Opioid Stewardship in Pain Management
Opioid therapy should be reserved for pain severe enough to require opioids when nonopioid therapies are inadequate, initiated at the lowest effective dose with immediate-release formulations, titrated cautiously with frequent reassessment, and accompanied by robust risk mitigation strategies including prescription drug monitoring program checks, urine drug testing, and proactive management of adverse effects. 1
Core Principles of Opioid Stewardship
When to Initiate Opioids
Nonopioid therapies must be maximized first for both acute and chronic pain, as they are at least as effective as opioids for many common pain conditions including low back pain, neck pain, musculoskeletal injuries, minor surgeries, dental pain, and kidney stones. 1
Reserve opioids only when alternative treatments have failed or are inadequate, specifically when nonopioid analgesics or combination products have not been tolerated, are not expected to be tolerated, have not provided adequate analgesia, or are not expected to provide adequate analgesia. 2, 1
For acute pain, limit opioid prescriptions to 5-7 days maximum, with most acute pain conditions requiring no more than a few days of opioid therapy. 3, 4
For chronic pain (>3 months), establish clear treatment goals for both pain relief and functional improvement before initiating therapy, and discuss upfront how opioids will be discontinued if benefits do not outweigh risks. 5, 1
Initiation and Titration Strategy
Always start with immediate-release opioids prescribed as-needed (PRN) to establish an effective dose, never with extended-release/long-acting (ER/LA) formulations. 1, 3
Begin at the lowest possible dose to achieve acceptable analgesia, with early assessment and frequent titration. 1, 4
Reassess benefits and harms within 1-4 weeks of starting therapy or any dose escalation, then every 3 months or more frequently thereafter. 5, 1
Dose escalation should generally increase by 25-50% increments, though patient factors such as frailty, comorbidities, and organ function must be considered. 1
Prescribe opioids as-needed rather than on a scheduled basis (e.g., "hydrocodone 5 mg/acetaminophen 325 mg, one tablet not more frequently than every 4 hours as needed" rather than "one tablet every 4 hours"). 1
Dosing Thresholds and Caution Points
Up to 40 mg morphine milligram equivalents (MME) per day is considered low dose, 41-90 MME as moderate dose, and >91 MME as high dose. 6, 3
Exercise caution at any dose, but carefully reassess when considering doses ≥50 MME/day, as overdose risk increases with higher doses. 1, 5
Avoid or carefully justify titration to ≥90 MME/day, as observational data show increased overdose prevalence above 100 mg. 5, 1
Most patients with chronic non-cancer pain can be managed with <300 mg/day of morphine equivalent. 7
Mandatory Monitoring and Risk Mitigation
Prescription Drug Monitoring Programs (PDMPs)
Check PDMP data before initiating opioid therapy and before each refill to identify patterns of doctor shopping or concurrent prescriptions from multiple providers. 5, 3
Review PDMP data when considering dose escalation to detect high-risk combinations or dosages. 1
Urine Drug Testing (UDT)
Perform UDT before initiating opioid therapy and periodically throughout treatment to monitor adherence, identify non-adherence, and detect illicit drug use. 5, 3, 6
UDT must be implemented from initiation along with subsequent adherence monitoring to decrease prescription drug abuse. 6
Clinical Reassessment
Document comprehensive reassessment of pain, function, and quality of life using validated tools such as the PEG scale (Pain, Enjoyment, General activity). 5
Monitor for signs of opioid use disorder, including difficulty controlling use, continued use despite harm, and work/family problems related to opioid use. 5
Assess for adverse effects at each visit, including constipation, sedation, respiratory depression, and QT prolongation (particularly with methadone). 5, 1
Naloxone Co-Prescribing
- Offer naloxone when risk factors for overdose are present, including history of overdose, substance use disorder, doses ≥50 MME/day, or concurrent benzodiazepine use. 5
High-Risk Medications and Special Populations
Methadone
Methadone should not be the first choice for an ER/LA opioid and should only be prescribed by clinicians with specific training in its unique risks and complex pharmacokinetics. 5, 1
Clinicians without extensive methadone prescribing experience should consult palliative care or pain specialists when initiating or rotating to methadone. 1
Obtain an electrocardiogram before initiating methadone, at 30 days, and yearly thereafter to monitor for QT prolongation. 6, 1
Transdermal Fentanyl
Only clinicians familiar with the dosing and absorption properties of transdermal fentanyl should prescribe it, and it should be limited to opioid-tolerant patients. 1
Be aware that unpredictable absorption can occur with fever, exercise, or heat exposure. 1
Renal and Hepatic Impairment
For patients with renal impairment, consider rotating to methadone (if not contraindicated) as it is excreted fecally. 1
Carefully titrate and frequently monitor fentanyl, oxycodone, and hydromorphone in renal impairment due to risk of accumulation. 1
Avoid morphine, meperidine, codeine, and tramadol in renal impairment unless there are no alternatives, due to accumulation of toxic metabolites. 1
Perform more frequent clinical observation and dose adjustment in patients with renal or hepatic impairment. 1
Substance Use Disorder
- Collaborate with palliative care, pain, and/or substance use disorder specialists to determine the optimal approach to pain management in patients with substance use disorder. 1
Dangerous Drug Combinations
Avoid concurrent prescribing of opioids and benzodiazepines whenever possible, as this combination is associated with significantly increased overdose risk, particularly in elderly adults. 5, 1, 3
Be aware of pharmacokinetic interactions between other medications and opioids, particularly methadone, fentanyl, oxycodone, and tramadol. 1
Breakthrough Pain Management
In patients receiving around-the-clock opioids, prescribe immediate-release opioids at 5-20% of the daily morphine equivalent dose for breakthrough pain. 1
Evidence remains insufficient to recommend a specific short-acting opioid for breakthrough pain. 1
Opioid Rotation
Offer opioid rotation to patients with pain refractory to dose titration, poorly managed side effects, logistical or cost concerns, or trouble with route of administration. 1
When switching opioids, reduce doses by at least 25-50% to avoid inadvertent overdose due to incomplete cross-tolerance. 1
Adverse Effects Management
Proactively offer education and strategies to prevent known opioid-related adverse effects, monitor for their development, and manage them when they occur. 1
Initiate a bowel regimen as soon as deemed necessary, as constipation must be closely monitored. 6
Monitor sedation scores and respiratory rate to detect opioid-induced ventilatory impairment. 3
Patient Education and Agreements
Establish a robust treatment agreement that is followed by all parties, as such agreements reduce overuse, misuse, abuse, and diversion. 6
Provide education on safe self-administration, weaning protocols, and disposal of unused medications. 3
Educate patients on the dangers of driving or operating machinery while taking opioids. 3
Store opioids in a secure, preferably locked location and discuss options for safe disposal of unused medications. 5
Discontinuation and Tapering
When discontinuing opioids, initiate the taper by a small enough increment (no greater than 10-25% of the total daily dose) to avoid withdrawal symptoms, proceeding with dose-lowering at an interval of every 2-4 weeks. 8
Patients who have been taking opioids for briefer periods may tolerate a more rapid taper. 8
Reassess the patient frequently to manage pain and withdrawal symptoms, which may include restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, mydriasis, irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. 8
If withdrawal symptoms arise, pause the taper or raise the dose to the previous level, then proceed with a slower taper. 8
Ensure a multimodal approach to pain management, including mental health support if needed, is in place prior to initiating a taper. 8
Critical Pitfalls to Avoid
Never prescribe opioids as repeat/refill prescriptions without reassessment—they must only be documented as acute medications with explicit justification for continuation. 3
Avoid adding postoperative opioids to repeat prescription templates, as this can lead to inadvertent chronic therapy. 3
Do not automatically refill prescriptions without reassessing benefits and risks at each encounter. 5
Avoid prescribing beyond 7 days without documented medical necessity and specialist input for acute pain. 3
Do not use ER/LA opioids for acute pain or as first-line therapy, as they are associated with higher overdose risk, especially within the first 2 weeks of therapy. 1
Recognize that "abuse-deterrent" formulations do not prevent oral misuse (the most common route) or eliminate overdose risk. 1