II. Pharmacology: Metabolism of Opioids

  1. Common Metabolites
    1. Codeine: Metabolizes to Hydrocodone and morphine
    2. Heroin: Metabolizes to 6-MAM and then to Morphine
    3. Morphine and Hydrocodone: metabolize to Hydromorphone
  2. Renal dysfunction
    1. Safe
      1. Fentanyl (consider reduced dose)
      2. Methadone
    2. Caution (risk of metabolite accumulation)
      1. Hydromorphone
      2. Morphine
      3. Oxycodone
    3. Unsafe (avoid)
      1. Codeine
  3. Hepatic dysfunction
    1. Safe
      1. Fentanyl
    2. Caution
      1. Hydromorphone (decrease starting dose by 50%)
      2. Oxycodone (decrease starting dose by 50%)
      3. Morphine (decreased conversion to active metabolite, increased dosing frequency may be needed)
    3. Unsafe (avoid)
      1. Codeine
      2. Methadone
  4. References
    1. Johnson (2007) Opioid Safety in Patients With Renal or Hepatic Dysfunction, Pain Treatment Topics
      1. http://paincommunity.org/blog/wp-content/uploads/Opioids-Renal-Hepatic-Dysfunction.pdf

III. Precautions: Ineffective Oral Opioids (Not recommended)

  1. Darvocet N-100 (Acetaminophen 650, Propoxyphene 100)
    1. Dose: 1 PO q4-6 hours
    2. Not available in U.S. as of 2007-2010
    3. Not recommended due to low efficacy and toxicity risk
  2. Tylenol #3 (Acetaminophen 300, Codeine 30)
    1. Dose: 1-2 PO q4-6 hours
    2. Avoid due to low efficacy and increased toxicity risk

IV. Precautions: Variable metabolism of oral Opioids

  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 [PubMed] (or open in [QxMD Read])

V. Preparations: Acute pain IV Opioids (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

VI. Preparations: Oral Opioids 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 [PubMed] (or open in [QxMD Read])
  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

VII. Preparations: Oral Opioids 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

VIII. Preparations: Equivalent Opioid Doses (for comparison only - do not use these doses)

  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)
  11. Tramadol (900 mg orally)

IX. Preparations: Transdermal Opioid

  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

X. Preparations: Transmucosal Opioid

  1. Precaution
    1. Indicated for breakthrough Cancer Pain in those using >60 mg/day of morphine or equivalent
  2. Fentanyl
    1. Sublingual tab (Abstral) 100 mcg
    2. Sublingual spray (Subsys) 100 mcg
    3. Nasal spray (Lazanda) 100 mcg

XI. Preparations: Rectal Opioids

  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

XII. Preparations: By Opioid origin

  1. Naturally occurring opiates (Opioid subset)
    1. Morphine
    2. Codeine
    3. Heroin (Morphine metabolite)
  2. Semi-synthetic Opioids (structurally similar to opiates)
    1. Hydrocodone
    2. Oxycodone
    3. Hydromorphone
    4. Oxymorphone
  3. Synthetic Opioids
    1. Methadone
    2. Buprenorphine
    3. Meperidine
    4. Fentanyl
    5. Tramadol

XIII. Preparations: Opioid Abuse deterrents (e.g. Tamper resistant)

  1. Precautions
    1. Abuse deterrents are inconsistent among products
      1. Long-acting Hydrocodone (Zohydro) is not tamper resistant
    2. Abuse deterrents are not shown to reduce abuse
      1. abuse deterrent may simply offset abuse to other substances (e.g. Heroin)
    3. Abuse deterrents increase Opioid costs up to four fold
  2. Agents with abuse deterrents
    1. Opioids with abuse antagonists
      1. Buprenorphine with Naloxone (Suboxone, Zubsolv)
    2. Opioids with tamper resistance (e.g. break into clumps when crushed or thick gel when wet)
      1. Long-Acting Oxycodone (Oxycontin)
      2. Extended Release Hydromorphone (Exalgo)
  3. References
    1. (2014) Presc Lett 21(5): 28

XIV. Preparations: Adjunctive medications

XV. 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

XVI. 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 [PubMed] (or open in [QxMD Read])

XVII. References

  1. Dachs (2003) AAFP Board Review, Seattle
  2. (2000) Tarascon Pocket Pharmacopoeia
  3. (2000) Med Lett Drugs Ther 42(1085):73-8 [PubMed] (or open in [QxMD Read])

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Ontology: Opioids (C0242402)

Definition (NCI) A substance used to treat moderate to severe pain. Opioids are like opiates, such as morphine and codeine, but are not made from opium. Opioids bind to opioid receptors in the central nervous system. An opioid is a type of alkaloid.
Definition (NCI) A class of synthetic chemicals/drugs similar to opiates (opium derivatives) with analgesic properties. Due to binding to opiate receptors, opioids mimic opiate activity on neurons, various cells (i.e. lymphocytes), pain suppression and other neurobehavioral activity. (NCI)
Concepts Organic Chemical (T109) , Pharmacologic Substance(T121) , Hazardous or Poisonous Substance(T131)
MSH D000701
SnomedCT 255663005, 373303004, 404642006, 360204007, 3622004
English OPIATE AGONISTS, Opiate agonist, NOS, Opioid (product), Opioids, Opiate agonist agent, opiates in any form, opioids in any form, opioids, opioid product, 606-607 OPIATE AGONISTS, opiate agonist, opiate agonists, opioid, Opioid, Opiate agonist (substance), Opiate agonist product, Opiate agonist, Opioid product, Opiate product, Opiate (substance), Opiate agonist (product), Opioid (substance), Opioid agent, Opiate Agonists
Spanish opioide (producto), Opioides, agonista opioide, agonista opiáceo (producto), opioide (sustancia), opioide, opiáceo, agonista opiáceo (sustancia), agonista opiáceo
Czech opioidy
Portuguese Opióides
French Opioïdes
German Opioide
Italian Oppioidi