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1. Mild pain

acetaminophen
325-650 mg, every 4 h regularly
$0.06/day

or ASA
325-650 mg enteric-coated or plain, every 4 h regularly
$0.06/day

or NSAIDs

ibuprofen
400-600 mg, qid regularly
$0.15-0.19/day

or naproxen
250-500 mg, bid regularly
$0.21-0.42/day

or indomethacin
25-50 mg, tid regularly
$0.29-0.50/day

2. Moderate pain - weak opioid analgesics

i. acetaminophen/caffeine/codeine or ASA/caffeine/codeine

codeine dose
30 mg, 2 tablets every 4 h regularly
$0.35/day (acetaminophen combination)$0.79/day (ASA combination)

or ii.

codeine 60 mg, every 4 h regularly
$0.46-0.93/day

or iii. acetaminophen/ oxycodone

or ASA/oxycodone

oxycodone dose
5-10 mg, every 4 h regularly
$0.58-1.34/day

3. Severe pain - strong opioid analgesics

i. Oral and subcutaneous routes

hydromorphone
2-4 mg to start; increase dose to provide pain-free 4 h intervals
$0.82-1.92/day

or
3 mg per rectum; increase dose to provide pain-free 4 h intervals
$15.60/box of 6 suppositories

or

morphine
10-15 mg to start; increase dose to provide pain-free 4 h intervals
$0.96-1.44/day

ii. Transdermal when oral and subcutaneous routes are not possible

fentanyl
25 µg/h to start; increase every 2-3 days to maximum of300 µg/h (change patch every 3 days)
$8.50-84.00/3 days

Second-line therapies:

1. Breakthrough pain

see Drugs of choice for patients on oral drugs, 1/3 to1/4 of 4-h dose given every1-2 h prn in addition to regular doses; for patient using transdermal fentanyl use morphine or hydromorphone for breakthrough pain

2. If patients and/or families are unable to manage with a 4-h regimen of strong opioid analgesics, switch to sustained-release morphine preparations. If breakthrough pain occurs with sustained-release preparations, treat with immediate-release preparations.

3. Adjuvant analgesics (to be added to regular regimen)

i. Bone pain - NSAIDs

ibuprofen
400-600 mg, qid regularly
$0.15-0.19/day

or naproxen
250-500 mg, bid regularly
$0.21-0.42/day

or indomethacin
25-50 mg, tid regularly
$0.29-0.50/day

ii. Neuropathic pain

a. Dysesthetic or burning pain

amitriptyline
10-25 mg, hs; titrate to 150 mg, hs
$0.01/day ($0.05/day, maximum dose)

or imipramine
10\25 mg, hs; titrate to 150 mg, hs
$0.01/day ($0.06/day, maximum dose)

b. Lancinating, shock-like pain

carbamazepine

Initial dose
200 mg/day, divided bid; increase by 200 mg/day to
$0.08/day

Maintenance
600800 mg/day, divided bid to tid
$0.24-0.32/day

or phenytoin
300 mg, hs
$0.19/day

or valproic acid
250 mg, hs; increase to maximum of 1 g/day as single hs dose to divided bid
$0.28-1.24/day

iii. Acute nerve compression, soft tissue infiltration, visceral distention, increased

intracranial pressure

dexamethasone
4-8 mg, once daily to qid
$1.22-9.75/day

or
4-8 mg SC, once daily to qid
$2.72-21.75/day

iv. Abdominal colic

strong opioid analgesics, see Drugs of choice

or loperamide
2 mg, qid
$0.98/day

or hyoscine butylbromide
10-20 mg SC or IM, every 4-6 h
$2.00-4.05/day

Additional instructions and notes

-The goal of treatment should be continuous (24-h) control of pain, using regularly scheduled dosing, not prn alone. Long-acting opioid formulations do not provide better pain control but increase convenience and compliance.

-Adding codeine (60 mg) to acetaminophen (600 mg) produces a modest increase in pain relief. Smaller doses of codeine do not help. Adding caffeine to acetaminophen + codeine combinations does not yield any benefit in terms of pain relief.

-Opioid analgesia should be initiated when acetaminophen, ASA or NSAID therapy is insufficient. However, according to a recent meta-analysis, NSAIDs may provide superior analgesia compared with weak opioids (codeine) with or without ASA or acetaminophen.

-To switch from immediate-release to sustained-release morphine, calculate the total daily oral morphine dose and administer half that amount of sustained-release morphine every 12 h. The following are approximate oral-dose equivalents: 5 mg morphine = 1 mg hydromorphone = 2.5 mg oxycodone. Controlled-release suppositories are also available. Rectal doses are equivalent to oral doses.

-Opioid parenteral doses: half of oral dose, usually subcutaneously. Initial doses should be lowered in patients who are opioid-naive. Use lower doses of adjuvant therapy in frail or elderly patients or patients with hepatic or renal impairment.

-The analgesic efficacy of NSAIDs, specifically in malignant bone pain, has not been assessed in controlled trials.

-Prophylactic treatment of nausea-vomiting and constipation are important (see Bowel care for patients on opioid analgesics and Tumour-related nausea).

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