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Tizanidine
Tizanidine is used as monotherapy to manage spasticity.1 Its effectiveness appears similar to baclofen or diazepam.1 It produces sedative effects,2 while higher doses can cause hallucinations, psychosis, and delirium. Common adverse effects include dry mouth, sleepiness, weakness, and dizziness.2 Serious adverse effects may include low blood pressure, liver problems,2 and QT prolongation,3 a disturbance in the heart’s electrical timing.4
Dosage & Duration
Dosage
Doses are population estimates that vary widely between individuals.
Duration
Subjective Effects
Pharmacology
Pharmacodynamics
Tizanidine is a centrally acting alpha-2 adrenergic receptor agonist2 that reduces excitatory amino acid release, including glutamate and aspartate, and enhances presynaptic inhibition of motor neurons. Its strongest action is on spinal polysynaptic pathways, although the relationship between alpha-2 agonism and its antispastic action is not fully understood. In animal models, it has shown no direct action on skeletal muscle fibers or the neuromuscular junction and no significant effect on monosynaptic spinal reflexes. It also acts at alpha-1 adrenergic receptors with weaker affinity; alpha-2 agonism may contribute to its antinociceptive and anticonvulsant activity.
Pharmacokinetics
Tizanidine is largely absorbed after oral administration, but extensive first-pass metabolism limits absolute oral bioavailability to about 40%.2 Approximately 95% of an ingested dose is metabolized, primarily in the liver by CYP1A2.2 Food and whether the drug is taken as a tablet, an intact capsule, or capsule contents sprinkled on food can affect absorption. Tizanidine is extensively distributed, with a steady-state volume of distribution of 2.4 L/kg, also reported following intravenous administration, and approximately 30% plasma protein binding. Tizanidine has an elimination half-life of approximately 2.5 hours2; steady-state concentrations are reached within 24-48 hours after administration. Clearance is reduced by more than 50% in elderly patients with severe renal impairment (creatinine clearance below 25 mL/min) compared with healthy elderly people.5 In rats, tizanidine enters breast milk with a milk-to-blood ratio of 1.8:1;6 transfer into human milk is unknown, although its lipid solubility makes this likely.
Interactions
An unlisted combination is an unknown one, not a safe one. Check a dedicated combination chart before mixing.
Tolerance
Harm Potential
Addiction & Dependence
Physical
LowPhysical dependence is rare, but prolonged use exceeding 36 mg daily can cause hypertensive withdrawal. Abrupt discontinuation can produce rebound hypertension, tachycardia, and increased spasticity; tapering after dependence develops helps avoid a hypertensive crisis.
Toxicity
In a retrospective series of tizanidine ingestions, responses reported after naloxone administration were no response in five patients, poorly documented response in one, and arousal in one.7
LD50 Data
| Species | Route | Value |
|---|---|---|
| rat | oral | 414 mg/kg |
| rat | subcutaneous | 282 mg/kg |
| mouse | oral | 235 mg/kg |
Tizanidine lowers heart rate and blood pressure in humans, and excessive oral doses can cause dangerous hypotension and loss of consciousness; QT prolongation is also a reported serious adverse effect.8
Long-term tizanidine use has been associated with liver problems, including liver failure and death in extreme cases.
Tizanidine overdose can cause coma,7 and young nursing rats exposed through maternal milk showed abnormal results on tests of central nervous system function.
Tizanidine caused fetal harm in animal studies.2
Psychosis Risk
Psychosis is a reported serious adverse effect of tizanidine. High doses can induce hallucinations, psychosis, and delirium, with delirium also reported at extremely high doses; the hallucination and psychosis thresholds may be close in many users.
Seizure Risk
Tizanidine has shown anticonvulsant activity against strychnine-induced seizures but did not suppress GABA-induced seizures.
History & Culture
Tizanidine's first published synthesis appeared in a patent. It was approved for medical use in the United States in 19962 and became available as a generic…
Legality
By Country
United StatesPrescription only
CanadaPrescription only
TurkeyPrescription only
United KingdomPrescription onlyReferences
Citations
Article Status
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