1 Brigham and Women’s / Dana Farber Guidelines for Opiate Administration / Pain Management Tables (2002)] [references available from Faulkner Hospital Pharmacy ext. 7247] Pain Management Tables (7/02)1 Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Available Dosing Forms and Selected Comments ↓ - decreased incidence vs. other NSAIDs ↑ - increased incidence vs. other NSAIDs Drug Dosing Interval / Maximum Daily Dose Common Dosage Forms (mg) # Comments: Acetaminophen (Tylenol) 4-6 hours / 4000 mg Less than 2 grams/day appears to be tolerated in patients with cirrhosis, monitor closely; essentially no anti-inflammatory activity; low risk of GI side effects; no effect on platelets (Included for comparison; no anti-inflammatory activity) Aspirin 4-6 hours / 4000 mg Tabs: 325, 500 Soln: 160 mg/5 mL Supp: 120, 325, 650 Drops: 80 mg/ 0.8 mL Tab: 81, 325 EC Tab: 81, 325 Supp: 300, 600 Celecoxib (Celebrex) Choline Magnesium Trisalicylate (Trilisate) Ibuprofen (Advil, Motrin) 12 hours / 400 mg Tab: 100 ↓ incidence of GI ulcerations; minimal to no inhibition of platelet function; cross allergy with sulfonamides 8-12 hours / 3000 mg Tab: 750 (salicylate content) ↓ GI bleeding* vs. aspirin and perhaps vs. NSAIDs as a class, possibly due to minimal anti-platelet activity; use caution in preexisting liver disease and avoid in severe liver disease 4-8 hours / 3200 mg Tab: 200, 400, 600 Susp: 100 mg/5 mL Indomethacin (Indocin) Ketorolac (Toradol) 8-12 hours / 200 mg Cap: 25, 50 Supp: 50 mg Injectable: - 15 mg/mL - 30 mg/mL Tab: 500, 750 Repeated studies have shown doses of 1500 mg/day or less to have the lowest risk of inducing serious GI complications among non-salicylate NSAIDs; these studies did not include etodolac (Lodine—non-formulary) or nabumetone (Relafen); low risk of inducing hepatotoxicity, but should be avoided in severe hepatic impairment; possible ↑ nephrotoxicity High risk of nephrotoxicity vs. other NSAIDs; ↑ headache, tinnitus, dizziness, GI side effects; may aggravate depression or other psychological disturbances secondary to CNS penetration High incidence of headache; ↑ nephrotoxicity and GI complications; use no longer than 5 days; use 15 mg in patients greater than 65 years of age, less than 50 kg, or with renal impairment 6 hours / 120 mg 12-24 hours / 2000 mg Nabumetone (Relafen) 8-12 hours / 1500 mg Tab: 250, 375 Naproxen (Naprosyn) 4-6 hours / 400 mg Cap: 50 Meclofenamate (Meclomen) 24 hours / 25 mg chronic Tab: 12.5 Rofecoxib 50 mg acute (5 days) (Vioxx) 8-12 hours / 3000 mg Tab: 500 Salsalate (Disalcid) # Supp = suppository; Susp = suspension; EC = enteric coated; Soln = oral solution High risk of GI bleeding; use caution in preexisting liver disease and avoid in severe liver disease; least potent inhibitor of renal prostaglandins ↓ GI bleeding* and side effects; reduce dose in hepatic dysfunction. Daily to twice daily dosing. ↑ hepatotoxicity (↓ dose 50% in hepatic disease) and possible nephrotoxicity; high tissue penetration; potent inhibitor of leukocyte function; pregnancy category B (1st and 2nd trimester only) High incidence of diarrhea, ↑ GI side effects; do not use for more than 1 continuous week ↓ incidence of GI ulcerations; minimal to no inhibition of platelet function See choline magnesium trisalicylate * Limited data versus COX 2 inhibitors NSAID Selection* Situation or Patient Population Consider Generally Avoid GI Bleed, history of Hepatic dysfunction, current Hepatic dysfunction, high risk Lactation Peptic Ulcer Renal dysfunction, current Renal dysfunction, pts at risk for Thrombocytopenia Warfarin, concurrent use Acetaminophen, celecoxib, ibuprofen, nabumetone, rofecoxib, non-acetylated salicylates** Acetaminophen (reduced doses) Ibuprofen Acetaminophen, ibuprofen, ketorolac, naproxen Acetaminophen, celecoxib, rofecoxib, non-acetylated salicylates** Acetaminophen (reduced doses) Aspirin, non-acetylated salicylates** Acetaminophen, rofecoxib, celecoxib, non-acetylated salicylates** Acetaminophen, rofecoxib, celecoxib, non-acetylated salicylates** Aspirin, indomethacin, ketorolac, meclofenamate Aspirin, ibuprofen Naproxen Aspirin, non-acetylated salicylates** Aspirin, indomethacin, ketorolac, meclofenamate Aspirin, choline magnesium trisalicylate, indomethacin Ibuprofen, indomethacin, naproxen All other agents inhibit platelet function and prolong bleeding time to some degree All other agents inhibit platelet function and prolong bleeding time to some degree * Only formulary items are listed ** non-acetylated salicylates include salicylate salts (choline magnesium trisalicylate) and salsalate Equianalgesic Opioid Dose Chart and Available Formulations*** Drug Morphine (MSIR, MS Contin*) IV / IM 10 Equianalgesic Doses (mg) Oral 30 (chronic) Available Strengths and Dosage Forms Tab: 15 mg CR* Tabs: 15, 30, 60 mg Soln: 10 mg/5 mL Suppository: 10 mg Injectable Tab: 2 mg Injectable Tab: 5 mg CR* Tab: 10, 20 mg Soln: 5 mg/5 mL Hydromorphone (Dilaudid) Oxycodone (Roxicodone, OxyContin*) 1.5 7.5 N/A 20 Hydrocodone Codeine N/A 130 30 200 Fentanyl (Sublimaze, Duragesic patch) Meperidine (Demerol) 0.1 (100 mcg) N/A Tab: 15, 30 mg Injectable Transdermal Patch: 25, 50, 75, 100 mcg/hour Injectable 75 300 Tab: 50 mg Injectable 10 to 20 acute 2 to 4 chronic Tab: 5, 10 mg Soln: 5 mg/5 mL Methadone 5 to 10 acute (Dolophine) 1 to 2 chronic Tramadol ** (Ultram) * CR = Controlled release; Soln = oral solution Tab: 50 mg Comments Caution: Do NOT confuse with Morphine. Caution: Each Percocet 5 mg/325 mg contains 5 mg Oxycodone and 325 mg Acetaminophen. Percocet should be ordered as 5 mg/325 mg tablets (only strength on formulary). Caution: Each Vicodin tablet contains 5 mg Hydrocodone and 500 mg Acetaminophen. Doses greater than 60 mg not recommended. Increased nausea and constipation. Transdermal patch 25 mcg/hour is equianalgesic to approximately 50 mg of oral morphine per day. Not recommended for pain management. CNS excitation from metabolite accumulation. Dose MAX = 600 mg/day; limit to 48 hours. Long half life; accumulates with repeated dosing; may require dose decrease on days 2 to 5 Ceiling dose 400 mg/day (300 mg/day for elderly). 50 mg of tramadol is equianalgesic to approximately 60 mg of oral codeine. **Not an opioid; binds to opiate receptors ***These are NOT suggested starting doses; these are doses of opioids that produce approximately the same Equianalgesic Conversion Example: amount of analgesia. Published trials vary in the suggested doses that are equianalgesic to morphine. By using the Equianalgesic Opioid Dose Chart, you can determine a dose of a new (“NEW”) opioid and/or route of administration that is approximately equal in analgesic effect to the dose of the former (“OLD”). Titration to clinical response is necessary. Recommended doses do not apply to patients with renal or hepatic insufficiency or other conditions affecting drug metabolism and kinetics. Elderly patients generally require lower doses, titrated slowly to the desired effect or intolerable side effects. (reference: www.med.umich.edu/PAIN/APAINMGT) Patient takes OxyContin 20 mg po Q 12 hours and Percocet (5 mg/325 mg) 1 tablet po Q 3 to 4 hours PRN. Only 1 Percocet (5 mg/325 mg) has been required for breakthrough pain every day. Convert to continuous IV infusion of morphine. [{OxyContin 20 mg = oxycodone 20 mg CR} and {Percocet (5 mg/325 mg) = oxycodone 5 mg and acetaminophen 325 mg}] ****Incomplete cross-tolerance: Some studies and written clinical impressions suggest that during high-dose chronic treatment with one strong opioid, patients become somewhat tolerant to that drug but remain relatively sensitive to different opioids. This is one reason to consider reducing the dose of the NEW drug by 25% to 50%. (reference: Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain; 4th Edition; 1999) STEP I → DAILY OPIOID REQUIREMENT: Calculate patient’s total daily opioid requirement (NOTE – if taking different opioids, need to convert each to one common opioid) -- Total daily dose of oxycodone from OxyContin 20 mg → 20 mg x 2 doses → 40 mg -- Total daily dose of oxycodone from 1 Percocet (5 mg/325 mg) → 5 mg → 40 mg oxycodone + 5 mg oxycodone → 45 mg oxycodone/day STEP II → OLD to NEW: Convert the daily requirement of the old opioid to that of the new opioid. EQUIANALGESIC DOSE CONVERSION FORMULA: *** EXAMPLE: Opiate Allergy: True allergic reactions to opioids are rare (i.e., IgE involvement). Symptoms are usually secondary to mast cell activation and subsequent histamine release. Selection of another opioid class is usually necessary only if patient has had a true allergic reaction and not simply a sensitivity to histamine release. class (chemical structure) diphenylheptanes phenanthrenes phenylpiperidines opiates methadone, propoxyphene codeine, hydrocodone, hydromorphone, morphine, oxycodone, levorphanol (non-formulary) fentanyl, meperidine, sufentanil (non-formulary) Equianalgesic Dose for OLD (Chart) = 24-hour dose of OLD (total) Equianalgesic Dose for NEW (Chart) (x) 24-hour dose of NEW 20 mg po oxycodone 10 mg IV morphine = 45 mg po oxycodone (x) mg IV morphine → (x) = 22.5 mg IV morphine/day (i.e., 22.5 mg IV morphine/day is equianalgesic to 45 mg po oxycodone/day) STEP III → INCOMPLETE CROSS TOLERANCE: **** Consider incomplete cross tolerance and decrease total daily opiate dose by 25% to 50% → 11.25 mg to 16.9 mg STEP IV → NEW DRUG DOSE: → 11.25 mg to 16.9 mg/day divided by 24 hours/day → 0.45 mg to 0.7 mg of morphine per hour.