Could methadone cause peripheral edema?/nTwo patients were treated with methadone (20 mg x 4 in one

Fråga: Could methadone cause peripheral edema? Two patients were treated with methadone (20 mg x 4 in one patient and 30-80 mg/day in the other). Both have developed edema. The first patient felt swelling in his hands and the lower extremities and the other patient noted a > 15 kg weight gain in one month after the dose was increased from 20 to 40 mg. There was no kidney failure or other explanations for the edema in these patients.

Sammanfattning: Edema occurs in some patients during methadone treatment. It is not known what causes these symptoms and further research has to be made to elucidate this question. Diuretics have little effect in these cases. Lowering of the dose or withdrawal of methadone may resolve the symptoms.

Svar: There are a few reports of edema during methadone treatment. Betz reports in a letter about nine patients with generalised edema during methadone maintenance. Some of the patients had taken both heroin and methadone and three of them were hospitalised because of their symptoms (1). Longwell et al report three patients with massive fluid gain during methadone treatment. One patient noted a progressive 23 kg weight gain and marked swelling of the legs, arms, and face after the dose was increased from 100 mg/day to 110 mg/day. Another patient noted a 40 kg weight gain during 6 months treatment that began after the dose of methadone was increased from 100 mg/day to 120 mg/day (2). MacFadden et al reported three patients with unexplained peripheral edema. The doses in two of the cases were 30 respectively 40 mg/day (3). In the two latter reports no other drugs than methadone were used. O´Conor et al describe one patient with methadone maintenance who developed distal leg edema after years of uncomplicated methadone treatment (4).

In nearly all the cases the symptoms developed within 3-6 months, but in one case it occurred after years of treatment. No other cause could be found after tests including heart examination, EKG, complete blood tests or other investigations. Lowering or withdrawing the dose resolved the symptoms. If methadone was withdrawn and then reinstituted the symptoms appeared again. Diuretics alone did not seem be sufficient to treat and in many cases the patients became refractory to diuretics.

We recommend these cases be reported to SADRAC (The Swedish Adverse Drug Reactions Advisory Committee).