Mercadante et al developed a method for rapidly treating a patient with severe cancer pain, then using this dosage information to develop an oral regimen for continued pain relief. The authors are from La Maddalena Cancer Center in Palermo, Italy.


Patient selection: A patient with severe cancer pain from advanced metastatic cancer. In the study all patients had a Karnofsky <= 40 with a pain score >= 7 on a scale of 0 to 10.


Step 1: Administer intravenous 2 mg boluses of morphine every 2 minutes until there are either (a) initial signs of significant analgesia or (b) severe adverse effects occur.


Step 2: This dose is assumed to be effective for 4 hours, so multiply by 6 to get a dose that should be effective for 24 hours.


Step 3: Multiply this intravenous dose by a conversion factor to determine the daily equivalent oral dose.

(a) For lower doses (for example 30 mg), use a factor of 3.

(b) For higher doses (for example 60 mg), use a factor of 2.

NOTE: This does not offer guidance for intermediate doses like 40 or 50 mg, In the implementation, I use an equation factor = ((-1/30)*(IV dose)) + 4. This is needs to be validated.


Step 4: Divide this daily oral equivalent dose into 2 or 3 doses (every 12 or 8 hours respectively) of a time release formulation. This is started in 4 hours (duration of action for the intravenous morphine).


Step 5: Administer intravenous morphine for breakthrough pain. The total dose given intravenously is added to the previous day's dose, and steps 3 and 4 are repeated.


Adverse effects that may limit the dose administered:

(1) drowsiness

(2) confusion

(3) itching

(4) dizziness

(5) dry mouth

(6) vomiting

(7) nausea

(8) dysuria

(9) myoclonus

(10) sweating


One modification for the spreadsheet would be to balance the pain control and serious adverse effects. For example, if bothersome side effects occur and pain is controlled, then could decrease the daily dose by 10%.

• If adverse effects were still bothersome and pain controlled, then decrease dose by another 10%.

• If the adverse effects are better but pain not controlled, increase dose by 10%.

• This could all be table driven.


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