Narcotic Analgesic

1. See Also
   1. Chronic Pain Management
   2. Pediatric Analgesics
   3. Chronic Narcotic Guideline
2. Pharmacology: Metabolism of Opioids
   1. Codeine: Metabolizes to Hydrocodone and morphine
   2. Heroin: Metabolizes to 6-MAM and then to Morphine
   3. Morphine and Hydrocodone: metabolize to Hydromorphone
3. Precautions: Ineffective Oral Opioids (Not recommended)
   1. Darvocet N-100 (Acetaminophen 650, Propoxyphene 100)
      1. Dose: 1 PO q4-6 hours
      2. Propoxyphene 100 equivalent to Codeine 32 mg
      3. Efficacy
         1. Tylenol alone is as effective as Darvocet
            1. Li Wan Po (1997) BMJ 315
         2. Propoxyphene can cause serious arrhythmias
            1. Heaney (1983) Ann Emerg Med 12:780-2
            2. Madsen (1984) Acta Anaesthesiol Scand 28:661
   2. Tylenol #3 (Acetaminophen 300, Codeine 30)
      1. Dose: 1-2 PO q4-6 hours
      2. Efficacy
         1. Acetaminophen is a safe and effective Analgesic
         2. Codeine is no more effective than standard NSAIDs
            1. Naprosyn is as effective in post-operative pain
            2. Ouellette (1986) Curr Ther Res 39(5):839
            3. Busquets (1988) Curr Ther Res 43(2):311
         3. Codeine offers no significant benefit to Tylenol
            1. Zhang (1996) J Clin Pharm Ther 21(4):261
         4. Adding Codeine to Tylenol increases adverse effects
            1. Jochimsem (1978) J Am Geriatr Soc 26(11):521
         5. Codeine 60 mg equivalent to Aspirin 650 mg
         6. Non-responders to Codeine: 10% of patients
            1. Lack endogenous enzyme to convert to Morphine
         7. Risk of Opioid induced respiratory depression and other overdose adverse effects (especially in children)
            1. Associated with CYP2D6 ultrarapid metabolization (fast metabolizers) found in 5-30% (depending on ethnicity)
            2. Deaths in children have occurred with codeine Analgesics following Tonsillectomy and adenoidectomy
            3. Resulted in FDA black box warning in 2013
            4. FDA Drug Safety Communication
               1. http://www.fda.gov/Drugs/DrugSafety/ucm339112.htm
4. Precautions: Variable metabolism of oral Narcotics
   1. Most oral Opioids are metabolized to active form (e.g. Morphine) by Cytochrome P450 2D6 (CYP2D6)
      1. Codeine
      2. Tramadol (Ultram)
      3. Hydrocodone
      4. Oxycodone
   2. Ultrarapid CYP2D6 Metabolizers
      1. Accounts for 10% of caucasians (may be as high as 30% in some races)
      2. Risk of a rapid conversion to toxic levels of active Opioid (e.g., Morphine)
   3. Slow CYP2D6 Metabolizers
      1. Accounts for 10% of caucasians (or 3% of other races)
      2. Renders the oral Opioids less effective in slow metabolizing patients
   4. References
      1. (2012) Presc Lett 19(6): 33
      2. Crews (2012) Clin Pharmacol Ther 91:321-6
5. Preparations: Acute pain IV Narcotics (equivalent to Demerol 50 IV)
   1. Morphine 4 mg IV (2 mg IV in elderly)
   2. Fentanyl 50 mcg IV (25 mcg IV in elderly)
   3. Hydromorphone (Dilaudid) 0.5 mg IV
      1. Elderly, Opioid naive, or moderate pain: 0.4 mg IV every 15 to 30 minutes up to 3 doses
      2. Opioid tolerant or severe pain: Start with 1 mg IV
6. Preparations: Oral Narcotics by Strength
   1. Weak Opioids (WHO Step 2)
      1. Vicodin (Hydrocodone 5, Acetaminophen 500)
         1. Dose: 1-2 PO q4-6 hours
         2. Hydrocodone 10 mg equivalent to Codeine 60-80 mg
      2. Vicoprofen (Hydrocodone 7.5, Ibuprofen 200)
         1. Dose: 1-2 PO q4-6 hours
      3. Tramadol (Ultram)
         1. Dose: 50-100 mg PO q4-6 hours
         2. Tramadol 50 mg equivalent to Codeine 60 mg
         3. Higher cost, but less effective than other Opioids
         4. Inferior to Vicodin for analgesia
            1. Turturro (1998) Ann Emerg Med 32:139-143
   2. Strong Opioids (WHO Step 3)
      1. Oxycodone
         1. Adults (and over age 12 years) 5-10 mg every 4-6 hours as needed
         2. Child: 0.05 to 0.3 mg/kg/dose (up to 10 mg) every 4-6 hours as needed
      2. Percocet (Acetaminophen 325, Oxycodone 5)
         1. Dose: 1 PO q6 hours (adults)
      3. Hydromorphone (Dilaudid)
         1. Dose: 2 mg PO q4-6 hours
      4. Morphine Sulfate (MSIR, MS Contin)
         1. Fast Release: 15 to 30 mg PO q4 hours
         2. Sustained Release (MS Contin): 30 mg PO q8-12 hours
      5. Fentanyl Lollipop (100 ug, 200 ug, 300 ug, 400 ug)
         1. Dose: 5 to 15 ug/kg (maximum 400 ug)
      6. Methadone (Dolophine)
         1. Dose: 15 to 60 mg PO q6 to 8 hours
7. Preparations: Oral Narcotics by Duration
   1. Short acting Opioids
      1. Percocet PO every 6 hours
      2. MSIR 10 mg PO every 4 hours
      3. Hydromorphone 4 mg PO every 4 hours
      4. Vicodin PO every 6 hours
      5. Darvocet N-100 PO every 6 hours
   2. Long acting Opioids
      1. Methadone 20 mg PO every 8 hours
      2. Morphine Sulfate
         1. Controlled release (MS Contin) 30 mg PO q12 hours
         2. Sustained release (Oramorph) PO q8-12 hours
         3. Sustained release (Kadian) PO q12-24 hours
         4. Extended release (Avinza) PO q24 hours
      3. Oxycodone (Oxycontin) 20 mg PO every 12 hours
8. Preparations: Equivalent Narcotic Doses (for comparison only)
   1. Fentanyl (Sublimaze) 20 mcg per hour IV or transdermal
   2. Hydromorphone (Dilaudid) 1.5 mg IV (7.5 mg orally)
   3. Methadone 2.5 mg IV (5 mg orally)
      1. Conversion ratio to morphine is variable per dose
      2. See Methadone for conversion ratios
   4. Oxymorphone 10 mg orally
   5. Oxycodone 20 mg orally
   6. Morphine 10 mg IV (30 mg orally)
   7. Hydrocodone 30 mg orally
   8. Nalbuphine (Nubain) 10 mg IV
   9. Meperidine (Demerol) 75 mg IV (300 mg orally)
   10. Codeine 120 mg IV (200 mg orally)
9. Preparations: Transdermal Narcotics
   1. Fentanyl (Duragesic) Patch
      1. Dose: 25 to 100 ug/hour patch q72 hours
      2. Fentanyl 50 ug/hour equivalent Morphine IV 25 mg/day
10. Preparations: Rectal Narcotics
    1. General
       1. Do not use lubricant to insert (decreased absorption)
    2. Morphine suppository or tablet 10 to 30 mg rectally q4h
    3. MS Contin 30 mg rectally every 12 hours
       1. Available preparations: 15, 30, 60, 100, 200 mg
11. Preparations: Adjunctive medications
    1. Alternative non-Narcotics
       1. See Chronic Pain Management
       2. Acetaminophen (Tylenol)
       3. NSAIDs
       4. COX-2 Inhibitors
    2. Stool Softeners or Laxatives
       1. See Bowel Regimen in Chronic Narcotic Use
12. Protocol: Switching between Opioids
    1. Option 1: Rapid conversion
       1. Step 1: Discontinue Drug 1
          1. Calculate equi-Analgesic doses
       2. Step 2: Begin the new Drug 2
          1. Start dose at 20-50% of equi-Analgesic dose
          2. Accounts for drug tolerance to discontinued drug
    2. Option 2: Cross titration
       1. Step 1: Initiate new Opioid while still taking old Opioid
          1. Start new Opioid at lowest available dose
          2. Decrease old Opioid by 10-30%
       2. Step 2: Titrate up the new Opioid while tapering off the old Opioid over 3-4 weeks
          1. Increase new Opioid by 10-20% each week
          2. Decrease old Opioid by 10-25% each week
    3. Precautions
       1. Do not use equi-Analgesic dose or conversion charts for dosing Methadone or non-IV Fentanyl
    4. References
       1. (2012) Presc Lett 19(8): 43
13. Dosing: Maximal effective doses in Chronic Pain
    1. Immediate release agents
       1. One to two tablets up to 4 times daily
    2. Sustained release agents
       1. Morphine: 200 mg/day
       2. Oxycodone: 120 mg/day
       3. Fentanyl: 100 mcg/hour
       4. Methadone: 60 mg/day
    3. References
       1. Chou (2009) Journal of Pain
14. References
    1. Dachs (2003) AAFP Board Review, Seattle
    2. (2000) Tarascon Pocket Pharmacopoeia
    3. (2000) Med Lett Drugs Ther 42(1085):73-8