1. Treatment: other opioids Disclaimer: This presentation contains information on the general principles of pain management. This presentation cannot account for individual variation among patients and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It is the responsibility of the treating physician, or health care provider, to determine the best course of treatment for the patient. Treat the Pain and its partners assume no responsibility for any injury or damage to persons or property arising out of or related to any use of these materials, or for any errors or omissions.

2. Objectives Review strong opioids that are used as alternatives to morphine 2

3. Other opioids Morphine is the standard opioid for moderate or severe pain and is the foundation of treatment for the highest rung of the WHO analgesic ladder – Low-dose morphine is also commonly the drug of choice for Step 2 treatment in adults Other strong opioids include: – Fentanyl – Methadone – Oxycodone – Hydromorphone Beating Pain, 2 nd Ed. APCA (2012).3

4. Fentanyl transdermal patch Fentanyl is often delivered as a transdermal patch. Drug permeates a membrane to enter the body through the skin surface Serum concentration rises gradually, levels off after 12-24 hours, and then reduces Patches are changed every 72 hours – Change at the same time of day, but place the patch at a different site Apply to clean, dry, undamaged, non-hairy, flat area of skin Beating Pain, 2 nd Ed. APCA (2012).4

5. Fentanyl transdermal patch Fentanyl should not be used to titrate the dose or to treat acute or breakthrough pain – Titrate to get the right dose using morphine, and then change to fentanyl using the conversions below – Provide morphine rescue doses for breakthrough pain Beating Pain, 2 nd Ed. APCA (2012).5 4 hourly morphine dose (mg) 24 hourly oral morphine dose Fentanyl patch size (mcg/hr) 5-2030-13025 25-35140-22050 40-50230-31075 55-65320-400100

6. Practicing conversions 6 4 hourly morphine dose (mg) 24 hourly oral morphine dose Fentanyl patch size (mcg/hr) 5-2030-13025 25-35140-22050 40-50230-31075 55-65320-400100 You have been titrating with morphine to relieve pain in a 56 year-old woman with cervical cancer. She is getting good relief with 10mg every four hours, but she is complaining of constipation that is not relieved by using a laxative, so you decide to move her to a fentanyl patch. Q: Which patch size should you use? Q: Should you prescribe an extra patch for breakthrough pain? 25mcg/hr No. Prescribe 10mg morphine for breakthrough pain

7. Advantages of fentanyl transdermal patch Less constipating than morphine May be useful for patients with renal failure as it does not have active metabolites May be useful in patients with stable pain control who have difficulty swallowing Beating Pain, 2 nd Ed. APCA (2012).7

8. Disadvantages of fentanyl transdermal patch It is usually significantly more expensive than morphine Major side effect is respiratory depression, which is dose- dependent – Half life after removal is 13-25 hours In patients with fever, absorption is increased because skin is more permeable – Monitor patients for opioid side effects Beating Pain, 2 nd Ed. APCA (2012).8

9. Methadone Synthetic opioid with complex pharmacology – Methadone remains in the body for a long time and drug accumulation may lead to toxicity Refer or seek an expert consult before initiating There is no evidence that methadone is superior to morphine as an analgesic May be useful in management of neuropathic pain or renal failure Used in drug rehabilitation as a substitute for heroin Beating Pain, 2 nd Ed. APCA (2012).9

10. Oxycodone Strong semi-synthetic opioid Similar therapeutic and side effect profile to morphine There is no maximum dose-ceiling is determined by side effects such as drowsiness and respiratory depression Onset of action is 20-30 minutes and duration of effect is 4 to 6 hours, so it is usually given 6-hourly Guide to Pain Management in Low-Resource Settings. IASP (2010)10

11. References African Palliative Care Association. Beating Pain: a pocketguide for pain management in Africa, 2nd Ed. [Internet]. 2012. Available from: http://www.africanpalliativecare.org/images/stories/pdf/beating_pain.pdf African Palliative Care Association. Using opioids to manage pain: a pocket guide for health professionals in Africa [Internet]. 2010. Available from: http://www.africanpalliativecare.org/images/stories/pdf/using_opiods.pdf Amery J, editor. Children’s Palliative Care in Africa [Internet]. 2009. Available from: http://www.icpcn.org/wp-content/uploads/2013/08/Childrens-Palliative-Care-in- Africa-Full-Text.pdf Kopf A, Patel N, editors. Guide to Pain Management in Low-Resource Settings [Internet]. 2010. Available from: http://www.iasp- pain.org/files/Content/ContentFolders/Publications2/FreeBooks/Guide_to_Pain_ Management_in_Low-Resource_Settings.pdf The Palliative Care Association of Uganda and the Uganda Ministry of Health. Introductory Palliative Care Course for Healthcare Professionals. 2013. 11