Combating Another Side of Smoke Cyanide Poisoning and How to Treat It Using Two 2.5-g Vials of CYANOKIT® 5 g (hydroxocobalamin for injection)

Combating Another Side of SmokeCombating Another Side of SmokeCyanide Poisoning and How to Treat It Using Two 2.5-g Vials of CYANOKIT® 5 g (hydroxocobalamin for injection)

Cyanide Poisoning and How to Treat It Using Two 2.5-g Vials of CYANOKIT® 5 g (hydroxocobalamin for injection)

Please see Important Safety Information on slide 3 and full Prescribing Information for CYANOKIT® on slide 35.

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Table of Contents

Identifying Cyanide Poisoning 5

CYANOKIT® 5 g (hydroxocobalamin for injection) 11

How to Administer CYANOKIT® 16

Storing and Stocking CYANOKIT® 22

Grant Information 27

Full Prescribing Information 35

IndicationCYANOKIT® (hydroxocobalamin for injection) 5 g for intravenous infusion is indicated for the treatment of known or suspected cyanide poisoning. If clinical suspicion of cyanide poisoning is high, CYANOKIT® should be administered without delay.Important Safety InformationCyanide poisoning may result from inhalation, ingestion, or dermal exposure. Prior to administration of CYANOKIT®, smoke-inhalation victims should be assessed for: exposure to fire or smoke in an enclosed area; presence of soot around the mouth, nose, or oropharynx; and altered mental status. In addition to CYANOKIT®, treatment of cyanide poisoning must include immediate attention to airway patency, adequacy of oxygenation and hydration, cardiovascular support, and management of any seizure activity.Use caution in the management of patients with known anaphylactic reactions to hydroxocobalamin or cyanocobalamin. Allergic reactions may include: anaphylaxis, chest tightness, edema, urticaria, pruritus, dyspnea, rash, and angioneurotic edema.

Please see full Prescribing Information for CYANOKIT®.

Indication and Important Safety Information

3

Important Safety Information (cont’d)

Substantial increases in blood pressure may occur following CYANOKIT® therapy. Usage may interfere with some clinical laboratory evaluations. Also, because of its deep red color, hydroxocobalamin may cause hemodialysis machines to shut down due to an erroneous detection of a “blood leak.” This should be considered before hemodialysis is initiated in patients treated with hydroxocobalamin. Due to potential photosensitivity, patients should avoid direct sun until erythema resolves.

CYANOKIT® is Pregnancy Category C and should be used during pregnancy only if the potential benefit justifies the potential risk. Safety and effectiveness of CYANOKIT® have not been established in pediatric patients. The most common adverse reactions (>5%) are transient and include chromaturia, erythema, rash (predominantly acneiform), increased blood pressure, nausea, headache, decreased lymphocyte percentage, and injection site reactions.


4

Identifying Cyanide Poisoning

A hidden threat in some closed-space fires

►Click for Table of Contents



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Cyanide Is an Often Unrecognized Danger in Some Closed-Space Fires

• Cyanide (CN) can be released by virtually any material containing carbon and nitrogen when burned under high temperature and low oxygen conditions2

• There is potential for CN toxicity due to the increased use of synthetic materials that produce CN during combustion in closed-space fires2,3

1. Hertzberg T, Blomqvist P, Dalene M, Skarping G. Particles and Isocyanates From Fires. Borås, Sweden: SP Swedish National Testing and Research Institute; 2005:1-51. 2. Agency for Toxic Substances and Disease Registry. Cyanide toxicity. Am Fam Physician.1993;48(1):107-114. 3. Alcorta R. Smoke inhalation & acute cyanide poisoning. In: Losavio K, ed. Smoke Inhalation & Hydrogen Cyanide Poisoning. San Diego, CA: JEMS Communications; 2004:6-17.

Common Building Materials Known to Release High Levels of Cyanide During Combustion*1

*Items pictured may not be accurate representations.

Important NoteNot all smoke inhalation victims will have cyanide poisoning and may present with burns, trauma, and exposure to other toxic substances making a diagnosis of cyanide poisoning particularly difficult.


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Difficult to Diagnose, Easy to Suspect

• Many symptoms of cyanide (CN) and carbon monoxide poisoning are common to both or very similar,1 and

• There is no diagnostic test to confirm or distinguish cyanide poisoning from carbon monoxide poisoning in the field1

• Should be suspected in any person exposed to smoke in a closed-space fire,1,3 and

• When suspicion of cyanide poisoning is high, an antidote should be considered for empiric treatment1,3

1. O'Brien DJ, Augustine J, Walsh DW. Cyanide exposure, smoke inhalation, and pre-hospital treatment: recognizing the signs and symptoms and available treatment options. In: Smoke: Cyanide and Carbon Monoxide: The Toxic Twins of Smoke Inhalation. Cyanide Poisoning Treatment Coalition: Indianapolis, IN: 2009:20-24. 2. Lawson-Smith P, Jansen EC, Hyldegaard O. Cyanide intoxication as part of smoke inhalation—a review on diagnosis and treatment from the emergency perspective. Scand J Trauma Resusc Emerg Med. 2011;19:1-5. 3. Eckstein M, Maniscalco PM. Focus on smoke inhalation—the most common cause of acute cyanide poisoning. Prehosp Disaster Med. 2006;21(2):s49-s55.

BECAUSE…

CYANIDE POISONING…

Moderate to Severe Poisoning Signs/Symptoms1,2

Distinguishing between cyanide and carbon monoxide poisoning can be difficult


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When to Suspect Cyanide Poisoning*1,2

Cyanide poisoning in smoke-inhalation victims should be suspected if the following manifestations are present*1,2:

Exposure to fire or smoke in an enclosed area

Soot around mouth, nose, or back of mouth

Altered mental status (eg, confusion, disorientation)

1. Eckstein M, Maniscalco PM. Focus on smoke inhalation—the most common cause of acute cyanide poisoning. Prehosp Disaster Med. 2006;21(2):s49-s55. 2. Cyanokit (two 2.5-g vials) [package insert]. Columbia, MD: Meridian Medical Technologies, Inc.; 2011.

Important NoteIn some settings, panic symptoms including tachypnea and vomiting may mimic early cyanide poisoning signs. The presence of altered mental status (eg, confusion and disorientation) and/or mydriasis is suggestive of true cyanide poisoning although these signs can occur with other toxic exposures as well.

*List may not be comprehensive.


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How Cyanide Affects Cellular Respiration

Cyanide may disable the body’s ability to use oxygen so it can be fatal despite the amount of oxygen available to the body.1,2

1. Cyanokit (two 2.5-g vials) [package insert]. Columbia, MD: Meridian Medical Technologies, Inc.; 2011. 2. Schnepp R. Where there's fire—there's smoke! In: Smoke: Cyanide and Carbon Monoxide: The Toxic Twins of Smoke Inhalation. Indianapolis, IN: Cyanide Poisoning Treatment Coalition; 2009:3-8.


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How Hydroxocobalamin Interacts With Cyanide

CYANOKIT® 5 g (hydroxocobalamin for injection) is the only cyanide antidote that contains hydroxocobalamin, which binds to cyanide, allowing the body to use oxygen again.1,2

1. Cyanokit (two 2.5-g vials) [package insert]. Columbia, MD: Meridian Medical Technologies, Inc.; 2011. 2. Schnepp R. Where there's fire—there's smoke! In: Smoke: Cyanide and Carbon Monoxide: The Toxic Twins of Smoke Inhalation. Indianapolis, IN: Cyanide Poisoning Treatment Coalition; 2009:3-8.

CYANOKIT® 5 g (hydroxocobalamin for injection)

FDA-approved for the treatment of known or suspected cyanide poisoning.




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Indication1

• CYANOKIT® 5 g (hydroxocobalamin for injection) is indicated for the treatment of known or suspected cyanide poisoning

• If clinical suspicion of cyanide poisoning is high, CYANOKIT® should be administered without delay

1. Cyanokit (two 2.5-g vials) [package insert]. Columbia, MD: Meridian Medical Technologies, Inc.; 2011.

Important Safety InformationIn addition to CYANOKIT®, treatment of cyanide poisoning must include immediate attention to airway patency, adequacy of oxygenation and hydration, cardiovascular support, and management of any seizure activity. Consideration should be given to decontamination measures based on the route of exposure.


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For Known or Suspected Cyanide Poisoning1

• It has been shown that the concentration of blood lactate increases proportionally with the severity of cyanide (CN) poisoning and that hydroxocobalamin treatment results in rapid resolution of CN-induced lactic acidemia1-3

• Studies have shown CYANOKIT® 5 g (hydroxocobalamin for injection) to be generally well-tolerated even in the absence of cyanide poisoning4-7

• Has been used in France since 1996 and in the U.S. since 2007 to treat suspected or known cyanide poisoning8

1. Lawson-Smith P, Jansen EC, Hyldegaard O. Cyanide intoxication as part of smoke inhalation—a review on diagnosis and treatment from the emergency perspective. Scand J Trauma Resusc Emerg Med. 2011;19:1-5. 2. Baud FJ, Borron SW, Mégarbane B, et al. Value of lactic acidosis in the assessment of the severity of acute cyanide poisoning. Crit Care Med. 2002;30(9):2044-2050. 3. Torres EC, Bustamante RS, Granizo EG, et al. Hydroxocobalamin and lactate concentration in patients suspected of having cyanuric acid poisoning related to smoke inhalation syndrome. Emergencias. 2010;22:9-14. 4. Cyanokit (two 2.5-g vials) [package insert]. Columbia, MD: Meridian Medical Technologies, Inc.; 2011. 5. Borron SW, Baud FJ, Barriot P, Imbert M, Bismuth C. Prospective study of hydroxocobalamin for acute cyanide poisoning in smoke inhalation. Ann Emerg Med. 2007;49(6):794-801. 6. Borron SW, Baud FJ, Mégarbane B, Bismuth C. Hydroxocobalamin for severe acute cyanide poisoning by ingestion or inhalation. Am J Emerg Med. 2007;25(5):551-558. 7. Fortin JL, Giocanti JP, Ruttimann M, Kowalski JJ. Prehospital administration of hydroxocobalamin for smoke inhalation-associated cyanide poisoning: 8 years of experience in the Paris Fire Brigade. Clin Toxicol (Phila). 2006;44(suppl 1):37-44. 8. Borron SW. Recognition and treatment of acute cyanide poisoning. J Emerg Nurs. 2006;32(4 suppl):s12-s18.

Important Safety InformationSubstantial increases in blood pressure may occur following CYANOKIT® therapy. Usage may interfere with some clinical laboratory evaluations. Also, because of its deep red color, hydroxocobalamin may cause hemodialysis machines to shut down due to an erroneous detection of a “blood leak.” This should be considered before hemodialysis is initiated in patients treated with hydroxocobalamin.


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Contents of CYANOKIT® 5 g

(hydroxocobalamin for injection)1



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Recommended Dosing1

• The starting dose of CYANOKIT® 5 g (hydroxocobalamin for injection) for adults is 5 g – Two 2.5-g vials

– Administer by intravenous (IV) infusion over 15 minutes, that is, 7.5 minutes per vial

• Depending upon the severity of the poisoning and the clinical response, a second dose of 5 g may be administered by IV infusion up to a total dose of 10 g

– The rate of infusion for a potential second dose may range from 15 minutes (for patients in extremis) to 2 hours, as clinically indicated

Important Safety InformationUse caution in the management of patients with known anaphylactic reactions to hydroxocobalamin or cyanocobalamin. Allergic reactions may include anaphylaxis, chest tightness, edema, urticaria, pruritus, dyspnea, rash, and angioneurotic edema. Substantial increases in blood pressure may occur following treatment with CYANOKIT®.


How to Administer CYANOKIT® 5 g

(hydroxocobalamin for injection) Prepare and administer in 4 steps.




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Step 1: RECONSTITUTE1

• Add 100 mL of 0.9% Sodium Chloride Injection to vial using sterile transfer spike

– 0.9% Sodium Chloride Injection is the recommended diluent

– Diluent is not included in the kit– Lactated Ringer's Solution and

5% Dextrose Injection have also been found to be compatible with hydroxocobalamin

• Fill to line, which represents 100 mL• Keep vial in upright position



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Step 2: MIX1

• Rock or rotate vial for 30 seconds to mix solution

• Do not shake



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Step 3: INFUSE FIRST VIAL1

• Use vented IV tubing

• Hang and infuse over 7.5 minutes



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Step 4: INFUSE SECOND VIAL1

• Repeat steps 1 and 2 before second infusion1. Reconstitute

2. Mix

• Use vented IV tubing

• Hang and infuse over 7.5 minutes for a total of 15 minutes



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Considerations During Administration1

• Inspect CYANOKIT® 5 g (hydroxocobalamin for injection) solution for particulate matter and color prior to administration

– Discard if particulate matter is present– Discard if solution is not dark red

• Use a separate IV line for infusion– A separate line is required as a number of drugs used in resuscitation efforts are incompatible

with CYANOKIT®• Use caution when administering other cyanide antidotes simultaneously with CYANOKIT®

– If the decision is made to administer another antidote, do not use the same IV line

Important Safety InformationIn addition to CYANOKIT®, treatment of cyanide poisoning must include immediate attention to airway patency, adequacy of oxygenation and hydration, cardiovascular support, and management of any seizure activity. Consideration should be given to decontamination measures based on the route of exposure.


Storing and Stocking CYANOKIT® 5 g

(hydroxocobalamin for injection)




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Storage of Lyophilized Form1

• CYANOKIT® 5 g (hydroxocobalamin for injection) should be stored at 25°C (77°F)

– Excursions are permitted to 15° to 30°C (59° to 86°F)

• CYANOKIT® may be exposed, during short periods, to temperature variations of usual transport, transport in the desert, and freezing/defrosting cycles

– Usual transport defined as 15 days subjected to temperatures ranging from 5° to 40°C (41° to 104°F)

– Transport in the desert defined as 4 days subjected to temperatures ranging from 5° to 60°C (41° to 140°F)

– Freezing/defrosting cycles defined as 15 days subjected to temperatures ranging from –20° to 40°C (–4° to 104°F)



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Storage of Reconstituted Drug Product1

• CYANOKIT® 5 g (hydroxocobalamin for injection) may be kept up to 6 hours at a temperature not exceeding 40°C (104°F)

• Do not freeze

• Product not used by 6 hours should be discarded



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Prehospital Stocking

• Reasons to consider stocking CYANOKIT® 5 g (hydroxocobalamin for injection) directly on first responder vehicles:

– Existence of cyanide in fire smoke from closed-space fires1

– Toxic threat cyanide presents to fire victims as well as firefighters1,2

Death can occur within minutes of exposure to moderate to high concentrations of cyanide 1

– Apparent low risk of causing harm by administering hydroxocobalamin for prehospital empiric treatment of smoke inhalation-associated cyanide poisoning1

1. Eckstein M, Maniscalco PM. Focus on smoke inhalation—the most common cause of acute cyanide poisoning. Prehosp Disaster Med. 2006;21(2):s49-s55. 2. Walsh DW, Eckstein M. Hydrogen cyanide in fire smoke: an underappreciated threat. Emerg Med Serv. 2004;33(10):160-163.

Important Safety InformationUse caution in the management of patients with known anaphylactic reactions to hydroxocobalamin or cyanocobalamin. Allergic reactions may include anaphylaxis, chest tightness, edema, urticaria, pruritus, dyspnea, rash, and angioneurotic edema. Substantial increases in blood pressure may occur following treatment with CYANOKIT®.


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Hospital Stocking

• It has been recommended by an expert panel of physicians for consensus guidelines for stocking antidotes that hydroxocobalamin be stocked in the emergency department1

– It must be available immediately because the administration of a cyanide antidote can resuscitate a patient only of it is given before irreversible injury develops1

1. Dart RC, Borron SW, Caravati EM, et al. Expert consensus guidelines for stocking of antidotes in hospitals that provide emergency care. Ann Emerg Med. 2009;54:386-394.

Important Safety InformationUsage may interfere with some clinical laboratory evaluations. Also, because of its deep red color, hydroxocobalamin may cause hemodialysis machines to shut down due to an erroneous detection of a “blood leak.” This should be considered before hemodialysis is initiated in patients treated with hydroxocobalamin. Due to potential photosensitivity, patients should avoid direct sun until erythema resolves.

Grant Information




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Grant Eligibility

• CYANOKIT® 5 g (hydroxocobalamin for injection) is approved on the Department of Homeland Security's Authorized Equipment List (AEL), making it eligible for the following grant programs1:

– State Homeland Security Program (SHSP)– Urban Area Security Initiative (UASI)– Metropolitan Medical Response System (MMRS)– Transit Security Grant Program (TSGP)

• Additional grant information and resources can be found at:– emsgrantshelp.com– firegrantshelp.com– usfa.dhs.gov/grants – fema.gov/firegrants/ – usfa.dhs.gov/fireservice/grants/afgp

1. Department of Homeland Security. Authorized equipment list. https://www.rkb.us/mel.cfm?subtypeid=549. Accessed September 2, 2011.

These Web sites are neither owned nor controlled by Meridian. Meridian is not responsible for the content or services of these sites.

http://www.dhs.gov/xgovt/grants/

http://www.fema.gov/government/grant/hsgp/index.shtm

http://www.fema.gov/government/grant/hsgp/index.shtm

http://www.fema.gov/government/grant/tsgp/index.shtm

http://emsgrantshelp.com/

http://firegrantshelp.com/

http://www.usfa.dhs.gov/grants

http://www.fema.gov/firegrants/



http://www.usfa.dhs.gov/fireservice/grants/afgp





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Questions?

For more information about CYANOKIT® 5 g (hydroxocobalamin for injection):

Call 1-800-638-8093

or

Visit CYANOKIT.com

For medical questions concerning CYANOKIT® call 1-800-438-1985, Monday through Friday, 8:00 am to 8:00 pm EST.

To report an adverse event or speak to a member of Pfizer U.S. Medical Information, call 1-800-438-1985.

http://www.cyanokit.com/

http://cyanokit.com/ordering.cfm


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SUSPECT IT.*

Cyanide poisoning in smoke-inhalation victims should be suspected if the following manifestations are present*1,2:

Exposure to fire or smoke in an enclosed area

Soot around mouth, nose, or back of mouth

Altered mental status (eg, confusion, disorientation)

Cyanide poisoning should be suspected.

1. Eckstein M, Maniscalco PM. Focus on smoke inhalation—the most common cause of acute cyanide poisoning. Prehosp Disaster Med. 2006;21(2):s49-s55. 2. Cyanokit (two 2.5-g vials) [package insert]. Columbia, MD: Meridian Medical Technologies, Inc.; 2011.

Cyanide Poisoning1,2

Important Safety InformationCyanide poisoning may result from inhalation, ingestion, or dermal exposure. Prior to administration of CYANOKIT®, smoke-inhalation victims should be assessed for: exposure to fire or smoke in an enclosed area; presence of soot around the mouth, nose, or oropharynx; and altered mental status. In addition to CYANOKIT®, treatment of cyanide poisoning must include immediate attention to airway patency, adequacy of oxygenation and hydration, cardiovascular support, and management of any seizure activity.

*List may not be comprehensive.


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TREAT IT.

Cyanide Poisoning1

Prepare and administer CYANOKIT® 5 g (hydroxocobalamin for injection) in 4 steps1:

1. Reconstitute 2. Mix 3. Infuse first vial

4. Infuse second vial (repeat steps 1 and 2 before second infusion)


IndicationCYANOKIT® (hydroxocobalamin for injection) 5 g for intravenous infusion is indicated for the treatment of known or suspected cyanide poisoning. If clinical suspicion of cyanide poisoning is high, CYANOKIT® should be administered without delay.Important Safety InformationCyanide poisoning may result from inhalation, ingestion, or dermal exposure. Prior to administration of CYANOKIT®, smoke-inhalation victims should be assessed for: exposure to fire or smoke in an enclosed area; presence of soot around the mouth, nose, or oropharynx; and altered mental status. In addition to CYANOKIT®, treatment of cyanide poisoning must include immediate attention to airway patency, adequacy of oxygenation and hydration, cardiovascular support, and management of any seizure activity.Use caution in the management of patients with known anaphylactic reactions to hydroxocobalamin or cyanocobalamin. Allergic reactions may include: anaphylaxis, chest tightness, edema, urticaria, pruritus, dyspnea, rash, and angioneurotic edema.

Indication and Important Safety Information

32



Important Safety Information (cont’d)

Substantial increases in blood pressure may occur following CYANOKIT® therapy. Usage may interfere with some clinical laboratory evaluations. Also, because of its deep red color, hydroxocobalamin may cause hemodialysis machines to shut down due to an erroneous detection of a “blood leak.” This should be considered before hemodialysis is initiated in patients treated with hydroxocobalamin. Due to potential photosensitivity, patients should avoid direct sun until erythema resolves. CYANOKIT® is Pregnancy Category C and should be used during pregnancy only if the potential benefit justifies the potential risk. Safety and effectiveness of CYANOKIT® have not been established in pediatric patients. The most common adverse reactions (>5%) are transient and include chromaturia, erythema, rash (predominantly acneiform), increased blood pressure, nausea, headache, decreased lymphocyte percentage, and injection site reactions.

Please see full Prescribing Information for CYANOKIT®.CYANOKIT® is a registered trademark of Merck Santé s.a.s., licensed by Meridian Medical Technologies™, Inc., a Pfizer company.

Copyright © 2011 Meridian Medical Technologies™, Inc., a Pfizer company. All rights reserved. CYK290629-01 10/2011

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Prescribing Information for CYANOKIT® 5 g

(hydroxocobalamin for injection)


Documents

Combating Another Side of Smoke Cyanide Poisoning and How to Treat It Using Two 2.5-g Vials of CYANOKIT® 5 g (hydroxocobalamin for injection)