| Drug | Suggested initial dose* and titration | Selected characteristics relevant to older adults |
| Acetaminophen (paracetamol) | 325 to 500 mg orally every 4 hours or 500 to 1000 mg every 6 to 8 hours (maximum 3 g per day) | - Effective analgesic that may decrease opioid requirements; often used in combination with tramadol
- Clearance is reduced with aging
- Maximum 2 g per day suggested for older adults who are frail, aged ≥80, with significant organ dysfunction, or at risk for hepatotoxicity (eg, regular alcohol use or malnourished)
- Interacts with warfarin (prolongs INR) and CYP450-inducing drugs (increased risk of hepatic inflammation)
- Warn patients concerning acetaminophen content in combination prescription analgesics (eg, oxycodone-acetaminophen) and OTC preparations
- For short-term or one-time use, a total dose of up to 4 g per day may be considered in selected older adults under medical supervision (eg, nursing facility)
|
| Opioid analgesics¶Δ: Older adults are more susceptible to opioid-induced adverse effects, including respiratory depression, hypotension, delirium, constipation, excessive sedation, and drug accumulation. Low doses should be used initially and titrated gradually to decrease risk of accumulation and overdose. The initial dose should be decreased by 25% for a 60-year-old patient and by 50% for an 80-year-old patient, from the initial dose that a 40-year-old would receive, but administered at the same intervals. |
| Tramadol |
| Immediate release◊ | Start with 25 mg orally once daily May increase daily dose by 25 to 50 mg after 3 to 7 days; give in 3 or 4 divided doses Age ≤75 years: Maximum 400 mg daily Age >75 years: Maximum 300 mg daily Renal impairment (CrCl <30 mL/min): Maximum 200 mg daily irrespective of age | - Partial mu-opioid agonist with norepinephrine/serotonin reuptake; associated with analgesic dose-ceiling effect, but may be less likely to cause physical dependence
- Approximately one-tenth as potent as morphine; wide inter-individual variation in response
- Metabolized by CYP2D6 (polymorphic) to active metabolites
- May cause nausea and dizziness; slowly titrate to improve tolerability in older adults
- Constipation and sedation less frequent than with strong opioids
- Renally cleared; dose adjust for renal impairment (CrCl <30 mL/min)
- Can interact with serotoninergic medications (eg, antidepressants and ondansetron)
- Avoid use in older adults at risk for seizures
|
| Extended release | Start with 100 mg orally once daily May increase daily dose by 100 mg after 5 or more days (maximum 300 mg daily) Avoid use in renal impairment (CrCl <30 mL/min) |
| Oxycodone |
| Immediate release◊ | Start with 2.5 to 5 mg orally every 4 hours as needed After 3 to 7 days, determine 24-hour dose requirement and convert to extended release | - Metabolized by CYP2D6 (polymorphic) and CYP3A4 to active metabolites
- Blood levels increased by approximately 50% in older adults with renal insufficiency (CrCl <60 mL/min); reduce dose and titrate gradually
- Some opioid-tolerant patients may require every-8-hour dosing of extended-release forms for effective analgesia; a 12- to 24-hour interval is appropriate for most older adults
|
| Extended release | Divide 24-hour dose requirement for oxycodone immediate release in 2 doses |
| Morphine |
| Immediate release | Start with 2.5 to 10 mg orally every 4 hours as needed (an oral solution is available for initial low doses; lowest tablet strength available in the United States is 15 mg) After 3 to 7 days, determine 24-hour dose requirement and convert to extended release | - In patients with renal impairment, clearance of active and potentially neurotoxic metabolites is decreased
- Hydromorphone or fentanyl may be a better choice for older adults with renal impairment (CrCl <60 mL/min)
- For extended-release forms, some patients may require every-8-hour dosing for effective analgesia; a 12- to 24-hour dosing interval is appropriate for most older adults
|
| Extended release¶ | Divide 24-hour dose requirement for immediate-release morphine in 1, 2, or 3 doses (depending on type of preparation) |
| Hydromorphone |
| Immediate release | Start with 1 to 2 mg orally every 4 hours as needed After 3 to 7 days, determine 24-hour dose requirement and covert to extended release | - Metabolism to apparently inactive metabolites is an advantage over morphine in older adults with renal or hepatic insufficiency
- Accumulation of a neurotoxic (excitatory) metabolite may become a concern in older adults with severe renal insufficiency or ESRD
|
| Extended release¶ | Divide 24-hour dose requirement for immediate-release hydromorphone in 1 or 2 doses (depending on type of preparation) |
| Transdermal fentanyl¶ | Determine 24-hour dose requirement using an immediate-release oral opioid; after 3 to 7 days, convert to an equianalgesic dose of transdermal fentanyl (refer to Lexicomp drug monograph for initial conversion) Or start with 12 mcg/hour patch every 72 hours; if ineffective after 1 week, increase to 25 mcg/hour patch | - Metabolized by CYP3A4 to inactive (nontoxic) metabolites and useful in patients with renal and/or hepatic dysfunction
- Full effect following application of first patch is delayed by 18 to 24 hours
- Steady state levels may not be reached in older adults until patch is used for 6 to 9 days
- Avoid in opioid-naïve patients
- Some opioid-tolerant patients may require a 48-hour dosing interval for effective analgesia; a 72-hour dosing interval is appropriate for most older adults
|
| Transdermal buprenorphine¶ | 5 mcg/hour patch every 7 days | - Partial mu agonist and weak kappa antagonist actions are associated with analgesic dose-ceiling effect but may be less likely to cause physical dependence than full agonist opioids
- Metabolized by CYP3A4 and glucuronidation to active metabolites
- Full effect following application of first patch is delayed by up to 72 hours
- Limited information on use in renal impairment
- Avoid or use with caution in opioid-naïve patients
- Precise role in treating older adults with painful conditions not well established
|
| Methadone | Start with 1 mg orally, buccal, or subcutaneously every 12 to 24 hours Increase daily dose by 1 to 2 mg after 7 or more days Further increases in daily dose of 1 to 2 mg should be made no more frequently than once every 7 days | - Consult with a pain specialist prior to prescribing
- Due to its highly variable half-life and wide inter-individual pharmacodynamics, methadone has the highest risk of accumulation and overdose during initial titration, periodic dose adjustment, and conversion from other opioids
- EKG should be obtained and monitored as methadone use is associated with QT interval prolongation
- Due to challenges inherent in safe prescribing of methadone, it is not a first-line analgesic choice
- For additional information, refer to the UpToDate topic reviews of treatment of chronic pain and cancer pain management with opioids
|
| Adjuvant analgesicsΔ: Includes options for painful polyneuropathies, muscle spasm, and multipurpose analgesics that may decrease opioid requirements. |
| Serotonin-norepinephrine reuptake inhibitors (SNRIs) |
| Duloxetine | Start with 20 to 30 mg orally per day May increase daily dose to 40 to 60 mg after 1 week Maximum 60 mg per day (CrCl ≥30 mL/min) | - Effective for painful neuropathies, low back pain, fibromyalgia, and chronic musculoskeletal pain due to osteoarthritis in older adults
- Titrate gradually over 2 weeks or more to improve tolerability
- Avoid in renal impairment (CrCl <30 mL/min) or hepatic impairment
|
| Venlafaxine (extended release) | Start with 37.5 mg orally per day May increase daily dose by 37.5 mg after 7 or more days; then may increase daily dose by 37.5 to 75 mg after 4 or more days Maximum 225 mg per day | - Effective for treatment of various painful polyneuropathies but not PHN
- Titrate gradually over 4 weeks or more to improve tolerability
- Dose-related increase in diastolic blood pressure may be seen
|
| Milnacipran | Start with 12.5 mg orally once per day (refer to Lexicomp drug monograph for titration) | - Useful for treatment of various painful conditions, including fibromyalgia
- Dose reduction needed for renal impairment
- Avoid use in older adults with ESRD or significant hepatic impairment
|
| Tricyclic antidepressants |
| Nortriptyline | Start with 10 mg orally at bedtime May increase daily dose by 10 mg after 7 or more days Maximum 50 mg per night | Applies to nortriptyline and desipramine: - Effective for treatment of neuropathies and other painful conditions
- Metabolized by CYP2D6 (polymorphic) to active and inactive metabolites
- Dose-related anticholinergic and cardiovascular side effects may be poorly tolerated in older adults relative to SNRIs
- Titrate gradually over 8 weeks or more to improve tolerability
- Use low maintenance dose of 25 to 50 mg to decrease risk of accumulation
- Accumulation toxicity in older adults is less likely with nortriptyline and desipramine than other tricyclic antidepressants (eg, amitriptyline)
- Low doses used for treatment of painful conditions may be insufficient for treatment of depression
|
| Desipramine | Start with 10 mg orally at bedtime May increase daily dose by 10 mg after 7 or more days Maximum 50 mg per night |
| Antiseizure medications |
| Gabapentin | Start with 100 mg orally at bedtime May increase daily dose by 100 mg after 7 or more days; give in divided doses Maximum 3600 mg per day (CrCl ≥60 mL/min) | Applies to gabapentin and pregabalin: - Effective for treatment of neuropathic and other painful conditions (eg, restless legs syndrome, fibromyalgia)
- Highly dependent on renal function for clearance
- Sedation and dizziness may limit usefulness in frail older adults
- Gradual titration over weeks is suggested to improve tolerability and to decrease risk of overdose due to the delayed onset of effect
- Maximum maintenance dose is determined by renal function; refer to Lexicomp monograph for detail
|
| Pregabalin | Start with 25 to 50 mg orally at bedtime May increase daily dose by 25 to 50 mg after 7 or more days; give in divided doses Maximum 300 mg per day (CrCl ≥60 mL/min) |
Oral nonsteroidal antiinflammatory drugs (NSAIDs)
Applies to all: - Due to increased side effects in older adults, use should be limited to brief course(s) in selected patients for painful flare-ups at lowest effective dose
- Avoid use of NSAIDs in older adults with renal insufficiency (CrCl <50 mL/min), GI bleeding, platelet dysfunction, reduced cardiac output, hypovolemic state, hyponatremia, hepatic impairment, or receiving an anticoagulant
- Dose- and age-associated risk of gastropathy; pharmacologic gastroprotection may be indicated even with COX-2 selective therapy (refer to UpToDate topic on prevention of NSAID-associated gastroduodenal toxicity)
- Can cause or worsen renal insufficiency, including age-associated decline in renal function
- Traditional NSAIDs (eg, ibuprofen, naproxen) reversibly inhibit platelet functioning and may alter cardioprotective effects of aspirin
- Use with serotonin reuptake inhibitor antidepressants (eg, SSRIs, nortriptyline, venlafaxine) additively decreases platelet functioning
|
| Naproxen sodium | 220 mg twice per day (equivalent to 200 mg naproxen base twice per day) | - Less cardiovascular toxicity than other nonselective NSAIDs
- Naproxen sodium has better absorption and more rapid onset than naproxen base
|
| Ibuprofen | 200 mg 3 times per day | - Short half-life may be advantageous in older adults
- Avoid combined use with cardioprotective (low-dose) aspirin therapy
|
| Celecoxib | 100 mg per day | - Relative reduction in GI toxicity compared with nonselective NSAIDs
- No effect on platelet functioning
- Patients taking cardioprotective aspirin may still need concurrent gastroprotection (eg, proton pump inhibitor)
|
| Diflunisal | 250 mg 2 or 3 times per day | Applies to nonacetylated salicylates: - No effect on platelet functioning at doses shown
- Generally tolerated by adults with asthma
- Relatively slow onset
|
| Salsalate | 500 mg 2 or 3 times per day |
| Topical therapies: Include topical NSAIDs, capsaicin, and topical lidocaine, which may be useful in combination with systemic therapies for reducing medication load and side effects for treatment of localized painful conditions; refer to separate table on topical analgesics. |
| Intraarticular glucocorticoids: Refer to topic review of initial pharmacologic therapy of osteoarthritis. |
