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Dr Pauline Kane Registrar in Palliative Medicine Beaumont Hospital 17th Sept 2009 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 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 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 Transdermal Patches Fentanyl patch  Durogesic  Matrifen  Replace patch every 72 hours 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 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 Fentanyl transdermal patch Matrix Patch Fentanyl Patch Fentanyl transdermal patch  Equivalence chart – Lasts 72 hours Fentanyl transdermal patch Morphine oral equivalent in 24 hours 12mcg/hr 45mg oral morphine in 24 hours 25mcg/hr 90mg oral morphine in 24 hours 50mcg/hr 180mg oral morphine in 24 hours 75mcg/hr 270mg oral morphine in 24 hours 100mcg/hr 360mg oral morphine in 24 hours Other users of fentanyl patches Buprenorphine Transdermal Patch  Butrans – lower strength opioid patch  Replace patch every 7 days  Transtec – higher strength opioid patch  Replace patch every 3 days 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 Buprenorphine transdermal patch Equivalence chart: Lasts 7 days Buprenorphine transdermal patch Butrans Morphine oral equivalent in 24 hours 5mcg/hr 7mg oral morphine in 24 hours 10mcg/hr 14mg oral morphine in 24 hours 15mcg/hr 21mg oral morphine in 24 hours 20mcg/hr 28mg oral morphine in 24 hours 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 Buprenorphine transdermal patch Equivalence chart:Lasts 72 hours/3 days Buprenorphine transdermal patch Transtec Morphine oral equivalent in 24 hours 35mcg/hr 30-60mg oral morphine in 24 hours 52.5mcg/hr 60-90mg oral morphine in 24 hours 70mcg/hr 90-120mg oral morphine in 24 hours 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 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 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 Precautions  Lack of appreciation that fentanyl is a strong opioid     analgesic Inappropriate use for short-term, intermittent or postoperative 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 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 Breakthrough Cancer Pain  Rapid onset  Short duration  1 min to 2-3 hours 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 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 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 Transmucosal routes  Sublingual  Abstral  Place tablet under tongue  Rapid absorption  Highly vascularised under the tongue  Highly permeable  High bioavailability Transmucosal:Nasal route  Nose has surface area of 150-180cm2  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 Directions for Use  Wait 4 hours between doses  No food/drink while tablet in mouth  Tablet disintegration takes 15-30 mins Buccal and Sublingual Medication  Do not suck/chew/swallow as this decreases plasma concentration  Xerostomia – drink water prior to tablet placement  Mouth ulcers  Mucositis 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 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 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