Background. In an open clinical study analgesia and side effects of methadone were assessed and the calculation of equianalgesic doses of oral morphine and methadone used in our patients was appraised.
Material and methods. Methadone was administered in 12 opioid - tolerant patients with severe cancer pain. Patients received methadone because of inadequate pain control (NRS > 5) (number of patients in brackets) during treatment with morphine (4), transdermal fentanyl (3), morphine, ketamine and transdermal fentanyl (1), tramadol (1), unsatisfactory analgesia with severe drowsiness during morphine with ketamine treatment (2) and very strong pain with nausea during morphine treatment (1). We used the following dose ratios while converting oral morphine equivalent to oral methadone: 4:1 (up to 100 mg morphine daily), 6:1 (100–300 mg morphine daily) and 12:1 (daily dose of morphine over 300 mg) although in this study because of daily doses of oral morphine over 100 mg we applied only the last two dose ratios. The starting daily dose of oral methadone in patient treated with tramadol was 9 mg. The single dose of oral methadone did not exceed 30 mg regardless the daily dose of oral morphine before the switch to methadone. After starting methadone we withdrew previous opioid treatment completely in 10 patients and 2 patients were treated concomitantly with methadone and other opioids. The mean equivalent daily dose of oral morphine before switching to methadone was 750.8 ± 464 mg. Methadone was administered usually 3 times a day and 11 patients were treated with oral methadone in water solution, 1 patient received the drug rectally in suppositories.
Results. The mean time of the methadone treatment was 31.7 ± 21.2 (range 7–82) days and the starting doses were increased in 11 of 12 treated patients. The mean daily doses varied from 46 ± 19.9 mg at the beginning till maximal 135.3 ± 99.9 mg and 117.7 ± 97.5 mg at the end of methadone treatment. Good analgesia expressed by decrease in pain intensity to NRS < 3 was achieved in 6 patients, partial effect (NRS 3–5) was present in 5 patients, unsatisfactory analgesia was observed in 1 patient (NRS > 5) who ceased methadone after 7 days of the treatment. The most frequent side effects were drowsiness (5 patients), constipation (5 patients), nausea and vomiting (2 patients). We did not observe serious adverse reactions especially respiratory depression, which would cause cessation of the treatment.
Conclusions. The results of this preliminary study confirmed high analgesic efficacy, good adverse event profile of methadone, safety and the effectiveness of the applied method of morphine to methadone dose calculation for the oral route.