|Opioid Agonists2,3 |
|Buprenorphine parenteral (Buprenex) || ||300 mcg intravenously slowly once, may be repeated after 30–60 minutes once; or 600 mcg intramuscularly once || ||300 mcg intravenously slowly once, may be repeated after 30–60 minutes once; or 600 mcg intramuscularly once; $18.20/300 mcg || || || || |
|Buprenorphine transdermal (BuTrans) ||Not available ||Not available || |
Not available orally.
Transdermal doses available: 5, 10, and 20 mcg/h. Initiate 5 mcg/h patch for opioid-naïve patients (may currently be using nonopioid analgesics); $114.77/10 mcg/h.
|Not available ||Not available ||Not available || |
analgesia; may be initiated in opioid-naïve patients with 5 mcg/h.
Can titrate up dose by 5 mcg/h after 72 hours, to a maximum dose of 20 mcg/h.
Concomitant use of other opioids for acute pain could be difficult due to strong receptor binding of buprenorphine, although this is often not found in clinical practice.
|Buprenorphine sublingual (Belbuca) ||Sublingual strip approved for pain || || |
In opioid-naive or opioid-intolerant patients, individualize dose every 12 h. Start: 75 mcg buccally every 12–24 h for at least 4 days, then increase to 150 mcg buccally every 12 h, then may increase by no more than 150 mcg buccally every 12 h no more frequently than every 4 days.
Maximum: 900 mcg/12 h;
| || || || || |
Used by pain management specialists.
Do no cut, chew, swallow strip. Taper slowly to discontinue.
Use lowest effective dose, shortest effective treatment duration. Titrate slowly in patients age > 65 yrs.
See footnote4 for dosing in opioid-experienced patients.
|Fentanyl ||Not available ||100 mcg every hour ||Not available || |
50–100 mcg intravenously/intramuscularly every hour or 0.5–1.5 mcg/kg/h intravenous infusion;
|Not available ||0.5–1 mcg/kg intravenously every 1–4 hours or 1–2 mcg/kg intravenously × 1, then 0.5–1 mcg/kg/h infusion ||Possibly less neuroexcitatory effects, including in kidney failure. || |
|Fentanyl oral transmucosal (Actiq); buccal (Fentora) ||Not available ||Not available ||200 mcg transmucosal; 100 mcg buccal; $18.80/200 mcg transmucosal; $81.60/200 mcg buccal ||Not available ||Not available ||Not available ||For pain breaking through long-acting opioid medication. ||Transmucosal and buccal formulations are not bioequivalent; there is higher bioavailability in buccal formulation. |
|Fentanyl transdermal ||Conversion to fentanyl patch is based on total daily dose of oral morphine:2 morphine 60–134 mg/day orally = fentanyl 25 mcg/h patch; morphine 135–224 mg/day orally = fentanyl 50 mcg/h patch; morphine 225–314 mg/day orally = fentanyl 75 mcg/h patch; and morphine 315–404 mg/day orally = fentanyl 100 mcg/h patch ||Not available || |
Not available orally
12.5–25 mcg/h patch every 72 hours; $14.43/25 mcg/h
|Not available ||12.5–25 mcg/h patch every 72 hours ||Not available ||Stable medication blood levels. ||Not for use in opioid-naïve patients. Minimum starting dose is 25 mcg/h patch in patients who have been taking stable dose of opioids for at least 1 week at the equivalent of at least 60 mg/day of oral morphine. |
|Hydrocodone, extended release (Zohydro ER) ||20 mg1 ||Not available ||10 mg every 12 hours; $11.11/10 mg ||Not available ||Not available ||Not available ||Available as an extended-release formulation without acetaminophen. || |
|Hydromorphone5 (Dilaudid) ||7.5 mg every 3–4 hours ||1.5 mg every 3–4 hours ||1–2 mg every 3–4 hours; $0.48/2 mg ||1.5 mg every 3–4 hours; $1.80/2 mg ||0.06 mg/every 3–4 hours ||0.015 mg/kg every 3–4 hours ||Similar to morphine. Available in injectable high-potency preparation, rectal suppository. ||Short duration. |
|Hydromorphone extended release (Exalgo) ||45–60 mg every 24 hours ||Not available ||8 mg every 24 hours; $16.73/8 mg ||Not available ||Not available ||Not available ||Similar to morphine. ||Taper dose 25–50% every 2–3 days to 8 mg/day to discontinue. |
|Levorphanol (Levo-Dromoran) ||4 mg every 6–8 hours ||Not available ||4 mg every 6–8 hours; $53.40/2 mg ||Not available ||0.04 mg/kg every 6–8 hours ||Not available ||Longer acting than morphine sulfate. || |
|Meperidine6 (Demerol) ||300 mg every 2–3 hours; usual dose 50–150 mg every 3–4 hours ||100 mg every 3 hours ||Not recommended ||100 mg every 3 hours; $2.72/100 mg ||Not recommended ||0.75 mg/kg every 2–3 hours ||Use only when single-dose, short-duration analgesia is needed, as for outpatient procedures like colonoscopy. Not recommended for chronic pain or for repeated dosing. ||Short duration. Normeperidine metabolite accumulates in kidney failure and other situations, and in high concentrations may cause irritability and seizures. |
|Methadone (Dolophine, others) ||10–20 mg every 6–8 hours (when converting from < 100 mg long-term daily oral morphine7) ||5–10 mg every 6–8 hours ||5–20 mg every 6–8 hours; $0.31/10 mg ||2.5–10 mg every 6–8 hours; $21.00/10 mg ||0.2 mg/kg every 6–8 hours ||0.1 mg/kg every 6–8 hours || |
Somewhat longer acting than morphine. Useful in cases of intolerance to morphine.
May be particularly useful for neuropathic pain. Available in liquid formulation.
|Analgesic duration shorter than plasma duration. May accumulate, requiring close monitoring during first weeks of treatment. Equianalgesic ratios vary with opioid dose. Risk of QT prolongation at doses > 100–150 mg/day. Baseline ECG recommended. |
|Morphine5 immediate release (Morphine sulfate tablets, Roxanol liquid) ||30 mg every 3–4 hours (around-the-clock dosing); 60 mg every 3–4 hours (single or intermittent dosing) ||10 mg every 3–4 hours ||4–8 mg every 3–4 hours; used for breakthrough pain in patients already taking controlled-release preparations; $0.52/15 mg tab; $0.84/20 mg liquid ||10 mg every 3–4 hours; $11.90/10 mg ||0.3 mg/kg every 3–4 hours ||0.1 mg/kg every 3–4 hours ||Standard of comparison; multiple dosage forms available. || |
No unique problems when compared with other opioids.
Active metabolite accumulates in kidney dysfunction.
|Morphine controlled release (MS Contin, Oramorph) ||90–120 mg every 12 hours ||Not available ||15–60 mg every 12 hours; $1.50/30 mg ||Not available ||Not available ||Not available || || |
|Morphine extended release (Kadian, Avinza) ||180–240 mg every 24 hours ||Not available ||20–30 mg every 24 hours; $5.69/30 mg ||Not available ||Not available ||Not available ||Once-daily dosing possible. || |
|Oxycodone (Roxicodone, OxyIR) ||20–30 mg every 3–4 hours ||Not available ||5–10 mg every 3–4 hours; $0.48/5 mg ||Not available ||0.2 mg/kg every 3–4 hours ||Not available ||Similar to morphine. || |
|Oxycodone controlled release (Oxycontin) ||40 mg every 12 hours ||Not available ||20–40 mg every 12 hours; $9.00/20 mg || || || || ||Physical and chemical pill formulation to deter misuse (injection or intranasal administration). |
|Oxymorphone5,8 oral, immediate release (Opana) ||10 mg every 6 hours ||Not available ||5–10 mg every 6 hours; $2.95/5 mg ||Not available || || || || |
Taking with food can increase serum levels by 50%.
Equianalgesic dosing conversion range is wide.
|Combination Opioid Agonist–Nonopioid Preparations |
|Codeine9,10 (with aspirin or acetaminophen)11 ||180–200 mg every 3–4 hours; commonly available dose in combination with acetaminophen, 15–60 mg of codeine every 4–6 hours ||130 mg every 3–4 hours ||60 mg every 4–6 hours; $0.64/60 mg ||60 mg every 2 hours intramuscularly/subcutaneously; not available in the United States ||0.5–1 mg/kg every 3–4 hours ||Not recommended ||Similar to morphine. ||Closely monitor for efficacy as patients vary in their ability to convert the prodrug codeine to morphine. |
|Hydrocodone8 (in Lorcet, Lortab, Vicodin, others)11 ||30 mg every 3–4 hours ||Not available ||10 mg every 3–4 hours; $0.54/5 mg ||Not available ||0.2 mg/kg every 3–4 hours ||Not available || ||Combination with acetaminophen limits dosage titration. |
|Oxycodone10 (in Percodan, Tylox, others)11 ||30 mg every 3–4 hours ||Not available ||10 mg every 3–4 hours; $1.37/5 mg ||Not available ||0.2 mg/kg every 3–4 hours ||Not available ||Similar to morphine. ||Combination with acetaminophen and aspirin limits dosage titration. |
|Combination Opioid Agonist–Norepinephrine Reuptake Inhibitor Preparations |
|Tapentadol (Nucynta) ||Not known ||Not known ||Start 50–100 mg once, may repeat dose in 1 hour. Can increase to 50–100 mg every 4 hours. Maximum daily dose 600 mg; $11.89/100 mg. ||Not available || ||Not available || ||Avoid in severe kidney or liver impairment. |
|Tapentadol, extended release (Nucynta ER) ||Not known ||Not known ||Start 50 mg orally every 12 hours. Can increase by 50-mg increments twice daily every 3 days to dose of 100–250 mg twice daily; $15.20/100 mg. ||Not available || ||Not available || ||Avoid in severe kidney or liver impairment. |
|Tramadol (Ultram) ||Not known ||Not known ||Start 25 mg orally daily. Can increase by 25 mg every 3 days to 25 mg orally 4 times daily, then may increase by 50 mg/day every 3 days to 100 mg orally 4 times daily. Limit of 300 mg/day in patients > 75 years old; $0.83/50 mg. ||Not available || ||Not available || ||If creatinine clearance less than 30, limit to 200 mg/day; with cirrhosis, limit to 100 mg/day. |