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Pain Management & Opioid Analgesics Objectives Determine proper opioid dosing Differentiate between specific opioid analgesics and be able to convert between agents Discuss basal and bolus doses for PCA Discuss adverse reactions of opioids Review the Sole Provider program Discuss how to properly write a prescription for a controlled substance 2 Pain Definition An unpleasant sensory & emotional experience associated with actual or potential tissue damage or described in terms of such damage Types Nociceptive Somatic – bone pain, skin, soft tissue trauma Visceral – ab pain due to tumor invasion Neuropathic – post herpetic neuralgia, postmastectomy, phantom limb 3 Choosing Analgesic Therapy What type of pain? Nociceptive vs. neuropathic Acute vs. chronic Mild vs. severe What route should be used? What agent should be used? Type, severity of pain Pt characteristics – side effects, elderly, allergy, co-morbid conditions, tolerance, previous narcotics used Insurance, cost 4 WHO Ladder of Analgesics www.anzsgm.org/vgmtp/Pain/analgesia_ladder.htm 5 Non-opioid analgesics Aspirin NSAIDs Acetaminophen Adjuvants Antidepressants – amitriptyline, duloxetine Anticonvulsants – carbamazepine, gabapentin, pregabalin Anesthetics – lidocaine patch (12 hours on, 12 hours off) 6 Potency of Opioids Weak Agonists Propoxyphene (Darvon, Darvocet) Codeine Hydrocodone/APAP (Vicodin, Lortab, Lorcet, Norco) Tramadol Strong Agonists Morphine Oxycodone Hydromorphone (Dilaudid) Fentanyl (Duragesic, Sublimaze) Methadone (Dolophine) Meperidine (Demerol) 7 Tramadol Synthetic analog of codeine but is NOT controlled Weak agonist/low affinity at mu receptor and also weak SNRI (which inhibits pain transmission in the spinal cord) Use with caution in pt on TCAs, MAOIs, SSRIs as it may lower seizure threshold Max dose is 400 mg/day but 300 mg/day if >75yo; renal dosing if CrCl<30 Tramadol is 5-10 times less potent than morphine and reported to cause less respiratory depression Approximately 50 mg tramadol = 60 mg codeine 8 Considerations in choosing opioids Renal impairment Preferred oral agent: hydromorphone Use with caution: morphine, codeine Avoid meperidine Metabolites can accumulate and cause seizures Other cautions with meperidine Avoid in pts with CHF, hepatic insufficiency, elderly Avoid use in pts on MAOIs (phenelzine, selegeline, linezolid) in past 14 days 9 Opioid Fentanyl Half-life IV: 2 – 4h Patch: 17h Hydromorphone 2 – 3h (Dilaudid) Onset Duration of analgesic effect IV: within minutes Patch: 12-24h IV: 0.5 – 1h Patch: 72h IV: 5 - 15 min PO: 30 min 3 – 5h Methadone** 8 – 59h 30 – 60 min 4 – 8h Morphine 2 – 4h IV:5 - 10 min PO (IR): 30 - 60 min IR: 3 – 6h SR: 8 – 12h Meperidine (Demerol) 3 - 5h (15-30h for metabolite) 10 – 45 min 2 – 4h Codeine 3 – 4h 30 – 60 min 4 – 6h Oxycodone IR: 2 – 5h SR: 5h 15 – 60 min IR: 3 – 6h SR: 12h Hydrocodone 3 – 4h 10 – 60 min 4 – 8h 10 Opioid Usual Starting Dose Comments Fentanyl* 25 – 100 mcg IV q1h, then 1 – 2 mcg/kg/h Patch: NOT for acute pain & NOT for opioid-naïve pts; do not cut patch in half Hydromorphone (Dilaudid) 0.5 – 1 mg q4h IV 1 – 2 mg q4h PO Very potent; preferred in pts with renal impairment Methadone 5 mg q8-12h PO Monitor for QT prolongation & drug interactions Morphine 2 – 5 mg q4h IV 5 – 10 mg q4h PO (IR) 15 – 30 mg q8 or 12h (SR) MSContin: NOT for acute pain; do not split/crush tablets Meperidine (Demerol) 50 mg q3-4h PO/IV NOT recommended for chronic use Codeine 30 – 60 mg q4h PO Has more side effects than morphine Oxycodone 5 mg q4h PO (IR) 10 – 20 mg q12h (SR) OxyContin: NOT for acute pain; do not split/crush tablets Hydrocodone 5 – 10 mg q4h PO always combined with APAP or ibuprofen – which limits its 11 dosing Opioid Available Doses Fentanyl IV: 25, 50, 100 mcg/ml Patch: 25, 50, 75, 100 mcg Hydromorphone (Dilaudid) IV: 2 mg/ml; PCA: 1mg/ml & 0.2 mg/ml PO: 2 mg Methadone PO: 5, 10 mg Morphine IV: 4 mg/ml; PCA: 1 mg/ml & 5 mg/ml PO: IR 15, 30 mg PO: ER (MS Contin): 15, 30, 60, 100 mg Solution (Roxanol): 20 & 2 mg/ml Meperidine (Demerol) IV: 25, 50, 100 mg/ml Codeine PO: 30 mg Oxycodone PO: IR 5mg PO: ER (OxyContin): 10, 20, 40, 80 mg Solution (Roxicodone): 20 & 1 mg/ml Oxycodone/APAP (Percocet) PO: 5mg oxycodone/325 mg APAP Hydrocodone/APAP (Norco) PO: 5mg hydrocodone/325 mg APAP 12 PCA Dosing Dosing considerations For opioid-naïve patients, use lower end of range Pain Assessment Respiratory Assessment Sedation Assessment Drug Usual Demand Dose Range of Demand Dose Lockout Interval (min) Usual Basal Rate Morphine (1mg/ml and 5 mg/ml) 1.0 mg 0.5-2.5 mg 5 - 15 None or 1 – 2 mg/hr Hydromorphone (Dilaudid) (0.1 mg/ml and 1 mg/ml) 0.2 mg 0.05-0.4 mg 5 - 15 None or 0.1 – 0.4 mg/hr (standard concentrations) When initiating PCA for first time (no conversion from outpatient med), the initial demand dose is 50% of the basal rate 13 PCA dosing 62 yo patient s/p TAH has been moved to PACU. You have been asked to start the patient on a PCA. Which of the following is an appropriate initial order: Morphine PCA 1 mg/ml: LD 2 mg, 1 mg demand dose, lock out 10 min, no basal Dilaudid PCA 1mg/ml: LD 2 mg, 1 mg demand dose, lock out 10 min, no basal Fentanyl patch 25 mcg q72 hours 14 Decreasing IV potency as you go down the table Conversions* Opioid Parenteral Oral Fentanyl 0.1 mg NA Hydromorphone (Dilaudid) 1.5 mg 7.5 mg 5 - 10 mg 2 - 20 mg*** 10 mg 30 mg 75 -100 mg 300 mg 120 mg 200 mg Oxycodone NA 20 mg Hydrocodone NA 30 mg Methadone** Morphine Meperidine (Demerol) Codeine *When switching between opioids, there is NOT a complete cross tolerance. If patient is controlled, consider decrease the dose by 1/2 to 1/3 to avoid side effects. **conversion ratio is highly variable 15 Initial Fentanyl Patch Dose Conversion PO 24-hour morphine (mg/day) Fentanyl Patch Dose (mcg/hr) 45-134 25 135-224 50 225-314 75 315-404 100 405-494 125 495-584 150 585-674 175 675-764 200 765-854 225 855-944 250 945-1034 275 1035-1124 300 For CHRONIC pain: 25 mcg/hr fentanyl patch = oral morphine 50 mg/24h Fentanyl patch NOT for acute pain or post-op pain Absorbed through the skin, producing a drug depot in the upper skin layers, then diffusing into systemic circulation Can have variable responses between patients (i.e. cachetic, elderly) Watch for drugs that inhibit its metabolism Ketoconazole, erythromycin, diltiazem, grapefruit juice 17 Morphine:methadone conversion Oral morphineequivalent daily dose (mg/day) Initial Dose Ratio (oral morphine:oral methadone) <30 2:1 30 – 99 4:1 100 – 299 300 – 499 8:1 12:1 500 – 999 15:1 >1000 20:1 or greater 18 Breakthrough Dosing Use immediate-release opioids Chronic oral meds Give 10 – 20% of the total daily dose q4hprn Example – MS Contin 60 mg PO q12h – should give 10 – 20 mg q4h prn of morphine immediate release IV dosing (PCA dosing) 10% of the 24 hr requirement, then: Divide by 4 if giving every 15 minutes Ex: 100 mg morphine daily 2.5 mg IV q15 min 19 Dose Adjustment Increasing the opioid dosage For moderate to severe pain, increase by 50 – 100% For mild to moderate pain, increase by 25 – 50% Convert to oral as early as possible: Pain is controlled GI function intact IV to oral dosage calculation Calculate total daily IV use Calculate breakthrough dose 10-20% of total daily dose of regularly scheduled opioid every 4 h as needed 20 Conversion problem Pt is taking Percocet 5/325 two tabs q6h What dose of oxycodone ER (OxyContin) would you start the patient? What dose of morphine ER (MS Contin)? What dose of fentanyl patch? 21 Conversion problem 8 tabs Percocet = 40 mg oxycodone per day Oxycodone ER (OxyContin) = 20mg q12h 22 Conversion Problem MS Contin conversion 40 mg po oxycodone = 20 mg po oxycodone x 30 mg po morphine X = 60 mg po morphine daily = MS Contin 30 mg q12h If you want to decrease dose to allow for decreased cross-tolerance, decrease dose by 1/2 to 1/3 = 30 to 40 mg morphine daily = MS Contin 15 mg q12h Fentanyl patch 30 – 60 mg po morphine daily = 25 mcg fentanyl patch 23 Conversion problem In the previous problem, your patient was stable on MS Contin 30 mg q12h Your attending wants to change over to the fentanyl patch How do you time the transition from MS Contin to the patch? 24 Conversion problem In the previous problem, your patient was stable on MS Contin 30 mg q12h Your attending wants to change over to the fentanyl patch How do you time the transition from MS Contin to the patch? It takes about 12 hrs for onset of fentanyl patch Give patient one last dose of MS Contin at the same time the patch is applied 25 Example of conversion from oral med to PCA Pt taking OxyIR 20 mg PO q4h Pt’s pain is well-controlled Want to convert to hydromorphone PCA What would be a basal dose (in mg/hr)? What would be the bolus/demand dose? 26 Example of conversion of oral med to PCA Pt taking OxyIR 20 mg q4h Convert total oral daily dose (120 mg oxycodone) to oral hydromorphone 120 mg po oxycodone = 20 mg po oxycodone x 7.5 mg po hydromorphone X = 45 mg po hydromorphone Convert to IV 45 mg po hydromorphone = 7.5 mg po x 1.5 mg IV x = 9 mg IV hydromorphone daily 27 Example of conversion to PCA Basal rate 9 mg daily total = 0.4 mg per hour May want to decrease basal by 1/2 to 1/3 to account for incomplete cross tolerance Bolus/demand dose is usually 10% of the daily dose divided by 4 Basal dose of 0.2 to 0.3 mg per hour (0.10 x 9 mg) / 4 = 0.2 mg q 15 minutes Titrate based on use & pt’s response 28 Example of PCA conversion to oral med Pt on post-op morphine PCA with basal of 1 mg/hr and bolus of 1 mg q15 minutes Pt used 40 bolus injections in 24 hours What dose of oral morphine (basal & breakthrough) should be used? What dose of oral oxycodone (basal & breakthrough) should be used? 29 Example of PCA conversion to oral med Total daily use of IV morphine 1 mg/h x 24 h + 40 bolus = 64 mg/24 hour Convert to oral morphine 64 mg IV morphine = 1 mg IV morphine x 3 mg po morphine X = 192 mg po morphine MS Contin 100 mg q12h (basal) Morphine IR 30 mg q4h prn for breakthrough 10 – 20% of daily dose q4h (10 – 20% of 200 mg is 20 to 40 mg) 30 Example of PCA conversion to oral med Converting to po oxycodone 192 mg po morphine = x X = 128 mg po oxycodone 30 mg po morphine 20 mg po oxycodone Decrease daily dose by 1/2 or 1/3 to allow for incomplete cross tolerance Total daily dose of oxycodone = 64 to 85 mg OxyContin dose (basal): 60 mg q12h or can use 30 to 40 mg q12h if want to account for incomplete cross tolerance Oxycodone IR (breakthrough): 5-10 mg q4h prn 31 Side Effects Constipation – worsens with dose increases Sedation, fatigue – wears off within 1 week Dizziness – wears off, may require slower titration Nausea – usually wears off; switching products may help Hallucinations – more common at higher doses Itching - anti-histamine; rotate narcotics Respiratory depression – rare side effect with chronic dosing; more common with IV, epidural 32 Respiratory Depression 0.2 – 2 mg naloxone IV, IM, SC Repeat doses every 2 to 3 min prn Total dose up to 10 mg After reversal, may need to readminister dose at a later interval (20 to 60 minutes) depending on the type/duration of opioid 33 Assessment Scales Respiratory Should be counted for at least 30 seconds If RR <12/min, then count for full minute If RR <10/min, stop PCA If RR <4/min, give naloxone Sedation 1 = agitated, restless 2 = cooperative, oriented 3 = asleep, easily arousable 4 = asleep, arouses to voice 5 = no response to verbal stimuli 6 = no response to pain Stop PCA & give naloxone for score 5 & 6 34 Constipation Need a stool softener Docusate 100 mg: 1 to 2 caps po twice daily Need a stimulant laxative Senna: usual dose is 1 tab at bedtime or twice daily but can titrate up to 4 tabs three times daily prn Bisacodyl 5 mg: 1 to 2 tabs twice daily prn 35 Constipation Medication www.toonpool.com Dose Polyethylene Glycol (Miralax) 17 g in 8oz water daily to twice daily Milk of Magnesia 30 – 60 ml daily to twice daily Lactulose 20 – 60 ml twice to four times daily Magnesium Citrate** 8oz daily Bisacodyl suppositories Daily to twice daily Fleet enemas Daily to twice daily 36 Opioid “Allergy” “Pseudoallergy” caused by histamine release – most commonly seen with codeine, morphine, meperidine Pt c/o flushing, itching, hives, sweating Mild hypotension Use H2RA Decrease dose Switch to a more potent opioid (i.e. fentanyl, hydromorphone) 37 Opioid “Allergy” Pts with “true” allergy Breathing, speaking, swallowing difficulties Swelling of face, lips, mouth, tongue, pharnyx, or larynx Severe hypotension Switch to a different class Phenylpiperidines: meperidine, fentanyl Diphenylheptanes: methadone, propoxyphene Morphine group: morphine, codeine, hydrocodone, oxycodone, hydromorphone, nalbuphine, butorphanol 38 Sole Provider Program Purpose To monitor patients exhibiting signs of drug-seeking behavior, insufficient analgesia, evidence of non-optimization in care options, psychosocial issues, or other complex pharmaceutical care issues Narcotic prescriptions only The primary care provider can be the Sole Provider or choose to refer a patient to a Sole Provider Opioid “contract” signed between patient and Sole Provider physician Pharmacy informed and note put in CHCS Sole Provider committee will monitor for violations 39 Sole Provider Program 1. NNMC Intranet 2. Site Map 3. Pharmacy 40 Sole Provider Program 41 Writing Prescriptions Link on Pharmacy Website Write legibly Write out your DEA number Spell out the quantity to be dispensed C-IIs are not refilled (new Rx required) & require separate prescriptions Use DoD Form 1289 for controlled substances 42 DEA numbers Retail and mail-order pharmacies are no longer accepting the NNMC DEA number Must apply for own practitioner DEA number Active military physicians (MD, DO, DDS, DMD, and DPM) are fee exempt and may be licensed in any state to obtain a DEA registration DEA number is to be used solely for DoD beneficiaries prescriptions and may not be used for off-duty employment 43 DEA numbers To apply for DEA number: Contact the Credentialing Office to complete the correct paperwork Contact person: Rebekah Byrd at 319-4157 44 Med Errors to Avoid Roxanol v Roxicodone oral solutions Roxanol (morphine) v Roxicodone (oxycodone) Correct strengths PCA strength Morphine: 1 mg/ml and 5 mg/ml Hydromorphone: 1 mg/ml and 0.2 mg/ml Fentanyl patch For inpatients, double check if patient has patch on from home 45 References Pharmacotherapy: A Pathophysiologic Approach. 6th edition: Chapter 58. End of Life/Palliative Education Resource Center Micromedex Drug Facts and Comparisons Equianalgesic Dosing of Opioids for Pain Management. Pharmacist’s Letter 2004. Opioid Intolerance Decision Algorithm. Pharmacist’s Letter 2006. Clinical Pharmacology 46 References Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain, American Pain Society, 5th Ed. 2003 Grammaitoni AR et al. Clinical Application of Opioid Equianalgesic Data. Clin J Pain 2003; 19(5): 286-297. McPherson M.L. Demystifying Opioid Conversion Calculations: A Guide for Effective Dosing. 2010. 47 QUESTIONS? 48