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URL:https://www.deadiversion.usdoj.gov/...lert/2008/sannerud.pdf
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Title:Methadone Mortality Working Group November 2008
Description:Methadone Mortality Working Group November 2008
Keywords:methadone
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Body:1 1

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Methadone Mortality Working Group Methadone Mortality Working Group November 2008 November 2008

Dr. Christine Sannerud Dr. Christine Sannerud Office of Diversion Control Office of Diversion Control Drug Enforcement Administration Drug Enforcement Administration

METHADONE METHADONE

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Methadone Methadone Background Background Pharmacology Pharmacology Toxicity Toxicity Diversion, Toxic Exposures, Mortality data Diversion, Toxic Exposures, Mortality data Methadone Distribution (ARCOS data) Methadone Distribution (ARCOS data) Methadone Initiative Methadone Initiative

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Methadone Methadone - - Background Background In late 1940s In late 1940s - - marketed as pain reliever marketed as pain reliever ("analgesic"), but not extensively used. ("analgesic"), but not extensively used. In the 70s In the 70s - - shown to be effective as once shown to be effective as once - - daily medication for narcotic (opioid) daily medication for narcotic (opioid) addiction treatment. addiction treatment. In the US In the US - - Established as the standard for Established as the standard for treatment of narcotic (opioid) addiction. treatment of narcotic (opioid) addiction. From late 1990s From late 1990s - - methadone is being methadone is being increasingly used in pain management increasingly used in pain management

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Methadone Methadone - - an Opioid an Opioid Methadone belongs to pharmacological class called Methadone belongs to pharmacological class called " " Opioids Opioids " " Opioids Opioids are among the most potent analgesic are among the most potent analgesic drugs and are widely used drugs and are widely used Opioids Opioids are used in the management of acute and are used in the management of acute and cancer cancer - - related pain, and chronic non related pain, and chronic non - - cancer pain cancer pain

5 5 Opioids Opioids are of either are of either natural natural origin or origin or semisynthetic semisynthetic , or , or synthetic synthetic Natural Natural : e.g., Morphine from opium poppy : e.g., Morphine from opium poppy Semisynthetic Semisynthetic : e.g., hydrocodone (Vicodin), : e.g., hydrocodone (Vicodin), oxycodone (Percocet, OxyContin) oxycodone (Percocet, OxyContin) Synthetic Synthetic : e.g., : e.g., Methadone Methadone ( ( Methadose Methadose ) ) meperidine (Demerol), fentanyl ( meperidine (Demerol), fentanyl ( Duragesic)etc Duragesic)etc . .

Methadone Methadone - - An Opioid An Opioid

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Opioid Actions on Opioid Actions on Brain and Spinal Cord Brain and Spinal Cord Pain relief Pain relief : Acts on pain pathways in brain : Acts on pain pathways in brain and Spinal cord to relieve pain and Spinal cord to relieve pain Abuse and Addiction Abuse and Addiction : Acts on brain reward : Acts on brain reward pathways to produce " pathways to produce " high high " " Widely abused Widely abused

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0

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3000

3500

4000

1 9 6 5 1 9 6 9 1 9 7 3 1 9 7 7 1 9 8 1 1 9 8 5 1 9 8 9 1 9 9 3 1 9 9 7 2 0 0 1 2 0 0 5

Year

Numbers of New Users

(in Thousands)

Illicit Drugs Marijuana Pain Relievers Heroin

New Drug User Patterns New Drug User Patterns

Source: Prescribing Opioids for Chronic Pain, SAMHSA Source: Prescribing Opioids for Chronic Pain, SAMHSA - - CSAT: CSAT: Clinical Challenges in Prescribing Controlled Drugs Clinical Challenges in Prescribing Controlled Drugs

8 8

9 9

0

2

4

6

8

'90 '92 '94 '96 '98 '00 '02 '04 '06 0 100

200 300

400

500 600

Deaths/100,000 Opioid sales (mg/person)

Deaths per 100,000 related to unintentional Deaths per 100,000 related to unintentional overdose and annual sales of prescription overdose and annual sales of prescription opioid pain relievers by year, 1990 opioid pain relievers by year, 1990 - - 2006 2006 Source: Source: Paulozzi Paulozzi , CDC, Congressional Testimony, 2007 , CDC, Congressional Testimony, 2007

Crude Rate per 100,000

Crude Rate per 100,000

Sales in mg/person

Sales in mg/person

10 10 -100

0

100

200

300

400

500

2000 2001 2002 2003 2004 2005

All poisoning deaths Methadone

Other opioid

Other synthetic narcotics Cocaine

Heroin

Poisoning Deaths in the U.S Poisoning Deaths in the U.S % Increase % Increase

Source: CDC Source: CDC

% Increase in deaths

% Increase in deaths

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0

5

10

15

1999 2000 2001 2002 2003 2004 2005

Methadone Related Deaths Methadone Related Deaths (% of all Poisoning Deaths) (% of all Poisoning Deaths) Source: CDC Source: CDC

Methadone related deaths

Methadone related deaths

(% of all poisoning deaths

(% of all poisoning deaths

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Methadone Methadone - - Pharmacokinetics Pharmacokinetics Well absorbed (>80%) taken orally. Well absorbed (>80%) taken orally. Body eliminates methadone Body eliminates methadone (half (half - - time up to time up to 59 hrs) 59 hrs) slowly, while methadone's pain slowly, while methadone's pain relieving action lasts much shorter relieving action lasts much shorter (4 (4 - - 8 hrs) 8 hrs) . . Patient may feel the need to repeat dose at Patient may feel the need to repeat dose at intervals shorter intervals shorter than body can handle than body can handle Repeated dosing may lead to Repeated dosing may lead to accumulation accumulation in in the body and result in serious toxicity. the body and result in serious toxicity.

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Methadone Single Dose Effects Methadone Single Dose Effects

Ref: Nilsson MI, et al. Acta anaesth. scand 1982, Suppl 74, 66-69 Source: Resource Manual for CME course entitled "Prescribing Opioids for Chronic Pain" - Offered by the New England Chapters of the American Society of Addiction Medicine with support form CSAT, SAMHSA 5 10 15 20

T½ 5-6 hrs

T½ 20-40 hrs PAIN

ANALGESIA

INTOXICATON

Time (hours) Time (hours)

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Dosage intervals

Ref: Nilsson MI, et al. Acta anaesth. scand 1982, Suppl 74, 66-69 Source: Resource Manual for CME course entitled "Prescribing Opioids for Chronic Pain" - Offered by the New England Chapters of the American Society of Addiction Medicine with support form CSAT, SAMHSA ANALGESIA

PAIN

TOXICITY

Toxic Effects of Multiple Toxic Effects of Multiple Methadone Doses Methadone Doses

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Examples of Substances Examples of Substances - - May Enhance Methadone Effects May Enhance Methadone Effects These reduce elimination of methadone by body These reduce elimination of methadone by body Some antidepressant drugs Some antidepressant drugs - - e.g., Prozac, e.g., Prozac, Paxil Paxil , , Zoloft etc. Zoloft etc. Depressants (e.g., alcohol, anesthetics, Depressants (e.g., alcohol, anesthetics, benzos benzos , , some sedatives, other opioids) some sedatives, other opioids) Some drugs used for fungal infections Some drugs used for fungal infections Some antibiotics Some antibiotics - - e.g., e.g., Erythrocin Erythrocin Grapefruit juice Grapefruit juice

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Examples of Substances Examples of Substances - - May Reduce Methadone Effects May Reduce Methadone Effects These upon These upon prolonged prolonged exposure reduce methadone exposure reduce methadone effects effects Anti Anti - - seizure drugs seizure drugs - - Tegetrol Tegetrol , , Dilantin Dilantin Sedatives (barbiturates) Sedatives (barbiturates) - - e.g., e.g., Amytal Amytal , , fioricet fioricet , , fiorinal fiorinal , etc., , etc., HIV/AIDS drugs HIV/AIDS drugs Drugs used to treat Tuberculosis Drugs used to treat Tuberculosis Cocaine Cocaine Smoking Smoking

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Methadone Deaths Methadone Deaths - - Two Major Mechanisms Two Major Mechanisms Respiratory depression Respiratory depression Major hazard (Similar to other opioid analgesics) Major hazard (Similar to other opioid analgesics) Respiratory depression typically occurs later and Respiratory depression typically occurs later and persist longer than its peak analgesic effects persist longer than its peak analgesic effects Toxicity on heart Toxicity on heart Not shared by other opioids Not shared by other opioids Shared by Shared by LAAM LAAM , a previously marketed addiction , a previously marketed addiction treatment drug. treatment drug.