
 the use of sodium hypochlorite as toilet detergent is related to a red - brown urine discolouration in patients taking mesalamine.it seems that the red - brown discolouration relates to a harmless reaction.polymerisation of mesalamine and/or metabolites could be a theoretical mechanism of this discolouration . 

the exact working mechanism of mesalamine is not fully understood , but it appears to have anti - inflammatory properties .
the drug blocks interleukin-1 and tumour necrosis factor-. mesalamine also inhibits the cyclo - oxygenase pathway , leading to inhibition of prostaglandin e2 in inflamed intestine .
the most common adverse drug reactions ( adrs ) , as described in the summary of product characteristics ( smpc ) , are headache , rash and gastrointestinal symptoms , including diarrhoea , nausea , vomiting and abdominal pain .
mesalamine is also associated with the renal adrs of renal failure , interstitial nephritis and haematuria [ 1 , 3 ] . in the period from august 2009 to april 2015 , the netherlands pharmacovigilance centre lareb received two case reports of red - brown urine discolouration in association with mesalamine .
both cases were reported by patients and the urine discoloured after contact with the toilet bowl .
this case concerned a 38-year - old male with a history of crohn s disease .
the patient reported separate several episodes of a red - brown deposit in the toilet bowl after the start of mesalamine in 1999 ( pentasa slow - release 500  mg tablet ) .
the latest episode occurred in april 2015 , 2  days after the use of mesalamine .
the patient had a mild form of crohn s disease that had been stable for 68  years and only used mesalamine during episodes of exacerbations .
due to an exacerbation in september 2014 , the daily dose of mesalamine was increased from 2 to 4  g. during this dose escalation , the patient recognised the same red - brown deposit that had occurred during previous use . in january 2015 , the mesalamine was tapered over a period of 2  months to 2  g once daily and he remained stable .
he observed that the urine initially had a normal colour and developed the red - brown colour after contact with the water in the toilet bowl .
most of the time the persistent deposit did not appear directly after contact with the toilet water but developed after a few days , despite flushing the toilet .
of note , the deposit in the toilet bowl was more intense during the use of an increased dose of 4  g a day .
the patient wondered whether the use of detergents could have caused this kind of discolouration and therefore he cleaned his toilet in the morning with a chlorine - containing detergent . in the evening
a red - brown deposit had developed in the toilet bowl and on the seat and the water was unaffected . as the patient wanted more information on the possibility of the discolouration being the result of a reaction with the sodium hypochlorite detergent , he reported it to lareb .
after the report had been assessed , the pharmacovigilance centre lareb asked the patient to collect his urine and to add household bleach as a test , to which he agreed ( fig .  1 ) .
the urine ( 40  ml ) was mixed with 20  ml of sodium hypochlorite bleach and within a few minutes the discolouration developed . after shaking the mixture ,
1 
 red  brown discolouration after adding sodium hypochlorite bleach to normal - appearing urine ( left , right ) .
agitation discoloured the urine completely ( right ) 
 
 red  brown discolouration after adding sodium hypochlorite bleach to normal - appearing urine ( left , right ) .
agitation discoloured the urine completely ( right ) this case concerned a 36-year - old woman with ulcerative colitis , for which she is treated with 2  g of mesalamine ( pentasa sachet 2  g prolonged - release granules ) twice daily .
since she started taking mesalamine in june 2009 , her urine appeared red - brown in the toilet bowl , but only when she had recently cleaned the toilet with sodium hypochlorite detergent .
when the patient added a drop of sodium hypochlorite detergent to her normal - coloured urine in the toilet , the same red - brown discolouration occurred immediately .
the patient is still taking mesalamine and the phenomenon is still present when cleaning the toilet .
this case concerned a 38-year - old male with a history of crohn s disease .
the patient reported separate several episodes of a red - brown deposit in the toilet bowl after the start of mesalamine in 1999 ( pentasa slow - release 500  mg tablet ) .
the latest episode occurred in april 2015 , 2  days after the use of mesalamine .
the patient had a mild form of crohn s disease that had been stable for 68  years and only used mesalamine during episodes of exacerbations .
due to an exacerbation in september 2014 , the daily dose of mesalamine was increased from 2 to 4  g. during this dose escalation , the patient recognised the same red - brown deposit that had occurred during previous use . in january 2015 , the mesalamine was tapered over a period of 2  months to 2  g once daily and he remained stable .
he observed that the urine initially had a normal colour and developed the red - brown colour after contact with the water in the toilet bowl .
most of the time the persistent deposit did not appear directly after contact with the toilet water but developed after a few days , despite flushing the toilet .
of note , the deposit in the toilet bowl was more intense during the use of an increased dose of 4  g a day .
the patient wondered whether the use of detergents could have caused this kind of discolouration and therefore he cleaned his toilet in the morning with a chlorine - containing detergent . in the evening
a red - brown deposit had developed in the toilet bowl and on the seat and the water was unaffected . as the patient wanted more information on the possibility of the discolouration being the result of a reaction with the sodium hypochlorite detergent , he reported it to lareb .
after the report had been assessed , the pharmacovigilance centre lareb asked the patient to collect his urine and to add household bleach as a test , to which he agreed ( fig .  1 ) .
the urine ( 40  ml ) was mixed with 20  ml of sodium hypochlorite bleach and within a few minutes the discolouration developed . after shaking the mixture ,
1 
 red  brown discolouration after adding sodium hypochlorite bleach to normal - appearing urine ( left , right ) .
agitation discoloured the urine completely ( right ) 
 
 red  brown discolouration after adding sodium hypochlorite bleach to normal - appearing urine ( left , right ) .
this case concerned a 36-year - old woman with ulcerative colitis , for which she is treated with 2  g of mesalamine ( pentasa sachet 2  g prolonged - release granules ) twice daily .
since she started taking mesalamine in june 2009 , her urine appeared red - brown in the toilet bowl , but only when she had recently cleaned the toilet with sodium hypochlorite detergent .
when the patient added a drop of sodium hypochlorite detergent to her normal - coloured urine in the toilet , the same red - brown discolouration occurred immediately .
the patient is still taking mesalamine and the phenomenon is still present when cleaning the toilet .
likewise , the disordered haem production in patients with porphyria can result in red - brown discolouration .
a red - brown urine discolouration could be perceived as a sign of possible renal impairment or other diseases ; however , neither of the described patients are known to have an impaired renal function or physical abnormalities .
furthermore , various drugs are associated with red and/or brown discolouration , e.g. rifampicin , doxorubicin , metronidazole , methyldopa , levodopa and sulfasalazine .
a notable difference from the described mesalamine cases is that the urine of patients taking the above - mentioned drugs , such as sulfasalazine , is already discoloured at micturition .
a pubmed search was conducted and it was found that two cases of red - brown urine associated with mesalamine have been reported previously by sacks and davis .
both of the male adolescents in these reports experienced the same red - brown urine discolouration after contact with sodium hypochlorite bleach .
a similar experiment was performed to that performed by patient  a , and after adding sodium hypochlorite bleach to the collected urine the discolouration developed spontaneously . to our knowledge
, there are no other published reports of this association after a chemical reaction with drugs structurally related to mesalamine ( sulfasalazine , olsalazine and 4-aminosalicylic acid ) .
notably , there has been discussion regarding this phenomenon in several patient forums and blogs .
case reports from altmann and mansell   do , however , describe urine discolouration in patients using methyldopa or levodopa after contact with lavatory bleach and exposure to light .
normal biotransformation of methyldopa produces a variety of metabolites ; presumably , these metabolites have properties that form melanin by spontaneous polymerisation , which results in darkening of the urine .
melanins are polymers of phenolic compounds ( e.g. dopaquinone , benzothiazole ) that are formed by an extensive bio pathway .
melanin is an aggregate of smaller component molecules such as pheomelanin and eumelanin ; both of these are initially formed by oxidation of tyrosine and then undergo cysteinylation and cyclisation , respectively . the end product is ultimately formed by polymerisation of several different derivatives .
altmann and mansell   found that urine samples that were made alkaline in patients treated with methyldopa or levodopa turned black on exposure to sunlight .
mesalamine is acetylated by the enzyme n - acetyltransferase  1 ( nat1 ) in the liver and gut mucosal wall into the metabolite n - acetyl-5-aminosalicylic acid ( n - ac-5asa ) .
evidence from the literature indicates that nat1 is polymorphic , but that these polymorphisms are associated with relatively minor effects on acetylation function .
it is unknown whether the patients in our reports have a nat1 polymorphism , but if so we would expect no significant effect on the propensity of discolouring .
furthermore , this acetylation is minimal when mesalamine and n - ac-5asa are both secreted back into the lumen by the drug efflux pump p - glycoprotein , excreted in the faeces , absorbed via the colon into the blood and , lastly , eliminated in the urine .
the theory is that n - ac-5asa and/or mesalamine react with the sodium hypochlorite - containing bleach .
sodium hypochlorite usually has a ph of 1113 and could therefore initiate the reaction as described by altmann and mansell . according to the cases reported by altmann and mansell ,
it is also possible that a similar polymerisation of mesalamine and/or n - ac-5asa could cause the discolouration of the urine . perhaps due to the alkaline environment
, partial deprotonation of n - ac-5asa and mesalamine could also contribute to this reaction .
since the introduction of the national spontaneous reporting system in 2003 to the general public , consumers have now become the largest group of reporters in the netherlands .
the quality of consumer reports are generally good and these reports highlight via first - hand information the real - life experience of an adr .
being unconstrained with regards to the probability of causality , consumers may report relevant adrs that healthcare professionals may not recognise initially or consider to be unlikely .
patient  b s gastroenterologist recognised the phenomenon , but it is conceivable that not every gastroenterologist will establish a direct relationship between urine discolouration , mesalamine therapy and the use of a specific detergent .
the two reports received provide important information about a harmless reaction as this phenomenon probably concerns a lot of other patients using mesalamine .
based on the described reports and the case reports in the literature , we suggest a causal relationship between red  brown discolouration of urine after contact with sodium hypochlorite detergent and the use of mesalamine .
the naranjo assessment scores for cases a and b were 9 and 6 , indicating a certain and probable relationship , respectively .
this seems to be a harmless reaction as the patients experienced no physical complaints and in both the lareb cases and those described by sacks and davis , the patients were under the care of a gastroenterologist . in the differential diagnosis it is important to be aware that the use of sodium hypochlorite as a toilet detergent could be the cause of coloured deposits in and on the toilet bowl .
the presence of sodium hypochlorite does not exclude the possibility of renal impairment ; therefore , it is important to distinguish already discoloured urine from normal - coloured urine that only discoloured after contacting the toilet bowl .
thus , to inform and reassure patients , it might be helpful to mention red - brown discolouration in the patient leaflet for mesalamine .
no financial support was received for the conduct of this study or preparation of this manuscript .
 a 38-year - old male and a 36-year - old female experienced red - brown urine discolouration after 2 and 3  days , respectively , during the use of mesalamine for inflammatory bowel disease . 
 both patients mentioned that the urine discoloured after contact with sodium hypochlorite detergent in toilet water . 
 mesalamine and the inactive metabolite n - acetyl-5-aminosalicylic acid are primarily excreted in the urine . 
 we hypothesised a possible reaction with sodium hypochlorite and/or light . 
 naranjo assessment scores of 9 and 6 were obtained for the reports , indicating a certain and probable relationship , respectively , between the red - brown urine discolouration and the use of the suspect drug mesalamine . 
 knowledge of this harmless reaction is desirable to avoid unnecessary physical examination and worry . 
Key Points
Introduction
Case Reports
Patient A (Report Date April 2015)
Patient B (Report Date August 2009)
Discussion
Conclusion
Competing interests/funding