Cystitis and nonsteroidal antiinflammatory drugs: an incidental association or an adverse effect?

Cystitis, a rare adverse effect of systematically administered drugs, was first reported to be associated with a nonsteroidal antiinflammatory drug, tiaprofenic acid, in 1991. Similar reports of adverse effect of tiaprofenic acid were received by a number of national drug monitoring centres. It was therefore decided to investigate the frequency of cystitis associated with tiaprofenic acid and to see whether this association is typical of tiaprofenic acid or also occurs with other nonsteroidal antiinflammatory drugs.

The Medicines Adverse Reaction Monitoring Centre has been monitoring drug related events/reactions since 1965. An analysis of the spontaneous adverse reaction reports received at this centre during the period 1965-92 was carried out.

Haemorrhagic cystitis was reported to be associated with tiaprofenic acid (n = 3) and indomethacin (n = 3). In addition 11 other reports of haematuria (not associated with any coagulopathy and/or hepatic disorders) in relation to other nonsteroidal antiinflammatory drugs, such as diclofenac, ketoprofen, naproxen and piroxicam were received. Five patients who were rechallenged with the suspect drug, suffered from recurrence of cystitis/haematuria.

In addition to tiaprofenic acid, cystitis appears to be associated with indomethacin and possibly also with other nonsteroidal antiinflammatory drugs. An allergic or immunological mechanism is probably responsible for this reaction. Although our centre received the first report of cystitis in relation to indomethacin in 1966, judging by the number of reports received, this association appears to be poorly recognised.