Analgesia New Drugs Transdermal Buccal Dr Pauline Kane

Analgesia: New Drugs Transdermal & Buccal Dr Pauline Kane Registrar in Palliative Medicine Beaumont Hospital 17 th 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 12 mcg/hr 45 mg oral morphine in 24 hours 25 mcg/hr 90 mg oral morphine in 24 hours 50 mcg/hr 180 mg oral morphine in 24 hours 75 mcg/hr 270 mg oral morphine in 24 hours 100 mcg/hr 360 mg 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 5 mcg/hr 7 mg oral morphine in 24 hours 10 mcg/hr 14 mg oral morphine in 24 hours 15 mcg/hr 21 mg oral morphine in 24 hours 20 mcg/hr 28 mg 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 35 mcg/hr 30 -60 mg oral morphine in 24 hours 52. 5 mcg/hr 60 -90 mg oral morphine in 24 hours 70 mcg/hr 90 -120 mg 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 5 mcg/hr patch = morphine 7 mg/24 hours orally Remember fentanyl 12 mcg/hr patch = morphine 40 mg/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 – CO 2 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 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

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 ≥ 60 mg/day Transdermal fentanyl ≥ 25 mcg/hr Oxycodone ≥ 30 mg/day Oral hydromorphone ≥ 6 mg/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 -180 cm 2 Continuous mucus in nose limits drug uptake to about 15 mins 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