Tizanidine

What it is

Tizanidine is a prescription-only small molecule taken as a tablet or capsule. It is a centrally acting alpha-2 adrenoceptor agonist, chemically related to clonidine, and is used as a short-acting antispastic agent. In the United States the label restricts it to spasticity in adults. It is almost entirely metabolised by the liver enzyme CYP1A2, which is why its blood levels swing enormously when CYP1A2 is blocked.

What the research says

The evidence is thin for its size of use. A systematic review in children with cerebral palsy found consistent reductions in measured muscle tone, but from five small studies. For low back pain, where tizanidine is the most commonly tested non-benzodiazepine muscle relaxant, two systematic reviews disagree: one rates short-term pain relief as moderate certainty, the other rates the class as very low certainty and not clinically important. Sedation, dry mouth, weakness, low blood pressure and liver enzyme rises are common, and combining it with ciprofloxacin or fluvoxamine raises exposure by roughly ten to thirty times.

Evidence grade: Limited evidence.

How it works

Drug class: Centrally acting alpha-2 adrenergic receptor agonist (antispastic skeletal muscle relaxant)

Tizanidine acts on alpha-2 receptors in the spinal cord and brainstem, damping the release of excitatory neurotransmitters onto the motor neurons that drive muscle tone. The result is reduced muscle spasm and stiffness without directly weakening the muscle fibre itself. It does not treat the underlying nerve injury. (Source 1)

What it is used for

• The label approves it for spasticity in adults. A systematic review in children with cerebral palsy found greater improvement in measured muscle tone than comparators across five small studies, but the reviewers themselves called for high-quality randomised trials. Evidence: limited. (Source 2)
• Tizanidine was the drug in 12 of the 50 trials in a 2025 systematic review of non-benzodiazepine muscle relaxants for low back pain, which found moderate-certainty short-term pain relief. A 2021 BMJ systematic review of the same class judged the evidence very low certainty, the effect not clinically important, and the risk of adverse events increased. Evidence: disputed. (Source 3)
• A 2024 narrative review in Journal of Pain Research reports tizanidine may help neuropathic pain and may suit people who respond poorly to other drugs, but this is an expert summary of small studies rather than a systematic review with pooled effects. Evidence: limited. (Source 1)
• Placebo-controlled trials exist (Fogelholm 1992, Saper 2002) but we could not reach their full texts, so we record no finding for this use. We did not find a systematic review we could read. Evidence: unknown.
• A narrative review reports that tizanidine, like clonidine, lowered postoperative pain scores at 2 and 4 hours and reduced morphine use over 48 hours in the trial it summarises. This is one small study reported second-hand in a review. Evidence: limited. (Source 1)

Interactions

• Ciprofloxacin (pharmacokinetic study): Ciprofloxacin blocks CYP1A2, the enzyme that clears tizanidine, so blood levels rise roughly seven to ten times and blood pressure can drop dangerously. The combination is contraindicated. Limit: The 7-fold and 10-fold figures quoted here come from a formal interaction study and are the ones to rely on. The same page also prints wider ranges, assigning 6–24-fold to the peak concentration and 4–21-fold to total exposure, which contradicts its own next sentence, where total exposure (10-fold) rises more than the peak (7-fold). Treat the direction as certain — ciprofloxacin raises tizanidine levels several-fold — and the exact ranges as unreliable as printed. (Source 4)
• Fluvoxamine and other strong CYP1A2 inhibitors (label): Strong CYP1A2 inhibitors are contraindicated with tizanidine because they multiply its exposure and its blood-pressure-lowering and sedating effects. (Source 1)
• Alcohol (pharmacokinetic study): Alcohol modestly raises tizanidine blood levels and adds to its sedating effect, so drowsiness and low blood pressure become more likely. (Source 5)
• Food (taking the tablet with a meal) (pharmacokinetic study): Taking the tablet with food raises both the peak level and the total amount absorbed by about 30%, so switching between fed and fasted dosing changes the effect. The tablet and capsule are not interchangeable in this respect. (Source 5)
• Benzodiazepines, opioids and tricyclic antidepressants (theoretical): Sedation stacks when tizanidine is combined with any other central nervous system depressant. (Source 1)

Stopping it

• The label instructs a taper of 2 mg to 4 mg per day when tizanidine is stopped, to reduce the risk of withdrawal reactions. It frames this particularly for people who have been on high doses for long periods or who are also being treated with narcotics. (Source 5)
• The withdrawal picture named in the older brand label and repeated in a 2024 pharmacology review is rebound high blood pressure, fast heart rate and a return of increased muscle tone. (Source 1)

What goes wrong

Sedation, dry mouth, weakness and dizziness are the commonest adverse effects in placebo-controlled spasticity trials, at several times the placebo rate. (Source 5)

• Official position, Moderate certainty.
• Size: 264 patients with spasticity in multiple-dose placebo-controlled studies (261 placebo)
• Who: Adults with spasticity in the registration trials summarised by the label.
• How long: Multiple-dose placebo-controlled studies.
• Result: Label Table 1 reports, as percentages of patients, dry mouth 49 on tizanidine versus 10 on placebo, somnolence 48 versus 10, asthenia 41 versus 16 and dizziness 16 versus 4, in 264 patients given tizanidine and 261 given placebo.
• Funding: industry-funded (sponsor registration trials, reported in the label)

Limit of this finding: The label prints these figures as bare numbers in a table whose two columns are headed "Placebo N = 261 %" and "Tizanidine Tablet N = 264 %", so the unit sits in the column heading rather than beside each number. Read 49 as 49% of the 264 patients who took tizanidine, not as 49 patients. These are rates from the sponsor’s own registration trials as summarised by the label, not from an independent review.

The most common adverse reactions (>10% of patients treated with tizanidine) reported in multiple dose, placebo-controlled clinical studies involving 264 patients with spasticity were dry mouth, somnolence/sedation, asthenia (weakness, fatigue and/or tiredness), and dizziness.

Tizanidine can injure liver cells, and the label recommends blood monitoring of liver enzymes. (Source 5)

• Official position, Low certainty.
• Size: Not stated in the label text we read.
• Who: Patients taking tizanidine.
• How long: Baseline and one month after the maximum dose is reached, and at any point when liver injury is suspected.
• Result: Hepatocellular injury; the label also records that liver function test abnormality and hepatotoxicity have been observed with tizanidine, and recommends aminotransferase monitoring rather than quoting a rate in the passage we read.
• Funding: not stated.

Tizanidine may cause hepatocellular liver injury. Liver function test abnormality and hepatotoxicity have been observed with tizanidine. Monitoring of aminotransferase levels is recommended at baseline and 1 month after maximum dose is achieved, or if hepatic injury is suspected.

A pharmacology review lists abnormal liver function and hepatotoxicity alongside low blood pressure, slow heart rate and hallucinations among tizanidine's adverse effects. (Source 1)

• Expert review, not systematic, Low certainty.
• Size: Not applicable; expert summary with no stated pooling method.
• Who: Patients taking tizanidine.
• How long: Not applicable.
• Result: No rates given in the review passage we read.
• Funding: not stated.

Adverse effects of tizanidine include somnolence, dry mouth, hypotension, bradycardia, dizziness, fatigue, weakness, hallucinations, abnormal liver function, and hepatotoxicity.

In the WHO global spontaneous-report database, 91 of 4,192 tizanidine reports involved co-prescribed ciprofloxacin, hypotension was the commonest reaction, and two reports described a fatal outcome. (Source 4)

• Case series, Low certainty.
• Size: 91 individual case safety reports with ciprofloxacin, out of 4,192 worldwide tizanidine reports.
• Who: Patients worldwide reported to the WHO pharmacovigilance database (median age 54 years, range 13 to 85; 64.8% female)
• How long: Not applicable; spontaneous reports.
• Result: Hypotension was the reaction reported most often (25 reports), then drug interaction (23), asthenia (8) and urinary tract infection (8); two reports had a fatal outcome. The percentages the paper prints beside those counts (5.6%, 5.2%, 1.8%, 1.8%) are shares of all reactions reported, not of the 91 co-exposed patients.
• Funding: not stated.

Limit of this finding: Two of this paper’s own numbers do not add up, and we have quoted it as it is printed rather than silently correcting it. It says "91 (2.0%) of the identified 4192 worldwide ICSR", but 91 out of 4192 is 2.2%, not 2.0%. And the percentages beside the individual reactions are shares of all the reactions reported, not of those 91 patients: 25 hypotension reports among 91 patients would be 27.5%, about five times the 5.6% printed. So do not read 5.6% as the chance of low blood pressure on this combination. These are voluntary spontaneous reports, which cannot give a rate at all, because nobody knows how many people took the two drugs together.

ADRs reported most often affected the nervous system and the cardiac function, especially with large tizanidine doses or drugs with CNS and cardiovascular depressant effects. In two cases, a fatal outcome was reported.

Stopping tizanidine abruptly can produce rebound high blood pressure, fast heart rate and a return of muscle stiffness. (Source 6)

• Official position, Low certainty.
• Size: Not stated.
• Who: Patients discontinuing tizanidine, particularly after high doses or long use.
• How long: Not stated.
• Result: Label instructs reducing by 2 mg to 4 mg per day.
• Funding: not stated.

the dose should be decreased slowly (2 mg to 4 mg per day) to minimize the risk of withdrawal and rebound hypertension, tachycardia, and hypertonia

What the evidence supports

In children with cerebral palsy, tizanidine reduced measured muscle tone more than comparators in four of five studies, but the review's authors say the trial quality is not good enough to settle the question. (Source 2)

• Systematic review, Low certainty.
• Size: 5 studies (3 randomised controlled trials, 2 observational), 264 participants in total.
• Who: Children with spastic cerebral palsy.
• How long: Varied across reports; not standardised.
• Result: Greater improvement on the modified Ashworth scale in all but one observational study; three studies reported better gross motor function than baclofen; only one included trial was judged low risk of bias across all parameters.
• Funding: not stated.

Excepting one observational study, tizanidine was associated with a greater improvement on the modified Ashworth scale. Pain reduction was also greater with tizanidine treatment compared to the placebo, as evidenced by one RCT.

The same systematic review reports no serious adverse events with tizanidine in the included studies and a safety profile at least as good as baclofen, while stating that high-quality trials are still needed. (Source 2)

• Systematic review, Low certainty.
• Size: 5 studies, 264 participants.
• Who: Children with spastic cerebral palsy.
• How long: Varied across reports.
• Result: Two RCTs indicated similar safety profiles between tizanidine and placebo; remaining studies favoured tizanidine over baclofen.
• Funding: not stated.

Tizanidine usage was associated with no serious adverse events, reflecting a better safety profile than baclofen. Nevertheless, high-quality RCTs are recommended to support tizanidine administration in pediatric patients.

In low back pain, where tizanidine is the most frequently tested drug of its class, a 2025 systematic review found moderate-certainty evidence of short-term pain relief over placebo. (Source 3)

• Systematic review, Moderate certainty.
• Size: 50 studies, 7,531 participants, 4,775 pooled; tizanidine was the drug in 12 studies.
• Who: Adults with acute (under 6 weeks) or chronic (over 12 weeks) primary low back pain.
• How long: Short-term follow-up of 5 to 7 days for the pain relief outcome.
• Result: Moderate-certainty evidence of an increased likelihood of pain relief in acute low back pain and of global efficacy versus placebo. The review prints RR 0.53 (p<0.0001) for pain relief and RR 0.49 (p=0.0001) for global efficacy; these ratios are calculated for the unfavourable outcome (failing to achieve relief), which is why they sit below 1 while describing a benefit. The pain-relief estimate comes from 5 studies with 446 participants at 5 to 7 days. No confidence intervals are reported for either ratio.
• Funding: not stated.

Limit of this finding: As printed, this review puts risk ratios below 1 — 0.53 and 0.49 — immediately next to the words "increased likelihood of pain relief", which contradicts itself on its face, because a ratio below 1 normally means less of whatever is being counted. What the paper is counting is the bad outcome, failing to get relief, so 0.53 means fewer failures, that is, a benefit. Two things follow: 0.53 does not mean people were about half as likely to get relief, and these figures should not be read as precise, because the review gives only p values for them and no confidence intervals.

Based on moderate-certainty evidence from 5 studies (446 participants), oral non-benzodiazepines demonstrated an increased likelihood of short-term (5–7 days follow-up) pain relief

What the evidence does not support

A 2021 BMJ systematic review of the same drug class reached the opposite conclusion: the reduction in pain intensity was small, not clinically important, of very low certainty, and came with an increased risk of adverse events. (Source 7)

• Systematic review, Very low certainty.
• Size: 49 trials in the review; 31 trials sampling 6,505 participants pooled.
• Who: Adults with non-specific low back pain.
• How long: Two weeks or less for the pain outcome.
• Result: Adverse event risk with non-benzodiazepine antispasmodics relative risk 1.6 (1.2 to 2.0); pain intensity reduction judged small and not clinically important.
• Funding: not stated.

Very low and low certainty evidence shows that non-benzodiazepine antispasmodics might provide small but not clinically important reductions in pain intensity at or before two weeks and might increase the risk of an adverse event in acute low back pain, respectively.

The same BMJ review states plainly that considerable uncertainty remains about whether muscle relaxants work or are safe. (Source 7)

• Systematic review, Very low certainty.
• Size: 49 trials; 31 trials, 6,505 participants pooled.
• Who: Adults with non-specific low back pain.
• How long: Two weeks or less for most outcomes.
• Result: No clinically important benefit established; certainty rated low to very low throughout.
• Funding: not stated.

49 trials were included in the review, of which 31, sampling 6505 participants, were quantitatively analysed.

Where the research disagrees

Whether non-benzodiazepine muscle relaxants, tizanidine chief among them, actually help low back pain

• European Spine Journal systematic review, 2025, systematic-review with meta-analysis, 50 studies, 7,531 participants, moderate certainty: Non-benzodiazepine MR for acute LBP were associated with increased likelihood of pain relief and global efcacy compared to placebo. (Source 3)
• BMJ systematic review and meta-analysis, 2021, systematic-review with meta-analysis, 49 trials, 6,505 participants pooled, very low to low certainty: Considerable uncertainty exists about the clinical efficacy and safety of muscle relaxants. (Source 7)

How much

• Reference intake: There is no reference intake for a prescription drug. Dosing is set by the prescriber. As a position, the US label describes starting at 2 mg with increases of 2 mg to 4 mg, and states the ceiling below. (Source 5)
• Upper limit: As a position, the US label (revised 3/2025) states a maximum total daily dosage of 36 mg. (Source 5)
• Studied: The label's placebo-controlled spasticity studies enrolled 264 patients on tizanidine and 261 on placebo, dosed by titration. (Source 5)
• Studied: In the paediatric cerebral palsy systematic review, tizanidine dose and duration varied between reports and were not standardised. (Source 2)

A common belief, and what the research shows

The belief: Tizanidine is just a mild muscle relaxant, so it is safe to take with anything.

What the research shows: It is a blood-pressure-lowering drug that happens to reduce muscle tone, and its clearance depends almost entirely on one liver enzyme. A common antibiotic raises its exposure about tenfold: "Ciprofloxacin at doses of 500 mg twice daily increased the peak concentration and AUC (0–∞) of tizanidine by 7-fold and 10-fold, respectively." In the WHO safety database, among reports where the two were combined, "In two cases, a fatal outcome was reported." Sedation and dry mouth affect roughly half of people in trials, and the label warns "Tizanidine may cause hepatocellular liver injury."

Questions and answers

What is it?

Tizanidine is a prescription tablet or capsule that acts on alpha-2 adrenergic receptors in the central nervous system. It is chemically a cousin of the blood pressure drug clonidine. It is classed as both an antispastic and an antispasmodic agent, and in the United States its approved use is spasticity in adults. (Source 1)

What does it do in the body?

It reduces the excitatory signalling that drives muscle tone, so spasm and stiffness ease. It does not strengthen muscle or repair the nerve injury behind the spasticity. Its effect is short-acting, which is why it is usually taken several times a day. In the United States the licensed use is spasticity in adults, not general back pain. (Source 5)

Is it good or bad for you?

It is both, depending on context. In spasticity the literature is favourable but thin: a systematic review in children with cerebral palsy found better muscle tone and no serious adverse events, while the reviewers themselves asked for better trials. Against that, about half of adults in placebo-controlled trials get dry mouth and drowsiness, the drug lowers blood pressure, and it can injure the liver. (Source 2)

How do you get more of it?

This is not a substance to seek more of. It is prescription-only and the prescriber sets the dose and the ceiling. One thing that changes how much reaches the blood is whether the tablet is taken with food, which raises absorption by about 30%, so being inconsistent about meals changes the dose you effectively receive. (Source 5)

If it is harmful, what reduces it?

When it is causing harm, the way to reduce it is a supervised taper rather than stopping suddenly, because abrupt withdrawal can cause rebound high blood pressure and a fast heart rate. The label specifies decreasing the dosage by 2 mg to 4 mg per day, and singles out people who have been on high doses for long periods or who are also taking narcotics. There is no antidote or binding agent in routine use. (Source 5)

Why might someone be low in it or missing it?

The nutrient sense of this question does not apply, but blood levels vary enormously between people for a related reason: tizanidine is cleared almost entirely by the liver enzyme CYP1A2. Anything that blocks that enzyme multiplies exposure many times over, which is why strong inhibitors are contraindicated; conversely, faster CYP1A2 activity leaves less drug in the blood. (Source 1)

Which whole foods contain it or feed it?

No whole food contains tizanidine; it is a synthetic drug. Food does matter for a different reason: taking the tablet with a meal raises the peak blood level by roughly 30%, so a dose taken with food is not the same as the same dose taken fasting. (Source 5)

What happens if you do not have it?

Nothing is deficient if you do not take it, because it is a drug rather than a nutrient. What the literature shows is what goes untreated: in trials, people given tizanidine had greater reductions in measured muscle tone than comparators, and in one randomised trial greater pain reduction than placebo. Without it, those symptoms are addressed by other drugs, physiotherapy or not at all. (Source 2)

How can you test for it?

There is no routine blood level test used in practice. What is tested is the liver: the label recommends checking aminotransferase enzymes before starting, a month after reaching the maximum dose, and if liver injury is suspected. Blood pressure and heart rate are also monitored because the drug lowers both. An aminotransferase test detects liver injury but does not predict who will get it. (Source 5)

References

1. Journal of Pain Research (Dove Medical Press). Tizanidine: Advances in Pharmacology & Therapeutics and Drug Formulations. 2024. PMID 38529017, DOI 10.2147/JPR.S461032. Read the source
2. Annals of Child Neurology. Effect of Tizanidine on Spasticity in Pediatric Patients with Cerebral Palsy: A Systematic Review. 2024. Read the source
3. European Spine Journal (author-accepted copy held by the German National Library). Oral non-benzodiazepine muscle-relaxants for people with acute and chronic primary low back pain: a systematic review with meta-analysis. 2025. PMID 40186696. Read the source
4. European Journal of Clinical Pharmacology (Springer). Coadministration of tizanidine and ciprofloxacin: a retrospective analysis of the WHO pharmacovigilance database. 2021. DOI 10.1007/s00228-020-02981-2. Read the source
5. DailyMed, US National Library of Medicine (label sponsored by Apotex Corp.). TIZANIDINE tablet - prescribing information (Apotex Corp.), revised 3/2025. 2025. Read the source
6. US Food and Drug Administration, Drugs@FDA label archive. ZANAFLEX (tizanidine hydrochloride) capsules and tablets - FDA approved prescribing information, Revised: 12/2020. 2020. Read the source
7. The BMJ. Efficacy, acceptability, and safety of muscle relaxants for adults with non-specific low back pain: systematic review and meta-analysis. 2021. PMID 34233900, DOI 10.1136/bmj.n1446. Read the source