Tizanidine for spinal muscular atrophy

Last updated Feb. 21, 2025, by Andrea Lobo, PhD
Fact-checked by Jose Lopes, PhD

What is tizanidine for SMA?

Tizanidine is a fast-acting muscle relaxant approved by the U.S. Food and Drug Administration to treat spasticity, a condition in which muscles become abnormally stiff, in adults.

It has been prescribed to treat spasticity due to multiple sclerosis, cerebral palsy, traumatic brain injury, and spinal cord injury, and following a stroke. It may also be used to help manage spasticity in people with spinal muscular atrophy (SMA).

Tizanidine was originally launched by Acorda Therapeutics, and is now marketed as Zanaflex by Legacy Pharma and as Ontralfy by Fidelity Biopharma. Generic formulations are also available.

Therapy snapshot

How does tizanidine work?

SMA is caused in most cases by mutations in the SMN1 gene, which provides instructions to produce the survival motor neuron protein, known as SMN. The loss of this protein leads to the dysfunction and death of motor neurons, the nerve cells that control voluntary movement, resulting in muscle weakness and wasting.

Nerve signaling for muscle movements normally involves a message sent from the brain that travels along motor neurons to muscle cells. In people with SMA, nerve signaling may be impaired, resulting in painful muscle spasms and spasticity.

Tizanidine works by activating alpha2 adrenoceptors to inhibit motor neurons in the brain and spinal cord, and by reducing painful muscle spasms.

How is tizanidine administered?

Tizanidine may be given orally as tablets, capsules, or a solution:

• Tablets and capsules are available at strengths ranging from 2 mg to 6 mg.
• An oral solution is available at 2 mg/5 mL.

Treatment with capsules or tablets usually starts with a dose of 2 mg, up to a maximum of three doses per day, which can be increased every 1-4 days based on clinical response and tolerability. The maximum recommended daily dose is 36 mg.

In general, lower doses may be needed in older patients, who are more likely to have decreased kidney function that might lead to a longer duration of clinical effect.

Common side effects of tizanidine

Several common side effects with tizanidine treatment were reported in clinical trials enrolling patients with spasticity, but not with SMA specifically. These include:

• dry mouth
• somnolence, or excessive drowsiness
• weakness, fatigue, and/or tiredness
• dizziness.

Low blood pressure

Tizanidine may cause low blood pressure, known as hypotension, and fainting. Patients should be monitored for low blood pressure, though the risk may be minimized by making dose adjustments.

Using tizanidine with strong CYP1A2 inhibitors, such as the antibiotic ciprofloxacin, is contraindicated (not recommended), as clinically significant hypotension has been observed in such cases.

Liver injury

Tizanidine may cause liver injury and abnormalities in liver function tests. SMA patients should be monitored for liver enzyme levels before starting treatment and one month after the maximum dose is achieved, or if liver injury is suspected.

Sedation

Tizanidine may cause sedation that can interfere with the patient’s ability to perform daily activities.

Hallucinations and psychosis-like symptoms

The treatment has been associated with hallucinations (seeing, hearing, or feeling things that seem real but are not) and delusions (false ideas or beliefs). If patients develop these symptoms, treatment discontinuation should be considered.

Allergic reactions

Tizanidine may cause severe allergic reactions, characterized by throat and tongue swelling; hives, which are medically known as urticaria; and breathing difficulties. The treatment is contraindicated in people with previous allergic reactions to tizanidine or any of its ingredients.

Adverse reactions associated with withdrawal

Stopping tizanidine abruptly may result in adverse reactions, including high blood pressure, fast heart rate, and increased muscle tone. A patient’s tizanidine dose should be reduced slowly, particularly for those who have been taking the medication at high doses or for long periods or may be on concomitant treatment with narcotics, or prescribed painkillers.

Pediatric use

The safety and efficacy of tizanidine in pediatric patients have not been established. The administration of tizanidine in juvenile rats has resulted in reduced weight gain, delayed sexual maturation, and cognitive deficits.

Use in pregnancy and breastfeeding

Data regarding the developmental risk associated with the use of tizanidine in pregnant patients are lacking. In animal studies, the administration of tizanidine during pregnancy resulted in growth deficits and mortality in the offspring.

In addition, data are not available on the presence of tizanidine in human milk, or the therapy’s effects on breastfed infants or human milk production. The benefits of breastfeeding should be considered along with the mother’s clinical need for tizanidine and potential adverse effects on the breastfed infant from this therapy or from the underlying maternal condition.

SMA News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.