“Breakthrough” in Chronic Non-Cancer Pain:
A Proposed Indication in Need of Further Study
Prepared for:
Joint Meeting of the Anesthetic and Life Support Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee
6 May 2008
John Markman MD
Breakthrough Pain in a Patient with Recurrent Osteosarcoma
The patient is a 36 year-old gentleman with osteosarcoma experiencing recurrent exacerbation of shooting left leg pain in the setting of relatively well-controlled baseline
pain taking around-the-clock opiods.
5
35
Cancer
Non Cancer
Portenoy RK et al. J of Pain 2006;7:583-91;Taylor DR et al. Pain Medicine 2007;8:281-88.
The Evidence Deficit
<
>
Under-Dosing Long Acting Opioid
Opioid ToleranceOpioid-Induced Hyperalgesia
End-Of-Dose Effect
Incident Pain
The Complexity of Breakthrough Pain in Cancer
Progression ofUnderlying Cancer
Dosing / Pharmacokinetic
Pharmacodynamic
Pain-Related
The patient is a 54 year-old man with osteoarthritis with recurrent exacerbations of left leg pain in the setting of
relatively well-controlled baseline pain taking around-the-clock opioids.
Transient Flare of Pain in a Patient with Chronic Knee Pain
2.4 flares “breakthrough”/day
24 years
21,024 rapid-acting opioid doses
Pain intensity and temporal pattern are
not sufficient to make an acceptable
risk benefit determination.
Under-Dosing Long-Acting Opioid
Opioid ToleranceOpioid-Induced Hyperalgesia
End-Of-Dose Effect
Incident Pain
Diverse Factors Modulate Pain Intensity
Diurnal Variation in Pain
Intensity
Dosing / Pharmacokinetic
Pharmacodynamic
Pain-Related
For Which Transitory Flares of Pain Is Rapid-Acting Opioid Treatment Indicated?
Odrcich M et al. Pain 2006;120:307-212.
Central Claims
The unmet need, definition, and scope of breakthrough phenomena in chronic non-cancer pain
lack sufficient characterization.
This evidence gap will prevent clinicians from safely weighing the risks of prescribing the fentanyl buccal tablet
for the proposed indication in opioid tolerant patients.
Five Key Areas of Further Research for theProposed New Indication
1. Assessment of Rapid-Acting Opioid Treatment Efficacy with Chronic Pain Endpoints
2. Demonstration of Durability of Treatment Effect and Resultant Tolerance Relative to Established Alternatives
3. Identification of Population Sub-Groups Most Likely to Benefit from Potent, Rapid-Acting Opioids and Those at Greatest Risk for Prescription Opioid Abuse
4. Evaluation of Abuse Liability Compared with Less Rapidly-Acting Analgesics
5. Prospective Demonstration that Risk Management Program Reduces Harm to Household Collaterals