The question concerns a 45-year-old man with chronic prostatitis who in January this year began tre

Fråga: The question concerns a 45-year-old man with chronic prostatitis who in January this year began treatment with Hiprex (methenaminehippurate) with good results and no side-effects. The patient has been examined earlier by a urologist and has had several types of treatment with bad results. What are the risks during long-term treatment with this drug? Is there a risk of a carcinogenic effect?

Sammanfattning: Administration of methenamine in doses above 500 mg four times a day can cause milder gastrointestinal disturbances and long-term treatment with more than 4 g daily may produce inflammatory changes in the urinary tract mucosa due to formaldehyde formation.

Svar: Methenamine is a urinary tract disinfectant active through formaldehyde liberation in acid urine (1). It is absorbed orally, but 10 to 30 per cent of the administered dose may be converted to formaldehyde in the stomach unless the drug is protected by an enteric coating (2). Methenamine is available as mandelate and hippurate, but only the latter is available in Sweden as Hiprex and it is not an enteric-coated tablet.

Hiprex is registered for short-term use but also for long-term use for recidive urinary tract infections.

Methenamine is generally well tolerated but may cause gastrointestinal disturbances such as vomiting, nausea and diarrhoea at doses greater than 500 mg four times a day.

Comparatively large amounts of formaldehyde are formed during prolonged administration or when large doses are used, and may give rise to irritation and inflammation of the urinary tract especially in the bladder (3). Painful and frequent micturition, haematuria, proteinuria and rash may result from doses of 4 to 8 g a day given for longer than three to four weeks (2).

Stomatitis, anorexia, headache, dyspnoea and generalized oedema are rare adverse effects (4).

In an evaluation provided by the manufacturer, it was concluded that the risk of mutagenicity and carcinogenicity seems low in man after intake of oral methenamine, mainly for pharmacokinetic reasons. However, such effects have been found in animals (5).