MUSC Opioid Analgesic Comparison Chart

MUSC Opioid Analgesic Comparison Chart Approved by the Pharmacy and Therapeutics Committee (February 2006, November 2009, March 2010, December 2011) Prepared by the MUSC Department of Pharmacy Services and the Pain Management Service Available online at http://academicdepartments.musc.edu/pharmacy_services/medusepol/pdf/opioidanalgesicconversionchart.pdf. Disclaimer: This document is a guideline, and not a policy statement. This conversion chart is designed to facilitate the rational conversion of one opioid regimen to an approximately equianalgesic dose of another opioid. The authors have strived to ensure that the information included in the chart reflects the current level of knowledge regarding opioid conversions. As a result, it is the user s responsibility to examine all available information on opioid conversions and to integrate with knowledge about the patient. Always use clinical judgment when making decisions for an individual patient. COMMONLY USED OPIOID ANALGESICS

Medication Fentanyl (Sublimaze, Duragesic, Actiq, Fentora ) HYDROmorphONE (Dilaudid ) Methadone (Dolophine, various) Route Onset of Duration of Usual Dosing Interval Appropriate for PCA Concentration for PCA Equi-analgesic Dosing IV immediate 30 to 60 min 1 to 2 hr Yes 50 micrograms/ml 100 micrograms IV (0.1 mg IV) See page 4 for details SC ** 15 min 30 min to 2 hr 3 to 6 hr N/A N/A 100 micrograms SC (0.1 mg SC) See page 4 for details TM 5 to 15 min highly variable See page 4 N/A N/A See page 4 See page 4 for details TD 12 to 24 hr 72 hr per patch 72 hr N/A N/A See page 4 See page 4 for details PO 15 to 30 min 4 to 6 hr 3 to 6 hr N/A N/A 7.5 mg PO HYDROmorphONE is not IV/SC 15 min 4 to 6 hr 3 to 6 hr Yes 1 mg/ml 1.5 mg IV equivalent to morphine PO 30 to 60 min > 8 hr (chronic use) 8 to 12 hr (chronic use) N/A N/A See page 5 Notes **See page 5 for details** Equianalgesic dosing is variable with chronic dosing MorphINE immediate release (MSIR, Roxanol, various) MorphINE extended release (MS Contin, various) MorphINE extended release (Kadian, Avniza )^ OxyCODdone immediate release (Roxicodone, OxyIR, various) OxyCODone controlled release (OxyContin, various) PO 30 to 60 min 3 to 6 hr 3 to 6 hr N/A N/A 30 mg PO IV 5 to 10 min 3 to 6 hr 3 to 6 hr Yes 1 mg/ml 5 mg/ml 10 mg IV SC 15 to 30 min 3 to 6 hr 3 to 6 hr Yes N/A 10 mg IM/SC PO 30 to 90 min 8 to 12 hr 8 to 12 hr N/A N/A 30 mg PO PO 30 to 90 min 12 to 24 hr 12 to 24 hr (Kadian ) 24 hr (Avniza ) N/A N/A 30 mg PO PO 10 to 15 min 4 to 6 hr 4 to 6 hr N/A N/A 20 mg PO PO 1 hr 12 hr 12 hr N/A N/A 20 mg PO OxyMORphone immediate release (Opana, various)^ PO N/A N/A 10 mg OxyMORphone extended release PO N/A N/A 10 mg (Opana ER, various)^ Equi-analgesic dosing is based on morphine 10 mg administered parenterally (ie, IV/SC). Calculation example on page 3. ^ Nonformulary status ** Subcutaneous use of fentanyl has not been well-studied; data presented are from a small pharmacokinetic study and a review of a subcutaneous infusion of fentanyl IV = intravenous; SC = subcutaneous; TM = transmucosal; TD = transdermal; PO = oral morphine is not equivalent to HYDROmorphONE morphine is not equivalent to HYDROmorphONE Do not crush, chew, or break. morphine is not equivalent to HYDROmorphONE Do not crush, chew, or break. oxycodone is not equivalent to OxyMORphone oxycodone is not equivalent to OxyMORphone Do not crush, chew, or break. OxyMORphone is not equivalent to oxycodone OxyMORphone is not equivalent to oxycodone Do not crush, chew, or break. 1 COMMONLY USED COMBINATION OPIOID ANALGESICS

Medication Route Onset of Duration of Usual Dosing Interval Equi-analgesic Dosing HydroCODONE combinations (see below) PO 30 to 60 min 4 to 6 hr 4 to 6 hr 30 mg PO Oxycodone combinations (see below) PO 10 to 15 min 4 to 6 hr 4 to 6 hr 20 mg PO Codeine combinations (see below) PO 30 to 60 min 4 to 6 hr 4 to 6 hr 200 mg PO Equi-analgesic dosing is based on morphine 10 mg administered parenterally (ie, IV/SC). Calculation example on page 3. Notes Maximum dose of hydrocodone is 40 mg/day Doses should not exceed 120 mg/day in opiate naïve patients ** The FDA does not recommend combination products with an acetaminophen content > 325 mg. These products will be phased out and may not be available after 2011** Acetaminophen Aspirin Opioid Brand Names Opioid Content Ibuprofen Content Content Lortab 167 mg (elixir) Lorcet 300 mg Maxidone * 2.5 mg 325 mg Norco * 5 mg 400 mg** -- -- Vicodin 7.5 mg 500 mg** Hydrocodone Xodol * 10 mg 650 mg** Zydone * 660 mg** 750 mg** Oxycodone Codeine Ibudone Reprexain Vicoprofen Percocet Roxicet * Roxilox * Tylox * 2.5 mg 5 mg 7.5 mg 10 mg 2.5 mg 5 mg 7.5 mg 10 mg -- -- 200 mg 300 mg 325 mg 400 mg** 500 mg** 650 mg** -- -- Percodan * Roxiprin * 4.5 mg -- 325 mg Combunox Capsules * 5 mg -- -- 400 mg Tylenol with Codeine Elixir Tylenol with Codeine No. 2 Tylenol with Codeine No. 3 Tylenol with Codeine No. 4 Aspirin with Codeine Empirin with Codeine No. 3 Empirin with Codeine No. 4 12 mg 15 mg 30 mg 60 mg 15 mg 30 mg 60 mg 120 mg 300 mg 650 mg** -- -- 325 mg Comments Maximum dose of acetaminophen is 4 g/day Maximum dose of acetaminophen is 4 g/day Maximum dose of acetaminophen is 4 g/day This chart is not considered all-inclusive. All orders/prescriptions must specify dose based on opioid content and acetaminophen, aspirin or ibuprofen content. * Nonformulary status HIGH-RISK, NON-PREFERRED OPIOID PRODUCTS 2

Medication Codeine phosphate (various) Codeine sulfate (various) Meperidine (Demerol ) Route Onset of Duration of Usual Dosing Interval Appropriate for PCA Concentration for PCA Equi-analgesic Dosing PO 30 to 60 min 4 to 6 hr 4 to 6 hr N/A N/A 200 mg PO Doses should not exceed 120 mg/day in opiate naïve IV 10 to 30 min 4 to 6 hr 4 to 6 hr N/A N/A 120 mg IV patients PO 30 to 60 min 4 to 6 hr 4 to 6 hr N/A N/A 200 mg PO PO 10 to 15 min 2 to 4 hr 3 to 4 hr N/A N/A 300 mg PO IV 1 to 5 min 2 to 4 hr 3 to 4 hr NO N/A 75 100 mg IV Notes See meperidine use guidelines on the MUSC Formulary and Drug Information Resources Web page Nalbuphine (Nubain ) IV 2 to 3 min 3 to 6 hr 3 to 6 hr N/A N/A -- SC/IM < 15 min 3 to 6 hr 3 to 6 hr N/A N/A -- Equi-analgesic dosing is based on morphine 10 mg administered parenterally (ie, IV/SC). IV = intravenous; SC = subcutaneous; PO = oral EQUIANALGESIC CONVERSION EQUATION Current opioid (single conversion dose & route) New opioid (single conversion dose & route) = Total 24 dose of current opioid Total 24 dose of new opioid Equianalagesic conversions should not be considered a simple straightforward calculation. Significant 'inter/intra' patient variability exists depending on the selected opiate, dose, and expected response. See information regarding cross- tolerance. Example: Patient is receiving morphine, with a 24-hr-dose total of 180 mg PO. What is the equivalent 24-hr dose of hydromorphone? Equianalgesic Dose morphine 30 mg PO hydromorphone 7.5 mg PO Total 24-hr dose morphine 180 mg PO hydromorphone X mg X = hydromorphone 45 mg PO/24 hrs. Accounting for cross tolerance of 50% = hydromorphone 22.5 mg PO/24 hrs Recommended dose = hydromorphone 2 4 mg PO every 3 hrs (2 mg for moderate pain; 4 mg for severe pain) OPIOID CROSS-TOLERANCE Incomplete cross-tolerance relates to tolerance to a currently administered opiate that does not extend completely to other opioids. This will tend to lower the required dose of the second opioid. It is importance to view the calculated data as approximations. A 50% reduction in calculated dose is recommended. Dose should be re-titrated to patient response. In all cases, repeated comprehensive assessments of pain are necessary in order to successfully control the pain while minimizing adverse effects. This dose not include conversions for methadone (see page 5) or transdermal fentanyl (reduction is built into the conversion see page 4). RECOMMENDATIONS FOR FENTANYL USE 3

Fentanyl to Fentanyl Conversion: 1:1 conversion Conversion between Fentanyl Transdermal System and Morphine To convert therapy to fentanyl transdermal system (Duragesic ), calculate the 24-hr ORAL morphine dose and select the appropriate transdermal system strength using the following chart: Oral 24-hr morphine (mg/day) < 60 60 to 134 135 to 224 225 to 314 315 to 404 405 to 494 495 to 584 585 to 674 675 to 764 765 to 854 855 to 944 945 to 1034 1035 to 1124 *12.5-microgram patch is nonformulary Fentanyl transdermal system (Duragesic ) (micrograms/hr) 12.5* 25 50 75 100 125 150 175 200 225 250 275 300 Conversion for Transmucosal Fentanyl Actiq (lozenge on a stick) 800 micrograms = 10 mg IV morphine Fentora (buccal tablet - nonformulary) 200 micrograms = 10 mg IV morphine Transmucosal Conversions Current Lozenge Dose (Actiq ) Initial Buccal Dose (Fentora ) 200 micrograms 100 micrograms 400 micrograms 100 micrograms 600 micrograms 200 micrograms 800 micrograms 200 micrograms 1200 micrograms 400 micrograms 1600 micrograms 400 micrograms Clinical Practice Points for Fentanyl Use Transdermal fentanyl should not be used in opioid naïve patients Re-consider analgesic option when transition from ICU to floor, especially with fentanyl Buccal tablet: Place above rear molar between the upper check and gum. Tablet should not be split, sucked, chewed, or swallowed. Disintegration usually takes up to 25 minutes. After 30 minutes, if remnants from the tablet remain, they may be swallowed with a glass of water. Lozenge: Place between cheek and lower gum, moving from one side to the other using the handle. Patient should suck, not chew, the lozenge. Lozenge should be consumed over 15 minutes. 4 RECOMMENDATIONS FOR METHADONE USE

NOTE: HIGHLY recommended that practitioners NOT FAMILIAR with prescribing or monitoring methadone call either pain management or pharmacy services for recommendations and guidelines for initiation, dose escalation and follow-up. Methadone conversion ratio: When switching from an opioid to methadone, the equianalgesic dose ration of methadone depends on the ORAL morphine-equivalent daily dose (MEDD) of the preceding opioid. Oral MEDD (mg/day) Methadone Dose Conversion Ratio 0 to 99 4:1 100 to 299 8:1 300 to 499 12:1 500 to 999 16:1 > 1000 20:1 Steps for conversion of opioid to methadone: 1. Convert to ORAL morphine equivalent (24 hr total dose) 2. Divide by ratio above 3. Divide by 50% to account for incomplete cross-tolerance 4. Divide by 3 for frequency (every 8 hr dosing) 5. Round down to the nearest tablet size 2.5-mg intervals Example: Patient receiving 860 mg morphine PO equivalent. 860 mg 16 53.75 26.87 53.75 26.87 8.9 2 3 Recommended starting dose: methadone 7.5 mg every 8 hours (dose rounded down based on available tables) Clinical Practice Points for Methadone Use ANY prescriber that can prescribe a C-II medication can prescribe methadone for PAIN Half-life can be as long as 130 hours; therefore, steady-state concentrations are reached in 4 7 days. Dose adjustments for pain management should not happen more frequently than every 4 7 days. Of note: Considerable inter-individual variability in elimination half-life; generally reported as 8 59 hours, but values have ranged from 9 87 hours in postoperative patients, from 8.5 75 hours in opiate-dependent patients, and up to 120 hours in outpatients receiving therapy for chronic malignant pain Once daily methadone is reserved for maintenance therapy in patients with opioid addiction and should not be used for treatment of pain. If naloxone is required, multiple intermittent doses or a continuous infusion may be required. US Boxed Warning for patients at risk for QT prolongation, with medications known to prolong the QT interval (eg, haloperidol), or for patients with a history of conduction abnormalities. QT interval prolongation and torsade de pointe may be associated with doses > 200 mg/day, but have been associated with lower doses. Correct potassium and magnesium abnormalities prior to initiation. Methadone is a substrate for the cytochrome P450 enzyme system; therefore, plasma concentrations may be inhibited or induced by certain concomitant medications. The dose may need to be adjusted based on any potential interaction. For questions regarding drug interactions, contact pharmacy or pain management service. GENERAL CLINICAL PRACTICE POINTS FOR OPIOID USE 5

The equianalgesic opioid doses are for severe pain in patients that are opioid naïve. When converting from one opioid to another, the calculated equianalgesic dose is an estimate, not the usual starting dose. Individualize and titrate the dose according to crosstolerance, patient age, condition, history (eg, chronic pain), response, and the clinical situation. Reduce dose by 25 to 50% in the elderly; by 25% in hepatic or renal dysfunction. Re-consider analgesic option when transition from ICU to floor, especially with fentanyl Cross allergenicity between opioids varies greatly between patients. Alternative analgesics such as acetaminophen, aspirin, and non-steroidal anti-inflammatory medications (eg, ibuprofen, naproxen) should be considered in a patient who has experienced a life-threatening reaction. Structural Class Phenanthrenes Piperidine/phenylpiperadine Diphenylheptanes Morphine Hydromorphone* Oxymorphone* Codeine Hydrocodone Oxycodone* Fentanyl* Meperidine Methadone* Propoxyphene For patients with Type I hypersensitivity reactions, all opioids must be used with caution. Selecting an opioid in a different structural class may result in the lowest chance of cross-sensitivity. For patients with non-allergic histamine-mediated adverse reactions, selecting an agent with lower potential for histamine release (denoted by *) may reduce symptoms. Tramadol (Ultram ) is contraindicated in patients who have a true opioid allergy. USE OF NALOXONE FOR REVERSAL OF APNEA/HYPOVENTILATION (POLICY C-154) Clinical Practice Points: Can be administered IV, IM, SC, or intratracheally (ETT), with the most rapid onset of action achieved following IV administration Can reverse some of the symptoms of opioid overdose which include respiratory depression, sedation, and hypotension. It is important to note that the analgesic effect of the opioid will also be reversed See page 7 for dosing and administration. 6 Dosing and Administration of Naloxone for Reversal of Opioid Sedation (Policy C-154)

Mix naloxone (0.4 mg/ml) with 9 ml of 0.9% sodium chloride for a total volume of 10 ml (unless otherwise stated). Dilution concentration will be 0.04 mg/ml. Patients with IV Access Patients without IV Access (IM, SC, ETT) Patients in the Neonatal ICU Patients 20 kg Dilute and give 0.02 mg (0.5 ml) IV every 3 minutes until desired respiratory rate is established NOT until return of desired sensorium. Patients > 20 kg Dilute and give 0.08 mg (2 ml) IV every 3 minutes until desired respiratory rate is established NOT until return of desired sensorium. Patients 20 kg Give undiluted (0.4 mg/ml) naloxone 0.01 mg/kg SC/IM/ETT every 2 minutes until desired respiratory rate is established NOT until return of desired sensorium. Patients > 20 kg Give undiluted (0.4 mg/ml) naloxone at 0.2 mg (0.5 ml) SC/IM/ETT every 2 minutes until desired respiratory rate is established NOT until return of desired sensorium. Patients 2 kg Dilute and give 0.01 mg/kg IV/SC every 3 minutes until desired respiratory rate is established NOT until return of desired sensorium. Patients > 2 kg Give undiluted (0.4 mg/ml) naloxone 0.01 mg/kg IV/SC every 3 minutes until desired respiratory rate is established NOT until return of desired sensorium. Naloxone Continuous Infusion To initiate a continuous intravenous Naloxone drip, a separate physician order is required. Recommended only after initial IV or IM administration for prolonged respiratory depression, when the patient has been subject to sustained release or long acting opioid (eg, Oxycontin, MS Contin, Oramorph, methadone) or has epidural opioid. Pharmacy will prepare the infusion. Start infusion at a rate of 2.5 micrograms/kg/hr. Titrate as needed to maintain analgesia and adequate respiratory drive. Cautions with naloxone administration Return to full alertness is often accompanied by withdrawal and return of pain. Giving a full undiluted ampule (1 ml = 0.4 mg/ml) of naloxone in a patient who has received opioids but is not in respiratory arrest may cause ischemia, heart attack, hypertension, stroke, heart failure, and/or pulmonary edema. Do not assume compatibility with any other medications. DO NOT use to reverse hypotension, nausea or vomiting from opioids. DO NOT use to reverse seizures from meperidine (Demerol ). When naloxone is given, there is a risk of acute withdrawal syndrome in habituated patients and infants of opioid-habituated mothers. Use cautiously in patients with known renal insufficiency as it may have a prolonged effect. 7