indication

For the management of increased muscle tone associated with spasticity

pharmacology

Tizanidine is a short-acting drug for the management of spasticity. Tizanidine is an agonist at a2-adrenergic receptor sites and presumably reduces spasticity by increasing presynaptic inhibition of motor neurons. In animal models, tizanidine has no direct effect on skeletal muscle fibers or the neuromuscular junction, and no major effect on monosynaptic spinal reflexes. The effects of tizanidine are greatest on polysynaptic pathways. The overall effect of these actions is thought to reduce facilitation of spinal motor neurons.

mechanism of action

Tizanidine reduces spasticity by increasing presynaptic inhibition of motor neurons through agonist action at a2-adrenergic receptor sites.

half life

2.5 hours

route of elimination

Approximately 95% of an administered dose is metabolized.

drug interactions

Amiodarone: Amiodarone may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.

Amlodipine: Amlopidine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.

Benazepril: Tizanidine increases the risk of hypotension with the ACE inhibitor

Captopril: Tizanidine increases the risk of hypotension with the ACE inhibitor

Cilazapril: Tizanidine increases the risk of hypotension with the ACE inhibitor

Cimetidine: Cimetidine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.

Ciprofloxacin: Ciprofloxacin inhibits the metabolism and clearance of Tizanidine. Concomitant therapy is contraindicated.

Diclofenac: Diclofenac may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.

Donepezil: Possible antagonism of action

Enalapril: Tizanidine increases the risk of hypotension with the ACE inhibitor

Ethanol: Ethanol increases the adverse effects of Tizanidine. The CNS depressant effects of these agents are additive.

Ethinyl Estradiol: Ethinyl estradiol may increase the serum concentration of tizanidine. Monitor for changes in the therapeutic and adverse effects of tizanidine if ethinyl estradiol is initiated, discontinued or dose changed.

Fluoxetine: Fluoxetine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.

Fluvoxamine: Fluvoxamine inhibits the metabolism and clearance of tizanidine. Concomitant therapy is contraindicated.

Fosinopril: Tizanidine increases the risk of hypotension with the ACE inhibitor

Galantamine: Possible antagonism of action

Gemfibrozil: Gemfibrozil may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.

Ketoconazole: Ketoconazole may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.

Lidocaine: Lidocaine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.

Lisinopril: Tizanidine increases the risk of hypotension with the ACE inhibitor

Mestranol: Oral contraceptives decrease the clearance of Tizanidine.

Methoxsalen: Methoxsalen may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.

Mexiletine: Mexilitene may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.

Miconazole: Miconazole may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.

Moexipril: Tizanidine increases the risk of hypotension with the ACE inhibitor

Moxifloxacin: Moxifloxacin may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.

Nifedipine: Nifedipine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.

Norethindrone: The contraceptive increases the effect of tizanidine

Norfloxacin: Norfloxacin may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.

Ofloxacin: Ofloxacin may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.

Perindopril: Tizanidine increases the risk of hypotension with the ACE inhibitor

Primaquine: Primaquine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.

Propafenone: Propafenone may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.

Propofol: Propofol may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.

Quinapril: Tizanidine increases the risk of hypotension with the ACE inhibitor

Quinupristin: This combination presents an increased risk of toxicity

Ramipril: Tizanidine increases the risk of hypotension with the ACE inhibitor

Rivastigmine: Possible antagonism of action

Spirapril: Tizanidine increases the risk of hypotension with the ACE inhibitor

Thiabendazole: The strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Tizanidine by decreasing Tizanidine metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Tizanidine if Thiabendazole is initiated, discontinued or dose changed.

Ticlopidine: Ticlopidine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.

Trandolapril: Tizanidine increases the risk of hypotension with the ACE inhibitor

Tranylcypromine: Tranylcypromine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.

Treprostinil: Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.

Trimipramine: Trimipramine may reduce the antihypertensive effect of the alpha2-agonist, Tizandine. Trimipramine may also increase the rebound hypertensive effect of Clonidine. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Clonidine if Trimipramine is initiated, discontinued or dose changed. Tizandine should be withdrawn very gradually to reduce the risk of hypertensive crisis.

Triprolidine: The CNS depressants, Triprolidine and Tizanidine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.