1. Dr Pauline Kane Registrar in Palliative Medicine Beaumont Hospital 17 th Sept 2009

2. Overview Transdermal opioid patches Used for stable chronic pain Frequently cancer pain is not stable pain Transmucosal opioids Short acting opioids Breakthrough cancer pain New drugs

3. Indications for Transdermal Opioid Patch Indication: Chronic pain Cannot take oral medications Nausea, Vomiting Mucositis Mouth ulcers Dysphagia Difficulty taking tablets Poor compliance Cognitive impairment Elderly

4. Transdermal route Avoidance of hepatic first pass metabolism Continuous pain relief Improves patient compliance with treatment Constant drug delivery providing a more stable plasma concentration without peaks Ease of administration despite nausea, vomiting and difficulties swallowing Absorption independent of food or fluid intake

6. Transdermal Patches Fentanyl patch Durogesic Matrifen Replace patch every 72 hours

7. Why fentanyl? Fentanyl citrate Absorbed easily through skin Low risk for skin irritation 100 times more potent than morphine Less constipating Less nausea and vomiting

8. Using Fentanyl Patch Apply patch to dry, flat, non-hairy skin on torso or upper arm Press firmly in place with the hand for 30 seconds to ensure good contact Replace patch every 72 hours Rotate patch sites Avoid same site for several days Wait 24 hours before evaluating pain relief

9. Fentanyl transdermal patch

10. Matrix Patch

11. Fentanyl Patch

12. Fentanyl transdermal patch Equivalence chart – Lasts 72 hours Fentanyl transdermal patchMorphine oral equivalent in 24 hours 12mcg/hr45mg oral morphine in 24 hours 25mcg/hr90mg oral morphine in 24 hours 50mcg/hr180mg oral morphine in 24 hours 75mcg/hr270mg oral morphine in 24 hours 100mcg/hr360mg oral morphine in 24 hours

13. Other users of fentanyl patches

14. Buprenorphine Transdermal Patch Butrans – lower strength opioid patch Replace patch every 7 days Transtec – higher strength opioid patch Replace patch every 3 days

15. Butrans Transdermal Patch Indication: Moderate pain unresponsive to non-opioid analgesics Apply to dry, non-hairy skin on torso or upper arm Replace patch every 7 days Rotate patch site Avoid using same area for 3 weeks Level of pain relief should not be assessed until patch is on for 3 days

16. Buprenorphine transdermal patch Equivalence chart: Lasts 7 days Buprenorphine transdermal patch Butrans Morphine oral equivalent in 24 hours 5mcg/hr7mg oral morphine in 24 hours 10mcg/hr14mg oral morphine in 24 hours 15mcg/hr21mg oral morphine in 24 hours 20mcg/hr28mg oral morphine in 24 hours

17. Transtec transdermal patch Indication: Moderate to severe pain Severe pain unresponsive to non-opioid analgesics Apply patch every 3 days Rotate patches Avoid same area for at least 6 days Only evaluate pain relief after patch is on for at least 24 hours

18. Buprenorphine transdermal patch Equivalence chart:Lasts 72 hours/3 days Buprenorphine transdermal patch Transtec Morphine oral equivalent in 24 hours 35mcg/hr30-60mg oral morphine in 24 hours 52.5mcg/hr60-90mg oral morphine in 24 hours 70mcg/hr90-120mg oral morphine in 24 hours

19. Buprenorphine transdermal patch Rates of absorption increase if skin is warm and dilated Safe to use in patients with renal impairment Not removed in haemodialysis Smaller starting doses are advised in hepatic impairment – highly protein bound drug More persistent erythema than with fentanyl patches Can cause pruritus

20. Transdermal Opioid Patches Important to remember that the patches contain a significant dose of morphine In patients who are opioid naïve Commence at lowest dose Remember buprenorphine 5mcg/hr patch = morphine 7mg/24 hours orally Remember fentanyl 12mcg/hr patch = morphine 40mg/24 hours orally Important to check daily that patch is still in place

21. Cautionary Use of Opioid Transdermal Patches COPD or other medical conditions predisposing to respiratory depression eg. Myasthenia gravis Elderly Cachetic Debilitated Susceptibility to hypercapnia – CO2 retention Raised intracranial pressure Impaired consciousness Coma Brain tumour Caution in bradyarrhythmias

22. Precautions Lack of appreciation that fentanyl is a strong opioid analgesic Inappropriate use for short-term, intermittent or post- operative pain in opioid naive patients Lack of patient education re safe use, storage & disposal Lack of awareness of signs of overdose Lack of awareness of increased absorption of opioid if skin under patch becomes vasodilated eg. Febrile patients, or by an external heat source eg. Electric blankets, sauna

23. Breakthrough Cancer Pain Incident pain – predictable Voluntary – onset with activity such as walking Involuntary – onset with activity such as coughing Procedural – onset related to intervention such as wound dressing Spontaneous pain - unpredictable

24. Breakthrough Cancer Pain Rapid onset Short duration 1 min to 2-3 hours

26. Fentanyl for breakthrough pain Indication: Patient has been on long acting opioid medication of the following strength for chronic cancer pain for at least a week; Oral morphine ≥ 60mg/day Transdermal fentanyl ≥ 25mcg/hr Oxycodone ≥ 30mg/day Oral hydromorphone ≥ 6mg/day An equianalgesic dose of another opioid Can commence on short acting opioid for breakthrough pain

27. Buccal Fentanyl: Actiq First transmucosal fentanyl preparation ‘Lozenge on a stick’ Fentanyl in hard sweet matrix Lozenge placed inside cheek and moved constantly up and down, and changed at intervals to other cheek Aim to consume lozenge in 15 mins

29. Transmucosal routes Buccal Effentora Place tablet in upper portion of buccal cavity above upper rear molar between cheek and gum Less permeable 75% is actually swallowed, reducing bioavailability Prolonged contact with mucosa and lozenge – problematic if inflamed mucosa

32. Transmucosal routes Sublingual Abstral Place tablet under tongue Rapid absorption Highly vascularised under the tongue Highly permeable High bioavailability

33. Transmucosal:Nasal route Nose has surface area of 150-180cm 2 Continuous mucus in nose limits drug uptake to about 15mins Rhinitis does not affect it Convenient to use in those with nausea, vomiting, dry mouth syndrome or mucositis Nasalfent Not reimbursed on GMS

35. Directions for Use Wait 4 hours between doses No food/drink while tablet in mouth Tablet disintegration takes 15-30 mins

36. Buccal and Sublingual Medication Do not suck/chew/swallow as this decreases plasma concentration Xerostomia – drink water prior to tablet placement Mouth ulcers Mucositis

37. Transmucosal fentanyl citrate 25% of dose is absorbed rapidly into systemic circulation Pain relief in 5-10 mins Remainder is swallowed or absorbed more slowly This is subject to hepatic first pass metabolism Only 1/3 of this amount is available systemically, 25% of the total dose

38. Fentanyl for Breakthrough Pain Use with caution Highly addictive Irish Medicines Board have 6 recorded cases of addiction to Actiq Only use for breakthrough pain caused by cancer

39. Conclusion Transdermal patches Indication: Chronic pain poorly controlled on non-opioid analgesics Start on lowest dose in opioid naïve patients Transmucosal route Indication: Only used for breakthrough pain secondary to cancer Highly addictive