OPIOIDs Adverse Drug Events Adverse Drug Reactions ARETE-ZOE, LLC | |

ARETE-ZOE, LLC | |

OVERDOSE DEATHS ARETE-ZOE, LLC | |

OVERDOSE DEATHS 2015 ARETE-ZOE, LLC | |

OPIOID DEATHS –ADRs Cumulative data ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

Adverse Drug Events An injury resulting from medical intervention related to a drug All harms that occur during medical care that are directly caused by the drug including medication errors, ADRs, allergic reactions, and overdoses. Medication error: “inappropriate use of a drug that may or may not result in harm;” such errors may occur during prescribing, transcribing, dispensing, administering, adherence, or monitoring of a drug. Adverse drug reaction (ADR): is “harms directly caused by a drug at normal doses”. ARETE-ZOE, LLC | | Medication Errors Adverse Drug Reactions Adverse Drug Events 1/21/2018 Data Source: National Action PlanNational Action Plan

ADE - Primary Concerns The three initial targets of the ADE Action Plan (2014) Anticoagulants: Bleeding Diabetes agents: Hypoglycemia Opioids: Accidental overdose, oversedation, respiratory depression Hospitalized patients experience 380,000 to 450,000 ADEs each year Two-thirds of admissions involved just four medication classes Majority attributable to anticoagulants and opioids Large percentage of ADEs preventable ARETE-ZOE, LLC | | Data Source: National Action PlanNational Action Plan

OPIOID PRESCRIPTIONS ARETE-ZOE, LLC | |

NUMBER OF BRANDS BY ACTIVE INGREDIENT ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

Top 200 Prescriptions RankActive ingredient Total Prescriptions Lisinopril115,508,573 2Levothyroxine99,992,248 3Metformin Hydrochloride86,125,658 4Simvastatin81,518,801 5Atorvastatin74,227,208 6Metoprolol72,320,918 7Omeprazole71,929,303 8Acetaminophen/Hydrocodone Bitartrate68,756,036 9Amlodipine Besylate63,722,510 10Hydrochlorothiazide50,428,398 26Tramadol Hydrochloride25,809,738 62Oxycodone13,888, Morphine7,172,178 ARETE-ZOE, LLC | | Data Source: ClinCalcClinCalc 1/21/2018

1/21/2018ARETE-ZOE, LLC | | National Public Health Emergency

Rx OPIOIDS SOURCES ARETE-ZOE, LLC | |

ATC Groups N NERVOUS SYSTEM N02 ANALGESICS N02A OPIOIDS N02AA Natural opium alkaloids N02AB Phenylpiperidine derivatives N02AC Diphenylpropylamine derivatives N02AD Benzomorphan derivatives N02AE Oripavine derivatives N02AF Morphinan derivatives N02AG Opioids in combination with antispasmodics N02AJ Opioids in combination with non-opioid analgesics N02AX Other opioidsNERVOUS SYSTEMANALGESICSOPIOIDSNatural opium alkaloidsPhenylpiperidine derivativesDiphenylpropylamine derivativesBenzomorphan derivativesOripavine derivativesMorphinan derivativesOpioids in combination with antispasmodicsOpioids in combination with non-opioid analgesicsOther opioids ARETE-ZOE, LLC | | Data Source: WHOWHO 1/21/2018

Natural Opium Alkaloids ARETE-ZOE, LLC | | ATC CodeACTIVE INGREDIENTDDD UnitRoute N02AA01 morphine 0.1 g O 30 mg P 30 mg R N02AA02 opium n/a N02AA03 hydromorphone 20 mg O 4 P 4 R N02AA04 nicomorphine 30 mg R 30 mg P 30 mg O N02AA05 oxycodone 75 mg O 30 mg P N02AA08 dihydrocodeine 0.15 g O N02AA10 papaveretum n/a N02AA51 morphine, combinations n/a N02AA55 oxycodone and naloxone 75 mg O N02AA58 dihydrocodeine, combinations n/a N02AA59 codeine, combinations excl. psycholeptics n/a N02AA79 codeine, combinations with psycholeptics n/a Data Source: WHOWHO 1/21/2018

MORPHINE ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

MORPHINE ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

OPIUM ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

HYDROMORPHONE ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

HYDROMORPHONE ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

OXYCODONE ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

OXYCODONE ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

OXYCODONE & ACETAMINOPHEN ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

DIHYDROCODEINE ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

CODEINE ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

CODEINE ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

PHENYLPIPERIDINES ATC code Name DDD Unit Route N02AB01 ketobemidone 50 mg O 50 mg P N02AB02 pethidine 0.4 g O g P g R N02AB03 fentanyl 1.2 mg TD 0.6 mg SL 0.6 mg N N02AB52 pethidine, combinations excl. psycholeptics N02AB72 pethidine, combinations with psycholeptics ARETE-ZOE, LLC | | Data Source: WHOWHO 1/21/2018

KETOBEMIDONE ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

FENTANYL ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

FENTANYL ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

DIPHENYLPPROPYLAMINES ATC code Name DDD Unit Route N02AC01 dextromoramide 20 mg O 20 mg P 40 mg R N02AC03 piritramide 45 mg P N02AC04 dextropropoxyphene 0.3 g O 0.2 g O N02AC05 bezitramide 15 mg O N02AC52 methadone, combinations excl. psycholeptics N02AC54 dextropropoxyphene, combinations excl. psycholeptics N02AC74 dextropropoxyphene, combinations with psycholeptics ARETE-ZOE, LLC | | Data Source: WHOWHO 1/21/2018

DEXTROMORAMIDE ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

Piritramide ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

METHADONE ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

METHADONE ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

BENZOMORPHANS ATC code Name DDD Unit Route N02AD01 pentazocine 0.2 g O g P N02AD02 phenazocine 3 mg P ARETE-ZOE, LLC | | Data Source: WHOWHO 1/21/2018

PENTAZOCINE ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

ORIPAVINES ATC code Name DDD Unit Route N02AE01 buprenorphine 1.2 mg P 1.2 mg SL 1.2 mg TD ARETE-ZOE, LLC | | Data Source: WHOWHO 1/21/2018

BUPRENORPHINE ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

BUPRENORPHINE ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

MORPHINANS ATC code Name DDD Unit Route N02AF01 butorphanol 12 mg P N02AF02 nalbuphine 80 mg P ARETE-ZOE, LLC | | Data Source: WHOWHO 1/21/2018

BUTORPHANOL ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

NALBUPHINE ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

OTHER OPIOIDS ATC code Name DDD Unit Route N02AX01 tilidine 0.2 g O g P N02AX02 tramadol 0.3 g O g P g R N02AX03 dezocine N02AX05 meptazinol 1.2 g O g P N02AX06 tapentadol 0.4 g O ARETE-ZOE, LLC | | Data Source: WHOWHO 1/21/2018

TILIDINE ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

TRAMADOL ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

TRAMADOL ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

DEZOCINE ARETE-ZOE, LLC | | Data Source: FAERSFAERS 1/21/2018

TAPENTADOL ARETE-ZOE, LLC | | 50 Data Source: FAERSFAERS 1/21/2018

FIDELITY OF IMPLEMETATION 1/21/2018ARETE-ZOE, LLC | | What makes pain the fifth vital sign? Where are those 14,600 deaths a year in FAERS? Did the reporting systems accurately capture trends in overdose, abuse and deaths? Do data from FAERS correspond with information from other sources? Is overdose death subject to expedited reporting in PV? How are signals detected in pharmacovigilance? How do PV reporting systems detect ADR prevalence, incidence and frequency? How do PV reporting systems detect changes in trends? How did the introduction of REMS for ER/LA affect the trends? How the data from FAERS compare to data from DEA? For what indications are Rx opioids typically prescribed? How do labelled indications compare to actual prescriptions? What will change with package level identifiers imposed by DSCSA?

ARETE-ZOE, as a consultancy, provides solutions to complex problems in the high stakes and high consequence environment of Global Pharmaceuticals, including clinical research, healthcare informatics, and public health. We blend established, Pharma sector methodologies, innovation, and adaptations/transfers from other sectors to identify and resolve consequential practices that pose risk and often result in avoidable patient casualty. However, we are specifically, not a patient advocacy group but believe in optimizing organizational effectiveness and that smart business is agile, competitive and profitable, while intrinsically safe, secure, and resilient. We work within a global context because transnational interests influence national circumstances and choices at point of prescription. ARETE-ZOE, provides full spectrum organizational and operational risk management consultancy. Our published materials provide a glimpse of some aspects of our services to demonstrate both knowledge and ongoing participation within the Pharmaceutical Industry. Our analysis and consultancy includes all channels of misuse, diversion, counterfeiting and illicit exploitation of pharmaceuticals, medical devices, and precursor chemicals. Our advisement is to manufactures, jurisdictional entities, insurers, legislators, litigators, patients, and health care providers. ​ This scope also frequently segues into the nexus of crime and terrorism as significant influencers that undermine sector integrity differentiated from other criminal activity. Obviously, vulnerability assessment, information collection management and intelligence production supporting decision-making for risk reduction and interventions are routinely within the scope of our services as well as design and implementation of operational control measures. ARETE-ZOE, LLC | |