VA/DoD CLINICAL PRACTICE GUIDELINE FOR OPIOID THERAPY FOR CHRONIC PAIN

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Short-Acting Opioid Initial Oral Dosage (in opioid-naïve) Additional Dosage Information • Maximum dose: • 60 mg/d (4000 mg/d APAP; 2000 mg/d APAP in chronic alcoholics or hepatic impairment) for hydrocodone + APAP combination OR • 37.5 to 50 mg/d (1000 mg/d IBU) for hydrocodone + IBU combination • There is no optimal or maximum dose of hydromorphone; patients on LOT are likely to become tolerant 4 and require doses higher than the usual dosage range to maintain the desired effect Analgesic Onset (min) Peak (min) Duration (hr) Dosing In Special Populations • Elderly or debilitated: Use with caution; start with reduced dose (2.5-5 mg) of hydrocodone component • Hepatic dysfunction: Use with caution Other Considerations • Conversion to the active metabolite, hydromorphone, may be decreased in patients with decreased CYP-2D6 activity (due to poor CYP-2D6 metabolism or CYP-2D6 inhibiting drugs 2 ) • CYP-2D6 ultra-rapid metabolizers 3 can have extensive conversion to hydromorphone with potential increase in opioid-mediated effects Hydrocodone (in combination with APAP, ASA, or IBU) • Combination products vary in hydrocodone content (2.5 to 10 mg per dosage unit) • 5 to 10 mg every 6 hr (hydrocodone component) • Initial dose based upon hydrocodone component • Maximum dose based upon non-opioid component 10 to 20 60 to 100 4 to 8 Hydromorphone • Available as oral liquid 1 mg/ml, and 2, 4, and 8 mg tablets • 2 mg every 4 to 6 hr • May give an initial dose of 4 to 8 mg for severe pain 15 to 30 30 to 60 3 to 4 • Elderly or debilitated: Use with caution, start at 25 to 50% of usual dose at low end of dosing range • Hepatic / Renal dysfunction: Reduce initial dose for moderate impairment, more with severe impairment February 2017 Page 82 of 192
Short-Acting Opioid Initial Oral Dosage (in opioid-naïve) Additional Dosage Information Analgesic Onset (min) Peak (min) Duration (hr) 30 60 3 to 5 Dosing In Special Populations Other Considerations • M6G, an active metabolite, may accumulate in renal impairment • M3G, a metabolite without analgesic activity, may accumulate in renal impairment; this metabolite has been implicated in morphine-induced neurotoxicity, hyperalgesia, and allodynia Morphine • Available as oral solution (10 or 20 mg/5 ml, or 100 mg/5 ml for opioidtolerant patients only) or as 15 or 30 mg tablets • 10 to 30 mg every 4 hr • There is no optimal or maximum dose of morphine; patients on LOT are likely to become tolerant 4 and require doses higher than the usual dosage range to maintain the desired effect • Elderly or debilitated: Give with extreme caution; use lower dose • Hepatic dysfunction: Use carefully in patients with cirrhosis and consider reducing dose or extending dosing interval by 1.5 to 2 times; half-life may be doubled (3 to 4 hr) and bioavailability is increased • Renal dysfunction: Reduce dose or, if severe renal impairment exists, avoid use (see Other Considerations) February 2017 Page 83 of 192
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VA/DoD CLINICAL PRACTICE GUIDELINE FOR OPIOID THERAPY FOR CHRONIC PAIN

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