Abuse Liability of Hydromorphone Extended Release Capsules

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Abuse Liability of Hydromorphone Extended Release
Capsules

• Silvia N. Calderon, Ph.D.
• Controlled Substance Staff
• Center for Drug Evaluation and Research
• Food and Drug Administration
• ALSDAC
• September 10, 2003

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Hydromorphone Formulations

• Immediate release tablets (Dilaudid 2, 4 and
  8 mg), injectable (1, 2, 4 and 10 mg/ml), oral
  solution (5 mg/5ml) and suppositories (3 mg) have
  been marketed in the United States for many years
• Extended release formulations marketed in the UK
  and Canada for once or twice a day use
• Palladone represents a new extended release
  formulation under FDA review

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Palladone CapsulesProposed

• Strengths 12 mg, 16 mg, 24 mg and 32 mg
• Boxed Warning For use only in opioid tolerant
  patients
• Indication For the management of chronic
  moderate to severe pain in patients requiring
  continuous around the clock opioid analgesia for
  an extended period of time
• Dosage Once a day

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Hydromorphone as Schedule II (CII)

• High abuse potential
• Highest level of control for an approved drug
• Prescriber and dispenser registration, separate
  record-keeping by dispenser, distribution order
  forms, no refills, manufacturing security and
  quotas, import and export permits

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abuse potential social and public health factors
Abuse Liability
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Hydromorphones Relative Potency

• Physiological Opioid Effects - analgesia, miosis,
  respiratory depression
• 4 times more potent than oxycodone and morphine
  (oral route)
• 6-7 times more potent than morphine (intravenous
  route)
• Subjective Opioid Effects - euphoria and drug
  liking
• 10 times more potent than morphine (oral or
  intravenous routes) (Jasinski et al., 1977 Hill
  and Zacny, 2000)

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History of Hydromorphone Abuse

• Hydromorphone abuse dates back to 1970s
• In 2002, DEA field offices reported that 4 mg
  hydromorphone tablets (Dilaudid) street price
  averaged 40/tablet

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Drug Abuse Related Deaths DAWN-Medical Examiners

• For 1999-2001 period
• 132 hydromorphone-related deaths 7.5
  deaths/100,000 Rx
• 1,272 oxycodone-related deaths 1.8
  deaths/100,000 Rx
• 6.1 deaths/100,000 Rx - oxycodone single entity
  products
• Rx Source IMS Health, National Prescription
  Audit PlusTM

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Limitations Deaths/Prescriptions

• These ratios are crude estimates
• DAWN medical examiners deaths do not represent
  national estimates
• DAWN medical examiner reports may include
  multiple drug mentions and rarely include brand
  names
• Sales data represent the whole U.S. market
• Denominators include all formulations of the drug

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Summary

• Based upon the data reviewed, hydromorphone
  appears to have higher abuse liability than other
  Schedule II opioids
• When compared to immediate release hydromorphone
  products currently available, Palladone has
  higher potential risks of misuse and overdose
  that might result in death
• Palladone poses significant risks of overdose in
  non-opioid tolerant patients or if misused and
  abused

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Conclusion

• Risk management programs should be designed to
  address the risks associated with high-dose
  opioid analgesic drug products, such as Palladone