Concerns over its long half-life, its variable relative potency, and potential cardiotoxicity have led to the common opinion that methadone is difficult to manage in the outpatient setting.
To the contrary, Dr. Eduardo Bruera and associates at the University of Texas M. D. Anderson Cancer Center in Houston found in their chart review that methadone “is an ideal drug for opioid rotation because of its efficacy, higher oral bioavailability, lack of known active metabolites, incomplete cross tolerance with other mu receptor agonists, and lower cost.”
Dr. Bruera and his team studied 89 consecutive “strong opioid-naïve” cancer patients treated with methadone and 100 who were switched to it from another opioid, all between 2003 and 2007. Their findings are published online in the journal Cancer.
The median times from baseline to the first and second follow-ups were 13 and 37 days, respectively. Factors that defined success were an improvement in pain of at least 30% or at least 2 points in the Edmonton Symptom Assessment Scale pain score and/or disappearance of side effects at the first follow-up visit, and – in patients originally given a different opioid – resolution of the problem with the previous drug.
Success rates were 92% in the first-line group, 85% in patients switched from other drugs, and 88% overall. Median pain scores at baseline and the first and second follow-ups were 6, 4, and 3, respectively.
Pain scores improved in all groups, and nausea and constipation were reduced in both groups. Side effects were “tolerable,” and there was no increase in sedation, hallucinations, myoclonus or delirium.
At the first follow-up visit, median methadone doses were 10 mg/day for first-line patients and 15 mg/day for patients who switched from another drug. Corresponding values at the second follow-up visit were 10 and 18 mg/day.
The authors report that patients who switched to methadone had been taking a median morphine equivalent daily dose (MEDD) of 100 mg/day (range, 60 to 185). On both univariate and multivariate analyses, the MEDD of the previous drug was significantly associated with the MEDD:methadone ratio. Furthermore, in the multivariate models, the reason for rotation and previous opioid doses were independently associated with higher MEDD:methadone ratios.
These findings, the authors warn, suggest that with regard to opioid sensitivity, “methadone behaves in a different manner as compared with other opioids,” and patients who had escalation of their previous opioids require particularly cautious treatment.
In addition, they advise, because methadone is metabolized via cytochrome 3A4, patients taking 3A4 inhibitors (e.g., fluconazole, ciprofloxacin, venlafaxine, fluoxetine, and macrolides) are at risk for elevated, possibly toxic methadone levels. Similar effects are possible from inhibitors of cytochrome 2B6 (e.g., haloperidol, levopromazine, paroxetine, sertraline, fluoxetine, and chlorimipramine) and inhibitors of P-glycoprotein (doxorubicin, vimblastin, and actinomycin).
And because of potential cardiac effects, clinicians must check for electrolyte imbalances or concomitant use of other cardiotoxic drugs, such as tricyclic antidepressants, diuretics, and antipsychotics.
Summing up, the authors write, “Our study adds to the growing evidence in the literature” to recommend the use of methadone in these circumstances.
Furthermore, they point out, methadone is much less expensive – and therefore more affordable for patients – compared to other pain-controlling medications.