What is baclofen used for. How does baclofen work. What are the side effects of baclofen. How should baclofen be taken. What precautions should be followed when using baclofen. How is baclofen stored and disposed of. What should you do in case of a baclofen overdose.

Understanding Baclofen: A Powerful Muscle Relaxant

Baclofen is a widely prescribed medication that belongs to the class of skeletal muscle relaxants. Its primary function is to alleviate pain and reduce muscle stiffness and tightness, particularly in patients with multiple sclerosis, spinal cord injuries, or other spinal cord diseases. By acting on the spinal cord nerves, baclofen effectively decreases the frequency and intensity of muscle spasms, providing relief and improving overall muscle movement.

How Does Baclofen Work?

Baclofen’s mechanism of action involves targeting the spinal cord nerves. This unique approach allows it to:

• Reduce the number of muscle spasms
• Decrease the severity of muscle spasms
• Alleviate pain associated with muscle stiffness
• Enhance muscle movement and flexibility

By modulating nerve signals in the spinal cord, baclofen helps patients regain better control over their muscle function, leading to improved quality of life.

Proper Usage and Dosage Guidelines for Baclofen

Administering baclofen correctly is crucial for achieving optimal therapeutic results. The medication is available in two forms: tablets and oral solution. Typically, it is prescribed to be taken three times a day at evenly spaced intervals. To ensure proper usage:

1. Follow your doctor’s instructions precisely
2. Use an oral syringe for accurate measurement of the liquid form
3. Maintain consistent timing for each dose
4. Do not alter the dosage without consulting your healthcare provider

Can baclofen be stopped abruptly? It is strongly advised against discontinuing baclofen suddenly, especially if you have been taking high doses for an extended period. Abrupt cessation may lead to severe withdrawal symptoms, including seizures, fever, confusion, muscle stiffness, and hallucinations. Your doctor will likely recommend a gradual reduction in dosage to ensure a safe discontinuation process.

Potential Side Effects and Precautions

While baclofen is generally well-tolerated, it may cause certain side effects. Common side effects include:

• Dizziness
• Weakness
• Confusion
• Headache
• Nausea
• Constipation
• Sleep disturbances
• Fatigue
• Frequent urination

Are there any serious side effects associated with baclofen? Yes, although rare, some patients may experience more severe reactions. These include:

• Hallucinations (visual or auditory)
• Seizures

If you experience any of these serious side effects, it is crucial to contact your healthcare provider immediately or seek emergency medical attention.

Precautions and Interactions

Before starting baclofen treatment, inform your doctor about:

• Any allergies to medications or ingredients
• All current medications, including over-the-counter drugs and supplements
• Pre-existing medical conditions, especially epilepsy, stroke history, rheumatic diseases, cerebral palsy, Parkinson’s disease, psychiatric conditions, or kidney disease
• Pregnancy or breastfeeding status

Does baclofen interact with other medications? Yes, baclofen may interact with various drugs, including:

• Antidepressants
• Anxiety medications
• Medications for mental illness
• Antiepileptic drugs
• Sedatives
• Sleeping pills
• Tranquilizers

Your doctor may need to adjust your medication regimen or monitor you closely for potential interactions.

Safe Storage and Disposal of Baclofen

Proper storage and disposal of baclofen are essential for maintaining its effectiveness and ensuring safety. Follow these guidelines:

• Keep baclofen in its original container, tightly closed
• Store tablets at room temperature, away from excess heat and moisture
• Refrigerate the oral solution
• Keep out of reach of children
• Use child-resistant safety caps when possible
• Dispose of unused medication properly, following local guidelines or pharmacy recommendations

Why is proper storage important? Correct storage helps maintain the medication’s potency and prevents accidental ingestion by children or pets. Additionally, proper disposal prevents environmental contamination and reduces the risk of medication misuse.

Managing Missed Doses and Overdose Situations

Adhering to the prescribed dosing schedule is crucial for achieving optimal results with baclofen. However, if you miss a dose:

1. Take the missed dose as soon as you remember
2. Skip the missed dose if it’s almost time for your next scheduled dose
3. Never take a double dose to compensate for a missed one

What should you do in case of a baclofen overdose? If you suspect an overdose, seek emergency medical attention immediately. Symptoms of overdose may include:

• Severe drowsiness
• Confusion
• Muscle weakness
• Slow or shallow breathing
• Seizures
• Loss of consciousness

Prompt medical intervention is crucial in managing overdose situations and preventing potentially life-threatening complications.

Lifestyle Considerations While Taking Baclofen

While baclofen can significantly improve quality of life for many patients, it’s important to be aware of how it may affect your daily activities:

• Exercise caution when driving or operating machinery, as baclofen may cause drowsiness
• Consult your doctor about alcohol consumption, as it may exacerbate baclofen’s side effects
• Maintain regular check-ups with your healthcare provider to monitor your response to the medication
• Stay hydrated and maintain a balanced diet to support overall health

Can baclofen affect your ability to perform daily tasks? Yes, especially when you first start taking the medication or after a dosage adjustment. It’s important to understand how your body responds to baclofen before engaging in activities that require full alertness and coordination.

Long-term Use and Monitoring of Baclofen Therapy

For patients on long-term baclofen therapy, regular monitoring is essential to ensure continued effectiveness and safety. Your healthcare provider may:

• Schedule periodic check-ups to assess your response to the medication
• Perform blood tests to monitor kidney function
• Adjust dosage based on your symptoms and any side effects
• Evaluate the need for continued therapy or potential alternatives

How long can baclofen be used safely? While baclofen can be used long-term for chronic conditions, the duration of therapy should be determined by your healthcare provider based on your individual needs and response to treatment. Regular assessments help ensure that the benefits of baclofen continue to outweigh any potential risks.

Alternative Treatments and Complementary Therapies

While baclofen is effective for many patients, some may benefit from exploring alternative or complementary treatments. These may include:

• Physical therapy
• Occupational therapy
• Acupuncture
• Massage therapy
• Yoga or gentle stretching exercises
• Mindfulness and relaxation techniques

Can alternative therapies replace baclofen? In some cases, alternative therapies may be used in conjunction with baclofen to enhance its effects or potentially reduce the required dosage. However, it’s crucial to discuss any complementary treatments with your healthcare provider to ensure they are safe and appropriate for your condition.

Understanding baclofen’s mechanism of action, proper usage, potential side effects, and necessary precautions is crucial for patients and caregivers alike. By following prescribed guidelines and maintaining open communication with healthcare providers, individuals can maximize the benefits of baclofen therapy while minimizing potential risks. As with any medication, personalized care and regular monitoring are key to achieving optimal outcomes in managing muscle spasticity and related conditions.

Baclofen: MedlinePlus Drug Information

pronounced as (bak’ loe fen)

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Baclofen is used to treat pain and certain types of spasticity (muscle stiffness and tightness) from multiple sclerosis, spinal cord injuries, or other spinal cord diseases. Baclofen is in a class of medications called skeletal muscle relaxants. Baclofen acts on the spinal cord nerves and decreases the number and severity of muscle spasms caused by multiple sclerosis or spinal cord conditions. It also relieves pain and improves muscle movement.

Baclofen comes as a tablet and a solution (liquid) to take by mouth. It usually is taken 3 times a day at evenly spaced intervals. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take baclofen exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Use an oral syringe (measuring device) to accurately measure and take your dose of baclofen solution. Ask your pharmacist for an oral syringe if one is not included with your medication.

Continue to take baclofen even if you feel well. Do not stop taking baclofen without talking to your doctor, especially if you have taken large doses for a long time. Abruptly stopping this medication can cause seizures, fever, confusion, muscle stiffness, or hallucinations. Your doctor probably will want to decrease your dose gradually.

This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.

Before taking baclofen,

• tell your doctor and pharmacist if you are allergic to baclofen, any other medications, or any of the ingredients in baclofen tablets and oral solution. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: antidepressants, medications for anxiety, medications for mental illness, medications for seizures, sedatives, sleeping pills, or tranquilizers. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have or have ever had epilepsy, a stroke, a rheumatic disease, cerebral palsy, Parkinson’s disease, a psychiatric condition such as schizophrenia or a confusional state, or kidney disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking baclofen, call your doctor immediately.
• you should know that baclofen may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
• ask your doctor about the safe use of alcoholic beverages while you are taking baclofen. Alcohol can make the side effects from baclofen worse.

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Baclofen may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• dizziness
• weakness
• confusion
• headache
• nausea
• constipation
• difficulty falling asleep or staying asleep
• tiredness
• frequent urination

Some side effects can be serious. If you experience either of the following symptoms, call your doctor immediately:

• seeing things or hearing voices that do not exist
• seizures

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online (http://www. fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store the tablets at room temperature and away from excess heat and moisture (not in the bathroom). Store the oral solution in the refrigerator.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA’s Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can’t be awakened, immediately call emergency services at 911.

Symptoms of overdose may include:

• vomiting
• weak muscle tone
• drowsiness
• vision problems
• coma
• difficulty breathing
• seizures

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Last Revised – 12/15/2019

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Baclofen Uses, Dosage & Side Effects

Generic name: baclofen (oral) [ BAK-loe-fen ]
Brand names: Lioresal, Lioresal Intrathecal, Gablofen, FIRST Baclofen, Ozobax, Fleqsuvy, Lyvispah
Dosage forms: oral granule (10 mg; 20 mg; 5 mg), oral liquid (5 mg/5 mL), oral suspension (1 mg/mL; 5 mg/mL), oral tablet (10 mg; 20 mg; 5 mg)
Drug class: Skeletal muscle relaxants

Medically reviewed by Kaci Durbin, MD. Last updated on Apr 19, 2023.

What is baclofen?

Baclofen belongs to a class of medications called skeletal muscle relaxants. Baclofen is an antispasmodic agent that acts on spinal cord nerves and decreases the number and severity of muscle spasms in patients with certain conditions affecting the spinal cord.

Baclofen is used in adults and children at least 12 years old to treat certain types of spasticity (muscle stiffness and tightness) and muscle pain in people with multiple sclerosis or a spinal cord injury or other spinal cord diseases.

Baclofen relieves pain and improves muscle movement.

Warnings

Do not use baclofen at a time when you need muscle tone for safe balance and movement during certain activities. Baclofen may make you drowsy. Do not drive or operate heavy machinery until you know how this medicine affects you.

Do not stop using this medicine suddenly, or you could have unpleasant withdrawal symptoms.

Ask your doctor about the safe use of alcoholic beverages while you are taking baclofen. Alcohol can make the side effects from baclofen worse.

Before taking this medicine

You should not use this medicine if you are allergic to baclofen.

To make sure this medicine is safe for you, tell your doctor if you have ever had:

• mental illness or psychosis;

• epilepsy or other seizure disorder;

• problems with balance;

• cerebral palsy;

• Parkinson’s disease;

• schizophrenia or a confused state;

• high blood pressure, or fast heart rate;

• a rheumatic disease;

• a stroke or blood clot; or

• kidney disease.

Using baclofen may increase your risk of developing an ovarian cyst. Talk with your doctor about your own risk.

Tell your doctor if you are pregnant or plan to become pregnant, or breastfeeding or plan to breastfeed. If you take baclofen while pregnant or breastfeeding, withdrawal symptoms such as tremors, stiff muscles, or seizure may occur in the baby.

How should I take baclofen?

Take baclofen exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

Shake the oral suspension (liquid).

Measure a dose with the supplied measuring device (not a kitchen spoon).

Shake and pour the entire oral granules packet to dissolve in your mouth or swallow whole at once, with or without liquids.

You may also mix the granules with liquids (milk, or apple juice) or soft food (apple sauce, yogurt, or pudding).

The oral granules can also be given through a feeding tube. Ask your doctor or pharmacist if you do not understand these instructions.

Call your doctor if your symptoms do not improve, or if they get worse.

You may have withdrawal symptoms if you stop using baclofen suddenly. Ask your doctor before stopping the medicine.

Store the oral suspension (liquid) at room temperature away from moisture and heat. Throw Fleqsuvy away after 2 months of first opening.

Store Ozobax in the refrigerator, do not freeze.

Dosing information

Usual Adult Dose for Spasticity:

Oral:
-Initial dose: The following gradually increasing dosage regimen is suggested, but should be adjusted to suit individual patient requirements: 5 mg orally 3 times a day for 3 days, then 10 mg orally 3 times a day for 3 days, then 15 mg orally 3 times a day for 3 days, then 20 mg orally 3 times a day for 3 days
-Maintenance dose: Should be individualized.
-Maximum dose: 80 mg/day (20 mg orally 4 times a day).

Usual Pediatric Dose for Spasticity:

12 years and older:
Oral:
-Initial dose: The following gradually increasing dosage regimen is suggested, but should be adjusted to suit individual patient requirements: 5 mg orally 3 times a day for 3 days, then 10 mg orally 3 times a day for 3 days, then 15 mg orally 3 times a day for 3 days, then 20 mg orally 3 times a day for 3 days
-Maintenance dose: Should be individualized.
-Maximum dose: 80 mg/day (20 mg orally 4 times a day)

Comments:
-The lowest dose compatible with an optimal response is recommended.
-Slowly withdraw therapy if benefits are not evident after a reasonable period.

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include increasing drowsiness, dizziness, sleepiness, trouble focusing on objects, shallow breathing, seizure, or muscle weakness leading to loss of consciousness.

What should I avoid while taking baclofen?

Avoid drinking alcohol.

Avoid driving or hazardous activity until you know how baclofen will affect you. Your reactions could be impaired.

Do not share this medicine with another person, even if they have the same symptoms you have.

Baclofen side effects

Get emergency medical help if you have signs of an allergic reaction to baclofen: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Baclofen may cause serious side effects. Call your doctor at once if you have:

• severe drowsiness, breathing problems;

• confusion, hallucinations;

• muscle weakness, itching, tingling, or twitching in your hands, arms, feet, or legs; or

• fever.

Common baclofen side effects may include:

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect baclofen?

Using baclofen with other drugs that make you drowsy can worsen this effect. Ask your doctor before using opioid medication, a sleeping pill, a muscle relaxer, or medicine for anxiety or seizures.

Other drugs may interact with baclofen, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all other medicines you use.

Popular FAQ

Common antidepressants used for orthopedic pain relief may include SSRIs like fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft), SNRIs such as duloxetine (Cymbalta), or tricyclic antidepressants (TCAs) like amitriptyline (Elavil) or nortriptyline (Pamelor). Continue reading

More about baclofen

• Check interactions
• Compare alternatives
• Reviews (426)
• Drug images
• Side effects
• Dosage information
• Patient tips
• During pregnancy
• Support group
• Drug class: skeletal muscle relaxants
• Breastfeeding

Patient resources

• Advanced Reading
• Baclofen (Oral) (Advanced Reading)
• Baclofen Intrathecal Injection
• Baclofen Tablets
• Baclofen Oral Solution

Other brands

Lioresal, Gablofen, Fleqsuvy, Lyvispah, Ozobax

Professional resources

• Prescribing Information

Related treatment guides

• Alcohol Withdrawal
• Cerebral Spasticity
• Cervical Dystonia
• Chronic Spasticity

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use baclofen only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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Baclosan (Baclofen): what kind of drug is it, how does it work, signs of use, consequences, addiction treatment

In modern realities, more and more people are pathologically dependent on various synthetic drugs. The universal availability of these drugs only increases the risk of developing drug addiction. Some of the drugs hunted by drug addicts are widely used in traditional medicine for the treatment and correction of various pathological conditions.

Baclofen – pills for treatment or drug?

Baclosan (Baclofen) is a synthetic drug that belongs to the group of muscle relaxants. It is used in traditional medical practice to relieve seizures of epilepsy, correct spastic reactions in various muscle groups that are provoked by various diseases. But, unfortunately, baclofen is a drug that is widely popular in the criminal world. The pathological interest in this drug is explained by the mechanism of action of Baclofen on the central nervous system.

What does the drug do to a person that the frequency of pathological addictions to these pills regularly increases:

• dulls mental reactions, reduces the effect of external stimuli on the receptors of the nervous system;
• promotes hallucinations;
• helps to relax and get rid of fatigue;
• improves mood and resistance to stress;
• relieves muscle spasms.

Traditional neurology and neurosurgery recommend the use of Baclofen for medicinal purposes. What doctors prescribe medicine for:

• spastic processes;
• epilepsy;
• traumatic brain injury;
• spinal cord surgery.

The systematic use of baclofen tablets leads to the formation of receptor resistance at the biochemical level. Therefore, the patient constantly requires increasing dosages of the drug to obtain the desired effect. Drug addicts constantly increase the amount of the drug baclofen. What is the unauthorized use of the drug leads to irreversible consequences, drug addicts do not even think about it.

Drug abuse leads to receptor resistance to regular use of Baclofen tablets. An overdose against the background of a significant excess of the doses recommended by the doctor occurs almost instantly and is manifested by the following symptoms:

Treatment of addiction to baclofen

consultation with a narcologist at home and in a hospital

removal of withdrawal symptoms

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Baclofen drug.

Effect of unauthorized use

Baclofen is widely used in the criminal environment. The effect of the drug on the central nervous system, which is manifested by a decrease in the reactivity of nervous processes, explains the use of the drug to achieve the effect of euphoria. The drug has a pronounced sedative effect, increases adaptation to stress factors. The systematic use of the remedy leads to:

• resistance to stress factors;
• cheer up;
• achieve the effect of euphoria.

Balcofen. Consequences of illegal use

CNS suppression is often negative and can lead to irreversible consequences:

• heart failure;
• stop spontaneous breathing;
• disorders of the nervous regulation of vital organs;
• the appearance of malignant tumors in the central and peripheral nervous system.

In addition, a significant excess of dosages recommended by specialists leads to negative consequences from taking Baclofen tablets. Side effects at high doses:

• gastrointestinal bleeding;
• severe intoxication;
• acute renal or hepatic insufficiency;
• memory problems;
• loss of consciousness;
• acute heart failure;
• convulsions that are difficult to control.

These negative reactions are due to the action of Baclofen on nerve cells. Overdose develops quickly enough. This is due to the specific effect of the main drug on nerve receptors. This condition requires urgent specialized care to prevent negative consequences and death.

Only in the conditions of a specialized clinic can one get rid of the biochemical and psycho-emotional dependence on baclosan and its derivatives.

Call 8 (495) 150-85-96

Clinical pharmacology of muscle relaxants uMEDp

Today, muscle relaxants are widely used in the treatment of spasticity and various pain syndromes. This article is devoted to a review of the clinical pharmacology of three muscle relaxants – tizanidine, baclofen and tolperisone. Particular attention is paid to the safety and tolerability of these drugs.

Table 1. Pharmacokinetic characteristics of oral tizanidine in different patient populations

Table 2. Pharmacokinetic characteristics of tolperisone at a single dose of 150 mg

Table 3. The frequency of the most common adverse reactions in patients with spasticity when using tizanidine, baclofen or diazepam

Table 4. Head-to-head safety studies of tizanidine and baclofen in patients with spasticity

Table 5. Overall tolerance of tizanidine, baclofen and diazepam in comparative clinical studies in patients with spasticity, % of patients

Introduction

Muscle relaxants are widely used in the complex treatment of spasticity in multiple sclerosis or after a stroke, as well as pain syndromes.

Scientists from the USA found that only 16% of patients with multiple sclerosis had no spasticity, in 31% of cases it was expressed to a minimum degree, in 19% – in mild, in 17% – moderate, in 13% – severe, in 4% cases – was of a total nature, making everyday activity impossible [1].

Another group of patients who require the appointment of muscle relaxants are stroke survivors [2]. Thus, in the first three months after a stroke, more often hemorrhagic, spasticity was observed in 17–25% of patients [3].

Muscle relaxants are also used for pain in the lower back, mostly acute and associated with muscle spasm [4]. According to different researchers, the prevalence of pain in the lower back ranges from 1.4 to 20.0% [5]. In the Russian Federation, according to the World Health Organization, pain in the lower back among people over 50 years of age occurs in 56% of cases [6]. At the same time, it has been established that from 50 to 80% of the adult population experience such pain at least once in their lives [7, 8].

To compare the effectiveness of muscle relaxants for pain in the lower back, R. Chou et al. conducted a systematic review [9]. Scientists noted that there are not enough high-quality clinical studies to evaluate this [9].

Since the most effective muscle relaxant in the treatment of low back pain has not been determined, consideration should be given to its tolerability and safety profile when choosing a drug.

Good tolerability in outpatient treatment is especially important, since the development of adverse drug reactions may be accompanied by a decrease in compliance and even discontinuation of the drug [10].

The article considers the pharmacology of the most studied and widely used muscle relaxants in clinical practice: tizanidine, baclofen and tolperisone.

Pharmacodynamics and pharmacokinetics

Tizanidine

Tizanidine is a centrally acting muscle relaxant. The drug is an alpha-2-adrenergic receptor agonist. Their stimulation in the region of the presynaptic membrane leads to a decrease in the secretion of amino acids (glutamate and aspartate) that activate the motor neurons of the spinal cord [11, 12]. As a result, the polysynaptic reflexes of the spinal cord responsible for muscle hypertonicity are inhibited. Along with this, inhibition of interneuronal activity, also caused by stimulation of alpha-2-adrenergic receptors, causes additional antinociceptive and anticonvulsant activity [12].

The pharmacokinetic profile of tizanidine has been studied in a number of clinical studies, both in healthy volunteers and in patients with spinal cord injury or multiple sclerosis. It has been established that when taken orally, tizanidine is rapidly absorbed (53-66% of the dose taken). The maximum concentration in blood plasma (C _max ) with a single oral dose of 5 and 8 mg varies from 3.2 to 25.8 µg/l, respectively [13]. Time to reach maximum concentration (T _max ) in blood plasma is 0.75–2.00 hours (Table 1) [13].

A study involving healthy volunteers demonstrated that food intake had no significant effect on the pharmacokinetics of tizanidine [13].

The absolute bioavailability of tizanidine when taken orally is from 20 to 34%, which is due to the pronounced effect of the first passage through the liver [12].

Tizanidine is metabolized in the liver by oxidation with the participation of isoenzymes of the cytochrome P450 system (CYP1A2) with the formation of inactive metabolites, 19-23% of which are excreted with faeces, 53-66% – with urine. Less than 3% of the dose of tizanidine is excreted unchanged in the urine [14].

Most clinical studies have shown that the half-life (T _1/2 ) of tizanidine is 2.1-4.2 hours [13]. In case of impaired renal function (creatinine clearance less than 1.5 l / h (25 ml / min)) the half-life with a single dose of 4 mg increases to 13.6 hours [13].

Baclofen

Baclofen is also a centrally acting muscle relaxant. The drug is a lipophilic derivative of gamma-aminobutyric acid (GABA) and has a high affinity for its B-receptors. It activates GABA B receptors on mono- and polysynaptic neurons in the spinal cord and brain. By acting on B-receptors, baclofen causes a decrease in spasticity.

As is known, GABA affects two types of receptors – A and B [15]. A receptors are ionotropic. When GABA binds to them, an ion channel opens in the nerve cell membrane, chloride ions penetrate the cell, reducing its reactivity. This type of receptor is the target of benzodiazepines, barbiturates, volatile anesthetics, and alcohol [15]. B receptors are metabotropic. Indirectly, through the G-protein system, they reduce the level of excitation in the cell. A decrease in cell sensitivity to excitatory effects is provided due to the effect on calcium and potassium channels. B receptors can be located both presynaptically and postsynaptically [16].

It is believed that the inhibitory effect on the brain upon activation of B receptors is realized by reducing the release of excitatory amino acids (for example, glutamate), as well as by hyperpolarization of postsynaptic neurons [16].

It should be noted that baclofen is characterized by a withdrawal syndrome. This can manifest as hallucinations, disorientation, confusion, tachycardia, tremors, seizures and muscle rigidity, as well as hypertension and hyperthermia. The development of these conditions is due to the rapid cessation of the inhibitory effect of the drug on GABA receptors. Risk factors for the occurrence of withdrawal syndrome are considered to be high doses, long-term therapy and its rapid withdrawal [17].

When administered orally, baclofen is rapidly absorbed from the gastrointestinal tract, with a bioavailability of 70–85% [18]. However, as the dose increases, absorption may decrease. With a single oral dose of 50 mg C _max in healthy volunteers was 737.6 ng/ml, T _max was 1.9 ± 0.3 hours [19].

It should be noted that the results of a prospective study in which 15 male volunteers aged 19up to 30 years [20], suggested the absence of significant pharmacokinetic interactions between baclofen and tizanidine. The study consisted of three periods: the first – taking tizanidine 4 mg three times a day for seven days, the second – taking baclofen 10 mg three times a day for seven days, the third – the joint administration of tizanidine and baclofen in the above doses also in within seven days. Washing periods of four days were carried out between these periods. C _max of baclofen when taken separately reached 211 ng/ml, when combined with tizanidine – 208 ng/ml [20].

Baclofen has a relatively short T _1/2 – from two to six hours.

About 15% of baclofen is metabolized in the liver by deamination. In clinical studies using a drug labeled with a radioactive isotope, it was found that about 85% is excreted unchanged, mainly with urine, as well as with faeces [18].

Complete elimination of the drug from the body is observed 72 hours after administration.

Tolperisone

Tolperisone is a centrally acting muscle relaxant, similar in chemical structure to local anesthetics (lidocaine). The drug is mainly used in European countries. It is not registered in the USA.

The mechanism of action of tolperisone is not fully understood. However, it has been found that it blocks voltage-dependent sodium and potassium channels at the level of the spinal cord, causing inhibition of the presynaptic release of neurotransmitters [21]. In addition, the drug suppresses mono- and polysynaptic reflexes at the level of the spinal cord, provides lidocaine-like analgesia, and stabilizes nerve cell membranes [21]. Along with this, tolperisone enhances peripheral blood flow, facilitates voluntary muscle movements [21].

Tolperisone is rapidly and almost completely absorbed from the gastrointestinal tract. Due to the effect of the first passage through the liver, its absolute bioavailability is 17–20% [21, 22]. The time to reach the maximum concentration is from 0.5 to 1.0 hours [21]. The elimination half-life averages 1.7 hours [22].

A distinctive feature of tolperisone is the significant variability of pharmacokinetic parameters depending on genetic characteristics. So, in the study by M. Pawlowska et al. (2015) [22] involved 28 healthy Caucasian men aged 27.3 ± 7.7 years [22]. Volunteers received a single oral dose of tolperisone at a dose of 150 mg. Using a real-time polymerase chain reaction, they were found to be carriers of alleles of the CYP2D6 and CYP2C19 genescytochrome P450, which are responsible for the metabolism of tolperisone.

C _max drug ranged from 4. 47 to 336.43 ng/ml, on average it was 90.88 ± 86.04 ng/ml (Table 2) [22].

The study also found that the frequency of genetic polymorphisms of the genes that provide slow / slow metabolism of tolperisone in healthy volunteers for CYP2D6 and CYP2C19 isoenzymes was 46.43 and 0%, respectively [22]. The results of the study by Z. Desta et al. indicate that the number of Caucasians with a genetically determined slow metabolism of tolperisone does not exceed 6% [23]. To obtain accurate information, a broader study of the problem in different populations and countries is required.

Similar data on the variability of the pharmacokinetic parameters of tolperisone were presented by J.W. Bae et al. (2007) [24]. The study was conducted with the participation of 15 healthy volunteers of the Mongoloid race (Koreans). The average age of men is 23.6 ± 1.3 years. Tolperisone was administered orally at a dose of 450 mg once. C _max ranged from 64.2 to 784.9 ng/ml. Area under the pharmacokinetic curve (AUC), starting from zero to infinity (AUC _0-∞ ), – from 125. 9up to 1241.3 ng × h/ml [24].

Thus, depending on the genetic characteristics of a person, the maximum concentration of tolperisone in blood plasma can vary significantly. As a result, either the ineffectiveness of therapy (at low concentrations due to a high level of metabolism of tolperisone), or a high risk of developing unwanted and toxic reactions (at a low level of metabolism, leading to high concentrations of the drug in the blood).

Tolperisone is excreted mainly by the kidneys (85%). At the same time 98% of the drug is eliminated from the body within 24 hours after ingestion [21].

Adverse reactions

Tizanidine

Tizanidine is generally well tolerated. According to the results of clinical studies, in patients with spasticity taking tizanidine ≤ 36 mg / day, the most common adverse reactions were dry mouth (23-57%), drowsiness (24-48%), muscle weakness (18-48%) and dizziness (10–19%). In 5-7% of cases, there was a clinically significant increase in the level of liver enzymes, which resolved after discontinuation of the drug [25-27].

In comparative studies, among the most common side effects while taking tizanidine ≤ 32 mg / day, drowsiness, dry mouth and muscle weakness were also indicated [13]. At the same time, the incidence of drowsiness in those who received tizanidine and those who took baclofen was comparable – from 15 to 67% (Table 3) [13].

It should be noted that baclofen (0–25%) had the highest rate of drug withdrawal due to muscle weakness, followed by diazepam (4–6%) and tizanidine (0–6%) (Table 4) [ 28–33].

Serious adverse reactions during tizanidine therapy were recorded in 0.18% of patients [34]. These were represented by hallucinations and severe liver dysfunction. In most cases, liver damage during tizanidine therapy manifests itself in the form of an increase in the level of liver enzymes (alanine aminotransferase and aspartate aminotransferase) – 5% of patients.

In addition to the safety profile, tolerability is considered an important characteristic of any drug. A survey of patients with spasticity treated with tizanidine showed that the overall tolerability of the drug was good or excellent in 44-100% of cases (Table 5) [13].

In comparative studies, tizanidine was better tolerated than baclofen and diazepam, which may affect adherence to therapy, especially in outpatient settings [13].

Baclofen

The incidence of adverse reactions with oral baclofen ranges from 10% to 75% [35]. The most common include drowsiness, excessive general weakness, severe muscle weakness and dizziness.

In patients with impaired renal function, the drug should be administered with caution due to a higher risk of adverse reactions. Data on this was received by F.T. Muanda et al. in a large retrospective cohort study of 15,942 elderly patients (66 years and older) with chronic kidney disease (estimated glomerular filtration rate (eGFR)

We also compared the relative risk of hospitalizations due to encephalopathy in those taking and not taking baclofen (n = 284,263). The weighted relative risk of hospitalization while taking the drug at a dose of less than 20 mg / day was 5.9(with 95% confidence interval (CI) 3.59–9.70), at a dose of 20 mg/day or more – 19.8 (95% CI 14.0–28.0).

Thus, it was found that in patients with impaired renal function, baclofen during the first 30 days of administration contributed to the development of encephalopathy requiring hospitalization, therefore, when prescribing it to such patients, the benefit / risk ratio should be assessed [36].

Tolperisone

Most often, weakness and muscle pain, dizziness, urticaria, nausea, vomiting, and dry mouth are observed during tolperisone therapy [21]. These reactions usually subside after discontinuation of the drug. However, the literature also describes severe adverse reactions, such as anaphylactic shock [37]. It should be noted that tolperisone does not have a sedative effect [6].

According to post-registration studies and the spontaneous reporting system, allergic reactions occurred in about 50% of cases, followed by adverse reactions from the gastrointestinal tract [38]. Among allergic reactions, the most common were urticaria (5.1%), itching (4.8%), shortness of breath (4.2%), angioedema (3%), erythema (2.6%), rash (1.8 %) and anaphylactic shock (1.2%). About 30% of allergic reactions developed when tolperisone was used with other drugs, most often with non-steroidal anti-inflammatory drugs [38]. Allergic reactions on the background of tolperisone therapy became the basis for the European Medical Agency to recommend to refrain from prescribing oral forms of tolperisone, with the exception of adult patients with spasticity after a stroke (2012) [39]. This statement was made after evaluating the benefit / risk ratio for various diseases.

Data from post-registration studies and spontaneous reporting systems also revealed serious side effects in the form of hypersensitivity reactions, as well as a lack of data confirming the effectiveness of tolperisone in the treatment of a number of diseases. In this regard, experts from the European Medical Agency recommended limiting the use of oral tolperisone, except for the treatment of spasticity after a stroke, in which the benefits of using the drug outweigh the potential risk [39].