By Carla Alexander, 4 th Year Pharmacy Student March 15, 2011

 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.

 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

 Relaxation, refocus  Physical Manipulation (physiotherapy)  Thermal therapy (heating pad, ice packs)  Physical Stimulation (massage)  Behavioural (support groups)

 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.

Note: not to be used for neuropathic pain

 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

Mild-to-Moderate PainSevere Pain First Linecodeine or tramadol morphine, oxycodone or hydromorphone Second Line morphine, oxycodone or hydromorphone fentanyl Third Line methadone Note: trial non-opioid options first (acetaminophen, NSAID)

 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

 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.

 1/10 th 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.

 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

 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

 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

 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

 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

 5x more potent than morphine  Available as: ◦ IR: tablet, liquid, suppository, injectable ◦ SR: capsule ◦ Unique SR: 24hr coverage  Tablet  Not listed in SK formulary

 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 hrs with repeated doses ◦ Takes 3-5 days to reach plasma steady state

 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)

 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).

 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)

 Less constipation, nausea, vomiting and itchiness compared to morphine  Very effective  Convenient dosing schedule (every 72 hrs)  No ceiling dose

 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

 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

 Continuous delivery of opioid for 72 hrs ◦ Breakthrough” doses may still be required  Blood levels reach steady state between hrs  Absorption is: ◦ 47% complete after 24hrs ◦ 88% complete after 48hrs ◦ 94% complete after 72hrs  Therefore a used patch contains residual drug

 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

 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)

 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.

Pain Medication Elderly Dosing Considerations AcetaminophenClcr 10-50ml/min: administer q6hrs; if Clcr <10ml/min: administer q8hrs. IbuprofenNSAIDS can compromise existing renal function especially when Clcr is <30ml/min. Be aware of comorbidities: GERD/PUD, GI bleed, Asthma, Renal failure, Heart failure. CodeineClcr 10-50ml/min: administer 75% of dose; if Clcr <10ml/min: administer 50% of dose. TramadolElderly >65 yrs old use with caution and initiate at the lower end of dosing range. Elderly >75 years old, do not exceed 300mg/day for IR formulation and use with great caution. IR formulation: Clcr <30ml/min: administer mg dose q12rs (max 200mg/day). ER formulation: should not be used in patients with Clcr<30ml/min because experience more adverse effects: constipation, fatigue, weakness, postural hypotension, dyspepsia.

Pain Medication Elderly Dosing Considerations MorphineClcr 10-50ml/min: administer 75% or normal dose; if Clcr <10ml/min: administer 50% of normal dose. Oxycodoneserum concentrations increase ~50% in patients with Clcr <60ml/min, adjust dose based on clinical situation. HydromorphoneModerate renal impairment: start with a reduced dose and monitor closely. Severe renal impairment: consider use of an alternate analgesic with better dosing flexibility. MethadoneClcr <10-ml/min: administer 50-75% of normal dose. Because of its long half life and risk of accumulation, methadone is difficult to titrate and is not considered a drug of first choice. FentanylElderly have been found to be twice as sensitive as younger patients to the effects of Fentanyl. A wide range of doses may be used. No renal adjustment necessary.

 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

 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

 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

 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

 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

 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

 Subcutaneous  Intravenous  Transdermal  Topical  Nebulized  Patient controlled analgesia (PCA)  Etc.

 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

 1. Idiopathic  unpredictable, unknown cause  2. End of dose failure  pain at the end of a scheduled interval  3. Incident pain  Secondary to stimulus

 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

 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.

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

Questions?