1. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Cancer Pain

2. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria PAIN Causes  Chronic pain 30%  back pain 43-47%  headache 8-19%  other chronic disease 30%  Cancer pain  Patients undergoing therapy 30%  Patients with advanced disease 70%

3. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria CANCER PAIN Causes  tumor-associated  infiltration or compression of nerves  soft tissue  bones  paraneoplastic syndromes  Veinous thrombosis  neuralgia  treatment-related  chemotherapy (taxanes, vinca-alkaloids)  radiation therapy (fibrosis)  surgery (phantom-pain)

4. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria PAIN Visual analogue scale   1 2 3 4 5 6 7 8 9 10 time: 10.00 10mg Morapid 23.00 10mg Morapid

5. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria PAIN Acute/chronic pain Acute pain  warning function  localizable  correlates with pain intensity  short-lived  tolerable Chronic pain  no function  diffuse  influenced by psychologic factors  lasting > 6 months  intolerable

6. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria General principles of pain management acute chronic  sedationaimed not aimed  duration of action2-4 hours as long as possible  intervall of administrationas needed fixed  routes of administrationparenteral oral, transdermal, rectal  dosestandardized individual  adjuvantsnot recommended recommended

7. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria PAIN Analgesic medication  Non-opioid analgesics  nonsteroidal anti-inflammatory drugs  paracetamol  Opiod analgesics  step-2-opiods  step-3-opiods  Adjuvant analgesics  tricyclic antidepressants  spamolytics  anticonvulsants  corticosteroids  oral local anesthesics  bisphosphonates

8. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria non-opioids + adjuvants opioids for moderate pain + non-opioids + adjuvants opioids for severe pain + non-opioids + adjuvants Pain Persisting pain PAIN 3-step-ladder (WHO)

9. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria PAIN Routes of administration  non-invasive administration: preferred  oral  mucosal: sublingual, nasal, rectal  transdermal  invasive administration: dysphagia, after surgery,...  subcutaneous  intramuscular  intravenous  spinal

10. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria PAIN Effect of non-opioids analgesic antiphlogistic antipyretic spasmolytic metamizol++++ +++ + every 4h; max. daily dose 4000mg Agranulocytosis (rare!!) paracetamol +- ++ - every 4h; max. daily dose 4000mg hepatic toxicity diclofenac ++ ++++ - every 8h; max. daily dose 200mg; gastric ulcer

11. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria PAIN Side-effects of non-opioids  erosive gastritis  inhibition of platelet-aggregation  allergic reactions  agranulocytosis (rare!!)  liver-/renal-impairment  thrombocytopenia  pulmonary obstruction

12. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria PAIN Step -2- opioids  Tramadol  analgetic  max. daily dose 600mg/every 4-6h, or „ret.“/every12h  Codein  analgetic, antitussive  180mg/every 4h  Dihydrocodein  analgetic, antitussive  240mg/every 12h

13. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria PAIN Step -3- opioids  Morphine  Hydromorphone  Oxycodone  L-Methadon  Pethidine  Piritramid  Fentanyl transdermal system  Sufentanil  Buprenorphinepartial agonist Morphine-like agonists

14. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria PAIN Step -3- opioids  Morphine10-200mg ret. (12h) or 10-100mg (3-4h)  Hydromorphone4-16mg ret. (12h) or 1.3-2.6mg (3-4h)  Oxycodone20-30mg (3-6h)  L-Methadon  Pethidine  Piritramid  Fentanyl transdermal system 25-100  g/h (72h)  Sufentanil  Buprenorphine

15. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Cancer pain  Compression  Radio-, chemotherapy, steroids  Osteolytic bone metastases  Radio-, chemotherapy  Bisphosphonates, calcitonin, strontium  Osteoblastic bone metastases  Radio-, chemotherapy  Calcitonin, Radionuclides (strontium, samarium)  Neuropathic pain (taxanes.,..)  Anticonvulsants, antidepressants, opioids  Opioids, NSAR, metamizol, antidepressants,... 

16. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria PAIN Adjuvant medication  antidepressants  neuroleptics  spasmolytics  anticonvulsants  anxiolytics  steroids  biphosphonates  calcitonin

17. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria PAIN Approaches to cancer pain management radiation therapy chemotherapy neurosurgical interventions epidural catheter plexus blockade acupuncture

18. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria PAIN Rules for pain management regular administration according to a fixed schedule the schedule for administering morphine is determined by the duration of action individual dosage possible combination with non-opioids and/or adjuvants never combine step-2 and step-3 opioids avoid side-effects by using concomitant medication administration of opioids orally or transcutaneously

19. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Durogesic ® Why Fentanyl ?  Fentanyl has a selective, high affinity for the μ-opioid receptor  100 times more potent than morphine  highly lipid-soluble  low molecular weight suitable for transdermal administration

20. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Durogesic ® Schema of the delivery system Administration of TTS fentanyl every 72 hours provides a sustained serum fentanyl concentration more conveniently than intravenous or subcutaneous opioids. Fentanyl TTS is composed of 4 layers plus a removable protective lining. Occlusive backing Drug reservoir Release membrane Contact adhesive Protective peel strip

21. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Durogesic ® Dosage  Opioid-naíve patients  Conversion of patients from other opioids to fentanyl TTS

22. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Durogesic ® Opioid-naíve patients  Start on 25μg/h fentanyl TTS.  Maintainace of previous analgesic medication during the first 12-24 hours is recommended.  Adequate rapid-onset, short-action rescue medication, such as immediate release oral morphine, should be availbale.  The first titration should be at least 3 days after initial patch application.  Subsequent titration at 3- to 6-day intervals.  Upward titration increments should be based on the daily supplementary analgesia requirements; a ratio of 25μg/h fentanyl TTS to 90 mg/24 hours of oral morphine is recommended.

23. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Durogesic ® Conversion of patients from other opiods to fentanyl TTS

24. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Durogesic ® Dosage  Adequate rapid-onset, short-action rescue medication, such as immediate release oral morphine, should be available in all patients who receive long-acting opioids.  Not all patients will achieve acceptable analgesia on he 72-hour administration regimen; some may require more frequent (i.e. 48-hour) patch replacement.  The maximum number of patches is determined by the area of suitable skin available for application.

25. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Durogesic ® Increase absorption rate  Changes of skin - erythema,... - trauma (i.e. after shaving)  Changes of body temperature - fever (>39°C) - sauna - heat lamps - heat pads

26. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Durogesic ® Interaction with other agents - centrally acting drugs (sedatives, anaesthetics, hypnotics, transquillizer, skeletal muscle relaxants, other opioids,...): increase toxicity - partially antogonists ( Pentazozin, Buprenorphin ): reduces the effect of fentanyl TTS - Alcohol: increases sedation

27. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Conclusions Pain is a significant health problem currently undertreated. Opioids are the mainstay in pharmacological treatment of chronic, moderate-to-severe pain. Choosing an appropriate opioid and delivery route is important for optimal pain relief. Fentanyl TTS is clinically proven to be effective in treating different types of chronic non-cancer pain.