1. Break-through pain and it’s management Slavica Lahajnar Institut of oncology Ljubljana

2. Break-through pain – patient’s statement This sudden, strong pain brings me in anger and fear, my heart beats faster, I can not do anything. It takes from me the courage for life. Patient with breast cancer and bone metastases

3. Break-through pain – incidence and consequences a half to two thirds of patients with chronic cancer pain often unrecognized and untreated worsens quality of life economic burden Portenoy RK et al. Pain 1999;81(1–2):129–134. Caraceni A et al. Palliat Med 2004;18:177–183. Fortner BV et al. J Pain 2002;3:38–44.

4. Break-through pain - definition transitory exacerbation of pain with relatively stable and adequately controlled baseline pain spontaneous or provoked Davies et all. Eur J Pain 2009;13: 331-338 Zappetella. Curr Opin Support Palliat Care 2009; 3: 1-6

5. Break-through pain - characteristics Cause Site Anticipation Onset speed Duration Intensity Frequency in 80% same as in baseline pain in 75% one-sided in 50 % ~ in 3 min. ~ 30 min ≥ 7 (VAS 0-10) 4x/day Portenoy et all. J Pain 2006; 7: 583-591

6. Break-through pain - treatment Treatment of basic illness: RT, CT.. Treatment of basic illness: RT, CT.. Non-pharmacologic methods Non-pharmacologic methods Change of lifestyle Change of lifestyle Psyhological support Psyhological support Intervening procedures: neuroaxilar inf., nevroablation Intervening procedures: neuroaxilar inf., nevroablation Pharmacotherapy: opioids, non-opioids, additional drugs Pharmacotherapy: opioids, non-opioids, additional drugs Multimodal treatment Multimodal treatment

7. Break-through pain – treatment with opioids Treating cancer pain - ideal Treating cancer pain - current

8. Break-through pain - treatment morphine morphine Current treatment is NOT optimal Davies A. BMJ 2009; in press

9. Break-through pain - treatment fentanyl oral transmucosal (lollipop), buccal (tablet), sublingual (tablet), nasal (sprey), inhaling

10. Fentanyl – 40 years long history of analgetic activity 1968 intravenous fentanyl 1993 fentanyl patch 1998 oral transmucosal fentanyl citrate 2006 fentanyl tablets (USA) 2008 fentanyl tablets (EU) pure agonist of mu-opioid receptors 80-100 x more potent than morphine without active metabolites very lipophylic: fast membrane crossing into CNS

11. Abstral® - new innovative drug release technology Rapid disintegration... Muco-adhesion... Rapid absorption.

12. Fentanyl sublingual tablet (Abstral ® ) rapid absorption into blood, high biologic availability (without first-pass metabolism in liver) for opioid tolerant patients, already taking ≥ 60 mg of morphine or equivalent dose of other strong opioid adverse events like in other strong opioids

13. Abstral ® - titration ABSTRAL - significant improvement in pain intensity after 15 minutes, maximum dose of 800μg per episode of pain, patients should receive no more than 4 doses (8 tbl.)/day first tabletsecond tablet 100 µg 200 µg100 µg 300 µg100 µg 400 µg200 µg 600 µg200 µg 800 µg– Different strengths available, the packaging is colour-coded and the tablets are differently shaped. Abstral – Prescribing information

14. Conclusions multimodal treatment of break-through pain tretment with opioids, which have rapid onset of action sublingual fentanyl designed to match the temporal profile of breakthrough pain effective dose should be titrated Bredenburg S et al. Eur J Pharm Sci 2003;20:327–334.