Joseph Rannazzisi
Deputy Assistant
Administrator
Office of Diversion Control
I	
  have	
  no	
  financial	
  rela.onships	
  to	
  disclose	
  	
  
and	
  
I	
  will	
  not	
  discuss	
  off-­‐label	
 ...
1.  Iden.fy	
  the	
  pharmacological	
  proper.es	
  of	
  
Zohydro™	
  ER.	
  	
  
2.  Outline	
  approaches	
  law	
  e...
  Background	
  of	
  opioid	
  use	
  and	
  abuse	
  –Scope	
  of	
  the	
  problem	
  
  Describe	
  the	
  hydrocodo...
Outline
Hydrocodone	
  historical	
  perspec.ve	
  
Background	
  on	
  Zohydro™	
  ER	
  
 Pharmacology	
  
 Indicated	...
INCB: Availability of opioids* for pain management (2010-2012 average)
(Consumption in defined daily doses for statistical...
Drug Overdose Mortality Rates
per 100,000 People 1999
Source:	
  Trust	
  for	
  America’s	
  Health,	
  	
  
www.healthya...
Source:	
  Trust	
  for	
  America’s	
  Health,	
  	
  
www.healthyamericans.org.	
  	
  “Prescrip.on	
  Drug	
  
Abuse:	
...
U.S. Rates of Opioid Overdose Deaths, Sales,
and Treatment Admissions, 1999-2010
Source:	
  Na.onal	
  Vital	
  Sta.s.cs	
...
Hydrocodone
Aggregate Production Quota History
16,314	
  
20,208	
  
21,417	
  
23,825	
  
25,702	
  
30,622	
  
34,000	
 ...
Worldwide Hydrocodone Use
SOURCE:	
  UN	
  Interna.onal	
  Narco.cs	
  Control	
  Board	
  
website.	
  Es.mated	
  	
  Wo...
Worldwide Hydrocodone Use
 Of the 20 Countries that reported an estimated needs
requirement for hydrocodone at one kilogr...
Top 10 List
SOURCE:	
  UN	
  Interna.onal	
  Narco.cs	
  Control	
  Board	
  
website.	
  Es.mated	
  	
  World	
  Require...
Most commonly prescribed
prescription medicine?
Hydrocodone/acetaminophen
U.S.	
  Drug	
  Enforcement	
  Administra.on	
  ...
Current FDA-approved hydrocodone-containing
products on the U.S. market (as of January, 2014)
U.S.	
  Drug	
  Enforcement	...
Top Five Prescription Drugs Sold in the U.S.
(2008-2011)
U.S.	
  Drug	
  Enforcement	
  Administra.on	
  
	
  Office	
  of	
...
Top 25 U.S. Pharmaceuticals by
Dispensed Prescriptions*
Source:	
  IMS	
  Health,	
  Na.onal	
  Prescrip.on	
  Audit	
  
U...
U.S.	
  Drug	
  Enforcement	
  Administra.on	
  
	
  Office	
  of	
  Diversion	
  Control	
  	
  	
  	
  
State Ranking* - H...
State Ranking* - Hydrocodone
January – September 2013
U.S.	
  Drug	
  Enforcement	
  Administra.on	
  
	
  Office	
  of	
  D...
Hydrocodone Combinations
CSA	
  defines	
  hydrocodone	
  substance	
  as	
  Schedule	
  II,	
  while	
  
its	
  combina.on...
  DEA	
  receives	
  a	
  pe..on	
  from	
  an	
  interested	
  party	
  (proceedings	
  may	
  
also	
  be	
  ini.ated	
...
Schedule II
  The	
  drug	
  or	
  other	
  substance	
  has	
  a	
  high	
  poten.al	
  for	
  abuse	
  	
  
  The	
  d...
NFLIS Cases
(Federal, State, and Local)
*2012	
  data	
  is	
  s.ll	
  being	
  submi^ed,	
  
data	
  queried	
  on	
  1/2...
U.S.	
  Drug	
  Enforcement	
  Administra.on	
  
	
  Office	
  of	
  Diversion	
  Control	
  	
  	
  	
  
How Supplied
Strength	
   Image	
   Capsule	
  color(s)	
   Capsule	
  Text	
   NDC	
  Number	
  
10	
  mg	
   White	
  op...
ZohydroTM ER Formulation
Mul.-­‐par.culate	
  formula.on	
  of	
  coated	
  carrier	
  beads	
  in	
  hard	
  
gela.n	
  c...
Alkermes SODAS® (Spheroidal Oral
Drug Absorption System) Technology
A	
  schema.c	
  representa.on	
  of	
  SODAS®	
  mul....
Background
OxyConIn®	
  (oxycodone)	
  vs.	
  Zohydro™	
  ER	
  (hydrocodone)	
  
– SimilariIes:	
  
•  High-­‐dose,	
  ex...
Dosing Data for Clinically
Employed Opioid Analgesics
Source: Goodman and Gilman’s The
Pharmacological Basis of Therapeuti...
Currently Marketed
Hydrocodone Products, U.S. only
Tabletscapsulesolu.on	
  (hydrocodone	
  +	
  acetaminophen
ibuprofen)	...
Background
U.S.	
  Drug	
  Enforcement	
  Administra.on	
  
	
  Office	
  of	
  Diversion	
  Control	
  	
  	
  	
  
Meeting of the Anesthetic and Analgesic
Drug Products Advisory Committee
(AADPAC)
Date:	
  Dec.	
  7,	
  2012	
  
Commi^ee...
Zohydro™ ER Pharmacology
Zohydro™	
  ER,	
  extended	
  release	
  capsules	
  contain	
  a	
  higher	
  
amount	
  of	
  ...
Indicated Use
Zohydro™	
  ER	
  is	
  indicated	
  for	
  the	
  management	
  of	
  pain,	
  severe	
  
enough	
  to	
  r...
Potential for Abuse
Like	
  other	
  opioids,	
  hydrocodone	
  has	
  high	
  abuse	
  and	
  
dependence	
  poten.al	
  ...
Toxicity
Zohydro™	
  ER	
  contains	
  high	
  amounts	
  of	
  hydrocodone	
  
Use	
  in	
  opioid	
  non-­‐tolerant	
  p...
What is a Risk Evaluation and
Mitigation Strategy (REMS)?
REMS	
  is	
  a	
  strategy	
  to	
  manage	
  known	
  or	
  po...
Risk Mitigation Elements of the ER/LA Opioid
REMS and the ZohydroTM ER Safe Use Initiative
ER/LA	
  Opioid	
  REMS	
   Zoh...
Prescriber Components of ER/LA
Opioid Analgesic REMS
Train	
  (Educate	
  Yourself)	
  -­‐	
  Comple.on	
  of	
  a	
  REMS...
Zohydro™ ER Safe Use
Initiative
PaIent	
  IniIaIves	
  
  Pa.ent	
  Treatment	
  Kit	
  
  Web-­‐based	
  and	
  print	
...
Concerns
A^orney	
  Generals	
  from	
  28	
  States	
  sent	
  a	
  le^er	
  
to	
  FDA	
  Commissioner	
  regarding	
  t...
Concerns
Recently	
  a	
  coali.on	
  of	
  more	
  than	
  40	
  
healthcare,	
  consumer	
  and	
  addic.on	
  
treatmen...
Potential methods of Diversion
Medicine	
  Cabinet	
  	
  
Friends	
  
Street	
  sales	
  
Prescrip.on	
  Fraud	
  
Doctor...
Law Enforcement Action Plan
for Zohydro™ (hydrocodone bitartrate ER)
Learn	
  from	
  our	
  previous	
  mistakes	
  -­‐	
...
Review
Questions / Comments
Background	
  on	
  Zohydro™	
  ER	
  
–  Pharmacology	
  
–  Indicated	
  Use	
  
–  Poten.al...
U.S.	
  Drug	
  Enforcement	
  Administra.on	
  
	
  Office	
  of	
  Diversion	
  Control	
  	
  	
  	
  
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Law Enforcement: Impact of Zohydro™ ER - Joe Rannazzisi

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Len 7 rannazzisi

  1. 1. Joseph Rannazzisi Deputy Assistant Administrator Office of Diversion Control
  2. 2. I  have  no  financial  rela.onships  to  disclose     and   I  will  not  discuss  off-­‐label  use  and/or   inves.ga.onal  drug  use  in  my  presenta.on   Disclosure Statement U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  3. 3. 1.  Iden.fy  the  pharmacological  proper.es  of   Zohydro™  ER.     2.  Outline  approaches  law  enforcement  should   consider  to  reduce  the  poten.al  effects  of   abuse  and  diversion.     3.  Describe  poten.al  methods  of  abuse  and   diversion  of  Zohydro™  ER.     Learning Objectives U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  4. 4.   Background  of  opioid  use  and  abuse  –Scope  of  the  problem     Describe  the  hydrocodone  situa.on  pre  Zohydro™   (hydrocodone  bitartrate  ER)     Discuss  pharmacology  of  Zohydro™  (hydrocodone  bitartrate   ER)     Iden.fy  methods  of  pharmaceu.cal  diversion    and  discuss  how   the  pharmacist  can  prevent  diversion  in  the  retail  seQng     Discuss  law  enforcement  role  in  preven.ng  abuse  and   trafficking     Goals and Objectives U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  5. 5. Outline Hydrocodone  historical  perspec.ve   Background  on  Zohydro™  ER    Pharmacology    Indicated  Use    Poten.al  for  Abuse    Toxicity   Law  Enforcement  Involvement   Methods  of  Abuse  and  Diversion   Risk  Management  Plan  for  Zohydro™  ER   What  The  Future  Holds   Review  /  Ques.ons  /  Comments   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  6. 6. INCB: Availability of opioids* for pain management (2010-2012 average) (Consumption in defined daily doses for statistical purposes (S-DDD) per million inhabitants per day) U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control         Date  Prepared/  Source:  4/14/14,       h^p://www.incb.org/incb/en/narco.c-­‐drugs/Availability/availability.html  
  7. 7. Drug Overdose Mortality Rates per 100,000 People 1999 Source:  Trust  for  America’s  Health,     www.healthyamericans.org.    “Prescrip.on  Drug   Abuse:    Strategies  to  Stop  the  Epidemic  (2013)”   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  8. 8. Source:  Trust  for  America’s  Health,     www.healthyamericans.org.    “Prescrip.on  Drug   Abuse:    Strategies  to  Stop  the  Epidemic  (2013)”   Drug Overdose Mortality Rates per 100,000 People, 2010 U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  9. 9. U.S. Rates of Opioid Overdose Deaths, Sales, and Treatment Admissions, 1999-2010 Source:  Na.onal  Vital  Sta.s.cs  System  (NVSS),    DEA’s  Automa.on  of    Reports  and    Consolidated  Orders  System,  SAMHSA’s    Treatment  Episode  Data  Set   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  10. 10. Hydrocodone Aggregate Production Quota History 16,314   20,208   21,417   23,825   25,702   30,622   34,000   37,604   42,000   46,000   55,000   55,500   55,000   59,000   79,700   99,652   99,625   0   20,000   40,000   60,000   80,000   100,000   120,000   (in  kilograms)   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        Date  Prepared/  Source:  04/14/2014,  ODQ   Revised  APQ  
  11. 11. Worldwide Hydrocodone Use SOURCE:  UN  Interna.onal  Narco.cs  Control  Board   website.  Es.mated    World  Requirements  of   Narco.c  Drugs  in  grams  for  2014.  h^p:// www.incb.org  .  Accessed  April  14,  2014     U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  12. 12. Worldwide Hydrocodone Use  Of the 20 Countries that reported an estimated needs requirement for hydrocodone at one kilogram or more  8 countries reported an estimated need of 1 kilogram to 5 kilograms  4 countries reported an estimated need over 5 kilograms to 10 kilograms  8 countries reported an estimated need over 10 kilograms SOURCE:  UN  Interna.onal  Narco.cs  Control   Board  website.  Es.mated    World   Requirements  of  Narco.c  Drugs  in  grams  for   2014.  h^p://www.incb.org  .  Accessed  April   14,  2014     U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  13. 13. Top 10 List SOURCE:  UN  Interna.onal  Narco.cs  Control  Board   website.  Es.mated    World  Requirements  of  Narco.c   Drugs  in  grams  for  2014.  h^p://www.incb.org  .  Accessed   April  14,  2014     U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  14. 14. Most commonly prescribed prescription medicine? Hydrocodone/acetaminophen U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control         U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  15. 15. Current FDA-approved hydrocodone-containing products on the U.S. market (as of January, 2014) U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        Date  Prepared/  Source:   Drug Name and Brand Name HYDROCODONE BITARTRATE and ACETAMINOPHEN; ANEXSIA; LORTAB; NORCET; NORCO; ZYDONE Active Ingredient(s) • ACETAMINOPHEN; HYDROCODONE BITARTRATE Form(s) and Strength(s) Available CAPSULE; ORAL: 500MG; 5MG SOLUTION; ORAL: TABLET; ORAL: U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  16. 16. Top Five Prescription Drugs Sold in the U.S. (2008-2011) U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        Source:  IMS    Health,  Na.onal  Prescrip.on  Audit,  Updated  02/24/14   0   20   40   60   80   100   120   140   160   2008   2009   2010   2011   2012   Hydrocodone/   Paracetamol   Levothyroxine   Sodium   Lisinopril   Simvasta.n   Metoprolol      Millions  of   Prescrip.ons  
  17. 17. Top 25 U.S. Pharmaceuticals by Dispensed Prescriptions* Source:  IMS  Health,  Na.onal  Prescrip.on  Audit   Updated  March  22,  2013   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  18. 18. U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control         State Ranking* - Hydrocodone January – September 2013 Source:  Drug  Enforcement  Administra.on,  Office  of  Diversion  Control,     Pharmaceu.cal  Inves.ga.ons  Sec.on,  Targe.ng  and  Analysis  Unit     Most  current  ARCOS  informa.on  as  of  March  18,  2014  
  19. 19. State Ranking* - Hydrocodone January – September 2013 U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control         Source:  Drug  Enforcement  Administra.on,  Office  of  Diversion  Control,     Pharmaceu.cal  Inves.ga.ons  Sec.on,  Targe.ng  and  Analysis  Unit     Most  current  ARCOS  informa.on  as  of  March  18,  2014  
  20. 20. Hydrocodone Combinations CSA  defines  hydrocodone  substance  as  Schedule  II,  while   its  combina.on  products  as  Schedule  III.   DEA  has  received  a  pe..on  to  reschedule  CIII   hydrocodone  combina.on  products  to  CII.     In  2004,  DEA  completed  an  ini.al  review  forwarded  the   data  to  DHHS  with  a  request  for  scien.fic  and  medical   evalua.on  and  scheduling  recommenda.on.     In  2008,  HHS  provided  a  scien.fic  and  medical  evalua.on     In  2009,  DEA  sent  addi.onal  data  to  FDA/HHS  and   requested  a  scien.fic  and  medical  evalua.on.     U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  21. 21.   DEA  receives  a  pe..on  from  an  interested  party  (proceedings  may   also  be  ini.ated  at  the  request  of  the  AG  or  Secretary  of  HHS)     Pe..on  is  reviewed  and  accepted     DEA  conducts  ini.al  8-­‐factor  analysis  review     Documents  and  material  gathered  during  the  ini.al  review  and   analysis  of  pe..on  is  sent  to  HHS/FDA  with  a  request  for  a  scien.fic   and  medical    evalua.on  and  a  recommenda.on  as  to  whether  the   drug  should  be  controlled     The  recommenda.on  and  review  document  is  received  back  from   HHS/FDA       Procedures to control a substance U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  22. 22. Schedule II   The  drug  or  other  substance  has  a  high  poten.al  for  abuse       The  drug  or  other  substance  has  a  currently  accepted  medical  use   in  treatment  in  the  United  States    or  a  currently  accepted  medical   use  with  severe  restric.ons     Abuse  of  the  drug  or  other  substance  may  lead  to  severe   psychological  or  physical  dependence   Schedule III   The  drug  or  other  substance  has  a  poten.al  for  abuse  less  than   the  drugs  or  other  substances  in  schedules  I  or  II       The  drug  or  other  substance  has  a  currently  accepted  medical  use   in  treatment  in  the  United  States       Abuse  of  the  drug  or  other  substance  may  lead  to  moderate  or   low  physical  dependence  or  high  psychological  dependence   21  USC  812(b)(2),(3)   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  23. 23. NFLIS Cases (Federal, State, and Local) *2012  data  is  s.ll  being  submi^ed,   data  queried  on  1/22/2013  -­‐          5,000      10,000      15,000      20,000      25,000      30,000      35,000      40,000      45,000      50,000     2006   2007   2008   2009   2010   2011   2012   2013*   Number  of  Cases   MEPERIDINE   OXYMORPHONE   CODEINE   HYDROMORPHONE   METHADONE   MORPHINE   HYDROCODONE   OXYCODONE   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  24. 24. U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  25. 25. How Supplied Strength   Image   Capsule  color(s)   Capsule  Text   NDC  Number   10  mg   White  opaque   “Zogenix  10  mg”  in  black   ink   43376-­‐210-­‐10  100  ct  bo^les   15  mg   Light  green  and  white   opaque   “Zogenix  15  mg”  in  black   ink   43376-­‐215-­‐10  100  ct  bo^les   20  mg   Light  green  opaque   “Zogenix  20  mg”  in  black   ink   43376-­‐220-­‐10  100  ct  bo^les   30  mg   Dark  blue  and  white   opaque   “Zogenix  30  mg”  in  black   ink   43376-­‐230-­‐10  100  ct  bo^les   40  mg   Dark  brown  and  white   opaque   “Zogenix  40  mg”  in  black   ink   43376-­‐240-­‐10  100  ct  bo^les   50  mg   Dark  brown  opaque   “Zogenix  50  mg”  in  black   ink   43376-­‐250-­‐10  100  ct  bo^les  
  26. 26. ZohydroTM ER Formulation Mul.-­‐par.culate  formula.on  of  coated  carrier  beads  in  hard   gela.n  capsules   –  Single-­‐en.ty  Hydrocodone  bitartrate   –  Rate-­‐controlling  polymers   –  Drug  release  by  diffusion   Extended  release  delivered  by  SODAS®  technology   –  Example  of  SODAS®  technology  used  in  Ritalin®  LA     U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  27. 27. Alkermes SODAS® (Spheroidal Oral Drug Absorption System) Technology A  schema.c  representa.on  of  SODAS®  mul.layer  drug  delivery   technology  (adapted  from  Elan  drug  technologies)   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  28. 28. Background OxyConIn®  (oxycodone)  vs.  Zohydro™  ER  (hydrocodone)   – SimilariIes:   •  High-­‐dose,  extended  release  (delivery  system)   •  Schedule  II  opioids  (developed  from  opium)   •  High  abuse  and  dependence  poten.al   •  Indicated  for  the  management  of  pain  severe  enough  to   require  daily,  around-­‐the-­‐clock,  long  term  opioid  treatment   and  for  which  alterna.ve  treatment  op.ons  (e.g.  non-­‐ opioid  analgesics  or  immediate-­‐release  opioids)  are   inadequate   •  Used  in  condi.ons  requiring  extended  period  of      pain  relief   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  29. 29. Dosing Data for Clinically Employed Opioid Analgesics Source: Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 12th edition U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  30. 30. Currently Marketed Hydrocodone Products, U.S. only Tabletscapsulesolu.on  (hydrocodone  +  acetaminophen ibuprofen)   –  Hydrocodone  dosage:  2.5  mg,  5  mg,  7.5  mg,  and  10  mg     –  Product  Names:  Anexsia,  Lortab,  Norcet,  Norco,  Reprexain,  Vicoprofen,   Zydone       Solu.oncapsule  (hydrocodone  +  chloropheniramine pseudoephedrine)   –  Hydrocodone  dosage:  4  mg,  5  mg,  8  mg,  10  mg,  60  mg   –  Product  Names:    Renzira,  Tussi  Caps,  Tussinox,  Vituz,  Zutripro   Syrup  (hydrocodone  +  homatropine)   –  Hydrocodone  dosage:  1.5  mg/5  mL,  5  mg/5  mL   –  Product  Names:  Hycodan,  Tussigen   As  of  January  2014   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  31. 31. Background U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  32. 32. Meeting of the Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) Date:  Dec.  7,  2012   Commi^ee  was  asked  to  determine  whether  the  benefit-­‐risk   assessment  of  this  product  favors  its  approval  for  marke.ng.   The  commi^ee  is  comprised  of  authori.es  knowledgeable  in  the   fields  of  anesthesiology,  surgery,  epidemiology  or  sta.s.cs  and   related  special.es.   AADPAC  voted  2-­‐11  [with  1  absten.on]  against  the  approval  of   ZohydroTM  ER  (hydrocodone  bitartrate  extended-­‐release   capsules)   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  33. 33. Zohydro™ ER Pharmacology Zohydro™  ER,  extended  release  capsules  contain  a  higher   amount  of  pure  hydrocodone  dosages  compared  to  other   hydrocodone-­‐containing  products  as  immediate  release  tablets   (e.g.,  50  mg  vs.  10  mg)   Zohydro™  ER  is  a  Schedule  II  opioid   –  Other  Schedule  II  opioids  include  Fentanyl,  Oxycodone,  Methadone,   Morphine   Hydrocodone  is  approximately:   –  1  .mes  as  potent  as  oxycodone   –  1.5  .mes  as  potent  as  morphine   –  10  .mes  as  potent  as  codeine   The  principal  therapeu.c  ac.on  of  hydrocodone  is  analgesia.                       As  with  other  opioids,  hydrocodone  causes  respiratory   depression.   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  34. 34. Indicated Use Zohydro™  ER  is  indicated  for  the  management  of  pain,  severe   enough  to  require  daily,  around-­‐the-­‐clock,  long-­‐term  opioid   treatment  for  which  alterna.ve  treatment  op.ons  (e.g.  non-­‐ opioid  analgesics  or  immediate-­‐release  opioids)  are   inadequate   Dosage  strengths  and  administra.on   –  10,  15,  20,  30,  40,  50  mg   –  Twice-­‐daily  (q12h)  administra.on   Not  indicated   –  Acute  pain   –  PRN  analgesia   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  35. 35. Potential for Abuse Like  other  opioids,  hydrocodone  has  high  abuse  and   dependence  poten.al   Can  be  abused  in  a  manner  similar  to  other  opioids,   legal  or  illicit   Pa.ents  at  increased  risk  of  opioid  abuse  will   require  intensive  monitoring  for  signs  of  abuse  or   addic.on   DEA  was  able  to  extract  95%  or  more  of  the  ac.ve   drug  ingredient  by  grinding  the  capsule  contents,   and  dissolving  the  powder  in  water  or  common   solvents   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  36. 36. Toxicity Zohydro™  ER  contains  high  amounts  of  hydrocodone   Use  in  opioid  non-­‐tolerant  pa.ents  may  lead  to   overdose,  par.cularly  acute  and  fatal    respiratory   depression   –  Capsules  are  indicated  to  be  swallowed  whole   –  Breaking  of  capsules  and  crushing  beads   Co-­‐inges.on  of  alcoholic  beverages  may  result  in  fatal   plasma  hydrocodone  levels   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  37. 37. What is a Risk Evaluation and Mitigation Strategy (REMS)? REMS  is  a  strategy  to  manage  known  or  poten.al  serious  risks   associated  with  a  drug  product.   FDA  requires  a  REMS  for  extended-­‐release  and  long-­‐ac.ng  opioid   analgesics.   The  goal  of  the  REMS  is  to  reduce  serious  adverse  outcomes   resul.ng  from  inappropriate  prescribing,  misuse,  and  abuse  of  these   products.   Developed  by  the  manufacturer  and  approved  by  FDA   A  REMS  is  an  a^empt  to  balance  the  need  for  access  to  the  drug   with  the  risks  associated  with  its  use  and  is  product  specific   Typically  implemented  prior  to  the  drug’s  approval  and  as  a   condi.on  of  approval   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  38. 38. Risk Mitigation Elements of the ER/LA Opioid REMS and the ZohydroTM ER Safe Use Initiative ER/LA  Opioid  REMS   ZohydroTM  ER  Safe  Use  IniIaIve   Pa.ent  Ini.a.ves   •  Medica.on  guide   •  Counseling   •  Pa.ent  Treatment  Kit   •  Web-­‐based  and  print  educa.on   •  Opioid  disposal  program   •  Locking  bo^le  cap/lock  box   Prescriber  Ini.a.ves   •  REMS  educa.on   •  Safe  use  training   •  Risk  training   •  Targeted  prescriber  marke.ng   •  Prescriber  training  and  educa.on,  including   mentoring   •  Prescriber  took  kit   •  Pa.ent  selec.on  tools   •  Urine  drug  screening   •  Web-­‐based  and  print  educa.on   •  Clinical  tools   Pharmacist  Ini.a.ves   •  Pharmacist  brochure   •  Web-­‐based  and  print  educa.on   Distributor  Ini.a.ves   •  Distributor  starter  kit   Assessments   •  Prescriber  training   •  Quality  of  materials   •  HCP  awareness   •  Pa.ent  risk  understanding   •  Misuse,  abuse,  overdose,  addic.on,  death   rates   •  U.liza.on  pa^erns   •  Prescribing  behaviors   •  Prescribing  pa^erns   •  Surveillance  for  medical  and  non-­‐medical  use   •  Teenager  surveillance   •  Internet  and  media  surveillance   •  Safe  Use  Advisory  Board   •  Cash  claim  data   •  Pharmacovigilance  review   Reproduced  from:  Advisory  CommiXee  Briefing  Document  NDA  20-­‐2880   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  39. 39. Prescriber Components of ER/LA Opioid Analgesic REMS Train  (Educate  Yourself)  -­‐  Comple.on  of  a  REMS-­‐compliant  educa.on  program   offered  by  an  accredited  provider  of  con.nuing  educa.on  (CE)  for  your   discipline     Counsel  Your  Pa.ents  -­‐  Discuss  the  safe  use,  serious  risks,  storage,  and   disposal  of  ER/LA  opioid  analgesics  with  pa.ents  and  caregivers  every  .me   you  prescribe  these  medica.ons   Emphasize  Pa.ent  and  Caregiver  Understanding  of  Medica.on  Guide  -­‐  Stress   pa.ents  and  their  caregivers  the  importance  of  reading  the  Medica.on  Guide   that  they  will  receive  from  their  pharmacist  every  .me  an  ER/LA  opioid  is   dispensed  to  them   Consider  Using  Other  Tools  –  In  addi.on  to  pa.ent  counseling,  there  are   publicly  available  tools  to  improve  pa.ent,  household  and  community  safety,   as  well  as  compliance  with  condi.ons  of  treatment,  including  pa.ent-­‐ prescriber  agreement  (PPA)  and  risk  assessment  instruments   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  40. 40. Zohydro™ ER Safe Use Initiative PaIent  IniIaIves     Pa.ent  Treatment  Kit     Web-­‐based  and  print  educa.on     Opioid  disposal  program     Locking  bo^le  cap/lock  box   Prescriber  IniIaIves     Targeted  prescriber  marke.ng     Prescriber  training  and  educa.on,   including  mentoring     Prescriber  tool  kit     Pa.ent  selec.on  tools     Urine  drug  screening     Web-­‐based  and  print  educa.on     Clinical  tools   Pharmacist  IniIaIves     Pharmacist  brochure     Web-­‐based  and  print  educa.on   Distributor  IniIaIves     Distributor  Starter  Kit   Assessments     Surveillance  for  medical  and  non-­‐ medical  use     Teenager  surveillance     Internet  and  media  surveillance     Safe  Use  Advisory  Board     Cash  claim  data     Pharmacovigilance  review   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  41. 41. Concerns A^orney  Generals  from  28  States  sent  a  le^er   to  FDA  Commissioner  regarding  the  approval   of  ZohydroTM  ER   The  le^er  requests  FDA  reconsider  its   approval  or  set  a  .meline  for  ZohydroTM  ER  to   be  reformulated  to  be  abuse-­‐deterrent  while   working  with  other  federal  agencies  to  impose   restric.ons  on  how  ZohydroTM  ER  can  be   marketed  and  prescribed   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  42. 42. Concerns Recently  a  coali.on  of  more  than  40   healthcare,  consumer  and  addic.on   treatment  groups  urged  FDA  to  revoke   approval  of  ZohydroTM  ER   In  a  le^er  to  the  Secretary  of  Health  and   Human  Services,  eight  members  of  the   United  States  Congress  requested  HHS  to   reconsider  approval  of  ZohydroTM  ER   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  43. 43. Potential methods of Diversion Medicine  Cabinet     Friends   Street  sales   Prescrip.on  Fraud   Doctor  Shopping   Burglary/Robbery   Rogue  pain  clinic  –  Rogue  prac..oner   Rogue  pharmacy   Hospital/medical  staff   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  44. 44. Law Enforcement Action Plan for Zohydro™ (hydrocodone bitartrate ER) Learn  from  our  previous  mistakes  -­‐  OxyCon.n™  (oxycodone  ER)   Contact  MEs  and  emergency  room  physicians  to  ensure  they  are  educated  on  this   product.    Ensure  that  first  responders  are  educated  as  well.  Liaison  with  poison  control   centers   Educate  students,  teachers  ,  guidance  counselors  ,  civic  and  community  groups   Introduce  yourself  to  local  addic.on  treatment  providers  and  ask  them  to  report   recent  trends  they  are  observing   Request  ARCOS  and  PDMP  informa.on  as  appropriate.       Follow  up  all  leads  as  quickly  as  possible  concerning  inappropriate  health  prac..oner   prescribing     Work  with  DEA,  pharmacy/medical  boards  and  other  LE  agencies  at  the  first  hint  of   diversion  and  abuse  in  your  area.  Our  ability  to  network  and  share                                                 resources  will  greatly  assist  in  quickly  iden.fying  and  shuQng  down                                                                   a  threat   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  45. 45. Review Questions / Comments Background  on  Zohydro™  ER   –  Pharmacology   –  Indicated  Use   –  Poten.al  for  Abuse   –  Toxicity   DEA’s  Zohydro™  ER  Ac.on  Plan   Risk  Evalua.on  and  Mi.ga.on  Strategy  (REMS)   What  The  Future  Holds   U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        
  46. 46. U.S.  Drug  Enforcement  Administra.on    Office  of  Diversion  Control        

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