Opioid Pain Management

1. Opioid Pain Management By Carla Alexander, 4th Year Pharmacy Student March 15, 2011

2. Obstacles With Geriatric Pain Control • Pain management in the elderly differs from that for younger people: • Clinical manifestations are often complex and multi-factorial • Underreport pain • Concurrent illnesses make pain evaluation and treatment more difficult • More likely to experience medication-related side effects and have higher potential for complications • However, despite these challenges, pain can usually be effectively managed in this age group.

3. Dosing Tips: • Elderly may see an increased sensitivity to analgesics • Start low and go slow • Reassess pain scale frequently • Monitor side effects • Consider renal and hepatic function as well as concurrent medications • Pain is dynamic • Consider IR dosing as well as scheduled • Treatment should be tailored to the level of pain

4. Nonpharmacological • Relaxation, refocus • Physical Manipulation (physiotherapy) • Thermal therapy (heating pad, ice packs) • Physical Stimulation (massage) • Behavioural (support groups)

5. Pharmalogical --Opioids • High alert medications • Heightened risk of causing significant harm if used in error • Morphine and Hydromorphone (Dilaudid) are the most frequent high alert medications to cause patient harm. • Dilaudid is 5x more potent than morphine • Serious adverse events • over-sedation, respiratory depression, seizures, myoclonus, death.

6. Note: not to be used for neuropathic pain

7. WHO Analgesic Ladder • Step #1: Non-opioid such as acetaminophen, NSAID • Step#2: Opioid such as codeine, oxycodone, tramadol (in combination with acetaminophen) • Percocet (oxycodone + acet.) • Tramacet (tramadol + acet.) • T#2, T#3 (codeine + acet.) • Step#3: Opioid such as Morphine, oxycodone, hydromorphone, fentanyl, methadone (used as monotherapy) • Note: • Steps 1 and 2 have a ceiling dose due to the combination with non-opioids (example: acetaminophen (4g/day)). • Step 3 has no ceiling dose • Must be on at least 60mg oral morphine equivalents for one week before started on fentanyl. • Adjunct treatment include: NSAIDS, antidepressants, anticonvulsants, dexamethasone

8. Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain Note: trial non-opioid options first (acetaminophen, NSAID)

9. Immediate and Sustained Release Opioids • Immediate Release (IR) • Duration 4-6 hrs • Used for acute pain “breakthrough” pain or when initiating someone on chronic therapy • Sustained Release (SR) • Usually lasts for 12 hrs • Up to 72 hrs for fentanyl patches • Unique once daily formulations • Morphine, hydromorphone, tramadol

10. Sustained Release Opioids • More consistent pain relief • More convenient for the patient • Dosing OD or BID • Do not crush, chew or dissolve SR products • Can lead to rapid absorption of the entire 12-24hr dose leading to sedation, respiratory depression and potentially fatal dose.

11. Codeine • 1/10th the potency of morphine • 200mg po codeine = 20mg po morphine • Increased risk of constipation & GI upset • Lower risk of overdose & addiction • Converted to morphine through CYP 2D6 metabolism in our body. • Some people are rapid metabolizers, therefore increased side effects because can convert faster • Some people do not have CYP 2D6 therefore no metabolism takes place, no morphine formed, no pain relief.

12. Codeine • Combination products with non-opioids • Acetaminophen (ex. T#1, #2, #3)- watch ceiling dose of 4g/day of acetaminophen when dosing • 3g/day limit with elderly? • Combination products also contain caffeine • IR: tablets, syrup, injectable (IM) • SR: tablets, can be halved on score line but patients must swallow half tablet intact • Exception: 50mg tablet cannot be halved • EDS criteria discussed later

13. Tramadol • Lower risk of addiction & abuse • Increased risk of seizures and nausea • Watch for patients with history of seizure or on concurrent medications that lower seizure threshold • Combination products • Tramacet(tramadol 37.5mg + acet. 325mg) max 8 tabs/day • IR: tablets- BID to QID • SR: tablets- daily • Note: none of the products are covered by SK Drug Plan

14. Oxycodone • 2x more potent than morphine • 10mg oxycodone po = 20mg morphine po • Equianalgesia with chronic dosing • Used for mild to moderate pain when in combination with non-opioid • Used for severe pain when used as single agent • Increased risk of abuse potential

15. Oxycodone • Combination products (not on SK formulary) • Percocet (acet. 325mg + oxycodone 5mg) • IR: tablets, suppository (not on SK formulary) • SR: tablets (oxycontin) • No parenteral formulation available

16. Morphine • Used as a standard for comparing potency • Available as: • IR: tablets, solution, suppository, injectable • SR: tablets, may be given rectally • Unique SR: 24 hr coverage • Kadian capsules- not interchangeable with other SR products • Should not be started in opioid naïve patients

17. Hydromorphone • 5x more potent than morphine • Available as: • IR: tablet, liquid, suppository, injectable • SR: capsule • Unique SR: 24hr coverage • Tablet • Not listed in SK formulary

18. Methadone • Potency is variable • The higher the dose of the original opioid, the more potent the methadone is. • Used for moderate to severe chronic pain as well as opioid addiction • Long acting and complicated dosing • Duration of pain relief: initially 4-8 hrs, increases to 24-48 hrs with repeated doses • Takes 3-5 days to reach plasma steady state

19. Methadone • Peak respiratory depressant effects occur later, and persist longer than its peak analgesic effects • Risk of QT prolongation • Many drug interactions • Available as: • Tablets, oral solution, powder (all which can be administered rectally)

20. Fentanyl Patches • Continue to be inappropriately prescribed, dispensed and administered to opioid naïve patients with acute pain. • Indicated for the management of persistent, moderate to severe chronic pain that can not be managed by other opioids. • Only to be used in patients: • who require continuous around the clock opioid analgesia for extended periods of time. • who are already receiving opioid therapy at a total daily dose of at least 60mg/day morphine equivalents for a minimun of 7 days (no longer considered opioid naïve).

21. Fentanyl Patches • 100x more potent than morphine! • 100mg po morphine/day = 25mcg fentanyl patch • Available as • Duragesic MAT and generic duragesic • Required EDS for SK drug plan (later discussed) • Parenteral solution (not on SK formulary)

22. Fentanyl Patch Advantages: • Less constipation, nausea, vomiting and itchiness compared to morphine • Very effective • Convenient dosing schedule (every 72 hrs) • No ceiling dose

23. Fentanyl Patch Contraindications: • Opioid naïve patients • Need to be on at least 60mg of morphine equivalents per day for a week or longer before initiating fentanyl patch. • Acute pain management • Takes 12-24hrs for analgesia to take effect • Unstable or poorly controlled pain • Pain controlled for at least 48 hrs

24. Fentanyl Patch Precautions: • Not appropriate for patients with: • Fever- heat activated absorptive system • Diaphoresis- difficult to adhere • Cachexia- lipophilic drug, won’t absorb • Morbid obesity- increased absorption, lose patch • Ascites

25. Fentanyl Patch • Continuous delivery of opioid for 72 hrs • Breakthrough” doses may still be required • Blood levels reach steady state between 12-24 hrs • Absorption is: • 47% complete after 24hrs • 88% complete after 48hrs • 94% complete after 72hrs • Therefore a used patch contains residual drug

26. Fentanyl Patch Application • Apply patch to a non-hairy area on chest, back, flank or upper arm • Avoid areas of excessive movement • If necessary, clip hair as close to skin as possible • Do not shave as this irritates skin and increases absorption • If patch falls off, discard it and put a new patch on at a different site. • If the gel contacts your skin, wash with water. Do not use soap as it can increase the drug’s ability to go through the skin

27. Application continued • Remove patch after 3 days • New patch should be applied to different site • Avoid sources of heat (hot tub, waterbeds, electric blankets) • Disposal: • Fold sticky sides together and flush down toilet or discard in safe place (sharps container)

28. Cutting Fentanyl Patches--NO • Recommended to not cut as this will disrupt the reservoir membrane and the entire dose will be available immediately. • Future: Duragesic-MAT patches may be cut, check with pharmacy first! • If only need ½ strength of patch use an occlusive barrier to cover half.

31. Routes of Administration • Potency varies by agent and route • Oral/rectal doses ≠ parenteral doses(IM, SC, IV) • Parenteral route is 2x more potent than oral/rectal route • morphine 5mg po = morphine 2.5mg SC

32. Oral Route • Onset 30-60mins • Advantages: • Preferred and easier to administer • Maintain patient independence • Portable • Less expensive • Disadvantages: • Caution with patients suffering form vomiting, difficulty swallowing or pain with swallowing

33. Unable to Swallow?? • IR formulations can be crushed • SR formulation CANNOT be crushed • Open capsule and sprinkle contents onto small amount of soft, cold food. • Ensure patient does not chew the spheres • Take within 30mins of sprinkling • Mouth should be rinsed to ensure all medication has been swallowed • Or switch formulation/route/opioid • Suppository, oral solution, injectable

34. Buccal / Sublingual Route • Onset varies depending on opioid • Use concentrated parenteral formulations • Advantages: • Rapid onset of action • Disadvantages: • Maximum of 2ml • Must retain volume in mouth for 10-15mins • Not all meds have good transmuscosal absorption (morphine) • Thrush, mucositis & dry mouth may impact absorption

35. Rectal Route • Onset similar to oral • Advantages: • Used if unable to swallow pills • Can administer controlled release oral opioids rectally • Disadvantages: • Not easy to administer • Patients feel uncomfortable • Limited commercial preparations • Avoid in patients with diarrhea, colostomy, hemorrhoids • Suppositories may be expelled before absorbed • High degree of inter-individual absorption variability

36. Intramuscular (IM) Route • Not recommended due to: • Painful, unreliable absorption • Nerve injury, sterile abscess formation and muscle/soft tissue fibrosis with chronic injections • 30-60min lag time until peak effect

37. Other Routes of Administration • Subcutaneous • Intravenous • Transdermal • Topical • Nebulized • Patient controlled analgesia (PCA) • Etc.

38. Breakthrough Pain • Defn: transient pain not controlled by around-the-clock analgesia • Use immediate release products • Used the same opioid for both scheduled and prn, when possible • Exception: fentanyl patch

39. Types of Breakthrough Pain • 1. Idiopathic • unpredictable, unknown cause • 2. End of dose failure • pain at the end of a scheduled interval • 3. Incident pain • Secondary to stimulus

40. Opioid Side Effects • Nausea/vomiting • Constipation • Laxative should always be used when on opioid • Dizziness/orthostatic hypotension • Respiratory depression • Urinary Retention • Improves within 1 week • Delirium/confusion • Usually resolves in 3-4 days • Sedation • Tolerance develops in 2-4 days • Pruritis • Dry mouth

41. Exceptional Drug Status • Codeine, controlled release tablet, 50mg, 100mg, 150mg, 200mg • For treatment of : • (a) Palliative and chronic pain patients as an alternative to ASA/codeine • combination products or acetaminophen/codeine combination products. • (b) Palliative and chronic pain patients as an alternative to regular release tablet when large doses are required. • In non-palliative patients, coverage will only be approved for a 6 month course of therapy, subject to review. • *Fentanyl Patch • For treatment of patients: • (a) Intolerant to, or unable to take, oral sustained-release strong opioids. • (b) As an alternative to subcutaneous narcotic infusion therapy. • *These brands of products have been approved as interchangeable.

42. References • Lecture Notes Pharmacy 557 • Saskatchewan Formulary • RX Files • Exceptional Drug Status Program • American Geriatrics Society • Therapeutic Choices, 5th edition

43. Questions?