1. Disclaimer
We do not guarantee the accuracy, currency or completeness of information regarding medications or medical products, and official sources should be verified before making any decisions. By using this blog, you agree to assume personal responsibility for relying on the information provided.
This article is intended for general educational and informational purposes only. It does not replace the prescribing information approved by the relevant regulatory authority, professional medical advice, diagnosis, or individualized treatment. Medication decisions should be based on the current official product information applicable to the specific country, formulation, strength, manufacturer, and patient.
2. Summary
Tizanidine is a centrally acting skeletal muscle relaxant and antispasticity agent. It is a central α2-adrenergic receptor agonist that reduces excessive muscle tone primarily through inhibition of excitatory neurotransmitter release within the spinal cord.
Tizanidine is mainly used for the management of spasticity, particularly when reduction of muscle tone and painful muscle spasms is clinically desirable. Its relatively short duration of action can make it useful when treatment is targeted to particular activities or periods during which relief of spasticity is most important.
The supplied Sirdalud information also describes its use for painful muscle spasms and spasticity associated with multiple sclerosis, spinal cord injury, and brain injury.
Tizanidine requires particular attention to sedation, dizziness, hypotension, bradycardia, hepatic injury, renal impairment, and clinically important CYP1A2-mediated drug interactions. Concomitant use with the potent CYP1A2 inhibitors fluvoxamine or ciprofloxacin is contraindicated.
3. Brand Name
- Sirdalud®
- Sirdalud® MR
- Generic products are marketed as tizanidine or tizanidine hydrochloride.
The supplied historical document identifies Sirdalud® / Sirdalud® MR as Novartis products.
Important: Brand availability, formulation, strengths, and marketing authorization may differ between countries. The current package and local regulatory information should therefore be checked before publication or prescribing.
4. Category
- Centrally acting skeletal muscle relaxant
- Antispasticity agent
- Central α2-adrenergic receptor agonist
ATC code: M03BX02.
5. Active Ingredient
Tizanidine hydrochloride
Tizanidine is the active pharmacologically relevant component. The historical Sirdalud document describes the active substance as tizanidine, as the hydrochloride.
6. Pharmaceutical Form & Strength
The supplied Sirdalud information describes:
Immediate-release tablets
- 2 mg
- 4 mg
- Scored tablets.
Modified-release (MR) capsules
- 6 mg
- 12 mg
- Sustained/modified release formulation.
Current U.S. tizanidine labeling also confirms availability of immediate-release 2-mg and 4-mg tablets, while capsule formulations are separately labeled and are not pharmacokinetically interchangeable with tablets on a simple milligram-for-milligram basis.
7. Manufacturer & Marketing Authorization Holder
The supplied historical Sirdalud document identifies:
Novartis Pharma AG, Basel, Switzerland
and states that the manufacturer information should also be checked on the folding box.
However, manufacturer and marketing-authorization-holder information is product- and country-specific and may have changed since the historical document was issued. Therefore, the current local carton, package leaflet, and national regulatory database should be consulted before presenting a current manufacturer/MAH statement.
8. Mechanism of Action
Tizanidine is a centrally acting α2-adrenergic receptor agonist.
Its principal therapeutic site of action is believed to be within the spinal cord. By stimulating presynaptic α2 receptors, tizanidine reduces the release of excitatory amino acids involved in excitatory neurotransmission, including pathways involving N-methyl-D-aspartate (NMDA) receptors.
This decreases excessive polysynaptic transmission at the spinal interneuron level and consequently reduces pathological muscle tone and spasticity.
The supplied Sirdalud document describes this mechanism and explains that inhibition of excessive spinal polysynaptic transmission results in reduced muscle tone.
9. Spectrum of Activity
Tizanidine does not have an antimicrobial spectrum of activity because it is not an antibiotic or antimicrobial drug.
Its pharmacological activity is directed toward skeletal muscle hypertonia and spasticity through central nervous system mechanisms.
It may reduce:
- Excessive muscle tone
- Muscle spasms
- Clonus
- Resistance to passive movement
The historical Sirdalud information states that the drug can improve voluntary muscle strength indirectly by reducing excessive muscle tone and spasticity.
10. Pharmacokinetics
Absorption
Tizanidine is rapidly absorbed following oral administration.
For immediate-release tablets, peak plasma concentrations are generally reached approximately 1 hour after administration. The historical product information reported a mean absolute bioavailability of approximately 34%.
Distribution
The historical Sirdalud document reported a mean steady-state volume of distribution of approximately 160 L following intravenous administration and plasma protein binding of approximately 30%.
Metabolism
Tizanidine undergoes extensive hepatic metabolism and is metabolized predominantly through CYP1A2.
Its metabolites appear to be pharmacologically inactive.
This CYP1A2 dependence is clinically important because inhibition of CYP1A2 can markedly increase systemic exposure to tizanidine and produce severe hypotension, bradycardia, sedation, and other toxicity.
Elimination
Most of the administered dose is ultimately eliminated through the kidneys, predominantly as metabolites.
The historical document reports that approximately 70% of total radioactivity was excreted through the kidneys, while only a small proportion of unchanged tizanidine was recovered in urine. The mean elimination half-life of unchanged tizanidine was approximately 2–4 hours.
Modified-release formulation
Sirdalud MR was designed to provide a smoother plasma concentration profile by reducing high initial plasma peaks and maintaining therapeutic concentrations over a longer period.
The historical information reports peak concentrations approximately 6 hours after administration of the MR formulation and describes therapeutic plasma concentrations being maintained over approximately 24 hours.
Food and formulation considerations
An important modern prescribing consideration is that the pharmacokinetics of tizanidine can differ depending on formulation and whether the product is administered with or without food.
Therefore, patients should follow the specific instructions for their formulation and administer it consistently with respect to food. Immediate-release tablets and capsules should not be assumed to be interchangeable on a simple milligram-for-milligram basis.
11. Indications
The primary current labeled indication for tizanidine in U.S. prescribing information is the management of spasticity.
The supplied Sirdalud information additionally lists:
- Painful muscle spasms
- Spasticity due to multiple sclerosis
- Spasticity due to spinal injury
- Spasticity due to brain injury
Because approved indications vary between countries and formulations, the current local product information should be checked before describing a particular indication as officially approved.
12. Administration
Tizanidine is administered orally.
Immediate-release tablets
The historical Sirdalud information described:
For painful muscle spasms:
- 2–4 mg three times daily.
- In severe cases, an additional 2–4 mg dose may be used at bedtime.
For spasticity associated with neurological disorders, the dose should be individualized according to therapeutic response and tolerability.
Modern U.S. labeling recommends a more conservative titration approach, beginning with 2 mg, with doses repeated at 6–8-hour intervals, up to three doses in 24 hours. Individual doses may subsequently be increased by 2–4 mg, generally allowing 1–4 days between dosage increases, with a maximum total daily dose of 36 mg.
Modified-release capsules
The historical Sirdalud MR information describes:
- Starting dose: 6 mg once daily
- Incremental increases by 6 mg when necessary
- Standard dosage range: 6–24 mg once daily
- An optimum dose of approximately 12 mg once daily was reported in most patients in the historical information.
- 24 mg/day was described as necessary only rarely.
The precise dosing instructions for MR products should be taken from the current local product information, because modified-release formulations and approved dosing recommendations may differ by market.
Discontinuation
Long-term or high-dose tizanidine should not be stopped abruptly.
Current prescribing information recommends gradual dose reduction to minimize withdrawal-related adverse effects, including rebound hypertension, tachycardia, and increased muscle tone/hypertonia.
13. Method of Preparation
Tizanidine tablets and capsules are supplied as finished oral dosage forms and generally do not require preparation or reconstitution before administration.
Patients should swallow the dosage form according to the instructions supplied with the specific product.
Modified-release capsules should be handled according to the manufacturer's instructions and should not be altered in a manner that could compromise the modified-release characteristics.
14. Contraindications
Tizanidine is contraindicated in patients with:
- Hypersensitivity to tizanidine or any component of the formulation.
- Concomitant use with potent CYP1A2 inhibitors, particularly:
- Fluvoxamine
- Ciprofloxacin
The supplied historical Sirdalud document also listed significant impairment of liver function as a contraindication.
Because the exact regulatory wording regarding hepatic impairment can differ among current labels and countries, the current local prescribing information should be consulted when determining whether a particular degree of hepatic dysfunction constitutes an absolute contraindication or requires dose reduction/avoidance.
15. Warnings & Precautions
Hypotension
Tizanidine can produce clinically significant hypotension, particularly at higher doses or when combined with other drugs that lower blood pressure.
Patients should be monitored for:
- Dizziness
- Light-headedness
- Syncope
- Excessive hypotension
The risk may be increased by concomitant antihypertensive therapy.
Bradycardia
Tizanidine may cause bradycardia, particularly when systemic exposure is increased or when it is combined with drugs affecting cardiovascular function.
Sedation and CNS depression
Common effects include:
- Drowsiness
- Dizziness
- Fatigue
- Reduced alertness
Patients should avoid driving or operating machinery if they experience drowsiness, dizziness, or impaired psychomotor performance. Alcohol and other CNS depressants may increase these effects.
Hepatic injury
Tizanidine has been associated with liver injury and elevations of hepatic aminotransferases.
Current labeling recommends appropriate liver-function assessment and monitoring, particularly in patients receiving higher doses or those at increased risk. Patients who develop unexplained nausea, loss of appetite, fatigue, or other symptoms suggestive of hepatic dysfunction should be evaluated.
The historical Sirdalud information recommended monthly liver-function monitoring during the first four months in patients receiving 12 mg/day or more, and discontinuation if ALT or AST remained above three times the upper limit of normal for a prolonged period.
Because monitoring recommendations have been updated in modern labels, the current product-specific recommendations should take precedence over the historical schedule.
Renal impairment
Tizanidine exposure may increase in patients with significant renal impairment.
The historical Sirdalud information recommended an initial dose of 2 mg once daily in patients with creatinine clearance below 25 mL/min, followed by cautious titration.
Current labeling similarly recommends individualized lower dosing and cautious titration in significant renal impairment. Patients should be monitored closely for adverse effects such as excessive somnolence, dizziness, weakness, and dry mouth.
Elderly patients
Tizanidine should be used cautiously in older adults because clearance can be substantially reduced. Current labeling specifically notes a marked reduction in clearance in elderly patients.
CYP1A2 inhibition
Tizanidine is highly sensitive to CYP1A2 inhibition.
Potent CYP1A2 inhibitors can dramatically increase tizanidine exposure and may result in severe hypotension, bradycardia, sedation, and impaired psychomotor function.
Withdrawal
Abrupt discontinuation, especially after prolonged therapy or high doses, may cause:
- Rebound hypertension
- Tachycardia
- Increased muscle tone
- Other withdrawal-related symptoms
Gradual dose reduction is recommended.
16. Drug Interactions
Fluvoxamine — CONTRAINDICATED
Fluvoxamine is a potent CYP1A2 inhibitor.
The historical Sirdalud information reported approximately a 33-fold increase in tizanidine AUC when tizanidine was administered with fluvoxamine.
This interaction can cause profound and prolonged hypotension, bradycardia, drowsiness, dizziness, and impaired psychomotor performance.
Ciprofloxacin — CONTRAINDICATED
Ciprofloxacin is another potent CYP1A2 inhibitor.
The historical information reported approximately a 10-fold increase in tizanidine AUC with concomitant ciprofloxacin.
Therefore, concomitant use is contraindicated.
Other CYP1A2 inhibitors
The supplied historical document identified several other CYP1A2 inhibitors for which concomitant use was not recommended, including:
- Amiodarone
- Mexiletine
- Propafenone
- Cimetidine
- Enoxacin
- Pefloxacin
- Norfloxacin
- Rofecoxib
- Oral contraceptives
- Ticlopidine
Modern labeling also advises avoiding concomitant use with moderate or weak CYP1A2 inhibitors when possible because clinically significant hypotension, bradycardia, or excessive drowsiness may occur.
Antihypertensive drugs
Concomitant use with antihypertensive agents, including diuretics, can increase the risk of hypotension and may contribute to bradycardia.
Alcohol and sedatives
Tizanidine can potentiate the CNS-depressant effects of:
- Alcohol
- Sedative medications
- Other CNS depressants
This may increase drowsiness, dizziness, impaired coordination, and psychomotor impairment.
17. Side Effects
Adverse effects are generally dose-related and may become more pronounced at higher doses.
Commonly reported adverse effects
- Drowsiness
- Somnolence
- Dizziness
- Light-headedness
- Fatigue
- Dry mouth
- Hypotension
- Bradycardia
The historical Sirdalud information described these effects as generally mild and transient at lower doses, while they may become more frequent and pronounced at doses used for spasticity.
Other adverse effects
- Muscle weakness
- Nausea
- Gastrointestinal disturbances
- Elevated serum transaminases
- Insomnia
- Sleep disturbances
- Hallucinations
- Hepatitis
Current prescribing information also recognizes hallucinosis/psychotic-like symptoms, hypersensitivity reactions, and withdrawal-related adverse reactions as clinically relevant safety concerns.
Frequency terminology
The historical document used the following frequency categories:
- Very common: >1/10
- Common: >1/100 to <1/10
- Uncommon: >1/1,000 to <1/100
- Rare: >1/10,000 to <1/1,000
- Very rare: <1/10,000
18. Overdose
Reported manifestations of tizanidine overdose may include:
- Nausea
- Vomiting
- Hypotension
- Dizziness
- Miosis
- Respiratory depression
- Coma
- Restlessness
- Severe drowsiness
Management is primarily supportive and symptomatic, with particular attention to airway, breathing, circulation, blood pressure, heart rate, and level of consciousness.
The historical document mentioned repeated administration of activated charcoal and forced diuresis; however, management of overdose should follow current toxicology/emergency-medicine recommendations rather than relying on the 2005 product information.
A suspected significant overdose requires urgent medical assessment.
19. Use in Special Populations
Pregnancy
Clinical data in pregnant women are limited.
Current labeling indicates that, based on animal data, tizanidine may cause fetal harm and should therefore be used during pregnancy only when the potential benefit justifies the potential risk.
The historical Sirdalud information reported no teratogenic effects in rats and rabbits but stated that clinical data in pregnant women were unavailable.
Breastfeeding
The historical Sirdalud document reported that small amounts of tizanidine were excreted into animal milk and therefore advised against use during breastfeeding.
Because modern labeling and evidence should be considered when making an individual breastfeeding decision, the current local product information and up-to-date lactation references should be consulted.
Children
The historical Sirdalud information states that clinical experience in children was limited and therefore did not recommend use in this population.
Current use in pediatric patients should follow the indication and prescribing information applicable to the specific country and formulation.
Elderly
Use with caution.
Reduced clearance may result in greater systemic exposure and increased risk of:
- Somnolence
- Dizziness
- Hypotension
- Bradycardia
- Other dose-related adverse effects
Current labeling reports a substantial reduction in clearance in elderly patients.
Renal impairment
Patients with significant renal impairment require lower starting doses and careful titration.
Particular attention should be paid to excessive sedation, dizziness, weakness, and dry mouth as possible manifestations of excessive exposure.
Hepatic impairment
Because tizanidine undergoes extensive hepatic metabolism and has been associated with liver injury, patients with hepatic impairment require particular caution, individualized dosing, and appropriate monitoring.
Severe hepatic dysfunction may constitute a contraindication depending on the applicable product label.
20. Storage Conditions
The historical Sirdalud information states:
- Store at a temperature not exceeding 30°C.
- Keep medicines out of the reach of children.
- Do not use after the expiry date printed on the package.
Storage conditions should always be confirmed against the current package labeling because they may differ between products and markets.
21. Additional Sections
Pharmacodynamic Effects
Tizanidine can reduce:
- Muscle tone
- Spasticity
- Spasms
- Clonus
- Resistance to passive movement
The supplied information describes efficacy in both acute painful muscle spasms and chronic spasticity of spinal and cerebral origin.
Preclinical Safety
The historical Sirdalud information reported:
- No evidence of mutagenic potential in several in-vitro and in-vivo studies.
- No evidence of carcinogenic potential in rat and mouse studies.
- No embryotoxic or teratogenic effects in pregnant rats and rabbits at doses up to 100 mg/kg.
However, reproductive studies in female rats showed prolonged gestation and dystocia at 10 and 30 mg/kg/day, associated with increased prenatal mortality.
These animal findings should not be interpreted as evidence of safety in humans.
Lactose
The historical Sirdalud tablet formulation contained lactose.
The supplied information advised that patients with rare hereditary galactose intolerance, severe lactase deficiency, or glucose-galactose malabsorption should not take those tablets.
Because excipients vary between manufacturers and formulations, the current package leaflet should be checked for the specific product.
Driving and Operating Machinery
Patients who experience drowsiness, dizziness, or impaired alertness should avoid:
- Driving
- Operating machinery
- Other activities requiring a high degree of alertness.
22. Frequently Asked Questions (FAQ)
What is Sirdalud?
Sirdalud is a brand name historically used for products containing tizanidine, a centrally acting α2-adrenergic agonist used primarily for the management of spasticity.
Is tizanidine a muscle relaxant?
Yes. It is a centrally acting skeletal muscle relaxant and antispasticity agent.
What is tizanidine mainly used for?
Its principal current labeled indication is the management of spasticity. Some Sirdalud product information also describes its use for painful muscle spasms and spasticity associated with neurological conditions such as multiple sclerosis and spinal or brain injury.
Does tizanidine cause sleepiness?
Yes. Drowsiness/somnolence is a common adverse effect and may be enhanced by alcohol or other sedative medicines.
Can tizanidine lower blood pressure?
Yes. Tizanidine can cause clinically significant hypotension, particularly when systemic exposure is increased or when it is combined with other blood-pressure-lowering medicines.
Can tizanidine cause a slow heart rate?
Yes. Bradycardia is a recognized adverse effect.
Can tizanidine affect the liver?
Yes. Elevation of liver enzymes and, rarely, clinically significant liver injury have been reported. Appropriate monitoring should be considered according to dose, duration, risk factors, and the current product labeling.
Can tizanidine be taken with ciprofloxacin?
No. Concomitant use of tizanidine and ciprofloxacin is contraindicated because ciprofloxacin strongly inhibits CYP1A2 and can markedly increase tizanidine exposure.
Can tizanidine be taken with fluvoxamine?
No. Concomitant use with fluvoxamine is contraindicated for the same CYP1A2-mediated reason.
Can tizanidine be stopped suddenly?
It should generally not be discontinued abruptly after prolonged or high-dose therapy. Gradual dose reduction is recommended to reduce the risk of rebound hypertension, tachycardia, and increased muscle tone.
Is tizanidine safe during pregnancy?
Safety has not been adequately established in humans. Current labeling warns that animal data suggest potential fetal harm; therefore, it should be used during pregnancy only when clinically justified.
Can tizanidine be used while breastfeeding?
The historical Sirdalud information advises against breastfeeding use based on animal milk-excretion data. An individual decision should be based on the current product label and up-to-date lactation evidence.
Can elderly patients take tizanidine?
They may, when clinically appropriate, but caution is necessary because clearance may be substantially reduced in older adults, increasing exposure and adverse-effect risk.
Can patients with kidney disease take tizanidine?
Tizanidine can be used cautiously in renal impairment, but significant renal impairment requires lower initial doses and careful titration and monitoring.
Can tizanidine be taken with alcohol?
Alcohol can increase the sedative and CNS-depressant effects of tizanidine and should therefore be avoided or used only according to medical advice.
Does food affect tizanidine?
Yes. Food can affect the pharmacokinetics of tizanidine, and the effect differs between formulations. Patients should follow the specific product instructions and maintain a consistent relationship with food.
23. References
- DailyMed – Tizanidine Tablets, USP. Current U.S. prescribing information, including indications, dosage, contraindications, warnings, drug interactions, renal/hepatic considerations, and withdrawal precautions. Current labeling accessed/reviewed in 2025.
- DailyMed – Tizanidine Tablets. Revised prescribing information, including the updated recommendations for dosing, discontinuation, contraindications, and use in specific populations.
- DailyMed – Tizanidine Hydrochloride Capsules. Current capsule prescribing information, including formulation-specific pharmacokinetic considerations and recommendations for renal/hepatic impairment.
- Historical Sirdalud® / Sirdalud® MR Product Information supplied with this article. Novartis Pharma AG, Basel, Switzerland; information last revised December 2005.
- The historical document supplied for this article was used as a source for the original Sirdalud formulation information, historical dosing information, pharmacokinetic data, adverse-effect classifications, preclinical data, storage information, and product-specific statements. Where this historical information conflicts with or is superseded by current regulatory labeling, current regulatory information takes precedence.
24. Final Clinical Note
Tizanidine is an effective centrally acting antispasticity agent, but its safety profile requires careful attention to dose titration, blood pressure, heart rate, sedation, liver function, renal function, and drug interactions.
The most clinically important interaction to remember is the contraindicated combination with ciprofloxacin or fluvoxamine, because CYP1A2 inhibition can produce a dramatic increase in tizanidine exposure and potentially severe hypotension and CNS depression.
The distinction between immediate-release and modified-release formulations is also important, as their pharmacokinetic profiles differ and they should not automatically be substituted on a milligram-for-milligram basis.
Finally, because the supplied Sirdalud document was last revised in December 2005, it should not be treated as a current prescribing reference by itself. Current official product information applicable to the specific country and formulation should always be checked before prescribing or making medication-related decisions.