Cancer pain pharmacotherapy and opioid titration

For moderate to severe cancer pain, move to a strong opioid and titrate it to effect. Know the label definition of opioid tolerance, never convert to methadone with a fixed ratio, and start a laxative with the opioid.

1. Climb the ladder to a strong opioid. On the WHO ladder, codeine and tramadol are step II; strong opioids such as morphine form the top rung. In two reviews (oral morphine, transdermal fentanyl), 96% of 850 participants reached no worse than mild pain ¹.
2. Titrate to effect, not to a fixed ceiling. Doses are balanced against adverse events rather than capped at an arbitrary maximum; rotation is mainly for dose-limiting toxicity ¹.
3. Fentanyl products need opioid tolerance. Patches and transmucosal fentanyl are restricted to patients who have taken at least 60 mg/day oral morphine, 30 mg/day oxycodone or an equivalent for at least a week ²³.
4. Methadone conversion is nonlinear. Its relative potency rises with the prior opioid dose, so fixed-ratio or milligram-for-milligram conversion can cause fatal overdose; use dose-dependent ratios and close monitoring ⁴.
5. Prevent constipation from day one. A stimulant laxative such as senna, with or without a softener, is usually needed with regular opioids; a softener or fiber alone should be avoided ⁵. Methylnaltrexone is labeled to treat established opioid-induced constipation ⁶.
6. Bone metastases need more than opioids. Bone-modifying agents are recommended in breast cancer with bone metastases, though their analgesic effect is modest; standard analgesia, radiotherapy and supportive care continue alongside them ⁷.

Transmucosal fentanyl in a patient whose opioid dose is high but only days old is not allowed: the tolerance definition requires at least one week at that dose ³.

• Switching between step II opioids, or escalating codeine, delays the strong opioid that is needed ¹.
• Transdermal fentanyl tolerance thresholds include 8 mg/day hydromorphone and 60 mg/day hydrocodone ².
• Starting transmucosal fentanyl at the lowest strength does not make it safe in a non-tolerant patient ³.
• Methadone is effective in cancer pain; the danger lies in the conversion method ⁴.
• CDC: stool softeners or fiber laxatives without another laxative should be avoided ⁵.
• Bone-modifying agents should not be used alone for bone pain ⁷.
• Methylnaltrexone is contraindicated in known or suspected bowel obstruction ⁶.

• Holding a strong opioid at a "maximum dose" in an alert patient with uncontrolled pain ¹.
• Rotating to methadone with a single 10:1 ratio at any morphine dose ⁴.
• Starting a fentanyl patch to simplify therapy in an opioid-naive patient ².
• Starting methylnaltrexone as prevention with the first opioid dose instead of a scheduled stimulant laxative ⁵⁶.