1. Transdermal pain management
Yousuf Zafar, MD
Duke Cancer Care Research Program

2. Case 68yo woman with pancreatic cancer
Abdominal pain controlled with 30mg Oxycontin q12hr
Interested in decreasing number of pills, and heard about “pain patch”
Started on 25mcg transdermal fentanyl
Two days later, her pain is unbearable
Switched back to oral analgesics

3. How transdermal fentanyl works How to use transdermal fentanyl
Outline
How transdermal fentanyl works
How to use transdermal fentanyl
Moving beyond transdermal fentanyl

4. Mechanism of action
Muijsers RBR, Wagstaff AJ. Drugs 2001

5. Mechanism of action µ-opioid receptor
fentanyl
seletive opiods attenuate pain through mechanisms mediated by the mu receptor at the cellular level. The mu receptor acheivs this in 2 ways: decreasing intracellular cyclic AMP and inhibiting neuronal firing y decreasing membrane excitability

6. Advantages of transdermal pain management
Useful for patients who are unable to swallow or patients experiencing nausea/vomiting
Useful for patients with poor IV access
Constant plasma concentrations
First-pass metabolism is avoided
Muijsers RBR, Wagstaff AJ. Drugs 2001

7. First-pass effect

8. First-pass effect

9. Dosing transdermal fentanyl
Calculate previous 24hr analgesic requirements
Convert to oral morphine dose
Convert 24hr oral morphine dose to transdermal fentanyl dose
Titrate every 3 days until pain is controlled
May take up to 6 days to achieve steady-state concentrations
Continue breakthrough medication

10. Examples Patient 1: 30mg Oxycontin q12hr = 60mg/day
60mg x 1.5 = 90mg/day oral morphine
Oral morphine:transdermal fentanyl = 2:1
45mcg/hr fentanyl ≈ 50mcg/hr fentanyl q72hr
Skaer TL. Health Quality Life Outcomes 2006

11. Johns Hopkins Opioid Program
hopweb.org

12. Examples
Patient 2: 20mg/day oral hydromorphone, inadequate pain relief
Morphine:hydromorphone = 4:1
80mg/day oral morphine
2 morphine:1 fentanyl = 40mcg/hr
Inadequate pain control, so round up to 50mcg/hr

13. Patch application considerations
Clean, dry skin
Clipped (not shaved) hair
After placing, hold in place for 30 seconds
Rub the top of patch for 3 minutes
Alternate patch sites
Avoid heating pads/electric blankets as heat can increase rate of release
Skaer TL. Health Quality Life Outcomes 2006

14. Disadvantage to transdermal fentanyl use
Delayed onset of pain control.
Delay for dosage adjustments to take effect
Patch size and skin surface area availability
Muijsers RBR, Wagstaff AJ. Drugs 2001

15. Beyond fentanyl Compounded transdermals
Compounding – preparation of medication for a specific patient
Useful for preparing administration routes not readily available
Must be prepared by accredited compounding pharmacy
Latta KS. J Pain Pall Care Pharm 2002

16. Topical morphine Not extensively studied
Primarily used for cutaneous pain from tumor infiltrating skin
Painful ulcers
Limited stability in topical formulations
Donnelly S et al. Supp Care Cancer 2002

17. Transdermal lidocaine and amitriptyline
Amitriptyline: tricyclic antidepressant used for neuropathic pain
Study compared topical amitriptyline to topical lidocaine or placebo for neuropathic pain
35 patients
Topical lidocaine reduced pain intensity compared to placebo minimally
Amitriptyline was ineffective
Ho KY et al. Clin J Pain 2008

18. Potential transdermal compounded drugs
Topical hydromorphone
Swish-and-spit hydromorphone
Rectal lidocaine
Ativan, benadryl, Haldol, Reglan (ABHR) cream for nausea
Opionds achieve their effect b yactivitating membrane bound receptors. The mu-reeptor is the major site for most medically-relevant opiod narcotics, just as fentanyl. Mu

19. Fentanyl via transdermal iontophoresis
Patient-controlled transdermal system
Allows for delivery of charged molecules across intact skin using electric current
On-demand button delivers fentanyl
Studies have shown PCTS to be comparable to morphine PCA
No IV interruptions/alarms, catheter-related problems
Fewer gaps in analgesia
Polomano RC et al. J PeriAnesthesia Nurs 2008

20. Conclusions
Transdermal fentanyl is a useful alternative to PO/IV opioid analgesics
Monitor patients during titration period to ensure adequate pain control
Think outside the box – consult compounding pharmacist for patients with special pain control needs

21. Johns Hopkins opioid program – hopweb.org
Resources
Johns Hopkins opioid program – hopweb.org
Ken Latta, BS, RPh – Manager, Duke Compounding Facility