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cardia 1 additional side effects of tizanidine may include drowsiness nervousness confusion hallucinations strange dreams depression vomiting constipation diarrhea stomach pain heartburn increased muscle spasms back pain rash sweating and tingling sensations in the arms legs hands and feet 14 tizanidine can cause withdrawal symptoms upon abrupt discontinuation and should be gradually tapered to avoid and minimize such symptoms 1 withdrawal symptoms include rebound hypertension tachycardia hypertonia tremor and anxiety 1 overdose edit symptoms of overdose with tizanidine have been reported to include lethargy somnolence bradycardia hypotension respiratory depression agitation confusion vomiting and coma 15 1 interactions edit concomitant use of tizanidine and moderate or potent cyp1a2 inhibitors such as zileuton certain antiarrhythmics amiodarone mexiletine propafenone verapamil cimetidine famotidine aciclovir ticlopidine and oral contraceptives is contraindicated concomitant use of tizanidine with fluvoxamine a potent cyp1a2 inhibitor in humans resulted in a 33 fold increase in the tizanidine auc plasma drug concentration time curve 2 for this reason fluvoxamine and tizanidine should not be taken at the same time fluoroquinolone antibiotics such as moxifloxacin levofloxacin and ciprofloxacin should also be avoided due to an increased serum concentration of tizanidine when administered concomitantly 16 tizanidine has the potential to interact with other central nervous system depressants 1 alcohol should be avoided particularly as it can upset the stomach the cns depressant effects of tizanidine and alcohol are additive 2 caution with the following interactions 17 18 19 antibiotics such as enoxacin gatifloxacin levofloxacin lomefloxacin moxifloxacin ofloxacin sparfloxacin trovafloxacin or norfloxacin blood pressure medications such as clonidine guanabenz guanfacine tenex or methyldopa heart rhythm medications such as amiodarone cordarone pacerone mexiletine mexitil propafenone rhythmol and verapamil calan covera isoptin pharmacology edit pharmacodynamics edit site k i nm species ref α 2a 62 human 20 α 2b 75 ok 20 α 2c 76 rat 20 tizanidine is an α 2 adrenergic receptor agonist and is closely related to clonidine it has approximately one tenth to one fifteenth of the blood pressure lowering effect or potency of clonidine the relation between the α 2 adrenergic receptor agonism and spasmolytic action of tizanidine is still not fully understood 4 pharmacokinetics edit absorption edit tizanidine is essentially completely absorbed with oral administration 1 the oral bioavailability of tizanidine is approximately 40 1 it is subject to extensive first pass metabolism and this is responsible for its incomplete bioavailability 1 the pharmacokinetics of tizanidine are linear across a dose range of 1 to 20 mg 1 the time to peak levels with tizanidine under fasting conditions is 1 hour and under fed conditions is 1 5 to 3 hours 1 the pharmacokinetics of tizanidine with oral tablet and capsule formulations are the same under fasting conditions but diverge and are non equivalent under fed conditions 1 the pharmacokinetics of tizanidine also change when capsules are opened and it is sprinkled onto applesauce versus intact capsules 1 21 distribution edit tizanidine is extensively distributed throughout the body 1 2 its volume of distribution is 2 4 l kg following intravenous injection 1 the drug s plasma protein binding is approximately 30 1 metabolism edit more than 95 of a dose of tizanidine is metabolized 1 the primary cytochrome p450 enzyme involved in the metabolism of tizanidine is cyp1a2 1 strong cyp3a4 inhibitors such as fluvoxamine and ciprofloxacin can increase tizanidine exposure by 10 to 33 fold indicating the key involvement of cyp1a2 in the metabolism of the drug 1 the metabolites of tizanidine are thought to be inactive 1 elimination edit tizanidine is eliminated 60 in urine and 20 in feces 1 its elimination half life is approximately 2 5 hours 1 the inactive metabolites of tizanidine have half lives of 20 to 40 hours 1 chemistry edit synthesis edit tizanidine is a derivative of 2 1 3 benzothiadiazole and its first published synthesis was reported in a patent 22 the 5 chloro 2 1 3 benzothiadiazol 4 amine intermediate was a known compound produced in three steps from 4 chlorophenylenediamine as shown 23 treatment with two equivalents of thionyl chloride in pyridine formed the heterocycle which was nitrated with sodium nitrate in sulfuric acid and reduced using iron and acetic acid the amine intermediate was treated with benzoyl chloride and ammonium thiocyanate followed by alkaline hydrolysis to form a thiourea this was activated as its isothiuronium salt before being treated with ethylene diamine to give tizanidine 22 24 analogues edit analogues of tizanidine include clonidine and dexmedetomidine among others history edit tizanidine was approved for medical use in the united states in 1996 1 society and culture edit names edit tizanidine is the generic name of the drug and its inn tooltip international nonproprietary name ban tooltip british approved name and dcf tooltip dénomination commune française 25 26 27 in the case of the hydrochloride salt its generic name is tizanidine hydrochloride and this is its usan tooltip united states adopted name and banm tooltip british approved name 27 developmental code names of tizanidine include an 021 and ds 103 282 and its major brand names include zanaflex and sirdalud 25 26 27 28 research edit in addition to muscle spasticity tizanidine was under development for the treatment of fibromyalgia and migraine but development for these indications was discontinued 28 several other formulations have also been developed for various indications including spastic paralysis musculoskeletal pain and back pain but likewise have not been marketed 29 30 31 32 33 an intranasal formulation was in phase 3 clinical trials for back pain as of 2017 32 references edit 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 highlights of prescribing information zanaflex tizanidine capsules for oral use pdf www accessdata fda gov 1 2 3 4 5 6 zanaflex tizanidine hydrochloride capsules and tablets for oral use full prescribing information pdf acorda therapeutics inc ardsley ny 10502 retrieved 1 september 2016 1 2 british national formulary bnf 76 76 ed pharmaceutical press 2018 p 1094 isbn 978 0 85711 338 2 1 2 katzung bg 30 november 2017 basic clinical pharmacology 14th ed new york mcgraw hill education p 487 isbn 978 1 259 64115 2 oclc 1015240036 1 2 kamen l henney hr runyan jd february 2008 a practical overview of tizanidine use for spasticity secondary to multiple sclerosis stroke and spinal cord injury current medical research and opinion 24 2 425 439 doi 10 1185 030079908x261113 pmid 18167175 s2cid 73086671 1 2 3 4 5 tizanidine hydrochloride monograph for professionals drugs com american society of health system pharmacists retrieved 3 march 2019 tizanidine pregnancy and breastfeeding warnings drugs com retrieved 3 march 2019 kane sp top 300 of 2023 clincalc archived from the original on 12 august 2025 retrieved 12 august 2025 kane sp tizanidine drug usage statistics united states 2014 2023 clincalc retrieved 18 august 2025 ghanavatian s derian a january 2026 tizanidine statpearls treasure island fl statpearls publishing pmid 30137790 it is also prescribed off label for migraine headaches insomnia and as an anticonvulsant off label use refractory insomnia in spastic quadriplegic patients 7 tanaka h fukuda i miyamoto a oka r cho k fujieda k effects of tizanidine for refractory sleep disturbance in disabled children with spastic quadriplegia no to hattatsu 2004 nov 36 6 455 60 pubmed broese m riemann d hein l nissen c september 2012 α adrenergic receptor function arousal and sleep mechanisms and therapeutic implications pharmacopsychiatry 45 6 209 216 doi 10 1055 s 0031 1299728 pmid 22290201 tizanidine is a centrally acting α2 receptor agonist structurally related to clonidine in a study by tanaka et al 75 tizanidine was used in children with spastic quadriplegia to treat refractory sleep disturbances tizanidine treatment improved sleep induction and or maintenance in 61 9 of the children tanaka h fukuda i miyamoto a oka r cho k fujieda k november 2004 effects of tizanidine for refractory sleep disturbance in disabled children with spastic quadriplegia no to hattatsu brain and development in japanese 36 6 455 460 pmid 15560387 smith hs barton ae 2000 tizanidine in the management of spasticity and musculoskeletal complaints in the palliative care population the american journal of hospice palliative care 17 1 50 58 doi 10 1177 104990910001700111 pmid 11094920 tizanidine can cause sedation which is minimized by dose titration when taken at night patients report improvement in getting to sleep and little drowsiness or hangover sensation upon waking tizanidine is potentially helpful to many palliative care patients with chronic muscle pain and sleep disturbances tizanidine pubmed health archived from the original on 11 november 2012 retrieved 4 september 2017 spiller ha bosse gm adamson la january 2004 retrospective review of tizanidine zanaflex overdose journal of toxicology clinical toxicology 42 5 593 596 doi 10 1081 clt 200026978 pmid 15462150 s2cid 38946270 tizanidine uses dosage side effects drugs com drugs com retrieved 4 september 2017 nhs wales 2011 tizanidine zanaflex gwent primary care prescribing guidance pdf aneurin bevan university health board tizanidine package leaflet information for the user pdf medicines and healthcare products regulatory agency uk 2016 archived from the original pdf on 16 september 2018 retrieved 16 september 2018 zanaflex tizanidine hydrochloride dose indications adverse effects interactions from pdr net www pdr net 13 april 2023 retrieved 16 september 2018 1 2 3 blaxall hs murphy tj baker jc ray c bylund db october 1991 characterization of the alpha 2c adrenergic receptor subtype in the opossum kidney and in the ok cell line the journal of pharmacology and experimental therapeutics 259 1 323 329 doi 10 1016 s0022 3565 25 20309 3 pmid 1656026 tizanidine medlineplus drug information medlineplus gov u s national library of medicine retrieved 29 october 2019 1 2 us patent 3843668 neumann p certain 4 substituted amino 2 1 3 benzothiadiozoles published 22 october 1974 issued 22 october 1974 assigned to sandoz ag and sandoz wander inc us pesin vg sergeev va 1969 research on 2 1 3 thia and selenadiazole chemistry of heterocyclic compounds 3 5 662 666 doi 10 1007 bf00468340 s2cid 98830770 pharmaceutical substances tizanidine thieme archived from the original on 16 february 2023 retrieved 16 february 2023 1 2 tizanidine pubchem retrieved 10 august 2026 1 2 elks j 14 november 2014 the dictionary of drugs chemical data chemical data structures and bibliographies springer isbn 978 1 4757 2085 3 retrieved 10 august 2026 1 2 3 index nominum 2000 international drug directory taylor francis 2000 isbn 978 3 88763 075 1 retrieved 10 august 2026 1 2 tizanidine adisinsight 16 april 2026 retrieved 10 august 2026 tizanidine trandermal patch adisinsight 28 november 2019 retrieved 10 august 2026 etoricoxib tizanidine adisinsight 16 july 2016 retrieved 10 august 2026 tizanidine extended release adisinsight 13 july 2022 retrieved 10 august 2026 1 2 tizanidine intranasal adisinsight 5 september 2017 retrieved 10 august 2026 tizanidine oral spray adisinsight 2 october 2021 retrieved 10 august 2026 wikimedia commons has media related to tizanidine v t e skeletal muscle relaxants m03 peripherally acting primarily antinicotinic nmj block non depolarizing curare alkaloids alcuronium dimethyltubocurarine tubocurarine 4 ammonium agents ultra short duration gantacurium short duration rapacuronium mivacurium chandonium intermediate duration atracurium cisatracurium fazadinium rocuronium vecuronium long duration doxacurium dimethyltubocurarine pancuronium pipecuronium laudexium gallamine unsorted hexafluronium hexafluorenium depolarizing choline derivatives suxamethonium succinylcholine polyalkylene derivatives hexamethonium ach release inhibitors botulinum toxin centrally acting carbamic acid esters carisoprodol cyclarbamate difebarbamate febarbamate meprobamate phenprobamate styramate tybamate benzodiazepines bromazepam diazepam clonazepam flunitrazepam lorazepam nitrazepam temazepam tetrazepam nonbenzodiazepines eszopiclone thienodiazepines etizolam quinazolines methaqualone anticholinergics antimuscarinics cyclobenzaprine orphenadrine other arbaclofen placarbil baclofen chlormezanone chlorphenesin chlorzoxazone eperisone fenyramidol flopropione gabapentin ghb inaperisone lanperisone mephenesin mephenoxalone metaxalone methocarbamol phenibut pregabalin pridinol promoxolane quinine silperisone thiocolchicoside tizanidine tolperisone zoxazolamine directly acting dantrolene v t e hypnotics sedatives n05c gaba a alcohols 2m2b chloralodol ethanol alcohol diethylpropanediol ethchlorvynol methylpentynol trichloroethanol barbiturates allobarbital amobarbital aprobarbital barbital butabarbital butobarbital cyclobarbital ethallobarbital heptabarb hexobarbital mephobarbital methohexital narcobarbital pentobarbital phenallymal phenobarbital propylbarbital proxibarbal reposal secobarbital talbutal thiamylal thiopental thiotetrabarbital vinbarbital vinylbital benzodiazepines brotizolam cinolazepam climazolam clobazam clonazolam doxefazepam estazolam flubromazolam flunitrazolam flunitrazepam flurazepam flutemazepam flutoprazepam loprazolam lormetazepam midazolam nimetazepam nitemazepam nitrazepam nitrazolam quazepam temazepam triazolam carbamates carisoprodol emylcamate ethinamate hexapropymate meprobamate methocarbamol phenprobamate procymate tybamate imidazoles etomidate metomidate propoxate monoureides acecarbromal apronal apronalide bromisoval capuride carbromal ectylurea neurosteroids acebrochol alfadolone alfaxolone brexanolone allopregnanolone eltanolone pregnanolone ganaxolone hydroxydione minaxolone progesterone renanolone zuranolone nonbenzodiazepines eszopiclone indiplon lirequinil necopidem pagoclone pazinaclone saripidem suproclone suriclone zaleplon zolpidem zopiclone phenols cipepofol ciprofol fospropofol propofol propofol hemisuccinate piperidinediones glutethimide methyprylon piperidione pyrithyldione quinazolinones afloqualone cloroqualone diproqualone etaqualone mebroqualone mecloqualone methaqualone methylmethaqualone nitromethaqualone sl 164 others acetophenone acetylglycinamide chloral hydrate bromide compounds lithium bromide potassium bromide sodium bromide centalun chloral betaine chloral hydrate chloralose clomethiazole dichloralphenazone gaboxadol thip ibotenic acid amanita muscaria kavalactones loreclezole muscimol amanita muscaria paraldehyde petrichloral sesquiterpene isovaleramide isovaleric acid valerenic acid sulfonyla...