Tizanidine: muscle relaxant for spasms and spasticity

The UK product information lists two groups of use. The first is painful spasm of skeletal muscle, associated with spinal conditions (cervical and lumbar syndromes) or following surgery on the musculoskeletal system, such as for a herniated disc or hip joint disorders. The second is spasticity due to neurological disorders such as multiple sclerosis, chronic myelopathy, degenerative spinal cord disease, cerebrovascular accidents and cerebral palsy.

The exact mechanism is not fully clarified, but it is believed to work mainly through alpha-2 adrenergic agonist effects, reducing abnormally increased muscle tone and easing painful spasms and clonus.

Because tizanidine has a narrow therapeutic index and blood levels vary a great deal between people, the product information says the dose has to be individually adjusted. A low starting dose reduces the risk of side effects, then the dose is increased gradually and with caution according to need and response.

For muscle spasm the usual range is 2mg to 4mg three times daily, with an optional extra late-evening dose in severe cases to reduce daytime sedation. For spasticity the initial daily dose should not exceed 6mg in three divided doses, increased in steps at intervals of half or one week; the usual best response is between 12mg and 24mg a day, and the total should not exceed 36mg. Safety in children and adolescents under 18 has not been established.

Many effects are dose related. At lower doses these include sleepiness, tiredness, dizziness, dry mouth, lower blood pressure, nausea and gut upset, and they become more frequent at the higher doses used for spasticity. Tizanidine can cause low blood pressure and, rarely, fainting, and slow titration reduces that risk. Hallucinations or delusions have been reported, and anaphylaxis is possible.

Liver problems have been reported, rarely at daily doses up to 12mg, so liver function tests are recommended monthly for the first 4 months in people receiving higher doses or who develop symptoms. Caution applies with cardiovascular, kidney or liver disease, and clinical laboratory and ECG monitoring is recommended in some circumstances.

The contraindications are hypersensitivity, severe liver impairment, and combined use with potent CYP1A2 inhibitors such as fluvoxamine or ciprofloxacin, which raise tizanidine levels sharply and can cause low blood pressure, a slow heartbeat or excessive drowsiness. Other CYP1A2 inhibitors can have a similar effect, and the combination should be avoided unless clearly necessary.

Combined hormonal contraceptives moderately increase tizanidine levels and may increase side effects. Antihypertensives, beta-blockers and digoxin can add to low blood pressure or slow heart rate, and other drugs that prolong the QT interval add risk.

The sedative effects add to those of other central nervous system depressants such as benzodiazepines, opioids and tricyclic antidepressants. Sedation tends to peak in the first week of titration and then settle. People who feel drowsy or dizzy should avoid driving or activities needing alertness, since tizanidine has a minor to moderate influence on driving ability.

Alcohol would be expected to increase drowsiness; ask your prescriber or pharmacist about your own circumstances.

Safety in pregnancy has not been established, so it should not be used in pregnant women unless the benefit clearly outweighs the risk. Its safety in breastfed infants is not known and it should not be used in nursing mothers.

Withdrawal can cause rebound high blood pressure, a fast heartbeat and increased muscle tone, particularly after high doses (20 to 28mg a day) or long use, so it should be reduced gradually under medical guidance. Do not stop or change treatment without speaking to your prescriber.