S. Mercadante et al., PATIENT-CONTROLLED ANALGESIA WITH ORAL METHADONE IN CANCER PAIN - PRELIMINARY-REPORT, Annals of oncology, 7(6), 1996, pp. 613-617
Background: Methadone is a very useful drug in cancer pain because of
its low cost, lack of active metabolites, high oral availability, and
the rapid onset of its analgesic effect. It seems to be well tolerated
in patients with difficult pain syndromes who are receiving high dose
s of opioids, and it may deter the development of tolerance, but a hig
h individual variation in terminal elimination half-life can result in
different rates and extents of drug accumulation. For this reason, or
al patient-controlled analgesia with methadone was used in 24 advanced
-disease patients with pain. Patients and methods: A regimen of self-a
dministered oral methadone at fixed doses and flexible patient-control
led dosage intervals to achieve adequate analgesia, while avoiding tox
ic effects of methadone accumulation, was used in 24 patients requirin
g opioid therapy. After a priming period of three days with fixed dose
s of 3-5 mg three times a day for naive patients and 50% of the morphi
ne equivalent of methadone in patients switched from morphine, patient
s and relatives were instructed to maintain the night-time dose and to
administer a second dose when the pain recurred. When more than four
doses of methadone a day were used, an increase of the dosage was pres
cribed. Continuous pain assessment and monitoring of symptoms were off
ered. Results: The majority of patients achieved good pain relief unti
l death, and three were switched to very low doses of subcutaneous mor
phine in their final days. The methadone escalation index was about 2%
a day, with a mean dosage increase of 0.3 mg a day for an average of
60 days of treatment at doses ranging from 9 to 80 mg. The plasma conc
entration in 14 patients ranged from 0.013 to 0.273 mcg/ml with dosage
s of 20-80 mg during chronic treatment. A mean of 2.4 doses a day was
reported, including the fixed night-time dose. The extent of side effe
cts was considered acceptable. Conclusion: Patient-administered analge
sia with oral methadone appears to be a simple, cheap and relatively s
afe technique for controlling cancer pain, permitting individualizatio
n by the patient him- or herself and avoiding the risk of accumulation
. Continuous assessment is necessary.