Opioids are the drugs of choice for pain in advanced disease.
Adjuvants and other therapies should always be considered.
Always consider total pain.
Essential opioid principles
There are 12 essentials to know when prescribing opioids:
- Opioids are the drug of choice for both pain and dyspnea in advanced disease.
- Patients with addiction should have pain/dyspnea treated — use long acting opioid medications, limited breakthroughs, small amount dispensed frequently.
- Opioids are safe in cardiopulmonary disease, but start low go slow.
- Persistent symptoms require regular dosing, i.e. short-acting opioid q4 hours.
- Not all opioids are the same, and inter-individual analgesia/side effects vary widely.
- Opioids with few or no active metabolites are preferred for those with renal failure or frailty.
- Always order breakthrough with regular dosing: 10% of total daily opioid dose q1h prn. Recalculate breakthrough dose when regular dose is changed.
- If 3 or more breakthroughs used in the last 24 hours, increase the regular dose.
- Titrate dose to the best symptom control with the fewest side effects.
- When you prescribe an opioid, prescribe a laxative.
- If side effects are intolerable, consider rotating opioid.
- Educate patient/family about control of symptoms and opioid safety.
Talk tip: “Controlling pain helps you to have better quality of life, and may even help you live longer.”
Talk tip: ”These medications can always be increased if you have more pain. They do not lose effectiveness over time.”
Talk tip: ”Our goal is to prevent pain, so take the medication as directed even if you don’t have pain at that time.”
Opioid Equianalgesic Table
|Tylenol #3 (codeine 30mg/acetaminophen 325mg)||2 tablets|
|Fentanyl – see note below|
Morphine to fentanyl
Fentanyl 25mcg/hr patch = 60-134mg morphine/day orally.
No active metabolites – good choice in frail elders and patients with renal failure – BUT – use upper conversion range.
Patients with normal renal function and non-elders use lower conversion range.
Calculate breakthrough dose based on morphine equivalents of the patch. Lowest dose patch=12mcg/hr
|Opioid||Starting p.o. dose
(For Frail Elders dose press “+”)
|Oral/ SC dose||Starting p.o dose frail,
|Tylenol 3||avoid||2 tabs/ n/a||avoid||+++|
|Morphine||5-10 mg q4h||10mg/5mg||2.5-5mg q4hr||+++|
|Hydromorphone||1-2mg q4h||2mg/1mg||.5-1mg q4h||++|
|Oxycodone||5-10mg q4h||7.5mg/ n/a||2.5-5mg q4h||0|
|2-5mg q8h||1mg/0.5mg||1mg q12h||0|
*Tap the orange + symbol to see additional information
Starting po dose based on patient being opioid naive: patient has NOT had 5 days of continuous opioid exposure (i.e. short-acting q4hr po/sc; long-acting q12hr; transdermal)
Morphine conversion factor: see Opioid Equianalgesic Table
Methadone Need special license to prescribe. Variable half life and dosing.
Calculating breakthrough dose
Breakthrough dose = 10% of the total daily regular opioid dose q1h prn
Morphine 50mg q4hr total daily dose 50×6=300mg. 300/10=30mg q1hr prn
Review + calc new dose
Add 24 hour total regular dose+total breakthroughs used=total daily opioid dose. Divide this by dosing intervals. This is new regular dose. Recalculate breakthrough dose.
Hydromorphone 12mg q4h, with 4 breakthroughs of 8mg q1h
Total daily opioid dose
104/6=16mg q4hr with breakthrough of of 10mg q1hr prn
Switching to sustained release (SR)
Titrate short-acting to optimal dose
Total daily dose
Add total regular dose+breakthroughs (if used)
Total daily dose /2
Opioid SR q12hours
Note about younger patients
They metabolize rapidly and may require q8hr dosing.
Add total regular dose+ breakthroughs (if used)=total daily dose. Total daily dose X morphine conversion factor=total daily morphine equivalents.
Total daily new opioid dose
Daily morphine equivalents/conversion factor to new opioid: reduce 25-50% in case of tolerance to previous opioid. Divide by dosing interval.
Morphine conversion factor
- morphine 10mg
- hydromorphone 2mg
- oxycodone 7.5mg
- Tylenol #3 – 2 tabs
Tylenol 3 12tabs/day=60mg morphine equivalents per day=12mg of hydromorphone per day=9mg hydromorphone per day (reduced for cross tolerance)=1.5 mg hydromorphone po q4hr, hydromorphone 1mg q1hr prn for breakthrough.
Oral to parenteral
Depending on the opioid, may have to rotate to either hydromorphone or morphine for sc.
Total daily oral dose
Add up regular oral doses + breakthroughs (if used). Total daily oral dose/2=total parenteral dose. Divide by 6 to get q4hr dose
Morphine SR 120mg po q12hx2=240mg total daily morphine dose po=120mg total parenteral morphine dose=20mg s.c. q4h regular, morphine 12mg sc q1hr prn for breakthrough.
Opioid side effects
Tolerance develops in 2-5 days. If not, rotate opioid. If symptom controlled, reduce dose.
Talk tip: “You may be drowsy for the first two days, but it should clear after that.”
Nausea is common in the first week.
- 10mg po/sc qid
- 0.5mg bid-tid
Rotate opioid if nausea persists
Constipation always occurs with opioid use.
Use stimulant laxative (senna) +/- osmotic laxative (PEG, lactulose).
spectrum of neurotoxicity symptoms from reduced LOC, myoclonus, hallucinations, delirium, and rarely to seizures.
Rotate opioid, consider hydration, treat concurrent infection.
Note: not a sign of allergy
Consider rotation if pruritis persists.
Respiratory depression secondary to opioids
Rare with appropriate dosing. Respiratory depression due to opioids = increased pCO2 + decreased pO2 + low respiratory rate. Assess O2 saturation, respiratory rate and signs of hypoventilation. Differential diagnosis: sedation from drugs (benzodiazepines or neuroleptics), hypoglycemia, head trauma, exhaustion, actively dying.
Mild – moderate: reduce/review dosing of all sedating medications
Severe: Risk of severe pain, aspiration and opioid withdrawal with full dose naloxone. Dilute dose naloxone: dilute 1ml (0.4mg/ml) naloxone in 9ml saline, slow IV push (0.5-1ml q2min) Goal of naloxone is to improve ventilation. Partial reversal of respiratory disturbance by naloxone does not confirm opioid as the primary cause particularly if problems develop during stable opioid dosing.
- metastatic bone and visceral pain
- raised ICP
- neuropathic pain where nerve compression occurring
- dexamethasone 8-16mg po/sc daily in am, if effective at 48 hours reduce to lowest effective dose
(includes pain secondary to ischemia)
- antidepressants: venlafaxine, mirtazapine, duloxetine, nortriptyline
- anticonvulsants: gabapentin, pregabalin
Metastatic bone pain
- bisphosphonates useful in widespread disease: pamidronate IV 90mg in 250ml of D5W over 2 hrs q 4 weeks. Avoid if severe renal failure
- NSAIDS: naproxen
- colicky pain: butylbromide 10-20mg po/sc tid-qid
- consider anaesthetic (e.g. nerve blocks), interventional radiology (e.g. vertebroplasty) or neurosurgical
- use topical for peripheral neuropathy and wound pain
- subtype of breakthrough pain with a predictable trigger i.e. movement, procedural (wound dressing change), body function (e.g. bowel movement with rectal tumor) Pain typically high intensity and short lasting.
- Sufentanil 12.5mcg-50mcg sublingual/subcutaneous for use in patients on regular opioids
- Onset: 10min Offset: 30-60min Must be held sublingual for >1min. Not absorbed if swallowed
- Pain has physical, psychological, spiritual, social, iatrogenic components
- Consider total pain when extensive investigation does not find source of pain, multiple medications trials not effective, pain resolving but distress still high, request for hastened death
- Multi-professional assessment needed, involve palliative care team
Contact us: severe, uncontrolled pain is an emergency
Contact other providers: social, financial, psychological or spiritual distress contributing to total pain, contact the appropriate provider to assess.