme. Vitrase Ovine (hyaluronidase) prescribing info, ISTA.

Question #1 Question #2 Which of the following are considered risk factors for KP to Which agent in KP’s treatment regimen is extravasate? classified as a vesicant? A. Brentuximab A. Small, fragile, or mobile veins B. Prolonged infusions (≥30 minutes or continuous) B. Doxorubicin C. Impaired circulation C. Cyclophosphamide D. Communication difficulty D. Prednisone E. Multiple courses of intravenous therapy F. All of the above

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Question #3 Question #4 Please match the extravasated agent to its appropriate List in order the appropriate steps for the management of KP’s extravasation (assume doxorubicin was the most likely agent). pharmacologic management. A. Withdraw blood to remove extravasated drug. Extravasated Agents Pharmacologic Management B. Administer dexrazoxane.  Doxorubicin  Sodium thiosulfate C. Apply dry cold compresses for 15 minutes every 6 hours.  Phenytoin  Hyaluronidase D. Remove infusion catheter or needle.  Potassium  Dexrazoxane E. Inform provider of extravasation.  Bendamustine  Phentolamine F. Delineate the affected area with a marker on the patient’s skin.  Brentuximab  No Specific Antidote G. Stop the infusion.  Norepinephrine

Question #5 Question #6 What is the appropriate storage of each antidote? SP23 Describe the mechanism of action of dexrazoxane? I. Binds topoisomerase II and prevents the formation of free radicals A. DMSO 99% – Room Temperature II. Modifies permeability of connective tissue increasing distribution and absorption B. Dexrazoxane – Room Temperature III. Binds free and bound iron to displace anthracycline-iron complexes and reduce oxidative stress to cardiac tissue C. Sodium Thiosulfate – Room Temperature A. I & II D. Phentolamine – Room Temperature B. I & III E. Hyaluronidase – Refrigerator C. All of the above F. All of the above

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