A 35-year-old woman has been treated with Citodon (paracetamol 500 mg + codeine 30 mg) five tablets

Fråga: A 35-year-old woman has been treated with Citodon (paracetamol 500 mg + codeine 30 mg) five tablets per day for one year. It has been written in her medical records that paracetamol can cause water retention and that codeine can cause histamine release. Is there any documentation in support of this statement?

Sammanfattning: We have found no documentation/information connecting paracetamol with water retention; however, it is documented that codeine can cause histamine release.

Svar: Paracetamol, an analgesic and antipyretic pharmaceutical preparation, is usually well tolerated in the recommended doses. Skin rashes and other allergic reactions occur occasionally (1). The most serious adverse effect of acute overdosage is a dose-dependent, potentially fatal hepatic necrosis. Renal tubular necrosis and hypoglycaemic coma may also occur (2). In all the literature searches done, in both textbooks and Medline, there was no record of paracetamol associated with water retention.

Codeine belongs to the opioid family. It is obtained from opium or made by methylating morphine. Codeine is an analgesic with uses similar to those of morphine but it is much less potent as an analgesic and has mild sedative effects. It is commonly used in combination with non-opioid analgesics in a number of proprietary preparations. Morphine and other opiates have been reported to have histamine-releasing effects, and reactions such as urticaria and pruritus may occur in some individuals (3). This assertion has also been supported by other textbooks (4,5). Medline searches also recognise the histamine-liberation property of codeine, as it is used as the basis for further studies of some other drugs in rats (6). 1 Martindale, The extrapharmacopoeia. 1989; 29th ed: 32

2 Goodman and Gilman, The pharmacological basis of therapeutics. 1990; 8th ed: 658
3 Martindale, The extrapharmacopoeia. 1989; 29th ed: 1311
4 Goodman and Gilman, The pharmacological basis of therapeutics. 1990; 8th ed: 409
5 Sir Colin Dollery, Therapeutic drugs. 1991; 1: C336

6 Grosman N: Histamine release from isolated rat mast cells: effect of morphine and related drugs and their interaction with compound 40/80. Agents Action 1981; 11: 196-203