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

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Long-Acting/ER Opioids 1 Initial Dosage (in opioidnaïve, unless specified) Other Dosing Information • Morphine CR or SR tablets should be swallowed whole, not broken, chewed, or crushed • For patients who have difficulty swallowing, SR and ER capsules may be opened and the pellets may be sprinkled onto a small amount of soft food (for administration without chewing) or administered via 16F gastrostomy tube • Steady state achieved with morphine ER within 24 to 36 hr Dosing In Special Populations Information applies to all formulations of morphine listed • Elderly patients: Use with caution and at lower dose • Patients with renal dysfunction: Bioavailability is increased and clearance is decreased; metabolites M3G and M6G accumulate significantly • Reduce dose or, if severe renal impairment exists, avoid use • Patients with hepatic dysfunction: Clearance decreases and half-life increases; M3G and M6G to morphine ratios are reduced; use carefully in patients with cirrhosis and consider reducing dose or extending dosing interval by 1.5 to 2 times Other Considerations • Morphine SR is preferred first-line long-acting agent because of similar efficacy to other longacting opioids, comparable safety profile, provider familiarity with use, and lower cost • M6G, an active metabolite, may accumulate in renal impairment and contribute to excessive opioid effects • M3G, a metabolite without analgesic activity, may accumulate in renal impairment; this metabolite has been implicated in morphine-induced neurotoxicity, hyperalgesia, and allodynia • Morphine/naltrexone ER capsule has abuse deterrent labeling related to potential to precipitate withdrawal if drug is taken by other than oral route Morphine Controlled (CR) or Sustained- Release (SR) • Available in 15, 30, 60, 100, and 200 mg strengths for every 8 to 12 hr administration • Morphine ER Capsules available in 10, 20, 30, 40, 50, 60, 70, 80, 100, 130, 150, and 200 mg capsule strengths for once daily administration Morphine and Naltrexone ER Capsule • Available as 20/0.8, 30/1.2, 50/2, 60/2.4, 80/3.2, and 100/4 capsule strengths (mg morphine/mg naltrexone) for once or twice-daily administration • Opioid naïve patients: Morphine CR or SR 15 mg every 8 to 12 hr • Total daily increments of
Long-Acting/ER Opioids 1 Initial Dosage (in opioidnaïve, unless specified) Other Dosing Information • Dose change increments: may increase to 20 mg (tablets) or 18 mg (capsules) every 12 hr after 1 or 2 days; thereafter, the total daily dose may be increased by 25-50% of the current dose every 1 or 2 days • ER tablets are not bioequivalent to ER capsules; 10 mg oxycodone HCl (ER tablet) = 9 mg oxycodone base (ER capsule) • Steady state achieved with tablets or capsules in 24 to 36 hr with repeat dosing Dosing In Special Populations • Elderly patients: Plasma concentrations of oxycodone are increased ~15% in the elderly; however, usual dosing and dosing intervals may be appropriate • Patients with renal dysfunction: Plasma concentrations of oxycodone are increased ~50% in patients with CrCl
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DRAFT 3 - DO NOT DISTRIBUTE VA/DoD
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VA/DoD CLINICAL PRACTICE GUIDELINE FOR OPIOID THERAPY FOR CHRONIC PAIN

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