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it is used as a muscle relaxant for spasticity caused by multiple sclerosis , amyotrophic lateral sclerosis ( als ) , spinal injury , and stroke.1 as a muscle relaxant , tizanidine is as effective as baclofen and diazepam.2 the most common side effects of tizanidine treatment include drowsiness , hypotension , dry mouth , muscle weakness , and fatigue.3 its prescription in patients taking antihypertensive medications needs careful consideration.4 it can also cause constipation and liver function test abnormalities.5 cystitis is a less frequently occurring problem with tizanidine , which has been rarely reported . to our knowledge ,
the first case report of tizanidine - induced hemorrhagic cystitis was published in literature in 2013.6 we discuss here a case of a 26-year - old asian female on famotidine ( h2 antihistaminic ) , who presented with acute severe dysuria after taking the second 2 mg dose of tizanidine .
a 26-year - old asian female presented to the emergency room for increased urinary frequency , severe pain , and burning overnight .
she was unable to hold urine ; however , she had no abdominal pain , blood in the urine , abnormal or cloudy urine color , strong or foul urine odor , or fever .
her menstrual periods had always been regular . she had a 5-year - old healthy child and no history of any obstetric or gynecological problems .
she had a pulse rate of 90 beats / minute and blood pressure of 100/60 mmhg .
investigations showed hemoglobin of 13.5 g / dl ( normal range : 1216 ) and a total white blood cell count of 6,800/mm ( normal range : 4,00011,000 ) ; urine microscopy test did not reveal any red blood cells or white blood cells .
the woman had presented to an outpatient clinic the day before for neck pain and headache ; with a diagnosis of torticollis , she was prescribed tizanidine 2 mg three times a day and acetaminophen 500 mg four times a day .
she developed symptoms an hour after the second dose of tizanidine , ie , within 10 hours of initiation of the drug .
she had been on famotidine 40 mg once a day for 4 weeks for dyspepsia .
there was no history of any allergies or predisposing conditions that could have been responsible for the acute onset of this adverse event .
tizanidine treatment was subsequently discontinued and the patient was treated with hydration ; her symptoms gradually improved within 24 hours . after stabilization , the patient was referred for urological consultation and ultrasonography of the urinary tract that failed to show any evidence of the current urinary problems .
the naranjo probability scale was used to evaluate the possible causal relationship between tizanidine and the acute urinary symptoms .
the scoring obtained by this algorithm was 4 , which indicates a possible causal association between the drug and the adverse reaction .
the naranjo probability scale categorizes adverse drug reaction ( adr ) probability based on predefined weighted questions evaluating factors like temporal association of drug use and adr occurrence , previous reports of adr , alternative explanation of the event , drug level , dose  response relationship , etc .
scoring for naranjo algorithm follows : > 9= definite adr ; 58= probable adr ; 14= possible adr ; 0= doubtful adr.7
acute severe urinary symptoms can be alarming to both the patient and the health care provider , especially in the context of no clearly differentiating etiology .
non - infectious cystitis is most common in women of childbearing years , which may be idiopathic ; or associated with bubble baths , feminine hygiene sprays , spermicidal jellies , radiation therapy to the pelvis ; or consumption of certain foods , such as tomatoes , artificial sweeteners , caffeine , chocolate , and alcohol can also cause bladder symptoms.8 tizanidine - induced cystitis is underreported due to challenges in establishing the causality with certainty ; however , according to a key principle of pharmacovigilance , it is better to report even a suspicious case to generate an alarm in the interest of protecting public health.6 in multiple doses , in placebo - controlled studies using tizanidine , the incidence of urinary tract infection was 10% ( 7% in placebo group ) and urinary frequency was 3% ( 2% in placebo group).9 between 2003 and 2012 , the us food and drug administration ( fda ) reported 54 cases of hemorrhagic cystitis related to tizanidine use in the usa.6 why tizanidine causes urinary burning and cystitis is not known . in our case , there was no predisposing factor for the urinary symptoms .
however , if we assume these symptoms were a result of tizanidine use , there was concomitant use of famotidine , which could have increased the blood levels of tizanidine by inhibiting the cyp1a2 system , thereby decreasing its metabolism which could accentuate any effects attributable to tizanidine
. tizanidine is metabolized in the liver by cyp1a2 , so drug interaction may occur when used with cyp1a2 inhibitors .
concomitant use of tizanidine with potent inhibitors of cyp1a2 , fluvoxamine or ciprofloxacin , is contraindicated because of potential serious adverse effects.911 less potent inhibitors of cyp1a2 , eg , zileuton , other fluoroquinolones , antiarrythmics , cimetidine , famotidine , oral contraceptives , acyclovir , and ticlopidine should be used with caution.9 given the very few case reports and the absence of references in the literature , this unique adverse effect of tizanidine needs a better consideration .
physicians , pharmacists , and other health care providers should be aware of this possible adverse event during treatment with tizanidine .
tizanidine is a centrally acting 2 adrenergic agonist prescribed as a muscle relaxant in various causes of spasticity and pain .
while dry mouth , dizziness , hypotension , and fatigue are frequently occurring side effects of the use of tizanidine , it has sometimes been associated with unexplainable symptoms of urinary infection and cystitis .
although rarely reported , health care providers and pharmacists should be aware of such possible reactions for better patient care .
when etiology and mechanisms are uncertain , there is little opportunity for intervention ; however , we can always help to minimize any drug reactions by closely following general precautions like avoiding drugs with contraindications , eg , the use of tizanidine with cyp1a2 inhibitors .
cystitis is a possible adverse drug reaction associated with the use of tizanidine . 
 such cases have been rarely reported in literature because of the difficulty in establishing the causality . however , from a pharmacovigilance point of view , it is better to report such cases of a possible association between a drug s use and potential adverse drug reactions . 
 we report a case of a 26-year - old asian female on famotidine who presented with acute severe urinary burning after taking tizanidine .