February 2005

Dear Readers: Here's the Article for this Month:

Name of article:

Opioid switching from transdermal fentanyl to oral methadone in patients with cancer pain

Author(s): Benitez-Rosario MA, Feria M, Salinas-Martin A, Martinez-Castillo LP, Martin-Ortega JJ
Abstract:  Cancer 2004; 101: 2866-73

According to the data in literature, opioid switching and/or route switching show a reduction in the prevalence and severity of gastrointestinal (GI) symptoms, pain, drowsiness and/or sedation, delirium or agitated confusion, and myoclonus.

Retrospective and prospective studies show the clinical efficacy of switching from oral or intravenous morphine to oral methadone and that from intravenous hydromorphone or fentanyl to intravenous methadone.

The authors evaluated 17 patients with cancer who switched from transdermal fentanyl to oral methadone (administered every 8 hours) because of uncontrolled pain in 41.1% of the patients despite using > 300 mcg/h of fentanyl, or > 3 escalating doses in 10 days, and secondly because of CNS related side effects due to fentanyl in 58.9% - myoclonus, hallucinations and delirium.

Some notes on the protocol:

The following dose ratios have been used:

A. 1. a dose ratio of 1:100 between fentanyl patch and oral morphine;

   2. a dose ratio of 5:1 from morphine to methadone;

   3. a dose ratio of 10:1 when patients were on high-dose fentanyl
   (400 mcg/h) or received a rapid increase in the dose or had delirium.

B. the rescue doses of oral morphine were not calculated in the daily methadone dose

C. with respect to the fentanyl withdrawal, methadone was administered after 8-12 hours, 12-16 hours, 16-18 or 18-24 hours according to the previous opioid dose exposure: < 100 mcg/h, 100-200 mcg/h, 200-300 mcg/h or >300 mcg/h respectively

D. rescue doses of methadone were administered (10% of the daily dose every 2 hours)

E. the dose of methadone was titrated every 72 hours

F. adjuvant drugs were continued at the same doses

The authors found that the mean dose ratio between transdermal fentanyl dose and final methadone dose was about 1:17 (range 1:8- 1:33 ). Previously fentanyl dose did not correlate with the final methadone dose.

Among the 17 patients who switched to oral methadone, 6 of them did not require a change in the initial methadone dose, seven patients required one or two dose adjustments, 4 patients had a dose decrease due to drowsiness or sedation. It is interesting to note that these patients had renal impairment and were among those who were administered a dose ratio of 5:1 between morphine and methadone. A significant decrease in pain intensity as well as in the number of rescue doses during methadone therapy were reported. Myoclonus disappeared in all patients within 2 days of fentanyl suspension whereas delirium disappeared in most of patients within 1 week.

No patient suspended methadone due to adverse effects.

Why I chose this article

Intra-individual variability in response to different opioids may be due to:

1. genetic make-up,

2. tolerance to different opioid effects,

3. incomplete cross-tolerance among opioids selective for the same receptor subtype affinity

4. differences in profile of active metabolites.

While opioid rotation has the practical advantage of minimizing polypharmacy, outcomes are variable and somewhat unpredictable. Moreover, familiarity with the use of the opioid dose conversion tables is paramount. This study gives us a preliminary report on an effective and safe modality for switching from fentanyl patch to oral methadone

Regards,

Carla Ripamonti, MD
Member of the Board of Directors, IAHPC