Drug | Sample initial dose for opioid naïve adults* | Onset of analgesia | Elimination half life | Duration of analgesic effect¶ | Metabolism and clearance | Comments |
Parenteral | ||||||
Fentanyl | 25 to 50 mcg IV for moderate pain or 50 to 100 mcg for more severe pain; repeat every 2 to 5 minutes as needed until adequate pain relief or side effects occur; then reassess pain control regimen | <1 minute; peak effect within several minutes | 2 to 4 hours for bolus | 30 to 60 minutes |
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Morphine | 1 to 3 mg IV; repeat every 5 to 10 minutes as needed until adequate pain relief; then 1 to 3 mg IV every 1 to 4 hours as needed | 5 to 10 minutes; peak effect within 20 minutes | 2 to 4 hours | 3 to 5 hours |
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Hydromorphone | 0.2 to 0.5 mg IV; repeat every 5 minutes as needed until adequate pain relief, then 0.2 to 0.5 mg IV every 3 to 4 hours as needed | 5 minutes; peak effect 10 to 20 minutes | 2 to 3 hours | 3 to 4 hours |
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Oliceridine | Initial dose 1.5 mg IV; subsequent doses of 0.75 mg IV no more frequently than hourly◊; maximum total cumulative daily dose 27 mg IV | 2 to 5 minutes | 1.3 to 3 hours; increased in patients with hepatic dysfunction | 1 to 3 hours |
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Oral | ||||||
Oxycodone (immediate release) | 5 to 10 mg orally every 3 to 4 hours as needed | 10 to 15 minutes; peak effect 0.5 to 1 hour | 3 to 4 hours; increased in kidney or hepatic dysfunction | 3 to 6 hours |
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Hydromorphone (immediate release) | 2 to 4 mg orally every 3 to 4 hours as needed | 15 to 30 minutes; peak effect 30 to 60 minutes | 2 to 3 hours | 3 to 4 hours |
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Hydrocodone (immediate release) | 5 to 10 mg orally every 4 to 6 hours as needed | 10 to 30 minutes; peak effect 60 minutes | ~4 hours | 4 to 8 hours |
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Morphine (immediate release) | 10 to 15 mg orally every 3 to 4 hours as needed | ~30 minutes | 2 to 4 hours | 3 to 5 hours |
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Tramadol (immediate release) | 50 to 100 mg orally every 4 to 6 hours as needed (maximum 400 mg per day) | Within 1 hour; peak effect 2 to 3 hours | 6 to 9 hours (including active metabolite); increased in kidney or hepatic dysfunction | 4 to 6 hours |
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Tapentadol (immediate release) | 50 to 100 mg orally every 4 to 6 hours as needed; maximum dose:
| Within 1 hour; peak effect 1.25 hours | 4 hours; increased in kidney or hepatic dysfunction | 4 to 6 hours |
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Codeine (immediate release) | 15 to 60 mg orally every 4 to 6 hours as needed | 0.5 to 1 hour; peak effect 1 to 1.5 hours (variable; refer to comment) | ~3 hours | 4 to 6 hours |
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Methadone | 2.5 to 5 mg orally every 8 to 12 hours | 0.5 to 1 hour | 8 to ≥59 hours | 4 to 8 hours for single dose, increases to 8 to 12 hours with repeated doses |
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AUC0-24: area under plasma concentration versus time at 0-24 hours after dose; CrCl: creatinine clearance; IV: intravenous; MAO-I: monoamine oxidase inhibitor; NMDA: N-methyl-D-aspartate; P-gp: P-glycoprotein; SNRI: serotonin-norepinephrine reuptake inhibitor; SSRI: selective serotonin reuptake inhibitor; TCA: tricyclic antidepressants.
* Lower doses may be effective for patients who simultaneously receive nonopioid analgesics. A dose reduction of approximately 50% and a reduced frequency is warranted for older or debilitated adults or patients with impaired liver or kidney functioning, low cardiac output, or respiratory compromise.
¶ The duration of action is highly variable among individuals and is influenced by the dose, variations in metabolism, subjective patient experience, and combination with other therapies. As such, the expected duration of action for each type of opioid is only a rough estimate.
Δ Opioids metabolized by CYP pathways or substrates of P-gp-mediated efflux may be subject to interaction with drugs that either inhibit or accelerate CYP metabolism or P-gp-mediated efflux. Lists of drugs that alter CYP3A4, 2D6, and P-gp-mediated efflux are available as separate tables in UpToDate. In addition, patients may have polymorphisms of cytochrome P450 (CYP) genes that affect drug metabolism. Polymorphisms may contribute to either diminished or absent metabolic enzymes or excessive metabolism, either of which can change the clinical effect of a given dose of opioid. Poor, intermediate, extensive, and ultrarapid CYP2D6 function types have been well characterized. Significant drug interactions may be identified by use of the drug interactions program included within UpToDate.
◊ After initial two doses, oliceridine dose may be titrated, if needed, based on tolerability and response up to a maximum of 3 mg per dose, at intervals of one hour or more; maximum cumulative dose is 27 mg per day.
§ Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) are usually administered on a regular basis as part of multimodal therapy. Avoiding combination preparations (ie, opioid plus nonopioid) allows fixed schedule administration of the nonopioid medication regardless of the patient's opioid utilization, without limitation by the maximum daily dose of the nonopioid.Do you want to add Medilib to your home screen?