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Is tizanidine a benzodiazepine: Is Tizanidine A Narcotic Or Benzo? Zanaflex Drug Class

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Is Tizanidine A Narcotic Or Benzo? Zanaflex Drug Class

Knowing the tizanidine drug class is important for anyone using the medication. However, there are a lot of misconceptions about the Zanaflex drug schedule and classification. Here is what users should know, including if tizanidine is a narcotic.

Learn About Zanaflex Drug Class:

Tizanidine As A Narcotic

Sirdalud, also known as Zanaflex and tizanidine, is a medication that treats muscle spasticity. Narcotics are medications that treat pain by binding to specific receptors in the brain.

Technically, Zanaflex can treat pain in that it stops muscle spasticity, which is a painful condition. This leads many to assume that the Zanaflex drug class is that of narcotics.

However, the answer to if Zanaflex is a narcotic is no. The pain relief it offers is a tizanidine side effect, not the primary action of the medication. As a result, those prescribed tizanidine 4 mg tablets do not need to worry about if they are taking a narcotic.

Zanaflex As A Controlled Substance

The term “controlled substance” can have different meanings depending on how it is being used. When used colloquially, it means any medication that has controlled access—in other words, those that need prescriptions to purchase them. Looking at it this way, the answer to if Zanaflex is a controlled substance is yes.
However, the other way the term is used is in an official capacity by the Drug Enforcement Agency. In this instance, it refers to substances that are on the DEA List of Controlled Substances. Given it does not appear on this list, in this case, the answer to if Zanaflex is a controlled substance is no. However, that does not mean that it cannot be problematic or that people do not use it for Zanaflex high.

Tizanidine As A Benzo

The benzodiazepine drug class encompasses medications that are used to relax or sedate patients by increasing the inhibitory neurotransmitter GABA in the brain. Zanaflex can also cause relaxation of the body, which is why many ask if Zanaflex is benzo.
Although it causes physical relaxation, the answer to if tizanidine is benzo is no. It does not function by increasing GABA in the brain, which means this cannot be the tizanidine drug class.

Tizanidine As An Opioid

Opioids are medications used to treat pain. Given that a side effect of tizanidine use can be a reduction in pain resulting from muscle spasms, it is common for people to ask if Zanaflex is an opioid.

This means that the answer to if Zanaflex is an opiate is no. An opioid is not the tizanidine drug class.

Zanaflex As An NSAID

Nonsteroidal Anti-inflammatory Drugs, or NSAIDs, are medications that tackle pain by reducing or eliminating the inflammation that causes it. These are mostly available over the counter. Some think Zanaflex is an NSAID because of its effects on pain. However, it does not treat inflammation, meaning this is not the Zanaflex drug class.

Tizanidine As A Muscle Relaxer

Zanaflex works by inhibiting nerve impulses that send messages to the brain that result in muscle tension. The resulting effect is muscle relaxation and a reduced sensation of pain. What tizanidine is used for is the treatment of muscle spasms and pain resulting from injuries or chronic conditions.
This means that those who believe Zanaflex is a muscle relaxer are right.

Tizanidine is a muscle relaxant. However, this isn’t technically the Zanaflex classification, as muscle relaxer is not an official drug category.

The Tizanidine Schedule and Classification

The correct tizanidine classification is alpha-2-adrenergic agonist. Drugs in the Zanaflex class reduce the nerve activity in the spinal cord that controls muscles, stopping muscle spasms, and addressing the associated pain.
The tizanidine half-life is relatively short, making it a good choice for those who do not want the medicine in the system for long. However, users and their doctors may want to look into alternatives, such as Zanaflex vs. Flexeril.
While there is no Zanaflex schedule from the DEA, it is a drug that can be abused. Recreational use does occur, and sometimes the drug is sold on the street. If someone is misusing the medication, no matter how they obtain it, they need to seek help from a substance abuse center. There, addiction is treated correctly, ensuring the patient can stop use safely and address the problems that drove them to abuse in the first place.

Zanaflex

addiction is a very real condition and one that can easily become life-threatening

Anyone who is misusing the medication should not be afraid to seek the help that they need. Drug rehabilitation centers offer the right level of care in an open and encouraging setting. There is no shame in asking for a helping hand.


Page Sources

  1. Pain medications – narcotics. Medline Plus. U.S. National Library of Medicine. https://medlineplus.gov/ency/article/007489.htm
  2. Controlled Substances – Alphabetical Order. Drug Enforcement Administration. https://www.deadiversion.usdoj.gov/schedules/orangebook/c_cs_alpha. pdf
  3. Benzodiazepines and Opioids. National Institute on Drug Abuse. https://www.drugabuse.gov/drugs-abuse/opioids/benzodiazepines-opioids
  4. Prevent Opioid Abuse And Addiction. U.S. Department of Health and Human Services. https://www.hhs.gov/opioids/prevention/index.html

Published on: February 19th, 2020

Updated on: May 24th, 2021

Uses, Dosage, Side Effects, Interactions, Warning

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Hypotension

Tizanidine is an α2-adrenergic agonist that can produce hypotension. Syncope has been reported in the post marketing setting. The chance of significant hypotension may possibly be minimized by titration of the dose and by focusing attention on signs and symptoms of hypotension prior to dose advancement. In addition, patients moving from a supine to fixed upright position may be at increased risk for hypotension and orthostatic effects.

Monitor for hypotension when Zanaflex is used in patients receiving concurrent antihypertensive therapy. It is not recommended that Zanaflex be used with other α2-adrenergic agonists. Clinically significant hypotension (decreases in both systolic and diastolic pressure) has been reported with concomitant administration of either fluvoxamine or ciprofloxacin and single doses of 4 mg of Zanaflex. Therefore, concomitant use of Zanaflex with fluvoxamine or with ciprofloxacin, potent inhibitors of CYP1A2, is contraindicated [see CONTRAINDICATIONS and DRUG INTERACTIONS].

Risk Of Liver Injury

Zanaflex may cause hepatocellular liver injury. Zanaflex should be used with caution in patients with any hepatic impairment. Monitoring of aminotransferase levels is recommended for baseline and 1 month after maximum dose is achieved, or if hepatic injury is suspected [see DOSAGE AND ADMINISTRATION and Use In Specific Populations].

Sedation

Zanaflex can cause sedation, which may interfere with everyday activity. In the multiple dose studies, the prevalence of patients with sedation peaked following the first week of titration and then remained stable for the duration of the maintenance phase of the study. The CNS depressant effects of Zanaflex with alcohol and other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants) may be additive. Monitor patients who take Zanaflex with another CNS depressant for symptoms of excess sedation [see DRUG INTERACTIONS].

Hallucinosis/Psychotic-Like Symptoms

Zanaflex use has been associated with hallucinations. Formed, visual hallucinations or delusions have been reported in 5 of 170 patients (3%) in two North American controlled clinical studies. Most of the patients were aware that the events were unreal. One patient developed psychosis in association with the hallucinations. One patient among these 5 continued to have problems for at least 2 weeks following discontinuation of tizanidine. Consider discontinuing Zanaflex in patients who develop hallucinations.

Interaction With CYP1A2 Inhibitors

Because of potential drug interactions, Zanaflex is contraindicated in patients taking potent CYP1A2 inhibitors, such as fluvoxamine or ciprofloxacin. Adverse reactions such as hypotension, bradycardia, or excessive drowsiness can occur when Zanaflex is taken with other CYP1A2 inhibitors, such as zileuton, fluoroquinolones other than ciprofloxacin (which is contraindicated), antiarrhythmics (amiodarone, mexiletine, propafenone), cimetidine, famotidine, oral contraceptives, acyclovir, and ticlopidine). Concomitant use should be avoided unless the necessity for Zanaflex therapy is clinically evident. In such a case, use with caution [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY].

Hypersensitivity Reactions

Zanaflex can cause anaphylaxis. Signs and symptoms including respiratory compromise, urticaria, and angioedema of the throat and tongue have been reported. Patients should be informed of the signs and symptoms of severe allergic reactions and instructed to discontinue Zanaflex and seek immediate medical care should these signs and symptoms occur [see CONTRAINDICATIONS].

Increased Risk Of Adverse Reactions In Patients With Renal Impairment

Zanaflex should be used with caution in patients with renal insufficiency (creatinine clearance < 25 mL/min), as clearance is reduced by more than 50%. In these patients, during titration, the individual doses should be reduced. If higher doses are required, individual doses rather than dosing frequency should be increased. These patients should be monitored closely for the onset or increase in severity of the common adverse events (dry mouth, somnolence, asthenia and dizziness) as indicators of potential overdose [see DOSAGE AND ADMINISTRATION and Use In Specific Populations].

Withdrawal Adverse Reactions

Withdrawal adverse reactions include rebound hypertension, tachycardia, and hypertonia. To minimize the risk of these reactions, particularly in patients who have been receiving high doses (20 to 28 mg daily) for long periods of time (9 weeks or more) or who may be on concomitant treatment with narcotics, the dose should be decreased slowly (2 to 4 mg per day) [see DOSAGE AND ADMINISTRATION].

Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Carcinogenesis

Tizanidine was administered to mice for 78 weeks at oral doses up to 16 mg/kg/day, which is 2 times the maximum recommended human dose (MRHD) of 36 mg/day on a body surface area (mg/m²) basis. Tizanidine was administered to rats for 104 weeks at oral doses up to 9 mg/kg/day, which is 2.5 times the MRHD on a mg/m² basis. There was no increase in tumors in either species.

Mutagenesis

Tizanidine was negative in in vitro (bacterial reverse mutation [Ames], mammalian gene mutation, and chromosomal aberration test in mammalian cells) and in vivo (bone marrow micronucleus, and cytogenetics) assay.

Impairment Of Fertility

Oral administration of tizanidine to rats prior to and during mating and continuing during early pregnancy in females resulted in reduced fertility in male and female rats at doses of 30 and 10 mg/kg/day, respectively. No effect on fertility was observed at doses of 10 (male) and 3 (female) mg/kg/day, which are approximately 3 times and similar to the MRHD, respectively, on a mg/m² basis.

Use In Specific Populations
Pregnancy
Risk Summary

There are no adequate data on the developmental risk associated with use of Zanaflex in pregnant women. In animal studies, administration of tizanidine during pregnancy resulted in developmental toxicity (embryofetal and postnatal offspring mortality and growth deficits) at doses less than those used clinically, which were not associated with maternal toxicity (see Animal Data).

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% – 4% and 15% – 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.

Data

Animal Data

Oral administration of tizanidine (0.3 to 100 mg/kg/day) to pregnant rats during the period of organogenesis resulted in embryofetal and postnatal offspring mortality and reductions in body weight at doses of 30 mg/kg/day and above. Maternal toxicity was observed at the highest dose tested. The no-effect dose for embryofetal developmental toxicity in rats (3 mg/kg/day) is similar to the maximum recommended human dose (MRHD) of 36 mg/day on a body surface area (mg/m²) basis.

Oral administration of tizanidine (1 to 100 mg/kg/day) to pregnant rabbits during the period of organogenesis resulted in embryofetal and postnatal offspring mortality at all doses. Maternal toxicity was observed at the highest dose tested. Oral administration of tizanidine (10 and 30 mg/kg/day) during the perinatal period of pregnancy (2-6 days prior to delivery) resulted in increased postnatal offspring mortality at both doses. A no-effect dose for embryofetal developmental toxicity in rabbit was not identified. The lowest dose tested (1 mg/kg/day) is less than the MRHD on a mg/m² basis.

In a pre- and postnatal development study in rats, oral administration of tizanidine (3 to 30 mg/kg/day) resulted in increased postnatal offspring mortality. A no-effect dose for pre- and postnatal developmental toxicity was not identified. The lowest dose tested (3 mg/kg/day) is similar to the MRHD on a mg/m² basis, respectively.

Lactation
Risk Summary

There are no data on the presence of tizanidine in human milk, the effects on the breastfed infant, or the effects on human milk production. Animal studies have reported the presence of tizanidine in the milk of lactating animals.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Zanaflex and any potential adverse effects on the breastfed infant from Zanaflex or from the underlying maternal condition.

Females And Males Of Reproductive Potential

There are no adequate and well-controlled studies in humans on the effect of Zanaflex on female or male reproductive potential. Oral administration of tizanidine to male and female rats resulted in adverse effects on fertility [see Nonclinical Toxicology].

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Zanaflex is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Clinical studies of Zanaflex did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. Cross-study comparison of pharmacokinetic data following single dose administration of 6 mg Zanaflex showed that younger subjects cleared the drug four times faster than the elderly subjects. In elderly patients with renal insufficiency (creatinine clearance < 25 mL/min), tizanidine clearance is reduced by more than 50% compared to healthy elderly subjects; this would be expected to lead to a longer duration of clinical effect. During titration, the individual doses should be reduced. If higher doses are required, individual doses rather than dosing frequency should be increased. Monitor elderly patients because they may have an increased risk for adverse reactions associated with Zanaflex.

Impaired Renal Function

Zanaflex is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. In patients with renal insufficiency (creatinine clearance < 25 mL/min), clearance was reduced by more than 50%. In these patients, individual doses should be reduced during titration. If higher doses are required, individual doses rather than dosing frequency should be increased. These patients should be monitored closely for the onset or increase in severity of Zanaflex common adverse events (dry mouth, somnolence, asthenia and dizziness) as indicators of potential overdosage [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].

Impaired Hepatic Function

The influence of hepatic impairment on the pharmacokinetics of tizanidine has not been evaluated. Because tizanidine is extensively metabolized in the liver, hepatic impairment would be expected to have significant effects on pharmacokinetics of tizanidine [see DOSING AND ADMINISTRATION, WARNINGS AND PRECAUTIONS, and CLINICAL PHARMACOLOGY].

Tizanidine – an overview | ScienceDirect Topics

MECHANISM OF ACTION:

Tizanidine is a newly introduced muscle relaxant. Structurally, it is an imidazoline derivative. Pharmacologically, it is a centrally acting alpha2 adrenergic agonist. Because of the pharmacologic and clinical evidence of its concomitant antinociceptive properties, it has gained acceptance in the treatment of both spasticity and rheumatologic conditions associated with painful muscle spasms.20

Animal experiments have revealed that tizanidine suppresses polysynaptic excitation of dorsal horn neurons in the spinal cord and depresses polysynaptic reflexes in spontaneous neuronal activity, probably by reducing the release of excitatory neural transmitters (glutamate, aspartate) from presynaptic sites. 21

Tizanidine exhibits a high affinity for alpha2 adrenergic receptors. This property, along with the structural similarity of tizanidine to alpha2-agonist clonidine (which has a mild antispastic action of its own), raises the possibility that the muscle relaxant function is at least partly mediated by the adrenergic system. The action of tizanidine may include inhibition on locus ceruleus firing and subsequent inhibition of the cerulospinal pathway, which normally exert a facilitatory effect on synaptic activity in the spinal cord. Finally, evidence suggests a possible postsynaptic action at the excitatory amino acid receptors.21 Because of its unique and various actions at different level, tizanidine induces hypotonia without undue muscle weakness.

Animal studies have demonstrated antinociceptive activity of tizanidine, mediated by inhibition of A and C fiber activity, as well as selective inhibition of dorsal horn neurons to nociceptive stimulation. 22,23

Well-controlled studies have revealed the effectiveness of tizanidine as an antispastic agent in about a third to half of patients with multiple sclerosis, spinal cord injury, motor neuron disease, and stroke.24,25 It is most beneficial in reducing the frequency of muscle spasms and clonus, but is less consistent in reducing the muscle tone. Assessment of neurologic functions and functional disability scores has failed to reveal consistent and significant treatment effects. Tizanidine provided little impact on scores of activities of daily living. When compared to baclofen, the results with tizanidine were about equal in most parameters assessed, except tizanidine caused less muscle weakness. Comparison with diazepam favors tizanidine in all parameters including side effects (particularly sedation). Tizanidine was better tolerated than diazepam and baclofen.26

Tizanidine Addiction | The Recovery Village Drug and Alcohol Rehab

Like many prescription medications, tizanidine can be addictive. Some people deliberately misuse the medication, while others may develop an addiction over time. Tizanidine is an FDA-approved medicine for the management of spasticity caused by:

  • An acquired brain injury
  • Multiple sclerosis
  • Spinal cord injury

It is also used in the management of pain associated with:

  • Lumbosacral neuralgia and chronic neck issues
  • Musculoskeletal pain syndrome
  • Migraine headaches

Tizanidine medication is an off-label prescription used as an anticonvulsant for the management of migraine headaches and insomnia.

Tizanidine abuse is possible due to its fast action on pain. A study to compare the muscle strength of Tizanidine and other approved skeletal muscle relaxants showed that there was increased improvement with Tizanidine.

Article at a Glance:

  • Tizanidine is a prescription muscle relaxer and pain management medication that can be addictive and misused, even though it is not a narcotic.
  • Withdrawal symptoms of Tizanidine include tremors, anxiety, hypertonia, tachycardia and hypertension.
  • Addiction to Tizanidine is more likely to occur when you take more than 35 mg within 24 hours for over two weeks.
  • Reduce the dosage of Tizanidine gradually to avoid withdrawal symptoms.
  • The Recovery Village can help people who are addicted to Tizanidine.

What Is Tizanidine?

It is an antispasmodic prescription drug that is taken orally at specified intervals of time to treat symptoms related to multiple sclerosis, stroke, spinal and brain injury. In simple terms, Tizanidine is a sharp pain-relief medicine that is acquired only with a doctor’s prescription.

Is Tizanidine a narcotic? No. Just because Tizanidine is sometimes abused doesn’t qualify it as a narcotic. Narcotics are substances traditionally used to ease pain by binding to pain receptors in the nervous system, whereas Tizanidine is a muscle relaxer. While Tizanidine muscle relaxers may help reduce pain, they do so in a different way than narcotics. Tizanidine is a muscle relaxer and blocks pain around the skeletal muscle areas. It is an alpha-2 adrenergic agonist that treats:

  • Cramping
  • Spasm
  • Tightness of muscles

Symptoms that may warrant Tizanidine use may be the result of:

  • Injury to the spine or central nervous system
  • Spastic diplegia
  • Back pain
  • Multiple sclerosis

What Is Tizanidine Used For?

Spasm and muscle tone are common in people who have experienced a stroke, multiple sclerosis, brain or spinal injury. Since the body functions abnormally during contraction and muscle tone, Tizanidine is used to slow down the brain and nervous system action so that the muscles can relax.

You might have seen people taking Tizanidine for other medical conditions and wondered what is Tizanidine used for? Tizanidine can be used to treat several medical conditions, including:

  • Spinal cord or acquired brain injuries
  • Multiple sclerosis
  • Regional musculoskeletal pain syndrome
  • Chronic neck and lumbosacral neuralgia

Other uses for Tizanidine include treatment for:

  • Insomnia
  • Migraine headaches
  • Anticonvulsant

Tizanidine can also be used as part of a detoxification regimen in rebound headaches caused by analgesic withdrawal.

Is Tizanidine Addictive?

Though Tizanidine isn’t a narcotic, it can be addictive. You can’t get self-prescribe or over-the-counter Tizanidine due to its addictive nature. Instead, it is available with a doctor’s prescription. All medical instructions should be followed closely. Most medicines that act on the central nervous system (brain) have withdrawal effects when stopped immediately.

When a person is under this type of medication, the doctor will gradually reduce the dose to avoid withdrawal symptoms. The withdrawal symptoms may include:

  • Hypertension
  • Tachycardia
  • Tremor
  • Anxiety
  • Hypertonia

Tizanidine withdrawal can be managed by restarting and gradually reducing the dosage until the cessation of the medication.

You might be wondering how Tizanidine is addictive. When Tizanidine is taken more than 35 mg within 24 hours for more than two weeks, you risk the chance of being addicted to it. High doses of Tizanidine range from 20 mg to 36 mg daily.

If you are taking Tizanidine in high doses for more than nine weeks, it is advisable not to stop without professional help due to:

  • Rebound hypertension
  • Increased spasticity
  • Tachycardia

Tizanidine recreational use is rising by the day, and most people combine it with other narcotics to achieve the feeling of a Tizanidine high. The high feeling usually lasts for a shorter time, and this may lead to a person taking more doses to stay high.

Tizanidine Street Names, Common Misspellings, and Generics

Although Tizanidine is a prescription medication, it may be sold illegally and be known by a variety of street names. Although Tizanidine is a generic medication itself, it may be known by other brand names.

Tizanidine brand names include:

  • Zanaflex
  • Sirdalud(Novartis)
  • Relentus(Beximco Pharma)

Tizanidine is sometimes misspelled deliberately or unknowingly. Sometimes people misspell it to hide the fact they are using the medicine incorrectly or illicitly. Common misspellings or variants include:

Tizanidine Ingredients

Tizanidine is made up of active and inactive ingredients to form a muscle relaxer that is effective for many patients. The ingredients found in Tizanidine can cause liver damage, especially if you have liver problems.

Active ingredient:

  • Tizanidine hydrochloride(HCL)

Inactive ingredients:

  • Gelatin
  • Colorant
  • silicon dioxide
  • Hypromellose
  • Sugar spheres
  • Titanium dioxide

Tizanidine Warnings

Tizanidine side effects are present after the medication is abruptly stopping. Most Tizanidine warnings are related to withdrawal of the medicine. Related warnings include:

  • Hypotension
  • Liver injury
  • Sedation. You can’t drive while taking Tizanidine medication
  • Hallucination
  • Hypersensitivity reactions
  • Withdrawal adverse reactions
  • Nonclinical toxicology( carcinogenesis, mutagenesis, fertility impairment).

Since it isn’t clear how the medicine affects a pregnant person, it is advisable to avoid Tizanidine unless it is used to save a life. Since it isn’t clear whether Tizanidine excretion is through milk, it is advisable to avoid it during lactation.

Tizanidine Addiction Statistics

According to NIH, cases reported of Tizanidine addiction often end with withdrawal symptoms when the medication intake is stopped. Addiction happens when the daily average dose of Tizanidine exceeds 20 to 36 mg. You can tell you are addicted to medicine when symptoms follow after cessation of consumption.

The dosage of the medicine is reduced gradually over time until it is stopped to avoid withdrawal symptoms.

If you or someone you know is addicted to Tizanidine or other prescription medications, help is available. Call The Recovery Village to learn more about treatment options for addiction and co-occurring mental health disorders.

  • Sources:

    Meythaler, J.M.; Guin-Rnfroe, S.; Johnson, A.; Brunner, R.M. Prospective assessment of tizanidine for spasticity due to acquired brain injury. Arch Phys Med Rehabil. September 2001. Accessed April 26, 2019.

    www.accessdata.fda.gov. HIGHLIGHTS OF PRESCRIBING INFORMATION, FDA approved labeling dated October 4, 2013

    Shirin Ghanavatian; Armen Derian. Tizanidine Mayo clinic. March 5, 2019. Accessed April 26, 2019.

    Haukka J, Kriikku P, Mariottini C, Partonen T, Ojanperä I Non-medical use of psychoactive prescription drugs is associated with fatal poisoning. Department of Public Health, University of Helsinki, Helsinki, Finland. Forensic Toxicology Unit, National Institute for Health and Welfare, Helsinki, Finland. Department of Forensic Medicine, University of Helsinki, Helsinki, Finland. Department of Health, National Institute for Health and Welfare, Helsinki, Finland. March 2018. Accessed April 26, 2019.

Medical Disclaimer: The Recovery Village aims to improve the quality of life for people struggling with a substance use or mental health disorder with fact-based content about the nature of behavioral health conditions, treatment options and their related outcomes. We publish material that is researched, cited, edited and reviewed by licensed medical professionals. The information we provide is not intended to be a substitute for professional medical advice, diagnosis or treatment. It should not be used in place of the advice of your physician or other qualified healthcare provider.

Differences, similarities, and which is better for you

Drug overview & main differences | Conditions treated | Efficacy | Insurance coverage and cost comparison | Side effects | Drug interactions | Warnings | FAQ

Brand-name Flexeril has been discontinued; however, it is still available as a generic—cyclobenzaprine—and as brand names Amrix and Fexmid.

Zanaflex (tizanidine) and Flexeril (cyclobenzaprine) are muscle relaxants used to treat painful musculoskeletal conditions. If you experience neck or back strains, you may be recommended a muscle relaxant like Zanaflex or Flexeril. These drugs can also help relieve muscle spasms and stiffness related to other physical conditions and injuries.

Like other muscle relaxants, Zanaflex and Flexeril work in the central nervous system (CNS). They also have similar side effects and costs. However, they have differences in how they’re used and formulated.

What are the main differences between Zanaflex and Flexeril?

Zanaflex

Zanaflex (What is Zanaflex?) is the brand name for tizanidine and acts as an alpha-2 adrenergic agonist. It was initially approved in 1996 for the treatment of muscle spasticity. Although its exact mechanism of action is unknown, it is believed to manage muscle spasticity through the inhibition of motor nerve signals.

Zanaflex is available as an oral tablet in strengths of 2 mg and 4 mg. It also comes as an oral capsule in strengths of 2 mg, 4 mg, and 6 mg. Zanaflex is usually taken up to three times per day.

Flexeril

Flexeril (What is Flexeril?) is a brand-name drug originally FDA-approved in 1977. The generic version of Flexeril, cyclobenzaprine, is widely available. Flexeril is structurally similar to tricyclic antidepressants and primarily works in the central nervous system (CNS). It helps reduce muscle hyperactivity through actions on the gamma- and alpha-motor systems.

Cyclobenzaprine is no longer available as Flexeril. Instead, cyclobenzaprine can be found under different brand names: Amrix (extended-release) and Fexmid (immediate-release). Immediate-release cyclobenzaprine is taken up to three times per day while the extended-release form can be taken once daily.

Main differences between Zanaflex and Flexeril
Drug class Muscle relaxant Muscle relaxant
Brand/generic status Brand and generic version available Brand and generic version available

Brand name Flexeril has been discontinued in the U.S. Other brand names include Amrix and Fexmid.

What is the generic name? Tizanidine Cyclobenzaprine
What form(s) does the drug come in? Oral tablet
Oral capsule
Oral tablet
Oral capsule, extended-release
What is the standard dosage? Initial dose of 2 mg, followed by subsequent doses every 6 to 8 hours. Maximum of 3 doses in 24 hours.

Dosage may be increased every 1 to 4 days by 2 mg to 4 mg. Maximum daily dose of 36 mg.

Immediate-release tablets: 5 mg to 10 mg three times daily.

Extended-release capsules: 15 mg to 30 mg once daily.

How long is the typical treatment? Short-term or long-term duration depending on the condition No more than 2 to 3 weeks
Who typically uses the medication? Adults aged 18 years and older Adults and young adults aged 15 years and older

 

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Conditions treated by Zanaflex and Flexeril

Both Zanaflex and Flexeril are drugs used for muscle spasms and pain relief from musculoskeletal conditions. Zanaflex is commonly prescribed to treat spasticity from multiple sclerosis, cerebral palsy, and spinal cord injury. Flexeril is often prescribed to relieve muscle pain and spasms caused by back and neck strains.

Zanaflex and Flexeril are sometimes prescribed off-label to treat fibromyalgia and migraines. Often combined with other drugs, Zanaflex or Flexeril can also help manage muscle stiffness and tremors associated with tetanus.

Muscle spasms Yes Yes
Musculoskeletal conditions Yes Yes
Tetanus Yes Yes
Fibromyalgia Off-label Off-label
Migraines Off-label Off-label

Is Zanaflex or Flexeril more effective?

Zanaflex and Flexeril are both effective drugs for muscle spasms and muscle pain. Their use depends on which one is more suitable on a case-by-case basis. Currently, there is no clinical data showing a direct comparison between these two drugs.

According to a meta-analysis, cyclobenzaprine has been studied in the most clinical trials with evidence to support its use. Tizanidine was shown to be effective for spasticity due to multiple sclerosis. Both cyclobenzaprine and tizanidine were found to be effective for musculoskeletal conditions such as acute neck or back pain.

The meta-analysis assessed over 100 different trials comparing several muscle relaxants, including Lioresal (baclofen), Soma (carisoprodol), Robaxin (methocarbamol), Skelaxin (metaxalone), and Valium (diazepam). Overall, the study found that these drugs are comparable in efficacy and safety. Other guidelines suggest that muscle relaxants cause increased drowsiness and should only be used short-term.

Drugs like Zanaflex and Flexeril are often recommended along with physical therapy to relieve pain. Consult a healthcare provider to determine the best treatment option for you.

Coverage and cost comparison of Zanaflex vs. Flexeril

Generic Zanaflex is typically covered by most Medicare and insurance plans. The quantity prescribed will vary depending on the strength of the drug and your doctor’s instructions. The average retail cost of Zanaflex is around $56. With a Zanaflex discount coupon, the retail cost can be less than $10 for 30, 4 mg tablets.

Flexeril is also covered by most Medicare and insurance plans when it’s prescribed as a generic. Immediate-release tablets are commonly prescribed to be taken multiple times per day. The average retail cost for a cyclobenzaprine prescription can run around $42. You can also take advantage of a Flexeril coupon to get a reduced price of around $7 at a participating pharmacy.

Typically covered by insurance? Yes Yes
Typically covered by Medicare? Yes Yes
Standard dosage 4 mg tablet every 6 to 8 hours 10 mg tablet three times daily
Typical Medicare copay $0–$41 $1–$35
SingleCare cost $9+ $7+

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Common side effects of Zanaflex vs. Flexeril

The most common side effects of Zanaflex include dry mouth, drowsiness, dizziness, muscle weakness or fatigue, and constipation. Other reported side effects include urinary tract infections (UTIs) and involuntary movements (dyskinesia).

The most common side effects of Flexeril include drowsiness, dry mouth, headache, fatigue, and dizziness. Flexeril is also known to cause other side effects such as constipation and nausea.

Side Effect Applicable? Frequency Applicable? Frequency
Drowsiness Yes 48% Yes 29%
Dry mouth Yes 49% Yes 21%
Headache No Yes 5%
Fatigue Yes 41% Yes 6%
Dizziness Yes 16% Yes 1%–3%
Nausea No Yes 1%–3%
Constipation Yes 4% Yes 1%–3%
UTI Yes 10% No
Involuntary movements Yes 3% No

This may not be a complete list of adverse effects that can occur. Please refer to your doctor or healthcare provider to learn more.
Source: DailyMed (Zanaflex), DailyMed (Flexeril)

Drug interactions of Zanaflex vs. Flexeril

Zanaflex is mainly processed by the CYP1A2 enzyme in the liver. Drugs that block, or inhibit, this enzyme can increase Zanaflex levels in the body. Increased drug levels can lead to increased adverse effects such as drowsiness and dizziness. Zanaflex should be avoided with CYP1A2 inhibitors like ciprofloxacin and cimetidine as well as birth control pills containing ethinyl estradiol.

Flexeril can interact with serotonergic drugs like antidepressants and MAO inhibitors. Taking these drugs with Flexeril can increase the risk of serotonin syndrome, a condition that requires immediate medical attention.

Both Zanaflex and Flexeril can interact with drugs that have CNS depressant effects. These types of drugs include barbiturates, opioids, and benzodiazepines. Zanaflex and Flexeril can enhance their effects and lead to increased dizziness and sedation.

Ciprofloxacin
Cimetidine
Fluvoxamine
Acyclovir
Ticlopidine
CYP1A2 inhibitors Yes No
Ethinyl estradiol
Norethindrone
Levonorgestrel
Oral contraceptives Yes No
Isocarboxazid
Phenelzine
Tranylcypromine
Monoamine oxidase inhibitors (MAOIs) No Yes
Amitriptyline
Nortriptyline
Clomipramine
Tricyclic antidepressants No Yes
Phenobarbital
Pentobarbital
Secobarbital
Barbiturates Yes Yes
Oxycodone
Hydrocodone
Tramadol
Opioids Yes Yes
Alprazolam
Lorazepam
Diazepam
Benzodiazepines Yes Yes

*Consult a healthcare professional for other drug interactions

Warnings of Zanaflex and Flexeril

Zanaflex has the potential to cause hypotension or abnormally low blood pressure. This effect typically manifests as orthostatic hypotension which occurs when a person moves to an upright position after lying down. In excess doses, Flexeril is also known to cause changes in blood pressure.

Zanaflex may cause liver injury in some people, especially those who have a history of liver impairment. Flexeril should also be used with caution in individuals with liver problems.

Flexeril is known to cause serotonin syndrome, especially when taken with certain antidepressants, MAO inhibitors, and opioids. Signs and symptoms of serotonin syndrome should be monitored when starting treatment with Flexeril.

Frequently asked questions about Zanaflex vs. Flexeril

What is Zanaflex?

Zanaflex, or tizanidine, is a muscle relaxant used to treat muscle spasticity due to multiple sclerosis and spinal cord injury. It works by blocking signals between motor nerves to relax muscle tone. It is usually taken as a 2 mg or 4 mg tablet every six to eight hours.

What is Flexeril?

Flexeril is the brand name for cyclobenzaprine. It is a muscle relaxant indicated for acute, painful musculoskeletal conditions such as neck or back pain. It works in the central nervous system (CNS) to relieve muscle pain and spasms. Cyclobenzaprine is available in immediate-release and extended-release forms.

Are Zanaflex and Flexeril the same?

Zanaflex and Flexeril are not the same. Zanaflex has a half-life of around 2.5 hours while Flexeril has a half-life of 18 hours on average. Zanaflex only comes in immediate-release oral tablets and capsules while Flexeril comes in an extended-release capsule.

Is Zanaflex or Flexeril better?

Zanaflex is a newer drug FDA-approved for muscle spasticity due to multiple sclerosis and spinal cord injuries. Flexeril is an older drug that has been more heavily studied for musculoskeletal pain and spasms. The better drug is the one that works best for your specific condition. Consult a doctor to help find the best option for you.

Can I use Zanaflex or Flexeril while pregnant?

Zanaflex may be harmful to the unborn baby according to animal studies. There have been no adequate animal or human studies that show Flexeril is harmful while pregnant. Muscle relaxers should only be used if there are clear benefits that outweigh potential risks. Seek medical advice from your healthcare provider for treatment options while pregnant.

Can I use Zanaflex or Flexeril with alcohol?

Drinking alcohol while taking Zanaflex or Flexeril can enhance the sedative effects of these drugs. It is not generally recommended to drink alcohol with muscle relaxants.

Is tizanidine better than cyclobenzaprine?

Tizanidine may be preferred for muscle spasms caused by multiple sclerosis, cerebral palsy, and spinal cord injury. Cyclobenzaprine is used along with physical therapy and rest to relieve pain and muscle spasms.

Is Zanaflex addictive?

Zanaflex is not a controlled substance according to the DEA. However, like other muscle relaxers, it can be abused by some people. Zanaflex is considered a short-term treatment option. Abuse and dependence may occur with long-term use and lead to addictive habits.

Does Flexeril help with pain?

Flexeril may indirectly relieve pain associated with muscle spasms. Depending on what’s causing the pain, your doctor may first recommend an over-the-counter drug like acetaminophen or ibuprofen.

Tizanidine: Uses, Interactions, Mechanism of Action

Indication

Tizanidine is indicated for the relief of muscle spasticity, which can interfere with daily activities. The general recommendation is to reserve tizanidine use for periods of time when there is a particular need for relief, as it has a short duration of action Label,11.

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Pharmacodynamics

A note on spasticity

Spasticity is an increase in muscle accompanied by uncontrolled, repetitive contractions of skeletal muscles which are involuntary.
The patient suffering from muscle spasticity may have reduced mobility and high levels of pain, contributing to poor quality of life and problems performing activities of personal hygiene and care 7.

General effects

Tizanidine is a rapidly acting drug used for the relief of muscle spasticity when it is required for performing specific activities. It acts as an agonist at Alpha-2 adrenergic receptor sites and relieves symptoms of muscle spasticity, allowing the continuation of normal daily activities. In animal models, tizanidine has not been shown to exert direct effects on skeletal muscle fibers or the neuromuscular junction, and has shown no significant effect on monosynaptic spinal reflexes (consisting of the communication between only 1 sensory neuron and 1 motor neuron) 10. The frequency of muscle spasm and clonus are shown to be decreased by tizanidine 9. Tizanidine shows a stronger action on polysynaptic reflexes, which involve several interneurons (relay neurons) communicating with motor neurons stimulating muscle movement 10.

Effects on blood pressure and heart rate

This drug decreases heart rate and blood pressure in humans 4,6. Despite this, rebound hypertension and tachycardia along with increased spasticity can occur when tizanidine is abruptly discontinued 8.

Mechanism of action

Tizanidine reduces spasticity by causing presynaptic inhibition of motor neurons via agonist actions at Alpha-2 adrenergic receptor sites.
This drug is centrally acting and leads to a reduction in the release of excitatory amino acids like glutamate and aspartate, which cause neuronal firing that leads to muscle spasm. The above reduction and excitatory neurotransmitter release results in presynaptic inhibition of motor neurons. The strongest effect of tizanidine has been shown to occur on spinal polysynaptic pathways. The anti-nociceptive and anticonvulsant activities of tizanidine may also be attributed to agonist action on Alpha-2 receptors. Tizanidine also binds with weaker affinity to the Alpha-1 receptors, explaining its slight and temporary effect on the cardiovascular system 9.

Absorption

This drug undergoes significant first-pass metabolism. After the administration of an oral dose, tizanidine is mostly absorbed. The absolute oral bioavailability of tizanidine is measured to be about 40% Label.

Effect of food on absorption

Food has been shown to increase absorption for both the tablets and capsules. The increase in absorption with the tablet (about 30%) was noticeably higher than the capsule (~10%). When the capsule and tablet were administered with food, the amount absorbed from the capsule was about 80% of the amount absorbed from the tablet Label. It is therefore advisable to take this drug with food for increased absorption, especially in tablet form.

Volume of distribution

Extensively distributed throughout the body. The average steady-state volume of distribution is 2.4 L/kg Label.

Protein binding

About 30% bound to plasma proteins Label.

Metabolism

About 95% of the ingested dose of tizanidine is metabolized. The main enzyme involved in the hepatic metabolism of tizanidine is CYP1A2 Label.

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Route of elimination

This drug is mainly eliminated by the kidney Label.

Half-life

Approximately 2.5 hours Label.

Clearance

A note on renal impairment

Tizanidine clearance is found to be decreased by more than 50% in elderly patients with renal insufficiency (creatinine clearance < 25 mL/min)
compared to healthy elderly subjects; this would be expected to lead to a longer duration of clinical effect. This drug should be used with caution in patients with renal impairment Label.

Adverse Effects

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Toxicity

LD50 information

Oral LD50 (rat): 414 mg/kg; Subcutaneous LD50 (rat): 282 mg/kg; Oral LD50 (mouse): 235 mg/kg MSDS

Use in pregnancy

Animal studies have determined that this drug causes fetal harm Label. Studies have not been performed in humans, and it is advisable to ensure that tizanidine use in pregnant women should be reserved for cases in which possible benefit clearly outweighs the possible risk to mother and unborn child 11.

Use in breastfeeding

In studies of rat models, this tizanidine was found excreted in the breastmilk with a milk-to-blood ratio of 1.8:1 Label. In young nursing rats, abnormal results were obtained in tests indicative of central nervous system function. Various developmental changes that may have been attributable to the drug were observed. It is unknown whether tizanidine is excreted in human milk. It is a lipid-soluble drug, however, and likely to be excreted into breast milk 11.

Carcinogenesis and mutagenesis

No signs of carcinogenicity were observed in two dietary studies performed in rodent models. Tizanidine was given to mice for 78 weeks at doses reaching a maximum 16 mg/kg (equivalent to twice the maximum recommended human dose). In addition, the drug was given to rats for 104 weeks at doses reaching 9 mg/kg (equivalent to 2.5 times the maximum recommended human dose). There was a lack of a statistically significant increase in the occurrence of tumors in either study group 11.

Tizanidine was not found to be mutagenic or clastogenic in several laboratory essays, including the bacterial Ames test, the mammalian gene mutation test, in addition to the chromosomal aberration test in Chinese hamster cells and several other assays 11.

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Which medications in the drug class Skeletal Muscle Relaxants are used in the treatment of Cervical Myofascial Pain?

Author

Grant Cooper, MD Co-Founder, Co-Director, Princeton Spine and Joint Center

Grant Cooper, MD is a member of the following medical societies: Sigma Xi

Disclosure: Nothing to disclose.

Chief Editor

Dean H Hommer, MD Chief Medical Officer, William Beaumont Army Medical Center

Dean H Hommer, MD is a member of the following medical societies: American Academy of Pain Medicine, American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine, American College of Healthcare Executives, American Association for Physician Leadership, American Society of Regional Anesthesia and Pain Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Beth B Froese, MD Consulting Staff, Department of Physical Medicine and Rehabilitation, Orthopaedic Associates of DuPage, Ltd

Beth B Froese, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Medical Association, Illinois State Medical Society

Disclosure: Nothing to disclose.

C Douglas Phillips, MD, FACR Director of Head and Neck Imaging, Division of Neuroradiology, New York-Presbyterian Hospital; Professor of Radiology, Weill Cornell Medical College

C Douglas Phillips, MD, FACR is a member of the following medical societies: American College of Radiology, American Medical Association, American Society of Head and Neck Radiology, American Society of Neuroradiology, Association of University Radiologists, Radiological Society of North America

Disclosure: Nothing to disclose.

Acknowledgements

Martin K Childers, DO, PhD Professor, Department of Neurology, Wake Forest University School of Medicine; Professor, Rehabilitation Program, Institute for Regenerative Medicine, Wake Forest Baptist Medical Center

Martin K Childers, DO, PhD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Congress of Rehabilitation Medicine, American Osteopathic Association, Christian Medical & Dental Society, and Federation of American Societies for Experimental Biology

Disclosure: Allergan pharma Consulting fee Consulting

Patrick M Foye, MD Associate Professor of Physical Medicine and Rehabilitation, Co-Director of Musculoskeletal Fellowship, Co-Director of Back Pain Clinic, Director of Coccyx Pain Service (Tailbone Pain Service: www.TailboneDoctor.com), University of Medicine and Dentistry of New Jersey, New Jersey Medical School

Patrick M Foye, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine, Association of Academic Physiatrists, and International Spine Intervention Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

SIRDALUD instructions for use, price in pharmacies in Ukraine, analogues, composition, indications | SIRDALUD tablets of the company “Sandoz”

pharmacodynamics. Tizanidine is a centrally acting skeletal muscle relaxant. The main point of application of its influence is the spinal cord. By stimulating presynaptic α 2 adrenergic receptors, it inhibits the release of amino acids that stimulate N-methyl-D-aspartate receptors (NMDA receptors). As a result, polysynaptic signal transmission at the level of interneuronal connections in the spinal cord, which is responsible for excessive muscle tone, is suppressed, and muscle tone is reduced.Sirdalud is effective both for acute painful muscle spasms and for chronic spasticity of spinal and cerebral origin. It reduces resistance to passive movement and suppresses spasm and clonic seizures and improves the strength of active muscle contractions.

Pharmacokinetics

Suction and distribution . Tizanidine is rapidly absorbed. C max in blood plasma is reached approximately 1 hour after application. The average absolute bioavailability is 34% (CV 38%).The average volume of distribution of a steady state (Vss) after i.v. application is 160 liters. Plasma protein binding – 30%. The relatively low deviation of pharmacokinetic parameters among patients (C max and AUC) facilitates a reliable preliminary assessment of blood plasma levels after oral administration.

Metabolism / excretion . The drug undergoes rapid and extensive metabolism in the liver. Tizanidine is metabolized by in vitro mainly by CYP 1A2.The metabolites are inactive. They are excreted mainly by the kidneys (70%). The elimination of the total radioactivity (that is, the substance in unchanged form and metabolites) is two-phase, with a fast initial phase (T ½ – 2.5 h) and a slower elimination phase (T ½ – 22 h). Only a small amount of the substance unchanged (about 2.7%) is excreted by the kidneys. Average T ½ of the substance in unchanged form is 2-4 hours

Linearity . The pharmacokinetics of tizanidine are linear at doses ranging from 1 to 20 mg.

Pharmacokinetics in certain groups of patients . In patients with renal insufficiency (creatinine clearance <25 ml / min), the mean C max in blood plasma is twice that in healthy volunteers, and the final T ½ increases to about 14 hours, as a result of which the AUC increased on average 6 times.

No studies have been carried out in patients with impaired liver function.

Tizanidine is metabolized by the CYP 1A2 isoenzyme in the liver.In patients with impaired liver function, higher plasma concentrations of the substance may appear.

Sirdalud is contraindicated in persons with severely impaired liver function.

Pharmacokinetic data on elderly patients are limited.

Gender does not affect the pharmacokinetic properties of tizanidine.

The effect of ethnicity and race on the pharmacokinetics of tizanidine has not been studied.

Food influence . Simultaneous food intake does not affect the pharmacokinetic profile of Sirdalud tablets.Although the C max increases by one third, this is not clinically significant. There was no significant effect on absorption.

Painful muscle spasm. Spasticity due to multiple sclerosis. Spasticity due to spinal cord injury. Spasticity due to brain damage.

Sirdalud has a narrow therapeutic range and high variability in plasma tizanidine concentration in different patients. Therefore, it is important to use it in optimal doses according to the patient’s needs.Treatment should be started with a low dose of 2 mg, which minimizes the risk of adverse effects from taking the drug. If necessary, the dose of the drug can be gradually increased with all the required precautions.

Adults

Relief of painful muscle spasms . Apply 2-4 mg 3 times a day. In severe cases, an additional dose of 2 or 4 mg may be taken before bedtime.

Spasticity in neurological disorders .The dose should be selected individually for each patient.

The initial daily dose should not exceed 6 mg, divided into 3 doses. It can be increased gradually to 2-4 mg 2 times at intervals of 3-7 days. Usually, the optimal therapeutic effect is achieved with a daily dose of 12-24 mg, divided into 3 or 4 doses. The total daily dose of 36 mg should not be exceeded.

Special patient populations

Application in children and adolescents . The experience of using the drug Sirdalud in children and adolescents is limited, therefore it is not recommended for use in this category of patients.

Use in the elderly . The experience of using the drug in elderly patients is limited, therefore, caution should be exercised when using the drug Sirdalud in this category of patients. It is recommended to start treatment with a minimum dose and gradually increase it with caution in “small steps” until the optimal balance of individual tolerance and therapeutic efficacy of the drug is achieved.

Use in patients with impaired renal function .For patients with impaired renal function (creatinine clearance <25 ml / min), the recommended initial single daily therapeutic dose is 2 mg. The dose is increased gradually and with caution, "in small steps", until the optimal balance of individual tolerance and therapeutic efficacy of the drug is achieved. In order to increase the therapeutic efficacy, you should first increase a single dose before moving on to a more frequent intake of the drug during the day.

Use in patients with impaired liver function .Treatment of persons with severely impaired liver function is contraindicated. Sirdalud is largely metabolized in the liver. There are limited data on the use of the drug Sirdalud in patients with impaired liver function (see Pharmacokinetics ). The use of the drug Sirdalud is associated with reversible abnormalities in liver function tests (see SPECIAL INSTRUCTIONS and SIDE EFFECTS). Sirdalud should be used with caution in the treatment of patients with moderately severe liver dysfunction.Treatment is required to start with a minimum dose, a possible dose increase should be carried out with caution and taking into account the patient’s individual tolerance of the drug Sirdalud.

Aborting treatment . If it is necessary to interrupt treatment, the dose should be reduced slowly and gradually. This is especially true for patients who have used the drug in an increased dose for a long time. Thus, the risk of developing a rebound increase in blood pressure and tachycardia is reduced.

Hypersensitivity to tizanidine or any other component of the drug.Severe liver dysfunction. Concomitant use of tizanidine with potent inhibitors of CYP 1A2, such as fluvoxamine or ciprofloxacin.

Adverse reactions – such as drowsiness, fatigue, dizziness, dry mouth, low blood pressure, nausea, disorders of the digestive tract and increased levels of transaminases in blood plasma – are usually mild and transient in patients using the drug in low doses, recommended for relief of painful muscle spasm.

When taken in doses higher than recommended, to eliminate spasticity, the above adverse reactions occur more often and are more pronounced, but they are rarely so serious as to stop treatment. Also, such side reactions may occur: arterial hypotension, bradycardia, muscle weakness, sleep disturbance, hallucinations and hepatitis.

The appearance of such symptoms has been reported after a sudden discontinuation of tizanidine, especially after long-term treatment and / or taking in high daily doses and / or concomitant therapy with antihypertensive drugs.Under these circumstances, patients may experience hypertension and tachycardia. In some cases, such rebound hypertension can cause a stroke. Therefore, treatment with tizanidine should not be stopped suddenly, but only by gradually reducing the dose (see SPECIAL INSTRUCTIONS and INTERACTIONS).

To assess the incidence of various adverse reactions, the following classification was used: very often (≥1 / 10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, <1/100), rarely (≥ 1/10 000, <1/1000), very rarely (<1/10 000), including isolated reports.

Mental disorders: often – insomnia, sleep disturbance.

From the side of the central nervous system: very often – drowsiness, weakness, dizziness.

From the heart: infrequently – bradycardia

From the vascular system: often – hypertension, a slight decrease in blood pressure.

From the digestive tract: very often – dry mouth, gastrointestinal disorders; often nausea.

Hepatobiliary disorders: often – elevated levels of transaminases in blood plasma.

From the musculoskeletal system: very often – muscle weakness.

General disorders: very often – increased fatigue.

Post-marketing research

Additional adverse reactions to the drug have been reported in post-marketing studies.

These adverse reactions have been reported from an unspecified number of patients, so it is not possible to reliably estimate their frequency.

From the immune system: hypersensitivity reactions (including anaphylaxis, angioedema, shortness of breath and urticaria).

Mental disorders: hallucinations, confusion.

From the side of the central nervous system: vertigo.

From the side of the cardiovascular system: syncope.

From the side of the organ of vision: blurred vision.

Hepatobiliary disorders: hepatitis, liver failure.

Skin and subcutaneous tissue disorders: rash, erythema, pruritus, dermatitis.

General disorders: asthenia, withdrawal syndrome.

The concomitant use of mild CYP 1A2 inhibitors with tizanidine is not recommended (see INTERACTIONS and CONTRAINDICATIONS).

After a sudden discontinuation of the drug, especially after prolonged use or rapid dose reduction and / or the use of high daily doses and / or with the simultaneous use of antihypertensive drugs, patients may experience a rebound phenomenon.Under such circumstances, patients may develop hypertension and tachycardia. In some cases, such rebound hypertension can cause a stroke. Treatment with tizanidine should not be stopped abruptly, but only by gradually reducing the dose (see INTERACTIONS and SIDE EFFECTS).

In patients with renal insufficiency (creatinine clearance <25 ml / min), the systemic exposure of tizanidine can be up to 6 times higher, therefore the recommended initial dose is 2 mg 1 time per day (see APPLICATION). The dose should be increased sequentially based on efficacy and tolerability.To achieve a more pronounced effect, it is recommended to first increase the dose, which is used once a day, and then increase the frequency of administration.

Hepatic impairment associated with the use of tizanidine has been reported, but this was rare in patients receiving daily doses up to 12 mg. In this regard, it is recommended to monitor liver function once a month during the first 4 months of therapy in those patients who are using tizanidine at a dose of 12 mg or higher and in patients with clinical symptoms indicating liver failure (such as nausea, loss of appetite or increased fatigue of unknown etiology).The use of the drug Sirdalud should be discontinued if the level of ALT or AST in the blood serum exceeds the upper limit of the norm by 3 times or more for a long period.

Hypersensitivity reactions have been reported with tizanidine, including anaphylaxis, angioedema, dyspnea, dermatitis, rash, urticaria, pruritus, and erythema. It is recommended that patients be closely monitored for 1 or 2 days after taking the first dose of tizanidine. If anaphylaxis or angioedema develops with anaphylactic shock or shortness of breath, the use of Sirdalud should be stopped immediately and the patient should be prescribed the necessary treatment.

Arterial hypotension can occur with the use of tizanidine, as well as as a result of drug interactions with CYP 1A2 inhibitors and / or antihypertensive drugs (see INTERACTIONS and SIDE EFFECTS). Severe manifestations of arterial hypotension, such as loss of consciousness and circulatory collapse, have been reported.

Caution should be exercised when using this drug concomitantly with agents that prolong the Q-T interval (such as cisapride, amitriptyline, azithromycin) (see.INTERACTIONS).

Caution is necessary for patients with coronary artery disease and / or heart failure. You should regularly monitor the ECG at the beginning of the use of the drug Sirdalud in such patients. Before using this drug in patients with myasthenia gravis, the risk / benefit ratio must be carefully evaluated.

The experience of use in children and adolescents is limited, therefore the use of the drug Sirdalud is not recommended in this category of patients.

Care should be taken when using the drug in elderly patients.

Sirdalud tablets contain lactose. For patients with rare hereditary diseases – galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption syndrome – Sirdalud tablets are not recommended.

Application during pregnancy or lactation. Women of reproductive age who are sexually active should have a pregnancy test before starting treatment with Sirdalud.

Women of reproductive age should be advised that animal studies indicate that Sirdalud is harmful to the fetus.Women of reproductive age who are sexually active should use effective methods of contraception (methods that allow pregnancy in less than 1% of cases) during the entire period of treatment with Sirdalud and within one day after stopping treatment with Sirdalud.

Pregnancy . Data on the use of the drug Sirdalud in pregnant women are limited, so it should not be prescribed during pregnancy, unless the potential benefit to the mother outweighs the possible risk to the fetus.Sirdalud does not have a teratogenic effect on rats and rabbits, but it causes obstructed labor, increased prenatal and postnatal mortality, and fetal growth retardation in rats.

Breastfeeding . When using tizanidine in rats and rabbits, no teratogenic effects were found. Consideration should be given to the risk to a breastfed baby. Experiments on animals have shown that tizanidine passes into breast milk in small quantities. Therefore, women who are breastfeeding should not be prescribed the drug.

Fertility . There was no impairment of fertility in male rats in which the drug was used at a dose of 10 mg / kg / day, and in female rats, in which the drug was used at a dose of 3 mg / kg / day. A decrease in fertility was observed in male rats receiving the drug at a dose of 30 mg / kg / day and in female rats receiving the drug at a dose of 10 mg / kg / day. Sedation, weight loss, and ataxia have also been reported with these doses.

The ability to influence the reaction rate when driving vehicles or other mechanisms .Even when prescribed as recommended, tizanidine can cause drowsiness, dizziness and / or arterial hypotension, thus impairing the patient’s ability to drive and operate machinery. The risks increase with the simultaneous use of alcohol. Therefore, one should refrain from activities that require a high concentration of attention and quick reactions, such as driving vehicles or working with other mechanisms.

Children . The experience of using the drug in pediatrics is limited.It is not recommended to prescribe Sirdalud to children.

Concomitant use of known inhibitors of CYP 1A2 may increase plasma levels of tizanidine. An increase in the level of tizanidine in blood plasma can lead to the appearance of symptoms of overdose, such as a prolongation of the interval Q – T .

The simultaneous use of known inducers of CYP 1A2 can reduce the level of tizanidine in blood plasma. A decrease in the level of tizanidine in blood plasma can lead to a decrease in the therapeutic effect of Sirdalud.

Concomitant use of potent CYP 1A2 inhibitors such as fluvoxamine or ciprofloxacin with tizanidine is contraindicated. The simultaneous use of tizanidine with fluvoxamine increases the AUC of tizanidine by 33 times, while the simultaneous use of tizanidine with ciprofloxacin increases the AUC of tizanidine by 10 times. This can lead to a clinically significant and long-term decrease in blood pressure, accompanied by drowsiness, dizziness, and decreased psychomotor performance.

Concomitant use of tizanidine with other inhibitors of CYP 1A2, such as antiarrhythmics (amiodarone, mexiletine, propafenone), cimetidine, some fluoroquinolones (enoxacin, pefloxacin, norfloxacin), rofecoxib, oral contraceptives, and ticlopidin is not recommended.

An increase in the level of tizanidine in blood plasma can cause symptoms of overdose, including prolongation of the interval Q – T .

The simultaneous use of the drug Sirdalud with antihypertensive drugs, including diuretics, can sometimes cause arterial hypotension and bradycardia. In some patients who used simultaneous treatment with antihypertensive drugs, rebound hypertension and rebound tachycardia were noted with abrupt withdrawal of tizanidine. In some cases, rebound hypertension can cause a stroke.SPECIAL INSTRUCTIONS and SIDE EFFECTS).

Care should be taken with the simultaneous use of the drug Sirdalud with drugs that lengthen the interval Q – T .

The combined use of the drug Sirdalud with rifampicin can lead to a 50% decrease in the concentration of tizanidine. Thus, the therapeutic effect can be reduced with the use of rifampicin during therapy with Sirdalud, which may be clinically significant for some patients.Long-term simultaneous use should be avoided, and if necessary, it is required to very carefully adjust the dose. Careful dose adjustment (increase) is necessary in the case of planned long-term combination therapy.

The use of the drug Sirdalud leads to a 30% decrease in the systemic effect of tizanidine in smokers (more than 10 cigarettes per day). Long-term use of the drug in patients who smoke a lot requires the use of the drug in higher doses.

The simultaneous use of the drug Sirdalud and other drugs of central action (for example, sedatives and hypnotics (benzodiazepine or baclofen), some antihistamines, general anesthetics and analgesics, psychotropic drugs, narcotic drugs) can increase the severity of the effects of each of the drugs and enhance the hypnotic effect of Sirdalud …This applies, in particular, to the simultaneous use of alcohol, which can unpredictably change or enhance the effect of Sirdalud and increase the risk of adverse reactions, therefore, you should refrain from drinking alcohol. The depressing effect of alcohol on the central nervous system can be enhanced by the drug Sirdalud.

The use of the drug Sirdalud simultaneously with α 2 -adrenergic agonists (eg clonidine) should be avoided due to their potential additive hypotensive effect.

very few reports have been received regarding an overdose of Sirdalud. All patients with isolated cases of overdose of this drug, including 1 patient who took 400 mg of the drug Sirdalud, recovered without complications.

Symptoms: nausea, vomiting, arterial hypotension, bradycardia, prolongation of the interval Q – T , dizziness, miosis, respiratory distress, coma, anxiety, drowsiness.

Treatment. To remove the drug from the body, multiple use of activated carbon in high doses is recommended. Forced diuresis may speed up the elimination of the drug. In the future, symptomatic treatment should be carried out .

at a temperature not exceeding 25 ° C out of the reach of children.

4-45-ANP-REC-0721

Information for healthcare professionals.

Date added: 06.08.2021

Centrally acting muscle relaxants in the treatment of myofascial pain | Goryachev D.B.

Myofascial pain is a very frequent event in clinical practice, reaching, according to some estimates, 30% of the total number of visits [1]. Myofascial pain is one of the main causes of back pain [2], the prevalence of which exceeds 50% in the population and increases dramatically in old age. According to L.A. Bogacheva (1996, 1998), in a study of 4 thousand patients with pain in the muscles of the back, only 5% revealed radiculopathy and tunnel neuropathies, while musculoskeletal dysfunction was observed in 95% of the examined patients [3].

The pathophysiology of muscle pain is quite complex, and some mechanisms have conflicting interpretations by researchers. However, the importance of muscle spasm in the development of pain syndrome remains undeniable. Local muscle pain occurs when thin myelinated Aδ and unmyelinated C-fibers are activated. This activation can be induced by thermal or mechanical stimuli, local inflammation, or ischemia. Various theoretical models of the development of myogenic pain are proposed [4].The first model is associated with changes in the dorsal horn leading to the formation of pathological interneuronal synapses. This results in the appearance of primary non-painful stimuli, which are interpreted as painful in connection with pathological sensitization of nociceptive neurons and the involvement of secondary neurons. The second model of pain development associates the occurrence of myogenic pain with impaired activation of descending inhibitory pathways, which normally suppress afferent stimulation. The third associates persistent peripheral sensitization of nociceptive peripheral fibers with repeated microtrauma or chronic local ischemia.Local ischemia occurs as a result of both vasoconstriction and neurogenic edema, which disrupts microcirculation. The influence of central mechanisms in depressive disorders on the modulation of painful afferentation is also actively discussed [5].
It is recognized that the main clinical element of myofascial syndrome is the trigger point, which is associated with the appearance of a dense palpable muscle cord [6]. It is she who creates the basis for the development and maintenance of pain. It is believed that persistent muscle tension is induced by increased release of acetylcholine and leads to the development of local ischemia and subsequent sensitization of nociceptive nerve fibers [7].The agreement between different specialists in the diagnosis of myofascial syndrome based on the presence of trigger points is considered sufficient to give this condition the status of a separate nosological form [8].
The clinical picture of myofascial pain is quite variable; it is often difficult to draw the line between myofascial syndrome and fibromyalgia. At the same time, without touching on the issue of making a diagnosis in detail, it should be pointed out that there are criteria developed by D.Simmons, J. Travell [6]. At the same time, the localization of pain syndrome can be very diverse and not limited to the muscles of the back and facial skull.
For the treatment of myofascial pain, methods of manual therapy, physiotherapy, physiotherapy exercises, injections of anesthetic into trigger points are widely used. Obviously, non-drug therapy occupies a leading place in the treatment of such syndromes, however, modern drugs also have a high therapeutic potential in relieving pain in myofascial syndrome with relatively low risks of developing adverse events.In this case, the main class of drugs reasonably used for the treatment of myofascial pain is centrally acting muscle relaxants.
It is important that the effectiveness of drugs with a central muscle relaxant effect in pain syndrome caused by an inflammatory process, in particular rheumatoid arthritis, has not been proven [9]. The 2012 Cochrane Review found no evidence to support the superiority of muscle relaxants, either benzodiazepine or non-benzodiazepine, over placebo.At the same time, attention is drawn to the rather high incidence of adverse events: NNTh2, when compared with placebo, reaches a value of 3 [95%, CI 2–7].
The list of drugs belonging to the class of muscle relaxants is quite wide. Let’s dwell on the distinctive features of some of them. It should be said that most of the centrally acting muscle relaxants themselves are not available on the Russian market. Table 1 shows preparations according to the anatomical-therapeutic-chemical classification (ATC) 2, which are centrally acting muscle relaxants.
A clinically significant muscle relaxant effect is characteristic of drugs from the benzodiazepine group (diazepam, lorazepam, clonazepam) due to the fact that these drugs from a clinical point of view are also considered as centrally acting muscle relaxants, despite a pronounced sedative effect. They are widely represented on the Russian market. Thus, it makes sense to dwell briefly on the most important members of the class of central muscle relaxants, such as baclofen, tizanidine, tolperisone, and benzodiazepines.
It is important that myofascial syndrome or its terminological equivalents, emphasizing the importance of functional disorders in the development of this syndrome, and not organic pathology, are present in the “indications” section of the instructions for use only for tizanidine, tolperisone and benzodiazepines. For baclofen preparations, the indication is conditions associated with an increase in muscle tone, more precisely, spasm, only with organic damage to the spinal cord and brain. Research data confirm the effectiveness of baclofen in myofascial syndrome [4], but its use in this case occurs in a certain sense “off-label”.Structurally, baclofen belongs to GABA-B receptor agonists, the stimulation of which results in a decrease in the release of excitatory neurotransmitters (substance P) and amino acids (glutamate and aspartate) from the terminals. Baclofen is taken orally or intrathecally, but myofascial syndrome is not an indication for both dosage forms of this drug.
For benzodiazepines (diazepam, lorazepam, clonazepam, etc.), the use of pain syndrome caused by functional disorders of muscle tone with the appearance of muscle spasm is quite reasonable, and this indication is regulated in the instructions for drugs of this group.However, their pronounced sedative effect requires constant assessment of the degree of its implementation in comparison with muscle relaxant and analgesic activity. In this regard, the rather long half-life of benzodiazepines, exceeding 10 hours, negatively affects the possibility of widespread use of this group of drugs in myofascial syndrome. That is, after taking benzodiazepines, therapeutic concentrations that significantly affect the concentration ability remain for a long time.Thus, there are 2 drugs that are most often used in Russia for the treatment of myofascial syndrome and related conditions.
Tolperisone has been used in medical practice since the 1960s. in the countries of Eastern Europe. In 2011, at the initiative of the German regulatory approval system, the Committee for Medicinal Products for Human Use (CHMP) of the European Agency for Medicinal Products for Human Use began to revise the assessment of the ratio of the expected benefit to the risk of using tolperisone drugs for various indications. …The result of the work was presented in the form of an EMA document dated January 21, 2013 [10]. The document provides the following information. Most studies of the use of oral forms of tolperisone were carried out in the 1960s – 1970s. and do not correspond to modern concepts of clinical trials. The available data justifying the use of the drug in diseases of the musculoskeletal system, vascular lesions, rehabilitation after surgical interventions and infantile cerebral palsy are extremely limited and inconclusive.Only the use of tolperisone in patients with spastic syndrome after a stroke makes it possible to ascertain the effectiveness of this drug. The efficacy of tolperisone compared with placebo was 32% versus 14%, respectively. At the same time, a large number of spontaneous reports on the frequency of adverse reactions (half of which are hypersensitivity reactions) do not correspond to the results of clinical studies. Based on these data, the CHMP concludes that for tolperisone, the ratio of the expected benefits to the possible risks of use can be considered favorable only when it is used to treat spastic syndrome in patients after a stroke [10].
It should be noted that published studies of the efficacy of tolperisone in the treatment of myofascial pain not associated with post-stroke changes justify its use. In particular, this concerns the work of H.G. Pratzel, conducted in 1996 at the Munich Institute of Balneology and Climatology (Germany) [11]. In a study with a parallel, double-blind, placebo-controlled design, tolperisone was shown to be superior to placebo. The therapy lasted for 21 days in 138 patients.Obviously, the EU regulator (EMA) could have received more detailed information, which made it possible to come to the above decision.
The last of this group of drugs, tizanidine, has been present on the Russian market since 1992 in the form of the original drug Sirdalud (Novartis Pharma). Tizanidine realizes its effect at the spinal and supraspinal levels. By stimulating presynaptic α2 receptors, it inhibits the release of excitatory amino acids that stimulate NMDA receptors.This leads to inhibition of the polysynaptic reflexes of the spinal cord, which are responsible for muscle hypertonicity, and suppression of the transmission of excitation through them, which causes a decrease in the increased tone of the flexor and extensor muscles and a decrease in painful muscle spasms. In addition to the muscle relaxant properties, tizanidine also has a central moderately pronounced analgesic effect (due to a decrease in the release of excitatory neurotransmitters in the brain at the level of the locus coeruleus).In animal studies, it has been shown that tizanidine can realize its effect through a decrease in central sensitization. The half-life of the drug from the systemic circulation is 2-4 hours.
Studies of the effectiveness of the drug for muscle pain were carried out mainly in the 1990s. In a study by J. Mojica, the efficacy of tizanidine in myofascial syndrome in the neck and shoulder girdle was studied [12]. There was a significant decrease in the intensity of pain by the 3rd day of treatment when taking 2 mg 3 r./ day In an international clinical study of the efficacy of tizanidine for the treatment of muscle pain syndrome in patients in polyclinic practice, more than 2 thousand patients participated, the effectiveness of therapy reached 89% [13]. A study involving 29 women with chronic torpid myofascial syndrome was conducted in the United States. The patients received therapy with various drugs, including NSAIDs, but their effectiveness did not reach the desired level. The duration of the pain syndrome ranged from 9 to 52 weeks.The daily dose of tizanidine in some patients was increased to 12 mg for 3 weeks. and remained stable for 2 weeks. The intensity of pain from a clinical point of view was significantly reduced by 3 weeks. therapy. Both the functional indicators and the pain threshold determined by the algometer significantly improved [14].
The issue of the safety of muscle relaxants when used for the treatment of myofascial syndrome is quite important, given that no significant difference in their effectiveness can be found based on the results of large meta-analyzes [15].The safety issue of tizanidine therapy is well understood. It can definitely be said that the drug has one of the best safety profiles; no fundamental difference in the spectrum of adverse events of the drug from adverse events with the use of other muscle relaxants was noted. At the same time, the post-registration use of the drug made it possible to identify a possible undesirable phenomenon associated with a possible prolongation of the QT interval. Special attention to this issue led to the fact that in 2013recruitment of patients was started in a new study of the safety of tizanidine, associated with the assessment of the effect of this drug on the characteristics of myocardial repolarization [16]. The study is planned to involve 116 healthy volunteers who will receive 24 mg of tizanidine daily for 14 days. By the end of therapy, the ECG will be evaluated, in particular the QT interval. This study will provide critical information regarding a group of conditions in which tizanidine should not be used or caution should be exercised when taking it.The study is planned to be completed by mid-2014
Thus, the choice of muscle relaxants for the treatment of myofascial pain is rather limited. The decisive issue in this case will be the issue of drug safety and tolerability. Sirdalud fully meets these requirements.
The doctor should make the optimal choice of a drug from this group of drugs, taking into account the individual characteristics of the patient, because the ratio of the expected benefit to the possible risks of adverse events varies greatly for each patient with myofascial pain.

1 NNTH – Number Needed to Treat, Harm: the number of patients who need to be treated with a specific method within a certain time to identify an additional adverse outcome
2 Anatomical Therapeutic Chemical Classification System – international drug classification system. The most common and used in the documents of the Ministry of Health of Russia is the abbreviation ATX.

Literature
1.Skootsky S.A. et al. Prevalence of myofascial pain in general medicine practice // West J Med. 1989. Vol. 151. P. 157-160.
2. Karlov V.A. Neurology: A Guide for Physicians. M .: Med. inform. agency, 1999.624 c.
3. Bogacheva L.A., Snetkova E.P. Dorsalgias: classification, mechanisms of pathogenesis, principles of management // Nevrol. zhurn. 1996. No. 2. P. 8–12.
4. Meleger, Muscle Relaxants and Antispasticity Agents // Phys Med Rehabil Clin N Am. 2006. Vol. 17.R. 401-413.
5.Bruckle W., Suckfull M., Fleckenstein W. et al. Gewebe-pO2-Messung in der verspannten Ruckenmuskulatur (m. Erector spinae) // Z Rheumatol. 1990. Vol. 49. P. 208-216.
6. Simmons D., Travell J. Trigger point manual. 2nd edition. Williams and Wilkins 1999. Vol. 1. P. 132.
7. Rachin A.P., Yakunin K.A., Demeshko A.V. Myofascial pain syndrome. M .: GEOTAR-Media, 2009.120 p.
8. Gerwin R.D. et al. Interratter reliability in myofascial point examination // Pain. 1997.Vol. 69. P. 65–73.
9. Richards B.L. Muscle relaxants for pain management in rheumatoid arthritis. Cochrane Database Syst. Rev. 2012, Jan, 18.
10. EMA / 673365/2012 rev. 1.
11. Pratzel H.G. et al. Effecacy and tolerance of repeated doses of tolperisone hydrochloride in treatment of painful muscle spasm: results of a prospective placebo-controlled double-blind trial. // Pain. 1996. Vol. 67. P. 417-425.
12. Mojica J.A.P., Mancao B.D., Perez M.L.P. et al.A dosefinding therapeutic trial on tizanidine in Filipinos with acute muscle spasm // Philipp J Intern Med. 1994.
13. Hutchinson D.R., Daniels F. A multinational study in general practice to evaluate the effectiveness and tolerability of tizanidine in the treatment of painful muscle spasms // Br J Clin Res. 1990. Vol. 1. P. 39–48.
14. Malanga G. A., Gwynn M. W., Smith R., Miller D. Tizanidine is effective in the treatment of myofascial pain syndrome // Pain Physician. 2002 Oct.Vol. 5 (4). R. 422-432.
15. Chou R., Peterson K., Helfand M. Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review // J Pain Symptom Manage. 2004 Aug. Vol. 28 (2). R. 140-175.
16. NCT01839279 A Study to Define the ECG Effects of Tizanidine Compared to Placebo and the Positive Control, Moxifloxacin, in Healthy Men and Women Using a Blinded ECG Evaluator: A Thorough ECG Trial (TQT). Http: //www.clinicaltrials.gov.

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Management of stroke patients with spasticity uMEDp

The article deals with the prevention of recurrent stroke and the management of patients with post-stroke spasticity.It is noted that comprehensive secondary prevention of ischemic stroke (non-drug methods, drug therapy and surgery) can significantly reduce the risk of recurrent stroke and other cardiovascular diseases. The effectiveness of therapeutic exercises, muscle relaxants and botulinum toxin preparations in the management of patients with post-stroke spasticity is discussed. It is emphasized that the introduction into clinical practice of modern methods of stroke prevention and treatment of the consequences of stroke will significantly reduce mortality from stroke, accelerate recovery and improve the quality of life of patients.

Introduction

More than a million people who have suffered a stroke live in Russia. More than half of them have movement disorders (most often, spastic paresis of the extremities), as a result of which persistent disability often develops and the quality of life is significantly reduced [1, 2].

The management of patients with a history of stroke is aimed at preventing recurrent stroke and other cardiovascular diseases, preventing possible complications, reducing existing disorders and maximizing functional capabilities [1-3].

Early mobilization of a stroke patient reduces the risk of developing venous thrombosis of the lower extremities, the formation of pressure ulcers, aspiration and pneumonia, the formation of contractures and has a beneficial effect on the psychological state of the patient. Constant physical activity is necessary to maintain a good functional state of motor functions. Regular walking and physical activity make it possible to firmly consolidate the positive results obtained during the patient’s rehabilitation in the early post-stroke period.Increasing the intensity of physical activity underlies the revitalization of patients with movement disorders, while great importance is attached to the treatment of spasticity, which is present in most of these patients.

Prevention of recurrent stroke

The risk of stroke is almost ten times higher in people who have had a stroke and a transient ischemic attack, while it is highest in the early stages after the onset of illness. In this regard, secondary prevention should begin as early as possible and be carried out for life [3, 4].Stroke prevention includes non-drug and drug methods, as well as, in some cases, surgery.

Non-drug methods

Quitting smoking or reducing the number of cigarettes smoked is accompanied by a gradual significant reduction in the risk of ischemic stroke. To prevent one recurrent ischemic stroke, it is enough for four patients with a history of ischemic stroke or transient ischemic attack to quit smoking.

Stopping alcohol abuse reduces the risk of recurrent hemorrhagic and ischemic stroke in former alcoholics. All stroke patients are advised to give up alcohol.

Stroke patients are shown regular physical activity. You should refrain from significant physical exertion, especially during the first month of the disease, however, a gradual increase in loads, regular walking in the fresh air are not contraindicated.The positive effect of systematic physical activity can be due to the normalization of body weight and blood pressure, an increase in glucose tolerance, and a decrease in serum cholesterol.

In addition, stroke patients are advised to reduce excess weight by eating a balanced diet, limiting calorie intake and increasing physical activity.

Drug prevention

Antihypertensive therapy .Most patients who have had hemorrhagic and ischemic stroke or transient ischemic attack require antihypertensive drugs. About a third of recurrent strokes can be prevented by gradually normalizing blood pressure.

A decrease in the incidence of ischemic stroke has been established when diuretics, angiotensin-converting enzyme inhibitors, and a combination of angiotensin-converting enzyme inhibitors with a diuretic are used as antihypertensive agents, but it has not been confirmed for beta-blockers.

The target blood pressure level is selected individually. It is recommended to decrease the pressure gradually, by an average of 10/5 mm Hg. Art. After an ischemic stroke, the blood pressure level should be at least 120/80 mm Hg. Art. [3, 4]. In patients with ischemic stroke or transient ischemic attack, the risk of recurrent stroke is increased with systolic blood pressure

The choice of a specific antihypertensive agent in a patient who has had a stroke is largely determined by concomitant diseases (diabetes mellitus, coronary heart disease, etc.)), often requiring a combination of several antihypertensive drugs.

In noncardioembolic stroke (atherothrombotic, lacunar and stroke with an unknown cause), antiplatelet agents are recommended as antithrombotic therapy, and anticoagulants are recommended for cardioembolic stroke.

Antiplatelet drugs. Antiplatelet therapy (mainly aspirin) is started on the first day of ischemic stroke.Although the issue of timing is not well understood, it is best to prescribe anticoagulants immediately after a transient ischemic attack and in the first 14 days after ischemic stroke. However, in case of uncontrolled arterial hypertension or large infarction (with its probable hemorrhagic transformation), the course of treatment can be carried out later.

Among antiplatelet agents, the most commonly used are acetylsalicylic acid (aspirin), clopidogrel, ticlopidine, a combined preparation of acetylsalicylic acid and dipyridamole.

Regular intake of aspirin reduces the risk of nonfatal stroke by 28% and fatal stroke by 16%, the risk of various vascular events (stroke, myocardial infarction, vascular death) – by an average of 13% [6]. To prevent recurrent ischemic stroke, it is recommended to take aspirin at a dose of 75 to 325 mg / day; aspirin in higher doses does not enhance the prophylactic effect, but increases the risk of gastrointestinal disorders and bleeding [6].

The regimen for taking ticlopidine (Tiklid), a thienopyridine derivative, is 250 mg twice a day. In about 2% of cases, neutropenia may develop, which requires regular monitoring of a complete blood count (every two weeks during the first three months of treatment) and in case of a positive result, discontinuation of the drug.

Clopidogrel (Plavix, Plagril) – A thienopyridine derivative is chemically similar to ticlopidine, but causes fewer side effects. In this regard, European experts recommend using only clopidogrel from thienopyridines to prevent recurrent ischemic stroke [3].Clopidogrel is prescribed at a dose of 75 mg once a day. It reduces the risk of recurrent stroke to a greater extent than aspirin, especially in patients with multifocal manifestations of atherosclerosis (lesions of the peripheral arteries of the lower extremities, coronary heart disease). In recent years, in patients with a minor stroke or a history of transient ischemic attack, the use of a combination of clopidogrel (75 mg / day) and aspirin (50-100 mg / day) for 6-12 months has been discussed, followed by a switch to taking only aspirin or only clopidogrel [7].

Sustained-release dipyridamole (200 mg) in combination with acetylsalicylic acid (25 mg) (Agrenox) for the secondary prevention of ischemic stroke is taken twice a day. This combination has a slight advantage over acetylsalicylic acid monotherapy in reducing the risk of recurrent ischemic stroke.

Anticoagulants. Among anticoagulants, warfarin is most commonly used, which is recommended for the secondary prevention of ischemic stroke in patients with atrial fibrillation, intraventricular thrombus, artificial heart valve and other pathology, dangerous recurrence of cardioembolic ischemic stroke.In this group of patients, warfarin reduces the risk of recurrent stroke and systemic embolism more than aspirin. The dose of warfarin (on average 2.5-10 mg / day) is selected gradually, focusing on the international normalized ratio, maintaining it at the level of 2-3.

Over the past ten years, the results of multicenter randomized trials have been published, in which the efficacy of new oral anticoagulants – apixaban [8], dabigatran [9], rivaroxaban [10], edoxaban [11], compared with warfarin in patients with atrial fibrillation was studied.A significant part of the patients included in these studies had previously suffered an ischemic stroke or transient ischemic attack, therefore, they took anticoagulants for the secondary prevention of a cardiovascular event. These studies have shown that new oral anticoagulants are as effective as warfarin in the prevention of ischemic stroke and other arterial embolism, while having the advantage of a lower risk of bleeding, especially intracranial bleeding [8-11].Based on the results of these studies in most countries of the world, including our country, for non-valvular atrial fibrillation, dabigatran (Pradaxa) 150 or 110 mg twice a day, rivaroxaban (Xarelto) 20 mg / day and apixaban (Eliquis) were recommended. 5 mg twice a day.

Statins. Taking statins is recommended for patients with a history of noncardioembolic ischemic stroke or transient ischemic attack [3, 4, 7]. Prescribing statins for ischemic stroke caused by cardiac embolism or unclear reasons is indicated in the case of concomitant coronary heart disease, diabetes mellitus, high serum low-density lipoprotein cholesterol.Atorvastatin (Liprimar) is used at 20–80 mg / day, simvastatin (Zokor) – 20–40 mg / day to achieve a low density lipoprotein cholesterol level of 2.5 mmol / L and below. The use of statins in doses higher than standard ones, for example, 80 mg of atorvastatin instead of 20 mg, can lead to an additional reduction in the risk of stroke, which is especially important in patients at high risk of recurrent ischemic stroke.

Surgical intervention

Carotid endarterectomy is recommended for severe stenosis (narrowing of 70–99% of the diameter) of the internal carotid artery on the side of the hemisphere concerned in the early stages (preferably in the first two weeks), but no later than six months after ischemic stroke or transient ischemic attack [3, 4, 7].Carotid endarterectomy can also be used for moderate stenosis (narrowing of 50–69% of the diameter) of the internal carotid artery in the presence of additional risk factors for stroke (for example, male sex) and the absence of pronounced concomitant diseases. Carotid endarterectomy should be performed by experienced surgeons whose perioperative morbidity and mortality does not exceed 6%. The effectiveness of carotid endarterectomy depends on the duration of the operation [12]. It is most effective in the early stages (in the first month after ischemic stroke or transient ischemic attack).With an increase in the period from the moment of ischemic stroke or transient ischemic attack, the effectiveness of carotid endarterectomy sharply decreases.

Carotid stenting has no advantages over carotid endarterectomy in patients who have had an ischemic stroke or transient ischemic attack and have stenosis of the internal carotid artery [3, 4, 7]. When stenting the carotid arteries, the best results are observed in those cases when a device (trap) is used to prevent possible arterio-arterial embolism.Carotid stenting should be performed by experienced surgeons whose perioperative morbidity and mortality do not exceed 4%.

The effectiveness of secondary prevention of ischemic stroke increases significantly when all possible means are used. The combination of several means of secondary prevention of ischemic stroke can significantly reduce the risk of recurrent stroke and other cardiovascular diseases.

Treatment of spasticity

Spasticity is observed in 65% of patients with movement disorders after a stroke [13, 14].It usually builds up in paretic limbs within weeks and months of the stroke. A spontaneous decrease in spasticity is comparatively rarely observed, most often when motor functions are restored [14]. In many patients with hemiparesis or monoparesis, spasticity impairs motor function because increased muscle tone can exacerbate muscle weakness. In addition, spasticity contributes to the development of contracture and deformity of the limb, makes it difficult to care for an immobilized patient and is sometimes accompanied by painful muscle spasms [14].

Lost motor functions are restored as quickly as possible within two to three months from the moment of a stroke; later, the rate of recovery is significantly reduced. A year after a stroke, the likelihood of a decrease in the degree of paresis is very small. However, it is possible to improve motor functions by training balance and walking, using special devices for locomotion and means to correct increased muscle tone in paretic limbs.

With pronounced spasticity, the functional activity of the limb is, on average, worse than in patients with mild spasticity [14].At the same time, with a pronounced degree of paresis, spasticity in the leg muscles can facilitate standing and walking, and a decrease in muscle tone can lead to a deterioration in motor function. In addition, with minimal movements in the limb, patients may not feel an improvement in motor functions after a decrease in spasticity. This justifies the need for treatment only in cases where spasticity worsens the patient’s motor functions, makes it difficult to care for him or causes his discomfort.

Treatment of post-stroke spasticity is aimed at improving the functionality of the paretic limbs. Unfortunately, its results are usually limited to reducing pain and discomfort associated with high muscle tone, facilitating the care of a paralyzed patient, or eliminating an existing cosmetic defect caused by spasticity.

Before starting treatment for a patient with post-stroke spasticity, it is necessary to determine the achievable goals in each specific case (improvement of motor functions, relief of painful spasms, facilitation of patient care, etc.).) and discuss them with the patient and (or) his relatives [14, 15]. If you start therapy early after the stroke that caused spastic paresis, you can achieve good results. This is due to the fact that treatment can lead to a significant improvement in motor functions, preventing the formation of contractures and increasing the effectiveness of rehabilitation during the period of maximum plasticity of the central nervous system. With a long duration of the disease, the chance to significantly improve motor functions is small, but it is possible to significantly facilitate patient care and eliminate the discomfort caused by spasticity.The less pronounced paresis in the limb, the higher the likelihood that therapy will improve motor functions [14, 15].

Non-drug methods

Therapeutic gymnastics (the basis of physiotherapy) due to the training of paretic limbs and the prevention of contractures is considered the most effective method for post-stroke spastic hemiparesis. As methods of physiotherapy, posture treatment, teaching patients to stand, sitting, walking (with the help of additional means and independently), bandaging a limb, orthopedic devices, thermal effects on spastic muscles, as well as electrical stimulation of certain muscle groups, for example, the extensors of the fingers of the hand or the anterior tibial muscle [16].

Intensive exercises that can significantly increase muscle tone are not recommended for patients with severe spasticity in the flexors of the upper extremities: squeezing a rubber ring or a ball, training with an expander to develop flexion movements in the elbow joint.

Massage of the muscles of the paretic limbs with a high tone is possible only in the form of light stroking. In contrast, in antagonistic muscles, rubbing and shallow kneading at a faster pace can be used.

In domestic practice, patients with post-stroke spastic hemiparesis are often prescribed acupuncture as part of a complex treatment. Controlled studies conducted abroad do not show reliable effectiveness of this method [17]. However, according to the latest meta-analysis conducted by Korean specialists, acupuncture can reduce spasticity and even improve the functional state of paretic limbs [18].

Muscle relaxants

Tizanidine, baclofen, dantrolene (dantrolene), and benzodiazepines (mainly diazepam) are recommended as drugs taken by mouth for the treatment of spasticity of various origins. The basis for the appointment of these antispastic agents (or muscle relaxants) are the results of double-blind, placebo-controlled randomized trials that have shown the safety and efficacy of these drugs [14, 15].Note that dantrolene (dantrolene) is not registered as a medicine in Russia. In domestic clinical practice, tolperisone is used, which is still available in some states, but is not registered in the United States and many other countries.

Antispastic agents, reducing muscle tone, can improve motor functions, relieve painful muscle spasms, enhance the effect of physiotherapy exercises and, as a result, prevent the development of contractures, and facilitate the care of an immobilized patient.With a mild degree of spasticity, muscle relaxant therapy can lead to a significant positive effect, but with severe spasticity, large doses of muscle relaxants may be required, which are often accompanied by the development of adverse events. Treatment with muscle relaxants begins with a minimum dose, which is then slowly increased to achieve an effect.

Baclofen (Baklosan) has an antispastic effect mainly at the spinal level. The drug is an analogue of gamma-aminobutyric acid (GABA).It binds to presynaptic GABA receptors, reducing the release of excitatory amino acids (glutamate, aspartate) and suppressing mono- and polysynaptic activity at the spinal level, which causes a decrease in spasticity. The drug also has a moderate central analgesic effect. It is well absorbed from the gastrointestinal tract, the maximum concentration in the blood is reached two to three hours after ingestion. Baclofen is used for spinal spasticity (spinal trauma, multiple sclerosis), less often for post-stroke or other cerebral spasticity.It is effective for painful muscle cramps. The initial dose is 5-15 mg / day (in one or three doses), then it is increased by 5 mg every day until the desired effect is obtained, the drug is taken with meals. The maximum dose of baclofen for adults is 60–75 mg / day. In patients who have had a stroke and have spastic hemiparesis or paresis of the arms or legs, the use of baclofen is limited due to the side effects that occur during the treatment period. As a rule, this is drowsiness and muscle weakness, which can lead to deterioration of motor functions and even falls.Sometimes nausea, constipation, diarrhea, arterial hypotension occur. Care is required when prescribing the drug to elderly patients.

Baclofen can be given intrathecally with a pump for spinal spasticity caused by a previous spinal injury or multiple sclerosis. There is a positive experience with the use of baclofen intrathecally and in post-stroke spasticity [23]. In our country, this method is rarely used in stroke patients, largely due to its high cost.

Tizanidine (Sirdalud) – centrally acting muscle relaxant, alpha-2-adrenergic receptor agonist. The drug reduces spasticity by suppressing polysynaptic reflexes at the level of the spinal cord. This may be due to the inhibition of the release of excitatory amino acids and the activation of glycine, which suppresses the excitability of interneurons in the spinal cord. Sirdalud also has a moderate central analgesic effect. There is evidence that tizanidine inhibits the release of substance P from small sensory afferent fibers, which helps to reduce muscle tone of flexors and extensors, as well as reduce painful muscle spasms.Sirdalud is effective for cerebral and spinal spasticity, as well as painful muscle spasms. When taken orally, the maximum concentration of tizanidine in the blood is reached in an hour, food intake does not affect its pharmacokinetics. The initial dose of the drug is 2-6 mg / day in one or three doses, the average therapeutic dose is 12-24 mg / day, the maximum dose is 36 mg / day. Side effects may include drowsiness, dry mouth, dizziness, and a slight drop in blood pressure.

The efficacy of tizanidine (Sirdaluda) in patients with post-stroke spasticity has been convincingly shown in a randomized controlled trial in patients who had a stroke more than six months ago and had severe spasticity [19]. Treatment was started with 2 mg at night, then the dose was increased every seven days by 2 mg to 16 mg / day in three divided doses, then the dose was increased by 2 mg every three to four days, trying to achieve a dose of 36 mg / day in three divided doses. If the patient did not tolerate the increase in dose due to the appearance of side effects, then he was left at the same dose for another week, and then continued to build up.The results of the study showed a significant decrease in spasticity during treatment, by the 16th week it decreased by 2.80 ± 0.47 points on the Ashworth scale (p

Currently, the widely used form of tizanidine is in the form of capsules of 6 or 12 mg with modified release (Sirdalud MR). Comparative studies of Sirdalud MR with modified release and ordinary Sirdalud in patients with spasticity of various origins have shown similar clinical efficacy of these forms [20].Thanks to the sustained release, it has become possible to take the drug once a day, which has a significant advantage, since it increases patient adherence to treatment.

A comparative study of baclofen and tizanidine shows some advantage of tizanidine (Sirdaluda) both in terms of the severity of the antispastic effect and in terms of a smaller number of side effects [21, 22].

An analysis of 20 studies comparing the effectiveness of various antispastic agents in various neurological diseases accompanied by spasticity showed that tizanidine, baclofen and diazepam are approximately equally capable of reducing spasticity, but tizanidine (Sirdalud) is more effective than other antispastic agents in reducing clones [22] …Unlike baclofen, tizanidine (Sirdalud) does not cause weakening of muscle strength, it is better tolerated by patients than baclofen and diazepam, side effects associated with its administration are less likely to cause discontinuation of treatment [22].

Tolperisone hydrochloride (Midocalm) has a predominantly central muscle relaxant effect. A decrease in spasticity when taking the drug is associated with a depressing effect on the caudal part of reticular pharmacy, suppression of spinal reflex activity, and central H-cholinolytic properties.The drug has a moderate central analgesic effect and a mild vasodilator effect. Therapy with tolperisone hydrochloride begins with 150 mg / day in one or three doses and gradually increases the dose (in adults, usually up to 300-450 mg / day) until the effect is obtained. Tolperisone hydrochloride is used to treat both cerebral and spinal spasticity and to relieve painful muscle spasms. May cause side effects (drowsiness, muscle weakness, hypotension).

Botulinum toxin

Botulinum toxin type A or botulinum toxin (Botox, Dysport, Xeomin) can be used in stroke patients with local spasticity in paretic muscles [23]. Botulinum toxin is indicated if a stroke patient has a muscle with increased tone without contracture, as well as pain, muscle spasms, decreased range of motion and impaired motor function associated with spasticity of this muscle [14, 15, 23].The action of botulinum toxin when injected intramuscularly is caused by the blocking of neuromuscular transmission due to the suppression of the release of the neurotransmitter acetylcholine into the synaptic cleft.

The clinical effect after injection of botulinum toxin is observed after a few days and lasts for two to six months, after which a second injection may be required. The results of treatment are higher with the introduction of botulinum toxin in the early stages (up to a year) from the moment of the disease and a mild degree of paresis of the limb.

Placebo-controlled studies have shown significant efficacy of botulinum toxin in patients with post-stroke spasticity in the arm [24]. In the BEST study, 273 patients with post-stroke spasticity were randomized to receive botulinum toxin type A treatment or placebo in combination with standard therapy [25]. It was found that in the botulinum toxin type A group, significantly more often than in the placebo group, spasticity decreased and basic self-care skills (washing, dressing, eating, etc.) were restored.). A positive effect was also noted in another study, which included 463 stroke patients with hand spasticity [26].

The optimal time of administration of botulinum toxin in post-stroke spasticity, apparently, is 2-12 months from the moment of illness. During this period, the restoration of motor functions is most likely to occur, a new stereotype of movements will be formed, caused by the loss of a number of motor functions. However, it is possible to get a result from the use of botulinum toxin in more distant terms from the moment of illness.Treatment of patients with post-stroke hemiparesis with botulinum toxin in some cases allows not only to significantly reduce spasticity, but also to improve the quality of life of patients. It should be noted that the use of botulinum toxin in stroke patients should always be combined with physiotherapy (remedial gymnastics) and social adaptation.

Conclusion

The management of stroke patients is an urgent medical and social problem.The introduction into clinical practice of modern methods of stroke prevention and treatment of the consequences of stroke will significantly reduce mortality from stroke, accelerate recovery and improve the quality of life of patients.

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90,000 List of drugs sold to the population free of charge or with a 50% discount

B02BA

vitamin K

menadione sodium bisulfite

solution for intramuscular administration

B02BC

local hemostatics

fibrinogen + thrombin

sponge

B02BD

coagulation factors

anti-inhibitory coagulant complex

lyophilisate for preparation of solution for infusion

moroktokog alpha

lyophilisate for preparation of solution for intravenous administration

nonakog alpha

lyophilisate for preparation of solution for intravenous administration

oktokog alpha

lyophilisate for preparation of solution for intravenous administration

coagulation factor VII

lyophilisate for preparation of solution for intravenous administration

coagulation factor VIII

lyophilisate for preparation of solution for intravenous administration;

lyophilisate for preparation of solution for infusion;

solution for infusion (frozen)

coagulation factor IX

lyophilisate for preparation of solution for intravenous administration;

lyophilisate for preparation of solution for infusion

coagulation factors II, VII, IX, X in combination (prothrombin complex)

lyophilisate for preparation of solution for intravenous administration

coagulation factors II, IX and X in combination

lyophilisate for preparation of solution for infusion

coagulation factor VIII + von Willebrand factor

lyophilisate for preparation of solution for intravenous administration

eptacog alpha (activated)

lyophilisate for preparation of solution for intravenous administration

B02BX

other systemic hemostatics

Romiplostim

powder for solution for subcutaneous administration

eltrombopag

film-coated tablets

etamsylate

solution for intravenous and intramuscular administration;

solution for injection;

solution for injection and external use;

tablets

B03

antianemic drugs

B03A

iron preparations

B03AB

oral ferric preparations

iron (III) hydroxide polymaltose

drops for oral administration

oral solution;

syrup;

chewable tablets

B03AC

parenteral ferric preparations

iron (III) hydroxide sucrose complex

solution for intravenous administration

iron carboxymaltose

solution for intravenous administration

B03B

vitamin B12 and folic acid

B03BA

vitamin B12 (cyanocobalamin and its analogs)

cyanocobalamin

injection solution

B03BB

folic acid and its derivatives

folic acid

tablets;

film-coated tablets

B03X

other antianemic drugs

B03XA

other antianemic drugs

darbepoetin alfa

injection solution

methoxypolyethylene glycol-epoetin beta

solution for intravenous and subcutaneous administration

epoetin alfa

solution for intravenous and subcutaneous administration

epoetin beta

lyophilisate for the preparation of a solution for intravenous and subcutaneous administration;

lyophilisate for the preparation of a solution for subcutaneous administration;

solution for intravenous and subcutaneous administration

B05

blood substitutes and perfusion solutions

B05A

blood and blood products

B05AA

blood substitutes and blood plasma preparations

human albumin

solution for infusion

hydroxy-ethyl starch

solution for infusion

dextran

solution for infusion

gelatin

solution for infusion

B05B

solutions for intravenous administration

B05BA

solutions for parenteral nutrition

fat emulsions for parenteral nutrition

emulsion for infusion

B05BB

solutions affecting the water-electrolyte balance

dextrose + potassium chloride + sodium chloride + sodium citrate

powder for preparation of oral solution;

powder for oral solution (for children)

potassium chloride + sodium acetate + sodium chloride

solution for infusion

meglumine sodium succinate

solution for infusion

sodium lactate solution complex

solution for infusion

(potassium chloride + calcium chloride + sodium chloride + sodium lactate)

sodium chloride complex solution (potassium chloride + calcium chloride + sodium chloride)

solution for infusion

sodium chloride + potassium chloride + calcium chloride dihydrate + magnesium chloride hexahydrate + sodium acetate trihydrate + malic acid

solution for infusion

B05BC

solutions with osmodiuretic action

mannitol

solution for infusion

B05C

irrigation solutions

B05CX

other irrigation solutions

dextrose

solution for intravenous administration; solution for infusion

B05D

solutions for peritoneal dialysis

solutions for peritoneal dialysis

B05X

additives to solutions for intravenous administration

B05XA

electrolyte solutions

potassium chloride

concentrate for preparation of solution for infusion;

concentrate for preparation of solution for infusion and oral administration;

solution for intravenous administration

magnesium sulfate

solution for intravenous administration;

solution for intravenous and intramuscular administration

sodium bicarbonate

solution for infusion

sodium chloride

solution for infusion;

solution for injection;

solvent for the preparation of dosage forms for injection

C

cardiovascular system

C01

drugs for the treatment of heart diseases

C01A

cardiac glycosides

C01AA

digitalis glycosides

digoxin

solution for intravenous administration;

tablets;

tablets (for children)

C01B

antiarrhythmic drugs, classes I and III

C01BA

antiarrhythmic drugs, class IA

procainamide

solution for intravenous and intramuscular administration;

solution for injection;

tablets

C01BB

antiarrhythmic drugs, class IB

lidocaine

gel for topical application;

eye drops;

solution for intravenous administration;

solution for injection; spray for local and external use;

spray for topical application, dosed

C01BC

antiarrhythmic drugs, class IC

propafenone

solution for intravenous administration;

film-coated tablets

C01BD

antiarrhythmic drugs, class III

amiodarone

solution for intravenous administration;

tablets

C01BG

other antiarrhythmic drugs, classes I and III

lappaconitine hydrobromide

tablets

C01C

cardiotonic drugs, except for cardiac glycosides

C01CA

adrenergic and dopaminergic agents

dobutamine

concentrate for preparation of solution for infusion;

lyophilisate for preparation of solution for infusion;

solution for infusion

dopamine

concentrate for preparation of solution for infusion;

injection solution

norepinephrine

concentrate for preparation of solution for intravenous administration

phenylephrine

injection solution

epinephrine

injection solution

C01CX

other cardiotonic drugs

levosimendan

concentrate for preparation of solution for infusion

C01D

vasodilators for the treatment of heart diseases

C01DA

organic nitrates

isosorbide dinitrate

concentrate for preparation of solution for infusion;

metered spray;

sublingual metered spray;

tablets;

prolonged release tablets

isosorbide mononitrate

capsules;

extended-release capsules;

retard capsules;

90,998 sustained release capsules;

tablets;

prolonged release tablets

nitroglycerin

sublingual metered aerosol;

sublingual capsules;

concentrate for preparation of solution for infusion;

gum film;

solution for intravenous administration;

sublingual metered spray;

sublingual tablets;

sublingual tablets

C01E

other drugs for the treatment of heart diseases

C01EA

prostaglandins

alprostadil

concentrate for preparation of solution for infusion;

lyophilisate for preparation of solution for infusion

C01EB

other drugs for the treatment of heart diseases

ivabradine

film-coated tablets

meldonium

capsules;

solution for intravenous and parabulbar administration;

solution for intravenous, intramuscular and parabulbar administration;

injection solution

C02

antihypertensive drugs

C02A

centrally acting antiadrenergic drugs

C02AB

methyldopa

methyldopa

tablets

C02AC

Imidazoline receptor agonists

clonidine

solution for intravenous administration;

tablets

moxonidine

film-coated tablets;

film-coated tablets

C02C

antiadrenergic agents of peripheral action

C02CA

alpha-blockers

urapidil

extended-release capsules;

solution for intravenous administration

C02K

other antihypertensive drugs

C02KX

antihypertensive agents for the treatment of pulmonary arterial hypertension

bosentan

dispersible tablets;

film-coated tablets;

film-coated tablets

C03

diuretics

C03A

thiazide diuretics

C03AA

thiazides

hydrochlorothiazide

tablets

C03B

thiazide-like diuretics

C03BA

sulfonamides

indapamide

capsules;

film-coated tablets;

film-coated tablets;

film-coated sustained release tablets;

film-coated tablets of prolonged action;

film-coated controlled release tablets;

modified release film-coated tablets

C03C

loop diuretics

C03CA

sulfonamides

furosemide

solution for intravenous and intramuscular administration;

solution for injection;

tablets

C03D

potassium-sparing diuretics

C03DA

aldosterone antagonists

spironolactone

capsules;

tablets

C04

peripheral vasodilators

C04A

peripheral vasodilators

C04AD

Purine derivatives

pentoxifylline

concentrate for preparation of solution for intravenous and intra-arterial administration;

concentrate for preparation of solution for infusion;

concentrate for preparation of solution for injection;

solution for intravenous administration;

solution for intravenous and intra-arterial administration;

solution for infusion;

injection solution

C07

beta-blockers

C07A

beta-blockers

C07AA

non-selective beta-blockers

propranolol

tablets

sotalol

tablets

C07AB

selective beta-blockers

atenolol

tablets;

film-coated tablets;

film-coated tablets

bisoprolol

tablets;

film-coated tablets

metoprolol

solution for intravenous administration;

tablets;

film-coated tablets;

film-coated tablets of prolonged action;

film-coated tablets, sustained-release

C07AG

alpha and beta blockers

carvedilol

tablets;

film-coated tablets

C08

calcium channel blockers

C08C

Selective calcium channel blockers with a predominant effect on blood vessels

C08CA

dihydropyridine derivatives

amlodipine

tablets;

film-coated tablets

nimodipine

solution for infusion;

film-coated tablets

nifedipine

solution for infusion;

tablets;

film-coated tablets;

film-coated tablets;

modified release film-coated tablets;

film-coated sustained release tablets;

film-coated tablets of prolonged action;

film-coated controlled release tablets;

film-coated controlled release tablets;

modified release film-coated tablets

C08D

Selective calcium channel blockers with direct action on the heart

C08DA

Phenylalkylamine derivatives

verapamil

solution for intravenous administration;

film-coated tablets;

film-coated tablets;

film-coated sustained release tablets;

film-coated tablets of prolonged action

C09

drugs acting on the renin-angiotensin system

C09A

ACE inhibitors

C09AA

ACE inhibitors

captopril

tablets;

film-coated tablets

lisinopril

tablets

perindopril

tablets;

orodispersible tablets;

film-coated tablets

enalapril

tablets

C09C

angiotensin II receptor antagonists

C09CA

angiotensin II receptor antagonists

Losartan

film-coated tablets;

film-coated tablets

C09DX

angiotensin II receptor antagonists in combination with other agents

valsartan + sacubitril

film-coated tablets

C10

hypolipidemic agents

C10A

hypolipidemic agents

C10AA

HMG-CoA reductase inhibitors

atorvastatin

capsules;

film-coated tablets;

film-coated tablets

simvastatin

film-coated tablets;

film-coated tablets

Podolsk KVD | Official website of Podolsk dermatovenerologic dispensary

Full name Position Qualification category Certificate Education
Eltsova Natalya Vladimirovna Chief Physician

dermatovenerologist

Higher
Dermatovenereology
Dermatovenereology
12.04.2019 0550270015119
Higher, 1998 Nizhny Novgorod State Medical Academy

Khamitsaeva Irina Romanovna Head of department

Dermatovenereologist

Higher

Dermatovenereology

Dermatovenereology
02/29/2016 0177180393915
Higher, Moscow State University of Medicine and Dentistry, 2000.
Borisova Tatiana Timofeevna Clinical laboratory diagnostics doctor Higher

Clinical lab.diagnostics

Clinical laboratory diagnostics
06/27/2017 0550270007479
Higher, 1998 Moscow Medical Academy named after I.M. Sechenov

Bogatova Elena Yurievna Head of laboratory

Clinical laboratory diagnostics doctor

Higher
Clinical lab. diagnostics
Clinical laboratory diagnostics
06/16/2016 No. 0377180538858
Higher, 1985Khabarovsk State Medical Institute

Kozlova Evgeniya Yurievna Dermatovenereologist Higher
Dermatovenereology
Dermatovenereology
16.02.2018 0550270010045
Higher, 1997 Moscow Medical Stomatological Institute
Kirillova Natalya Ivanovna Dermatovenereologist Higher
Dermatovenereology
Dermatovenereology
10.02.2017 0177040056222
Higher, 1983 2nd Moscow State Medical Institute named after I.I. N.I. Pirogov
Klimontova Tatiana Vladimirovna Medical laboratory assistant Higher
Clinical lab. diagnostics
Clinical laboratory diagnostics 12/16/2019
1178270024845
Higher, 1994 Kemerovo State University
Lyamina Elena Vladimirovna Dermatovenereologist, Candidate of Medical Sciences Higher
Dermatovenereology
Dermatovenereology
16.10.2020
0550270021262
Higher, 1996 Tver State Medical Academy
Samokhvalova Elena Viktorovna (parental leave) Dermatovenereologist b / k Dermatovenereology 09/01/2017
0550270008008
Higher, State Budgetary Educational Institution of Higher Professional Education “Russian National Research Medical University named after N.I. Pirogov “Ministry of Health of the Russian Federation 2015.
Sityukov Yuri Pavlovich Dermatovenereologist Higher
Dermatovenereology
Dermatovenereology
16.10.2020 0550270021267
Higher, 1st Moscow Medical Institute named after I.M. Sechenov, 1989
Staforova Ksenia Nikolaevna Dermatovenereologist b / k Dermatovenereology

08/31/2015

0550140010218

Higher, Moscow State University of Medicine and Dentistry. A.I. Evdokimova, 2013
Silakova Tatiana Aleksandrovna Dermatovenereologist b / k Dermatovenereology
27.03.2017
0146040012791
Higher, 2011 SBEE HPE “Kursk State Medical University” MH and SR RF
Zaitsev Maxim Eduardovich Dermatovenereologist b / k Dermatovenereology
31.08.2018
0277040002754
Higher, 2016
SBEE HPE “First Moscow State Medical University named after THEM. Sechenov “MH RF
Perevalova Maria Andreevna Dermatovenereologist b / k Dermatovenereology 03.07.2020
107718 241897
Higher, 2018 FSBEI HPE “Perm State Medical University named after Ak. E.A. Wagner “
Tsareva Ekaterina Dmitrievna Dermatovenereologist Higher
Dermatovenereology
Dermatovenereology
09.04.2016
0377060177925
Higher, 2004 GOU VPO Russian State Medical University
Rogova Maria Denisovna Dermatovenereologist b / c Dermatovenereology 27.11.2020
332400063533
Higher, Federal State Budgetary Educational Institution of Higher Education “Tula State University”, 2018
Filatenkova Victoria Petrovna Medical laboratory assistant Higher
Clinical laboratory diagnostics
Clinical laboratory diagnostics 03/15/2019 0177241849270 Higher, Siberian Order of the Red Banner of Labor Medical University, 1993

.